Term
|
Definition
nonspecific inhibitors of peripheral sensory, motor, & autonomic pathways via inhibition of AP conduction
no loss of consciousness or vital functions |
|
|
Term
|
Definition
| specific inhibitors of pain pathways via action on primary nociceptors & in the CNS |
|
|
Term
| How do local anesthetics block AP conduction? |
|
Definition
| block voltage-dependent sodium channels |
|
|
Term
| What are the 3 conformations of the sodium channel? |
|
Definition
1) b/w impulses: resting (closed)
2) after stimulation(depolarization): activated (open)
3) transition from an open to closed conformation (inactive) => back to resting once membrane repolarizes |
|
|
Term
| How do local anesthetics block voltage-dependent sodium channels? |
|
Definition
| reducing the influx of sodium ions (=> prevention of depolarization of membrane => blocking AP conduction) |
|
|
Term
| When is the local anethetic pharmacologically active? |
|
Definition
|
|
Term
| What does the Local Anesthetic (LA) do to the calcium channel? |
|
Definition
| binds open state & stabilizes the inactive state => blockade of sodium current (=> increase of threshold excitability, decreased rate of AP, decreased conduction) |
|
|
Term
|
Definition
aromatic ring connected to ionizable group (s.a. amines), connected by ester or amide bond
[image] |
|
|
Term
| Why is the hydrophobic aromatic ring & amino nitrogen substituents needed for LA? |
|
Definition
| increase potency & duration of action |
|
|
Term
| When will LA have a more rapid onset & a more concentration of nonionized base that can pass thru cell membrane? |
|
Definition
the closer pKa of a LA is to physiological pH
most LAs are weak bases (pKa b/w 8 & 10) |
|
|
Term
| Why is the presence of an ester bond or amide bond important in a local anesthetic? |
|
Definition
| suceptibility to metabolic hydrolysis |
|
|
Term
| What inactivates the ester-containing LA? |
|
Definition
|
|
Term
| Who are at an increased risk for LA toxic side effects with ester LA? |
|
Definition
| patients with genetically abnormal pseudocholinesterases => slower metabolism |
|
|
Term
| What metabolizes the amide-containing LA? |
|
Definition
|
|
Term
| What does rate of amide metabolism depend on? |
|
Definition
| drug itself (overall slower than ester hydrolysis) |
|
|
Term
| What can reduce the metabloic rate and predispose patients to systemic toxicity with amide LA? |
|
Definition
| decreases in hepatic function or liver blood flow |
|
|
Term
| What is needed for a LA to be effective? |
|
Definition
1) partition into
2) diffuse across
3) dissociate from
membrane in the cytosol
moderate hydrophobicity = more effective
(not enough hydrophobicity - can't penetrate membrane, too much - sticks in membrane) |
|
|
Term
| Do amide or ester LA have longer durations of action? |
|
Definition
|
|
Term
Where are ester LA excreted?
amide LA? |
|
Definition
|
|
Term
| Do ester or amide LA have more potential SE? |
|
Definition
|
|
Term
| What determines the therapeutic effect & extend of toxicity of LAs? |
|
Definition
|
|
Term
| What are the 6 clinical uses of local anethetics? |
|
Definition
1) Topical
2) infiltration
3) field block
4) nerve block
5) spinal
6) epidural |
|
|
Term
|
Definition
| short term pain relief when applied to skin or mucous membranes |
|
|
Term
| What must topical LA traverse to reach nerve endings of Aδ & C fibers of the dermis? |
|
Definition
|
|
Term
|
Definition
| numb an area of skin via injection intradermally or subcutaneously without considering course of cutaneous nerves |
|
|
Term
| Why is intrafiltration LA faster than topical LA? |
|
Definition
| doesn't have to cross epidermal barrier |
|
|
Term
| What is the disadvantage to infiltration LA? |
|
Definition
| large amount of LA for a sm. area |
|
|
Term
| How can duration of action be increased & amount of LA needed be decreased? |
|
Definition
| specifically block nerves that innervate area of interest |
|
|
Term
| How can specific nerves be blocked? |
|
Definition
1) subcutaneously at major nerves
2) level of spinal roots |
|
|
Term
|
Definition
| subcutaneous injection to anesthetize region distal to injection |
|
|
Term
|
Definition
| injection of LA into or around individual peripheral nerves or nerve plexuses |
|
|
Term
|
Definition
| injection into the CSF in the lumbar space usually b/w 3 & 4 lumbar vertebrae |
|
|
Term
|
Definition
| injection into the epidural space to produce anesthesia above & below injection site |
|
|
Term
Function
therapeutic nerve block |
|
Definition
| used to treat painful conditions |
|
|
Term
Function
diagnostic nerve blocks |
|
Definition
| used to determine source of pain |
|
|
Term
Function
prognostic nerve blocks |
|
Definition
| predict outcomes of current treatment |
|
|
Term
def
preemptive nerve block |
|
Definition
| prevent subsquent pain from a procedure than can cause problems |
|
|
Term
| What determines the degree of toxicity of a LA? |
|
Definition
| amount of LA that enters systemic circulation (absorption) |
|
|
Term
| Where does rapid absorption of LA occur? |
|
Definition
|
|
Term
| How can duration of local anesthetic action be prolonged & reduce toxicity of LA? |
|
Definition
| reduce blood flow to area via administration of a vasocontrictor s.a. epinephrine to reduce blood flow to the area |
|
|
Term
When is epinephrine use with LA contraindicated?
Why? |
|
Definition
| fingers, toes, ears, & nose due to limited collateral circulation => hypoxic damage, tissue necrosis, & gangrene |
|
|
Term
| What are the 3 types of nerve fibers comprising peripheral nerves? |
|
Definition
|
|
Term
| What 3 protective membranes surround the peripheral nerve fibers? |
|
Definition
epineurium
perineurium
endoneurium |
|
|
Term
| What peripheral nerve fibers mediate pain? |
|
Definition
|
|
Term
| What peripheral nrve fibers mediate temperature? |
|
Definition
|
|
Term
| What is mediated by Aα, Aβ, & Aγ nerve fivers? |
|
Definition
| postural, touch, pressure & motor |
|
|
Term
| Which nerve fibers are blocked first in a nerve blockade? |
|
Definition
|
|
Term
| What contributes to the differential sensitivity to LA of nerve fibers in a nerve blockade? |
|
Definition
1) fiber diameter (smaller = faster)
2) firing frequency (higher frequency = faster)
3) location in nerve bundle (periphery = faster) |
|
|
Term
def
differential functional blockade |
|
Definition
the general order in which functional deficits occur
(pain, temp, touch, pressure, motor) |
|
|
Term
| Do sensory or motor fibers have a slower firing rate? |
|
Definition
|
|
Term
| Do sensory or motor fibers have a longer action potential duration? |
|
Definition
|
|
Term
| Why are shorter diameter fibers preferentially blocked by LA over larger diameters? |
|
Definition
| the distance over which these fibers propagate an electrical impulse is shorter |
|
|
Term
| Why are nerve fibers in the periphery preferentially blocked by LA? |
|
Definition
1) exposed 1st
2) exposed to higher concentration |
|
|
Term
| What undesired CNS SE are seen due to LAs? |
|
Definition
1) stimulation (excitatory motor phenomena)
2) restlessness
3) dizziness, drowsiness
4) tremors, convulsions
5) confusion, agitation
6) resp. depression |
|
|
Term
| What is the primary site of action of cariovascular SE due to LAs? |
|
Definition
|
|
Term
| What are the LA cardiovascular SE? |
|
Definition
Myocardium:
decreased electrical excitability
decreased conduction
decreased contraction => decreased CO
Vascular smooth muscle:
relaxation => vasodilation (except cocaine) |
|
|
Term
| What other smooth muscle SE are seen in LA? |
|
Definition
| depress contractions/relaxation (GI, vascular, bronchial) |
|
|
Term
| What are the LA hypersensitivity SE? |
|
Definition
allergic dermatitis
asthmatic attacks |
|
|
Term
Are ester or amide LA more likely to cause hypersensitivity?
Why? |
|
Definition
| esters due to PABA dertivatives (known allergen) |
|
|
Term
| What are the 4 ester-derived LA? |
|
Definition
1) Cocaine
2) Procaine (novacaine)
3) Benzocaine
4) Tetracaine |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| amino ester associated with complex cyclic structure |
|
|
Term
| How is cocaine different in SE profile than other LA? |
|
Definition
|
|
Term
|
Definition
| adrenergic phenomenon: HTN, tachycardia, arrythmia, etc. |
|
|
Term
| What causes cocaine toxicity SE? |
|
Definition
| blockage of catecholamine uptake in CNS & PNS |
|
|
Term
SOA (spectrum of activity)
cocaine |
|
Definition
| anesthesia of mucous membranes (topical only) - due to LA & vasoconstriction, can be used to decrease operative bleeding |
|
|
Term
| Why is cocaine so addictive? |
|
Definition
| affects mesolimbic pathway (pleasurable feelings) |
|
|
Term
|
Definition
|
|
Term
CI (contraindications)
cocaine |
|
Definition
| traumatized mucosa & sepsis, heart issues, Tourette's, pregnancy |
|
|
Term
| What was the first synthetic anesthetic? |
|
Definition
|
|
Term
| What is procaine hydrolyzed to? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| Why is procaine anethesia slow to onset(2-5 min)? |
|
Definition
|
|
Term
| Why is procaine duration of action short |
|
Definition
| low hydrophobicity => dissociated rapidly from Na+ channel |
|
|
Term
| What happens once procaine dissociates from Na+ channel? |
|
Definition
| rapid removal from administration site via circulation (not retained in tissue) |
|
|
Term
|
Definition
| infiltration & dental procedures |
|
|
Term
|
Definition
warfarin
MAOIs
anti-HTN
sulfas |
|
|
Term
|
Definition
| liver/heart disease, PABA, low pseudocholinesterase |
|
|
Term
Onset/Duration/Potency
Benzocaine |
|
Definition
| rapid onset(1 min), short acting(15-20 min), low potency |
|
|
Term
| How does bezocaine MOA differ from that of other LA? |
|
Definition
| it's small, so it fits into the pore in the closed state to stabilize the closed form |
|
|
Term
| What are the 3 forms benzocaine comes in? |
|
Definition
1) cream
2) aerosol
3) ointment |
|
|
Term
|
Definition
1) topical pain reliever (sun burn, sore throat, teething, etc)
2) anesthesize mucous membranes
3) lubricant & LA for inserting medical devices s.a. catheters, endoscopic tubes, scopes, etc. |
|
|
Term
|
Definition
| sulfas, supplements, caffeine, EtOH |
|
|
Term
|
Definition
| methemoglobulinemia, enzyme deficiency, COPD, heart disease, infants, Advisory for cosmetic procedures (risk for systemic toxicity if not used appropriately) |
|
|
Term
Duration/Potency
Tetracaine |
|
Definition
| long lasting/high potency |
|
|
Term
| hy is tetracaine so potent & long lasting? |
|
Definition
| high hydrophobiticy due to butyl group =>
a) prolonged interaction with Na+ channel
b) increased time with tissue surrounding nerve |
|
|
Term
| Why can tetracaine cause increased systemic toxicity? |
|
Definition
| more slowly metabolized than other ester LAs since it's released gradually from the tissue to the blood |
|
|
Term
|
Definition
| spinal & topical anesthesia |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| What are the 3 amide LAs? |
|
Definition
1) Lidocaine
2) Bupivacaine
3) Ropicacaine |
|
|
Term
| What is the most widely used LA? |
|
Definition
|
|
Term
| What are the 5 forms lidocaine is available in? |
|
Definition
| ointment, jelly, patch, aerosol, solution |
|
|
Term
Onset/Duration/Potency
Lidocaine |
|
Definition
| fast onset/moderate duration(1-2 hrs)/medium potency |
|
|
Term
| Why does lidocaine have a fast onset? |
|
Definition
|
|
Term
| Why does lidocaine have a medium duration of action & potency? |
|
Definition
| moderately hydrophobic & metabolites retain a weak anethetic activity |
|
|
Term
|
Definition
infiltration
nerve block
epidural
spinal
topical |
|
|
Term
|
Definition
|
|
Term
|
Definition
| antiarrythmics, vasopressors, hypersensitive, liver failure, breat-feeding |
|
|
Term
Duration/Potency
bupivacaine |
|
Definition
|
|
Term
| Why is bupivacaine so potent? |
|
Definition
| highly hydrophobic due to butyl piperidine group attached to teriary nitrogen |
|
|
Term
| Does bupivacine have more sensory or motor block? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
epidural
infiltration
nerve block
spinal |
|
|
Term
|
Definition
|
|
Term
|
Definition
| liver disease, bleeding/clotting disorder, HTN, hypotension, kidney disease |
|
|
Term
| What is the newest amide local anesthetic? |
|
Definition
|
|
Term
| How does ropivacaine differ from bupivacaine? |
|
Definition
| low cardiotoxiticy & less lipid soluble |
|
|
Term
| What neurons are preferentially blocked by ropivacaine? |
|
Definition
|
|
Term
| Why does epinephrine have no effect on onset, duration, or systemic absorption for ropivacaine? |
|
Definition
| produces vasoconstriction (like cocaine) |
|
|
Term
|
Definition
epidural
infiltration
nerve block |
|
|
Term
|
Definition
|
|
Term
|
Definition
may increase labor
not reccomended for emergency situations
allergies, heart diease, liver disease
maternal/neonatal toxicity |
|
|
Term
| What are the 3 most potent LAs? |
|
Definition
tetracaine
bupivacaine
ropivacaine |
|
|
Term
| What 2 LAs have no parenteral use? |
|
Definition
|
|
Term
| What 2 LAs have no parenteral use? |
|
Definition
|
|
Term
| What 3 LAs have no topical use? |
|
Definition
procaine
bupivacaine
ropivacaine |
|
|
Term
| Do ester or amide LAs tend to havea higher potency? |
|
Definition
| amide (except tetracaine - ester with high potency) |
|
|
Term
| What was the first general anesthetic? |
|
Definition
|
|
Term
Function
general anesthesia |
|
Definition
reversible depression of the CNS =>
1) unconsciousness
2) analgesia (pain killer)
3) amnesia
4) immobility |
|
|
Term
| What are the 2 classes of general anesthesia? |
|
Definition
1) inhalation
2) intravenous |
|
|
Term
|
Definition
| combination of inhaled & intravenous anesthesia to take advantage of the favorable properties of each agent while minimizing their adverse reactions |
|
|
Term
| What are the 2 theories of anesthesia? |
|
Definition
1) Lipid theory (lipid soluble = potency)
2) protein theory |
|
|
Term
def
MAC (minimum alveolar concentration) |
|
Definition
| measure of inhaled anesthetic potency - the alveolar concentration required to immobilize 50% of patients when exposed to a surgical incision |
|
|
Term
| What happens to MAC values when several anesthetics are used simultaneously? |
|
Definition
|
|
Term
| What factors can make MAC vary among patients? |
|
Definition
1) Age
2) EtOH
3) underlying disease
4) DDIs
(NOT affected by height, weight, sex) |
|
|
Term
def
oil:gas partition coefficient |
|
Definition
|
|
Term
Equation
Potency on anesthetic |
|
Definition
|
|
Term
| What is the Unitary Theory of Anesthesia (lipid theory)? |
|
Definition
Anesthetics work by changing membrane dimension &/or membrane state.
dimension: change volume of membrane
physical state: increase fluidity |
|
|
Term
| What is the protein theory of anesthesia? |
|
Definition
| anesthetic interacts directly with hydrophobic domain of any membrane protein |
|
|
Term
| What are the primary targets of general anesthestics (GAs)? |
|
Definition
ligand-gated ion channels:
-GABA
-nAchR
-Glu
-5-HT3
-NMDA |
|
|
Term
What are the 2 inhibitory receptors that GAs work on?
3 excitatory? |
|
Definition
I: Glu & GABA
E: 5-HT3, NMDA, nAchR |
|
|
Term
MOA
GA on inhibitory receptors (GABA & Glu) |
|
Definition
| potentiate the action of endogenous agonists (stabilizes open state) => decreased AP at post-synaptic neuron => more potent agonists (i.e. need less concentration of agonists to achieve maximum response - decrease EC50) |
|
|
Term
MOA
GAs on excitatory receptors (5-HT3, NMDA, nAchR) |
|
Definition
| inhibits the action of endogenous agonists => no depolarization of post synaptic membrane => no AP (like adding a non-competitive antagonist, EC50 stays the same, but efficacy decreases) |
|
|
Term
def
dual process model of anesthesia |
|
Definition
1) inhibits excitatory receptors
2) ehances inhibitory receptors |
|
|
Term
| Why are GAs the most dangerous drugs in clinical use? |
|
Definition
| low safety margin & no antagonist |
|
|
Term
| What are the 2 types of inhaled GAs? |
|
Definition
1) non-halogenated
2) halogenated |
|
|
Term
| What is the inhalation non-halogenated GA? |
|
Definition
|
|
Term
| What are the 4 halogenated inhalation GAs? |
|
Definition
(volatile liquid):
sevoflurane, isoflurane, halothane, desflurane |
|
|
Term
| What inhaled anesthetic has the highest MAC? |
|
Definition
|
|
Term
SOA
NO inhalation anesthetic |
|
Definition
| analgesic (only used alone in dental procedures) |
|
|
Term
SOA
halothane inhalation anesthetic |
|
Definition
|
|
Term
SOA
isoflurane inhalation anesthetic |
|
Definition
most widely used
induction/maintenance |
|
|
Term
SOA
desflurane inhalation anesthetic |
|
Definition
| most widely used for outpatient surgery |
|
|
Term
SOA
sevoflurane inhalation anesthetic |
|
Definition
induction in children
outpatient surgery |
|
|
Term
SE
inhaled anesthetic on cardiovascular system |
|
Definition
|
|
Term
SE
inhaled anesthetic on resp. system |
|
Definition
| reduce or eliminate ventilatory drive & reflexes maintaining aairway patency (all except NO) |
|
|
Term
SE
inhaled anesthetic on brain |
|
Definition
| increase cerebral blood flow => increased cerebral blood volume => increased ICP |
|
|
Term
SE
inhaled anesthetic on kidney |
|
Definition
| decrease glomerular filtration rate & renal blood flow => increased filtration fraction |
|
|
Term
SE
inhaled anesthetic on liver |
|
Definition
| concentration-dependent decrease in hepatic blood flow (15-45% reduction) |
|
|
Term
def
malignant hyperthermia |
|
Definition
| autosomal dominant genetic disorder of skeletal muscle that occurs in susceptible individuals undergoing GA with volatile agents & muscle relaxants. An increase in free [Ca2+] in skeletal muscle => increase in anesthetic morbidity & mortality. |
|
|
Term
|
Definition
rapid onset tachycardia & HTN
severe muscle rigidity
hyperthermia
hyperkalemia
acidosis |
|
|
Term
|
Definition
| dantrolene to prevent Ca2+ release from SR |
|
|
Term
| What factor determines rate of uptake of an anesthetic & its distribution throughout the body? |
|
Definition
| solubility in blood & body tissue |
|
|
Term
| How is solubility of inhalation anesthetics most commonly measured & expressed? |
|
Definition
| Blood:Gas partition coefficient |
|
|
Term
def
blood:gas partition coefficient |
|
Definition
| main factor that determines the rate of induction & recovery from anesthesia (relative affinity for the blood compared to air) |
|
|
Term
| When will there be faster induction & recovery from a GA? |
|
Definition
| lower the blood:gas partition coefficient |
|
|
Term
| Why does a low blood:gas partition mean faster induction & recovery? |
|
Definition
| equilibriate faster since less has to be transferred via the lungs to the blood in order to achieve a given partial pressure |
|
|
Term
| What 2 inhaled anesthetics have a higher blood:gas partition coefficient? |
|
Definition
|
|
Term
| How does blood flow affect GA? |
|
Definition
| the greater the blood flow (perfusion), the faster the uptake of the anesthetic |
|
|
Term
def
tissue capacity for a GA |
|
Definition
| volume of compartment & solubility of anesthetic in tissue |
|
|
Term
| What are the 3 groups of tissue based on their perfusion & capacity to take up anesthesia? |
|
Definition
1) high flow, low capacity (brain, lung, heart, kidney)
2) medium flow, high capacity (skeletal muscles)
3) low flow, very high capacity (adipose tissue) |
|
|
Term
Which tissue group has the fastest rise in partial pressure of the anesthetic?
slowest? |
|
Definition
fast: high flow, low capacity
slow: slow flow, very high capacity |
|
|
Term
| How does % body fat affect uptake & distribution of a GA? |
|
Definition
| highlt lipid soluble dug + high body fat = slow recovery & patient remains drowsy |
|
|
Term
| What does the rate of the rise of anesthetic gas tension in arterial blood depend on? |
|
Definition
rate & depth of ventilation
magnitude varies dependent on the blood:gas partition coefficient |
|
|
Term
| How do you increase the rate of onset of an inhaled anesthesia? |
|
Definition
| increase the ventilation rate (hyperventilation) due to increased concentrations of the agent |
|
|
Term
| What happens to the rate of induction of an inhaled anesthetic when pulmonary blood flow increases (i.e. increase in cardiac output)? |
|
Definition
| slows (effect is larger for more blood soluble gases) |
|
|
Term
| Why does increased pulmonary blood flow decrease the rate of induction of an inhaled anesthetic? |
|
Definition
| increased blood flow = larger volume of blood exposed to anesthetic => takes longer for anesthetic & blood to equilibrate |
|
|
Term
| How are inhaled anesthetics cleared from the body? |
|
Definition
Major route: lungs
Minor route: some metabolism in liver |
|
|
Term
| How are inhaled anesthetics terminated? |
|
Definition
| redistribution from brain to the blood, down partial pressure gradient |
|
|
Term
| Is rate of recovery from inhaled anesthetics faster with a high or low blood:gas partition coefficient? |
|
Definition
|
|
Term
| What is rate of recovery from an inahled anesthetic proportional to? |
|
Definition
| duration under anesthesia. (the longer it's applied, the more anesthsia distributes to muscle groups & fat) |
|
|
Term
| Does hyper- or hypo- ventilation increase rate of recovery from an inhaled anesthetic? |
|
Definition
|
|
Term
| Which inhaled anesthetic is the only one with a significant portion of it (~40%) metabolized? |
|
Definition
|
|
Term
DO IV anesthetics have a more or less rapid rate of induction than inhaled anesthetics?
Why? |
|
Definition
| More rapid b/c they're more lipid soluble & easily cross the BBB |
|
|
Term
| Why are IV anesthetics often used for outpatient procedures? |
|
Definition
|
|
Term
| In balanced athesthesia, are IV anesthetics administered pre or post inhaled anesthetics? |
|
Definition
| pre, due to rapid onset & short duration of action |
|
|
Term
| Where is IV anesthetics trasported first via the vascular system? |
|
Definition
| heart => brain & highly vascularized tissues (peak within 1 min) |
|
|
Term
| Why is drug redistribution to adipose much later in IV anesthetics? |
|
Definition
| low blood flow to body fat |
|
|
Term
| How are IV anesthetics eliminated? |
|
Definition
| liver/plasma metabolism (NOT ventilation) |
|
|
Term
| What are the 4 IV anesthetics used? |
|
Definition
1) Barbituates
2) Propofol
3) Etomidate
4) Ketamine |
|
|
Term
| What 3 barbituates are used as IV anesthestia? |
|
Definition
1) Sodium Thiopental
2) Thiamylal
3) Methohexital |
|
|
Term
Onset/Duration
barbituates |
|
Definition
| rapid onset(seconds)/ultra-short |
|
|
Term
| What is the most populat IV anesthetic? |
|
Definition
|
|
Term
|
Definition
| rapid (half time to blood-brain equilibriation is 1-3min) |
|
|
Term
| Why is propofol a good choice anesthetic for outpatient procedures? |
|
Definition
|
|
Term
|
Definition
outpatient procedures
critical care prolonged sedation |
|
|
Term
| Where is porpofol rapidly metabolized? |
|
Definition
|
|
Term
| What IV anesthetic is the analog to PCP & produces dissociative anesthesia? |
|
Definition
|
|
Term
|
Definition
hallucinations
irrational behavior
dose-related cardiovascular stimulation (only IV anesthesia to do so) |
|
|
Term
|
Definition
| induction & maintenance (usually in comination with a sedative) |
|
|
Term
|
Definition
| noncompetitive antagonist of NMDA |
|
|
Term
def
dissociative anesthesia |
|
Definition
catatonia
amnesia
analgesia
w/o loss of consciousness |
|
|
Term
|
Definition
| rapid-acting w/ profound analgesia |
|
|
Term
| Where is katamine metabolized? |
|
Definition
|
|
Term
For which patients is etomidate primarily used?
Why? |
|
Definition
| those @ risk for hypotenstion b/c does not cause significant cardiovascular or resp. depression |
|
|
Term
What is usually co-administered with etomidate?
Why? |
|
Definition
| Lidocaine b/c high incidence of pain on injection |
|
|
Term
|
Definition
|
|
Term
| Where is etomidate metabolized |
|
Definition
| extensively in plasma & liver to inactive metabolites |
|
|
Term
| What 2 drug types are used as adjuvants, but also have some anesthetic quality when administered IV? |
|
Definition
1) benzodiazepines
2) opioids |
|
|
Term
| What are the 3 benzodiazepines used as an adjuvant to GA? |
|
Definition
1) Diazepam
2) Lorazepam
3) Midazolam |
|
|
Term
| Why are benzos given as an adjuvant to GA? |
|
Definition
| anxiolytic & anterograde amnestic propeties |
|
|
Term
SOA
benzos as an IV anesthetic |
|
Definition
|
|
Term
| What are the 2 opioids used as an adjuvant to GA? |
|
Definition
|
|
Term
| Why are opioids used an adjuvant to GA? |
|
Definition
| analgesia (poor amnestics) |
|
|
Term
|
Definition
|
|
Term
| How can the plant alkaloid opiate affect the brain? |
|
Definition
| opiate receptor in brain is specific w/ high affinity |
|
|
Term
| What are the 3 opioid receptors? |
|
Definition
1) mu (morphine - agonists & antagonists)
2) kappa (dynorphin - partial agonists)
3) delta (enkephalin) |
|
|
Term
| What opioid receptor genes encode the opioid receptors? |
|
Definition
1) MOP for mu
2) KOP for kappa
3) DOP for delta
(4) NOP for nociceptin/orphanin receptor - insensitive to traditional opioid antagonist) |
|
|
Term
| How many mu opioid receptors are there? |
|
Definition
|
|
Term
| How many delta opioid receptors are there? |
|
Definition
|
|
Term
| How many kappa opioid receptors are there? |
|
Definition
|
|
Term
| What is the gold standard of opioids? |
|
Definition
|
|
Term
| What limits morphine's use as an oral agent? |
|
Definition
| though readily absorbed in all routes, in PO route, extensive first pass metabolism decreases bioavailability to ~35% |
|
|
Term
| What form of avilability can morphone still be used orally? |
|
Definition
| long-acting slow release beads (can't chew or drink EtOH - will cause too much release) |
|
|
Term
| What is added to morphine SR beads to decrease risk of abuse? |
|
Definition
| naltrexone (if crushed, antagonist will be released) |
|
|
Term
| How is morphine excreted? |
|
Definition
kidney - polar metabolites
bile - glucuronide conjugates |
|
|
Term
| What metabolite form of morphine mediates the analgestic effect after long term chronic use? |
|
Definition
|
|
Term
SE
morphine use with renal failure |
|
Definition
|
|
Term
| What metabolite of morphine can cause convulsions? |
|
Definition
|
|
Term
| What morphine receptor primarily mediates the CNS effects of morphine? |
|
Definition
|
|
Term
|
Definition
1) CNS
a) pain releif w/o sensory effects or loss of consciousness
b) euphoria, tranquility
2) miosis
3) cough inhibition
4) resp. depression (dose related)
5) increased ICP
6) N/V
7) decreased BP (vasodilation, decreased resistance) => orthostatic hypotension
8) constipation
9) urinary stasis
10) prolongation of labor
11) itching |
|
|
Term
| What type of pain is morphine a better analgestic for? |
|
Definition
|
|
Term
| What paradoxical event can occur with morphine use? |
|
Definition
| hyper algesia, tho mech. unknown |
|
|
Term
| Why is morphine considered multimodal? |
|
Definition
| It's used as a surgical anesthetic (in combination with other drugs) as well |
|
|
Term
| What is the site of action for morphine as a mood enhancer? |
|
Definition
| Locus coeruleus, mesolimbic DA, nucleus accumbens |
|
|
Term
SE
morphine on pain-free individuals |
|
Definition
dysphoria
difficulty thinking
drowsiness
nausea |
|
|
Term
| When can morphine reduce the risk of PSTD? |
|
Definition
| when administered promptly in combat-injured soldiers |
|
|
Term
|
Definition
|
|
Term
| Why does morphine cause miosis? |
|
Definition
|
|
Term
| What mediates the cough reflex? |
|
Definition
|
|
Term
| For whom is the resp. depression of morphine particularly harmful? |
|
Definition
COPD
synergistic with other drugs |
|
|
Term
| Why does morphine cause increased ICP? |
|
Definition
| vasodilation + increased pCO2 |
|
|
Term
| When is N/V common in patients with morphine use? |
|
Definition
| ambulatory patients (not supine) => suggests a vestibular component |
|
|
Term
| When are CV effects NOT seen in a patient with morphine use? |
|
Definition
|
|
Term
| Why is morphine given to patients with pulmonary edema? |
|
Definition
immediate relief from dyspnea
decrease anxiety
vasodilation
decreased peripheral resistance |
|
|
Term
| What heart failure can cause pulmonary edema? |
|
Definition
|
|
Term
| What can cause morphine toxicity? |
|
Definition
1) iatrogenic overuse
2) renal insufficiency
3) accidental OD
4) suicide attempt |
|
|
Term
|
Definition
1) coma
2) resp. depression
3) pinpoint pupils |
|
|
Term
| How was heroin given it's name? |
|
Definition
| it's heroic i.e. fast acting & potent |
|
|
Term
| What is heroin converted to in vivo via deacetlyation? |
|
Definition
|
|
Term
|
Definition
| painkiller with morphine backbone, just more potent & orally active then morphine (tho with same efficacy) |
|
|
Term
|
Definition
1) ER form in cancer patients, etc.
2) short-term moderate pain (in conjunction) |
|
|
Term
| What is oxycodone used in conjunction with for short-term moderate pain? |
|
Definition
1) APAP
2) aspirin
3) ibuprofen |
|
|
Term
| What form of oxycodone can be lethal (but leads to a big high)? |
|
Definition
|
|
Term
| What is added to oxycodone to stop attempts at crushing them for abuse? |
|
Definition
| acurox = niacin + inactive ingrediants (causes unpleasant Sx & converts to gel upon attempted extraction) |
|
|
Term
|
Definition
| painkiller of rapid onset & short duration |
|
|
Term
| What causes meperidine toxicity? |
|
Definition
| accumulation of long-lived metabolite (therefore now used only for short-term acute pain) |
|
|
Term
|
Definition
Seizures
Twitches
Delirium
Psych changes |
|
|
Term
| Why does codeine have a high oral/parental ratio? |
|
Definition
| largely protected from first pass metabolism |
|
|
Term
| When does codeine display it/s modest analgestic effects? |
|
Definition
| after demethylation to morphine |
|
|
Term
| Why does codeine not work for some patients? |
|
Definition
| ~10% lack enzyme for conversion to morphine |
|
|
Term
| How is codeine most often seen? |
|
Definition
| in combination formulations (tylenol 3, etc) |
|
|
Term
| How does codeine have antitussive effect (cough suppressant)? |
|
Definition
| distinct receptors (efficacy questioned) |
|
|
Term
| What drug is 80-100x more potent than morphine? |
|
Definition
|
|
Term
| What metabolite is fetanyl converted to? |
|
Definition
| no active metabolite (short duration of action) |
|
|
Term
|
Definition
IV surgical anesthesia (w/ droperidol)
acute post-op pain: patient controlled
Opioid dependent:
a) transdermal patch
b) buccal tablet, buccal film, lozenge on a stick for breakthrough pain |
|
|
Term
|
Definition
| oral partial agonist painkiller w/ low therapeutic index |
|
|
Term
| What is propoxyphen used in combination with? |
|
Definition
1) APAP
2) aspirin/caffeine |
|
|
Term
| What causes toxicity of propoxyphen? |
|
Definition
| accumulation of toxic metabolite |
|
|
Term
|
Definition
cardiotoxicity
convulsion
(no longer used, pulled from market in 2010) |
|
|
Term
| What are the 3 kappa opioid agonisits? |
|
Definition
1) Nalbuphine
2) Butorphanol
3) Pentazocine |
|
|
Term
| Do kappa agonists also bind mu opioid receptors? |
|
Definition
| yes, but they can be weak mu agonists or antagonists |
|
|
Term
|
Definition
less analegsia, resp. depression, tolerance, naloxone reversibility
more adverse behavioral effects |
|
|
Term
| What drug is a codeine derivative? |
|
Definition
|
|
Term
| What opioid receptor does tramadol work at? |
|
Definition
|
|
Term
|
Definition
weak mu agonist
blocks 5-HT & NE uptake |
|
|
Term
| How is tramadol different from most other opioids? |
|
Definition
|
|
Term
| Why is tramadol's use mostly limited to chronic pain? |
|
Definition
|
|
Term
| What combinations of tramadol are available? |
|
Definition
1) ER
2) combination with APAP |
|
|
Term
|
Definition
Hx of seizures or anti-depressants (increase frequency of seizures)
any drug that can contribue to serotonin syndrome |
|
|
Term
|
Definition
|
|
Term
|
Definition
weak mu agonist
NE uptake inhibitor (not 5-HT) |
|
|
Term
|
Definition
| abuse, serotonin syndrome (unclear) |
|
|
Term
|
Definition
|
|
Term
| Why does methadone have a long half life? |
|
Definition
| slow metabolism, highly fat soluble |
|
|
Term
| Is methadone safe for patients with renal failure & chronic pain? |
|
Definition
| yes b/c no active metabolites after hepatic metabolism |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| Why does buprenorphine have a long duration of action & is resistant to naloxone reversal? |
|
Definition
| slow dissociation from receptor |
|
|
Term
|
Definition
|
|
Term
|
Definition
| buprenorphine + naloxone (to prevent abuse) |
|
|
Term
|
Definition
| opioid antagonists (mu>kappa, delta) |
|
|
Term
|
Definition
| ER form for opiate overdose |
|
|
Term
|
Definition
oral prevention of EtOH relapse (poor compliance)
Injectible ER prevention of EtOH use
Obesity (mix with buprenorphine) |
|
|
Term
|
Definition
| burprenorphine + naltrexone |
|
|
Term
|
Definition
| injectible for opioid-induced constipation in pallative care (doesn't cross BBB to block pain) |
|
|
Term
SOA
diphenoxylate (plus atropine) & loperamide |
|
Definition
| merperidine congeners with poor absorption => used to Tx diarrhea |
|
|
Term
|
Definition
| D isomer of methylated levorphanol w/o prototypical opioid effects |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
NMDA receptor antagonist
sigma receptor agonist |
|
|
Term
|
Definition
| new kappa opioid receptor agonist |
|
|
Term
|
Definition
reduce substance p induced itching/scratching
reduce itching in hemodialysis |
|
|
Term
| What are the 3 potential uses of opioids that are under investigation? |
|
Definition
1) antidepressant
2) anti-addiction
3) cardioprotective |
|
|
Term
| Why is APAP use restricted with opioid use? |
|
Definition
| potential for hepatotoxicity & OD |
|
|
Term
One of your patients is on an SNRI, but had complaints of back pain & some shooting pain down her legs. To alleviate this pain, she is given tramadol and told to come back in a month for follow up. She has a seizure 2 days later.
What may have happened?
Would it have been OK if she was on an SSRI instead? |
|
Definition
tramadol blocks uptake of 5-HT & NE, so excess NE => seizure in this patient
no anti-depressant should be given in combination with tramadol. With SSRI, patient is likely to experience serotonin syndrome |
|
|
Term
| What are the 4 steps to solving a therpeutic problem? |
|
Definition
1) Determine if the problem is due to
a) disease progression despite therapeutics
b) new , unrelated disease
c) therapeutic problem
2) Determine if the adverse effects are due to subeffective levels or toxic level of the therapeutics
3) Determine the basis for drug interation
4) Remedy the problem |
|
|
Term
57 y/o woman with end-stage renal disease underwent allograft transplant. She was given a regimen of prednisone, azathioprine & tacrolimus.
Two years later, she was given nefazodone for depression.
After 1 week of nefazodone therapy, patient experienced headache, confusion & "gray areas" in her vision w/ no abnormal ophthalmologic findings. Serum creatinine was elevated.
Assume step one was completed to rule out new disease & disease progression.
Step 2: Why do we know that this is not due to subeffective levels of therapeutics? |
|
Definition
Though elevated serum creatinine is indicative of allograft rejection, her neurological findings do not fit.
Also, subeffective levels of nefazodone would produce depression. |
|
|
Term
57 y/o woman with end-stage renal disease underwent allograft transplant. She was given a regimen of prednisone, azathioprine & tacrolimus.
Two years later, she was given nefazodone for depression.
After 1 week of nefazodone therapy, patient experienced headache, confusion & "gray areas" in her vision w/ no abnormal ophthalmologic findings. Serum creatinine was elevated.
Step 2: What Sx are expected from the 4 therapeutics she's on?
What one is suspected to be toxic for this patient? |
|
Definition
1) Prednisone: Cushingoid
2) Azathiopine: bone marrow depression
3) Nefazodone: neurotoxicity - xerostomia (strange taste), sedation, visual disturbances can occur
4) Tacrolimus: nephrotoxicity - increased serum creatinine, neurotoxicity - headache, confusion, & visual disturbances.
Suspected tacolimus toxicity |
|
|
Term
57 y/o woman with end-stage renal disease underwent allograft transplant. She was given a regimen of prednisone, azathioprine & tacrolimus.
Two years later, she was given nefazodone for depression.
After 1 week of nefazodone therapy, patient experienced headache, confusion & "gray areas" in her vision w/ no abnormal ophthalmologic findings. Serum creatinine was elevated.
Step 3: What is the basis for her tacrolimus toxicity? |
|
Definition
tacrolimus has low variable absorption & is metabolized by CYP3A4 and is then excreted in bile.
Nafzodone is also metabolized by CYP3A4.
Therefore they are competitive inhibitors of one another's metabolism, but the toxicity of tacolimus is more apparent. |
|
|
Term
57 y/o woman with end-stage renal disease underwent allograft transplant. She was given a regimen of prednisone, azathioprine & tacrolimus.
Two years later, she was given nefazodone for depression.
After 1 week of nefazodone therapy, patient experienced headache, confusion & "gray areas" in her vision w/ no abnormal ophthalmologic findings. Serum creatinine was elevated.
Step 4: How should her treatment regimen be remedied? |
|
Definition
| decrease dosage of tacrolimus & monitor patient's serum levels. |
|
|
Term
|
Definition
sedatives: produce caliming/drowsiness (anxiolytic)
hypnotics: facilitates onset & maintenance of sleep |
|
|
Term
| Why are sedative-hypnotics classified based on clinical use as opposed to chemical structure similarities? |
|
Definition
| considerable chemical heterogeneity |
|
|
Term
Function
sedative-hypnotics |
|
Definition
| produce dose-dependent CNS depressant effects |
|
|
Term
| What are the 3 subgroups of sedative hypnotics? |
|
Definition
1) Benzodiazepines (most important)
2) barbituates
3) Misc. |
|
|
Term
| How can sedative-hypnotics be classified within their subgroups? |
|
Definition
|
|
Term
| What are the 2 types of non-Rx hypnotics? |
|
Definition
1) antihistamines
2) Serotonin-related products (L-tryptophan & melatonin) |
|
|
Term
| What about the absorption of sedative-hypnotics makes them good candidates? |
|
Definition
| lipid soluble so can distrubute to the brain, thus not reliable as an IM injection, but better PO. |
|
|
Term
| What sedative-hypnotcs are used as induction agents in anesthesia? |
|
Definition
| those with the highest lipid solubility s.a. thiopental (barbituate) |
|
|
Term
| When should sedative-hypnotics be given cautiously? |
|
Definition
Pregnant (will cross placenta => vital depression of neonate)
Nursing mother (detectable in breast milk) |
|
|
Term
Metabolism/Elimination
Benzodiazepines |
|
Definition
MOST - oxidation by CYP3A4 & CYP2C19 (phase I)
then glucutonide conjugation (phase II) for urine excretion |
|
|
Term
| What happens to the metabolites of benzos? |
|
Definition
| active with long half lives |
|
|
Term
| After continuous dosing of what 2 benzos can lead to excessive sedation due to metabolite accumulation? |
|
Definition
|
|
Term
| What do benzos active metabolites bind to increase their half life? |
|
Definition
|
|
Term
| Which 2 benzos have a shorter half life & therefore continuous dosing (and metabolite accumulation) is less of a problem? |
|
Definition
|
|
Term
| **Why do oxazepam & lorazepam have a shorter half life? |
|
Definition
| skip phase I metabolism & go right to glucuronidate conjugation |
|
|
Term
| Why do zolpidem, zaleplon, & eszopiclone have shorter half lives? |
|
Definition
| rapid metabolism by liver enzymes |
|
|
Term
|
Definition
few hours (eszopiclone, zaleplon < zolpidem = triazolam < chloral hydrate)
to 30+ hours (chlordiazepoxide, clorazepate, diazepam, phenobarbital) |
|
|
Term
|
Definition
| not one for the whole group, different subgroups can act on specific neurotransmitter receptors. |
|
|
Term
|
Definition
| Benzo receptors are in brain regions s.a. thalamus, limbic structures, & cerebral cortex.
It's part of the GABAA receptor-chloride ion channel macromolecular complex.
Binding => enhance GABA inhibitory action via increased chloride ion conductance & hyperpolarizing membrane => increased FREQUENCY of GABA channel opening |
|
|
Term
| What drug is a benzo antagonist & binds to the benzo (BZ) receptors to reverse the CNS effects of benzos? |
|
Definition
|
|
Term
|
Definition
| prolong effects of GABA & glycine inhibitory effects via interacting with other sites (not BZ receptor) on GABAA receptor chloride ion channel => increased DURATION of GABA channel opening |
|
|
Term
|
Definition
| 1) partial agonist at 5-HT1A serotonin receptor
2) agonist/antagonist at DA D2 receptor
precise MOA = unknown |
|
|
Term
| Why is buspirone given to people with a tendency for addiction? |
|
Definition
No addiction
No cross tolerance with benzos
no potentiation of other sedative-hypnotics
no hypnotic, euphoric or muscle relaxant effects |
|
|
Term
| Why must patients be withdrawn slowly from benzos prior to buspirone administration (& preferable a perioid of NO anxiolytic prior to buspirone start)? |
|
Definition
Buspirone doesn't lessen effect of benzo withdrawl
Want a drug free interval to distinguish b/w benzo withdrawl & buspirone ineffectivity |
|
|
Term
| What 3 sedative-hypnotics are NOT benzos, but interact with BZ binding site on GABAA? |
|
Definition
1) zolpidem
2) zaleplon
3) eszopiclone |
|
|
Term
| Does flumazenil anatagonize zolpidem, zaleplon, & eszopiclone? |
|
Definition
|
|
Term
|
Definition
| melatonin receptor agonist |
|
|
Term
|
Definition
| sleep-onset insomnia, but NOT sleep mantinence |
|
|
Term
| Does ramelteon have an abuse potential? |
|
Definition
|
|
Term
|
Definition
increased serum prolactin
decreased serum testosterone |
|
|
Term
Effects
sedative-hypnotics |
|
Definition
dose dependent & can range from:
sedation/anxiolytic to hypnosis to anesthesia & coma |
|
|
Term
| What are the effects of 2+ sedative-hypnotics combined? |
|
Definition
|
|
Term
| What does the steepness of the dose-dependent curve reflect? |
|
Definition
| safer clinical use when flatter |
|
|
Term
|
Definition
| selective anxiolytic with minimal CNS depression |
|
|
Term
| What are the 7 possible effects of sedative-hypnotics? |
|
Definition
1) Sedation (all provide anxiolysis, usually accompanied by psychomotor impairment & behavioral disinhibition)
2) Hypnosis (promote sleep & increase duration of sleep)
3) anesthesia (high doses lead to loss of consciousness with anmesia & suppression of reflexes)
4) anticonvulsant action (high doses suppress convulsions, but increase sedation)
5) muscle relaxation
6) Medullary depression
7) tolerance/dependance |
|
|
Term
| What sleep stage is decreased with high does benzos? |
|
Definition
| REM (rebound increase occurs with withdrawl) |
|
|
Term
| With which sedative-hypnotics is anterograde amnesia more common with anesthetics effects? |
|
Definition
|
|
Term
| Which sedative-hypnotics can produce amnestic effects? |
|
Definition
| Most barbituates & selective benzos s.a. midazolam |
|
|
Term
| Which ssedative-hynotics produce anticonvulsant actions? |
|
Definition
| most barbituates & benzos |
|
|
Term
| Which 2 sedative-hypnotics are selective anticonvulsants that do not cause severe sedation? |
|
Definition
1) Phenobarbital
2) Clonazepam |
|
|
Term
| Which 3 sedative-hypnotics are given IV to induce heavy sedation & are used in treating status epilepticus? |
|
Definition
1) diazepam
2) lorazepam
3) phenobarbital |
|
|
Term
| Does muscle relaxation by sedative-hypnotics occur at high or low doses? |
|
Definition
|
|
Term
| Which 2 sedative-hypnotics are selective for muscle relaxation? |
|
Definition
1) Diazepam
2) meprobamate |
|
|
Term
| Does medullary depression by sedative-hypnotics occur at high or low doses? |
|
Definition
|
|
Term
| What occurs in medullary depression? |
|
Definition
| resp. arrest, hypotension & CV collapse (effects that cause death in suicide OD) |
|
|
Term
|
Definition
| decrease in responsiveness to drug overtime |
|
|
Term
| When does tolerance occur wit hsedative-hypnotics? |
|
Definition
| chronic use or high doses |
|
|
Term
| What happens to BZ receptors in benzo tolerance? |
|
Definition
| down regulation (rapid rebound after withdrawl) |
|
|
Term
Sx
benzo withdrawl (due to down regulation of BZ/GABA receptors) |
|
Definition
nuronal hyper-excitability:
anxiety
tremors
hyperreflexia
seizures |
|
|
Term
| Are benzo withdrawl Sx more prominent in benzos with long or short half lives? |
|
Definition
| short (s.a. pentobarbital & triazolam) |
|
|
Term
| Is the dependance liability of zolpidem, zapelon, & eszopicolne more or less than benzos? |
|
Definition
|
|
Term
|
Definition
1) Anxiolytic
2) Sleep disorders
3) Other |
|
|
Term
| Which benzos are favored as an axiolytic? |
|
Definition
those with intermediate or long duration.
Alprazolam & Clonazepam are used for panic/phobia disorders |
|
|
Term
|
Definition
| GAD, safe for patients with Hx of substance abuse |
|
|
Term
| Which sedative-hypnotics are used in sleep disroders? |
|
Definition
1) benzos s.a. flurazepam & traizolam for insomnia & other sleep disorders
2) Zolpidem, eszopiclone, & zaleplon cause less daytime impairment & have minimal effect on sleep patterns |
|
|
Term
| Which sedative-hypnotics are used as anesthetics or in anesthesia protocols? |
|
Definition
1) Thiopental = anethesia induction
2) Diazepam & Midazolam = in anesthesia protocols |
|
|
Term
| Which 2 sedative-hypnotics are used in management of seizure disorders? |
|
Definition
1) clonazepam
2) phenobarbital |
|
|
Term
| Which sedative-hypnotic is used for muscle spacicity? |
|
Definition
|
|
Term
| Which 2 longer-acting sedative-hypnotics are used the the management of withdrawl for those dependent on EtOH & other sedative-hypnotics? |
|
Definition
1) chlordiazpoxide
2) diazepam |
|
|
Term
Sx
Toxicity of sedative-hypnotics |
|
Definition
1) Psychomotor dysfunction (cognitive impairment, decreased psychomotor skills, daytime sedation)
2) Additive CNS depression (EtOH, antihistamines, antipsychotics, opioid analgetics, & TCAs)
3) OD (resp. & CV depression)
4) formation of liver microsomal enzymes
5) Other |
|
|
Term
| Which sedative-hypnotics are psychomotor dysfunction adverse effects more common? |
|
Definition
| benzos with long acting metabolites (diazepam, flurazepam) |
|
|
Term
| Why should sedative-hypnotic doses be decreased by 50% for elderly patients? |
|
Definition
| to avoid daytime drowsiness => falls/fractures |
|
|
Term
| Which hypnotcs can cause daytime anxiety & amnesia? |
|
Definition
|
|
Term
| Why are benzos used in "date rape"? |
|
Definition
| anterograde amnesia at high doses |
|
|
Term
| Why is benzo action potentiated but other drugs? |
|
Definition
| metabolism by P450 => DDIs |
|
|
Term
| Who is more likely to to have more pronounced effects of sedative-hynotic OD? |
|
Definition
| resp. depression, sleep apnea, CVD |
|
|
Term
| Which sedative-hypnotics do flumazenil NOT have effects on? |
|
Definition
|
|
Term
| Why must flumazenil be repeatedly dosed when treated for benzo OD? |
|
Definition
|
|
Term
| Which sedative-hypnotics can induce formation of liver microsomal enzymes (=> DDIs)? |
|
Definition
|
|
Term
| What "other" toxic SE is seen with barbituates? |
|
Definition
| acute intermittent prophyria (in susceptible patients) |
|
|
Term
| What "other" toxic SE is seen with chloral hydrate? |
|
Definition
| displace coumarin from plasma protein binding site => increased aticoagulant effects |
|
|
Term
| What paients are given marked decreased doses of sedative-hypnotics? |
|
Definition
|
|
Term
40 y/o white male with nervous disposition & liver disease is scheduled for surgery. Which preanestheticsd sedative should be administered?
Why? |
|
Definition
| Lorazepam or oxazepam b/c neither undergo Phase I metabolism & therefore less likely to cause excessive CNS depression in a patient with liver disease. |
|
|
Term
| Why is it important to assess pain? |
|
Definition
|
|
Term
|
Definition
1) Ask patient 1-10 scale
2) behavioral assessment
3) physcial assessment |
|
|
Term
| What are the 3 types of pain? |
|
Definition
1) acute
2) chronic non-malignant
3) chronic malignant |
|
|
Term
| What are the 3 components of pain? |
|
Definition
1) Physical
2) Psychological
3) Spiritual |
|
|
Term
|
Definition
1) idenified event, resolves days/weeks
2) ususally nociceptive |
|
|
Term
|
Definition
1) not easily idetifiable cause, multifactorial (may be a result of poorly treated acute pain)
2) CNS plasticity/memory
3) nociceptive &/or nuropathic |
|
|
Term
|
Definition
| direct stimulation of intact nocireceptors w/ transmission along normal neurons & tissue injury apparent |
|
|
Term
def
somatic nociceptive pain |
|
Definition
sharp/dull, aching, throbbing
easy to discribe/localize |
|
|
Term
def
visceral nociceptive pain |
|
Definition
dull, colicky
not always easy to localize/radiation |
|
|
Term
|
Definition
1) non-pharmacologic intervention
2) non-opioid drug
3) opioid
4) co-analgestics |
|
|
Term
|
Definition
disordered peripheral or central nerves due to compression, transection, infiltration, ischemia, or metabolic injury
burning, tingling, shooting, stabbing, electrical |
|
|
Term
| For what type of pain may pain exceed observable injury? |
|
Definition
|
|
Term
|
Definition
1) non-pharmacologic Tx
2) anti-epileptics, anti-depressants
3) opioids |
|
|
Term
Examples
non-pharmacologic pain Tx |
|
Definition
1) PT
2) heat
3) acupuncture
4) chiropractic
5) psychotherapy
etc |
|
|
Term
| What are the non-opioid analgestics? |
|
Definition
1) APAP
2) ASA
3) NSAIDS (oral or topical)
4) COX2 inh.
5) Tramadol
6) Lidocaine patch
7) Capsaicin |
|
|
Term
| What are the 4 adjuvant analgestics? |
|
Definition
1) anti-depressants
2) anti-convulsants
3) corticosteroids
4) nerve blocks (anesthetics or lytics) |
|
|
Term
| What is the analgestic ladder for cancer pain management according to WHO? |
|
Definition
when pain begins & as it persists/increases
1) Non-opioid ± adjuvant
2) lose does opioid ± non-opioid ± adjuvant
3) higher dose of opioid ± non-opioid ± adjuvant |
|
|
Term
|
Definition
1) Analgesia
2) Sedation
3) Resp. depression (rare) |
|
|
Term
| What can decrease post-op opioid use? |
|
Definition
| pre-op & intra-op analgestics |
|
|
Term
| *Why are opioids avoided when treating head trauma? |
|
Definition
|
|
Term
| What is the gold standard opioid? |
|
Definition
|
|
Term
| Why should a bowel stimulant be given in prolonged opioid use? |
|
Definition
|
|
Term
| How is morphine excreted? |
|
Definition
|
|
Term
| *When should long acting, slow release opioids be used? |
|
Definition
| chronic pain (NOT for acute pain - must wait til tolerance is established) |
|
|
Term
| When should immediate release, short acting opioids be used? |
|
Definition
|
|
Term
Duration of action
opioids |
|
Definition
up to 4 hrs
(methadone = longer, fentanyl = shorter) |
|
|
Term
| What resource should be utilized when switching a patient from one opioid to another? |
|
Definition
| conversion charts (DON'T GUESS) |
|
|
Term
| Which opioid is 7x more potent than morphine, but safe for renal failure patients? |
|
Definition
|
|
Term
| Why is the conversion ratio of methadone to morphine not static? |
|
Definition
| long half life (therefore trained & experienced professionals only) |
|
|
Term
| What are the 4 "other" commonly used opioids? |
|
Definition
1) hydrocodone/APAP (equipotent)
2) oxycodone (+APAP = ocy-contin)
3) codeine (± APAP)
4) Fentanyl (safe in renal failure) |
|
|
Term
| What OTC drug should be monitored when giving opioids? |
|
Definition
| APAP (limit use to < 4gm/day - less in liver impairment/EtOH use) |
|
|
Term
| What % of patients taking opioids for pain become addicted? |
|
Definition
|
|
Term
| How is addiction of opioids prevented in patients? |
|
Definition
1) Long acting agents for chronic pain
2) no early refills
3) MI automated Rx System reports
4) "Opioid contracts" for some patients |
|
|
Term
| Is there any place in Michigan to legally buy marijuana? |
|
Definition
|
|
Term
| Who is eligible to participate in Michigan's Medical Marijuana Program (MMMP)? |
|
Definition
|
|
Term
| Can a physician perscribe merijuana? |
|
Definition
no, can reccomend it's use to ease Sx due to debilitating medical condition s.a.
Cancer, Glaucoma, HIV, AIDS, Hep C, ALS, Crohn's, AD, Nail patella |
|
|
Term
def
chronic/debilitating disease or medical condition (via MMMP) |
|
Definition
produces 1+ of the following:
1) cachexia
2) severe/chronic pain
3) severe nausea
4) seizures
5) severe/persistene muscle spasms |
|
|
Term
| How are new conditions added to the MMMP list of debilitating medical conditions? |
|
Definition
| review panel of physicians & non-physicians |
|
|
Term
How much marijuana can a certified patient possess in MMMP?
caregivers? |
|
Definition
patients: 2.5 oz (12 plants)
caregivers: 15 oz (72 plants) - up to 5 patients |
|
|
Term
| When is it NOT ok to use marijuana, though a certified patient? |
|
Definition
1) when would constitute negligence or professional malpractice
2) operating, navigating, or in physical control of a motor vehicle, aircraft, or motor boat
3) in public places |
|
|
Term
| How are many certified marijuana patients recieving the benefits without being exposed to the tars/CO? |
|
Definition
|
|
Term
| What are the 2 "perscription" marijuanas? |
|
Definition
1) Dronabinol (THC)
2) Sativex (THC + cannabadiol) - Canada only |
|
|
Term
|
Definition
|
|
Term
|
Definition
| cannacinoid receptors in CNS & PNS and mu opioid receptors |
|
|
Term
|
Definition
| finite episodes of brain dysfunction resulting from abnormal discharge of cerebral neurons |
|
|
Term
def
partial simple seizures |
|
Definition
| consciousness preserved during seizure |
|
|
Term
def
partial complex seizure |
|
Definition
| impaired consciousness precedded, accompanied, or followed by psychological Sx |
|
|
Term
|
Definition
formerly grand mal seizures
tonic phase (less than 1 min) = abrupt loss of consciousness, muscle rigidity, & resp. arrest
clonic phase (2-3 min) = jerking of body muscles, with lip or tongue biting, & fecal/urinary incontinence |
|
|
Term
|
Definition
impaired consciousness sometimes with automatisms, loss of postural tone, or enuresis.
begin in childhood & usually cease by age 20 |
|
|
Term
|
Definition
| single or multiple myoclonic muscle jerks |
|
|
Term
|
Definition
| series of seizures without recovery of consciousness b/w attacks (life threatening emergency) |
|
|
Term
| What are the age specific risk factors for seizures? |
|
Definition
Children: fever, MR, cerebral palsy, genetics
Adults: trauma, tremors
Elderly: AD, stroke |
|
|
Term
| How does a partial seizure occur? |
|
Definition
| seizure focus is outside of thalamus & mediates it's effects |
|
|
Term
| How does a secondary generalized seizure occur? |
|
Definition
| Seizure focus is outside the thalamus, but is read by the thalamus to exert it's effects |
|
|
Term
| How does a generalized seizure occur? |
|
Definition
| The thalamus is the seizure focus & mediates it's effects |
|
|
Term
| What did 1st generation anticonvulsants treat? |
|
Definition
| generalized tonic-clonic, partial, & generalized absence seizures |
|
|
Term
MOA
1st generation anticonvulsants |
|
Definition
| 1) Rate-dependently prolong inactivation of voltage-sensitive NA+ channels (similar to lidocaine)
2) potentiate GABA
3) block T-type CA2+ channel-mediated current in thalamic neurons (for generalized absence seizures) |
|
|
Term
| How are newer AED (anti-epileptic drugs) being identified? |
|
Definition
| 1) newer phenotypic models
2) targeting defined biochemical mechanisms
3) novel AED targets (Glu receptors, K+ or Ca2+ channels) |
|
|
Term
| How do some AEDs have a broader spectrum of activity? |
|
Definition
| multiple mechanisms of action &/or novel mechanisms of action |
|
|
Term
| What do AEDs do to NMDA receptors? |
|
Definition
|
|
Term
| What do AEDs do to HVA Ca2+ channels? |
|
Definition
|
|
Term
| What do AEDs do to GABA channels? |
|
Definition
|
|
Term
| What do AEDs do to voltage-gated Na+ channels? |
|
Definition
| stabilize inactivated state |
|
|
Term
| What do AEDs do to T-type Ca2+ canncels? |
|
Definition
| block them via binding to receptor site |
|
|
Term
| What 8 drugs are DOC for partial & generalized tonic-clonic seizures? |
|
Definition
1) Phenytoin
2) Carbamezapine
3) Valproic acid
4) Phenobarbital
5) *Lamotrigine
6) *Levetiracetam
7) *Gabapentin (& pregabalin)
8) *Topiramate
* = second generation AEDs |
|
|
Term
| What is the oldest nonsedative AED? |
|
Definition
|
|
Term
|
Definition
| blockade of Na+ channels = strongest (not only) effect |
|
|
Term
| What does absorption of phenytoin depend on? |
|
Definition
|
|
Term
|
Definition
| soluble prodrug of phenytoin for use IM or IV |
|
|
Term
| How is phenytoin eliminated? |
|
Definition
|
|
Term
| Why musst dose be gradually increased with pheytoin? |
|
Definition
| liver elimination is dose dependent |
|
|
Term
|
Definition
nystagmus early
diplopia & ataxia dose-limiting
gingival hyperplasia & hirsutism long-term |
|
|
Term
|
Definition
tricyclic compound related to antidepressants
bipolar
trigeminal neuraldia
partial/generalized tonic-clonic |
|
|
Term
| What type of seizures can carbamezapine exacerbate? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| Why might dose of carbamezapine need to be adjusted with time? |
|
Definition
| significant microsomal induction |
|
|
Term
|
Definition
diplopia & ataxia dose-related
idiosyncratic blood dyscrasia seen in elderly (imbalance of the 4 humors: phlegm, blood, yellow & black bile) |
|
|
Term
| How are SE of carbamezapines decreased? |
|
Definition
|
|
Term
What is a rare but serious side effect of carbamezapines?
Who is at risk? |
|
Definition
| Stevens Johnson syndrome (SJS) w/ genetic risk (i.e asians 10x more likely) |
|
|
Term
| Which AED was discovered accidentally? |
|
Definition
|
|
Term
|
Definition
partial seizures
generalized tonic-clonic
myotonic
atonic
combination seizures
absense seizures
bipolar |
|
|
Term
|
Definition
| blackade of Na+ channels
GABA effects
Histone deacetylase inhibition (=> increase gene expression)
Ca2+ channels
All MOA unclear, but broad spectrum due to many MOAs |
|
|
Term
|
Definition
| idiosyncratic hepatotoxicity (therefore must monitor liver function) |
|
|
Term
| What is the extended release version of valproic acid for complex partial or absence seizures or migranes? |
|
Definition
| Divalproex sodium extended release |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| Why is phenobarbitol a DOC for partial & generalized tonic-clonic seizures? |
|
Definition
rapid effect
safety profile
cost |
|
|
Term
|
Definition
rare, but life-threatening dermatitis in infants
(broad spectrum therefore multiple MOAs?) |
|
|
Term
|
Definition
|
|
Term
|
Definition
| adult/child refractory seizures |
|
|
Term
MOA
gabapentin & pregabalin |
|
Definition
| NON-GABA MOA: binds voltage-gated Ca2+ channels |
|
|
Term
SOA
gabapentin & pregabalin |
|
Definition
neuropathic pain
migraine
anxiety
surgical analgesia
AED |
|
|
Term
| What is THE drug for off-label (refractory migrane, bipolar, etc)? |
|
Definition
topiramate
(muliple MOAs? broad spectrum) |
|
|
Term
|
Definition
| typical CNS SE + memory problems |
|
|
Term
| What are the 3 DOC for generalized absence seizures? |
|
Definition
1) Ethosuximide
2) Valproic acid
3) clonazepam |
|
|
Term
|
Definition
| First line absence seizures ONLY |
|
|
Term
|
Definition
|
|
Term
Absorption/Metabolism
ethosuximide |
|
Definition
| good absorption, complete metabolism (good relationship b/w dose & plasma levels) |
|
|
Term
|
Definition
dose-related gastric distress
normally well tolerated |
|
|
Term
|
Definition
absence seizures (less effective than ethosuximide & valproic acid)
myoclonic & atonic seizures
infantile spasms |
|
|
Term
|
Definition
| typical benzo SE: sedation, tolerance, withdrawl syndrome |
|
|
Term
Tx
status epilepticus
(life-threatening emergency) |
|
Definition
| IV diazepam followed by IV fosphenytoin or phenobarbital (watch out for synergistic CNS depression) |
|
|
Term
|
Definition
Hard to assess since seizure & med heterogenicity, but most patients deliver normal infants
apparent overall risk is 2x increase of congenital malformations therefore use liwest effective dose of monotherapy while pregnant |
|
|
Term
| Which 2 types of AEDs is withdrawl most difficult for? |
|
Definition
|
|
Term
| What risks increase with chronic use of AEDs? |
|
Definition
suicide
decreased bone density |
|
|
Term
| What diet has been used to Tx seizures? |
|
Definition
| ketogenic diet: low cal with 4 gm fat/gm protein or carbs => ketones made by fat metabolism to mimic fasting & ketones replace glucose as brain fuel |
|
|
Term
|
Definition
| refractory seizures in children |
|
|
Term
| What 3 surgical procedures are used to Tx seizures? |
|
Definition
1) Anterior temporal lobectomy (partial seizures of adults if refractory & harmful)
2) Corpus collosotomy (Lennox-Gastaut)
3) Hemispherectomy ( other sever childhood forms) |
|
|
Term
| When might vagus nerve stimulation be used to Tx seizures? |
|
Definition
| refractory complex partial/generalized seizures, poor surgery candidates |
|
|
Term
MOA
vagus nerve stimulation to reduce seizures |
|
Definition
|
|
Term
| What are the steps in treatment of seizures? |
|
Definition
1) ascertain cause if possible (for children do a wait & see before anything else)
2) use DOC appropriate to seizure type
3) if failure, try another DOC
4) if continued failure, consider surgery or vagal never stimulation |
|
|
Term
Patient treated with carbamezapine for what was through to be a clear cut case of generalized tonic-clinic seizures. Although he responded to Tx initially, his seizure frequency is increasing after some weeks of Tx.
What is the next course of action? |
|
Definition
| Adjust does of carbamezapine to insure dose is correct. Carbamezapine is notorious for inducing it's own metabolism. |
|
|
Term
| What are the antidepressant classes? |
|
Definition
1) TCAs
2) SSRIs
3) MOAIs
4) SNRIs
5) Other |
|
|
Term
| What non-Rx Tx are there for depression? |
|
Definition
Electroconvulsive Therapy
CBT & other psychotherapy |
|
|
Term
| How do TCAs, SSRIs, SNRIs, & MAOIs elicit their therapeutic effect on depression? |
|
Definition
| modulating function of monoamine systems in brain |
|
|
Term
Function
monoamine neurotransmitters (s.a. NE & 5-HT) |
|
Definition
| regulate how neurons function (do not transmit fast exciatory or inhibitory signals) |
|
|
Term
| How do TCAs, SSRIs & SNRIs regulate 5-HT & NE neurotransmission? |
|
Definition
|
|
Term
|
Definition
1) Imipramine
2) Chlorimipramine
3) Desipramine |
|
|
Term
|
Definition
| inhibits reuptake of NE & 5-HT |
|
|
Term
|
Definition
| preferentially inhibits 5-HT uptake |
|
|
Term
|
Definition
| preferentially inhibits NE uptake |
|
|
Term
|
Definition
|
|
Term
|
Definition
| well absorbed PO, bind to plasma proteins, lipophilic, accumulates in tissues |
|
|
Term
Metabolism/Elimination
TCAs |
|
Definition
| liver via P450 to inactive metabolite, eliminated over several days |
|
|
Term
| What limits TCAs usefulness? |
|
Definition
|
|
Term
|
Definition
| 1)Anti-muscarinic: dry mouth, constipation, blurred vision (mydriasis), etc.
2) anti-α1-adrenergic:postural hypotension, weight gain, sedation, sexual dysfunction
3) induce mania in undiagnosed bipolar
4) low safety factor - life-threatening in OD => cardiotoxicity (conduction delay & arrhythmia) |
|
|
Term
| What are the most widely used antidepressants? |
|
Definition
|
|
Term
|
Definition
1) Fluoxetine
2) Fluvoxamine
3) Paroxetine
4) Citalopram
5) Sertraline
6) Vilazodone
(you're sad when you have the FLU, bc your PARents will make you drink CITrus and sleep on your SERTa in your Vila) |
|
|
Term
|
Definition
1)Venlafaxine
2)Duloxetine
3)Milnacipran
(sad & sick with gi discomfort => VENtilation DUe to MI-NAsty farts) |
|
|
Term
| What SSRI has partial agonist acitivy at 5-HT1A?
What anxiolytic does this resemble? |
|
Definition
| Vilazodone resemble buspirone |
|
|
Term
|
Definition
|
|
Term
| How can therapeutic effect of SSRIs/SNRIs be augmented modestly? |
|
Definition
| addition of second generation antipsychotic - but will also increase adverse effects |
|
|
Term
|
Definition
| well absorbed PO, but vary in binding to plasma proteins |
|
|
Term
|
Definition
| metabolized by multiple hepatic enzymes => active norfluoxetine metabolites |
|
|
Term
|
Definition
jitteriness, insomnia, nausea, diarrhea, dizziness, fatigue, sexual dysfunction
(less prominent than TCAs) |
|
|
Term
|
Definition
| inhibit MAOs that catalyze oxidation of 5-HT & NE inside synaptic terminal => increase in intraterminal concentration & release of 5-HT & NE |
|
|
Term
|
Definition
1) Selegiline
2) Tranylcypromine
3) Moclobemide
4) Phenelzine
(SELl TRANYs MOCk PHENphen) |
|
|
Term
| What is different about the 2 isoforms of MAO? |
|
Definition
| differential expression for 5-HT & NE neurons |
|
|
Term
|
Definition
Dorsal raphe (5-HT) +
Locus coeruleus (NE) ++
Substantia Nigra (DA) ++ |
|
|
Term
|
Definition
|
|
Term
MOA
classic MAOIs s.a. phenelzine & tranylcypromine |
|
Definition
| irreversibly inhibit MAO-A & MAO-B |
|
|
Term
|
Definition
MAO metabolizes tyramine => increase circulating tyramine => hypertensive crisis
DDIs with uptake inhibitors |
|
|
Term
| Which MAOI (not available in the US) reversibly binds MAO-A & therefore produces less tyramine DDI? |
|
Definition
|
|
Term
|
Definition
| preferential irreversible inhibitor or MAO-B |
|
|
Term
| What are the 4 "other" antidepressants? |
|
Definition
1) Mirtazapine
2) Nefazodone
3) Trazodone
4) Buproprion
(moaning MIRTle NEver TRies BUtt sex) |
|
|
Term
| When are other antidepressants used? |
|
Definition
|
|
Term
| Though TCAs, SSRIs, SNRIs, MAOIs increase availability of monoamines instantaneously, why is their effect delayed? |
|
Definition
| suggests need for development of secondary adaptive response to Tx |
|
|
Term
| What are the possible mood stabilizers? |
|
Definition
1) Lithium
2) Anticonvulsants (s.a. valproate, carbamezapine, & lamotrigine)
3) Atypical Antidepressants |
|
|
Term
| What are the 2 possible sites for MOA of Lithium + Valproate? |
|
Definition
1) ptdlns signaling
2) GSK-3 |
|
|
Term
|
Definition
1) mania Tx + prevention of recurrant attacks, often used in conjunction with valproate or carbamezepine
2) in conjunction with an antipsychotic or potent benzo in acute mania |
|
|
Term
| Why must Li levels be periodically monitored? |
|
Definition
|
|
Term
|
Definition
readily absorbed from GI
eliminated by kidneys |
|
|
Term
| What formulation of LI is used to reduce peak levels? |
|
Definition
|
|
Term
|
Definition
| Kidney sodium clearance (i.e. diuretics) |
|
|
Term
|
Definition
N/V/D
mental confusion
tremor
ataxia
convulsions
coma |
|
|
Term
|
Definition
N/D
daytime drowsiness
polyuria
polydipsia
weight gain
fine tremor
acne |
|
|
Term
|
Definition
|
|
Term
| What 3 anticonvulsants are used as mood stabilizers? |
|
Definition
1) Valproate
2) carbamazepine
3) lamotrigine |
|
|
Term
| What is the sodium salt of Valproate? |
|
Definition
|
|
Term
| How effective are anticonvulsants are mood stabilizers compared to Li? |
|
Definition
1) lamotrigine is the only one with FDA approval & it's only for maintenance
2) neither valproate or carbamazepine are protective against suicide like Li
3) Valproate & Carbamazepine are not safe during pregnancy |
|
|
Term
| What are the 6 atypical antipsychotics? |
|
Definition
1) Olanzapine
2) Clozapine
3) Risperidone
4) Quetiapine
5) Aripiprazole
6) Ziprasidone
(it's atypical for Old Closets to Risper Quietly from A to Z) |
|
|
Term
Tx
Panic Attacks/Panic Disorders |
|
Definition
1) SSRIs
2) TCA or MAOI = second choice
3) Benzos (rapid relief) |
|
|
Term
| What is tricky about panic disorders/attacks? |
|
Definition
| often comorbid with other disorders |
|
|
Term
| How much of the population is affected by OCD? |
|
Definition
| 2.3%, but there's a high prevalence of subthreshold OCD |
|
|
Term
| What is OCD often comorbid with? |
|
Definition
anxiety & mood disorders
impulse control
substance use disorders |
|
|
Term
|
Definition
1) Chlorimipramine
2) SSRIs
3) MAOIs |
|
|
Term
| What uptake inhibitors are not effective in OCD Tx? |
|
Definition
|
|
Term
| What is the main clinical use of stimulants (amohetamines)? |
|
Definition
|
|
Term
| What Sx of ADHD do stimulants treat? |
|
Definition
| core Sx: impulsivity, inattention, & motor restlessness |
|
|
Term
|
Definition
6+ Sx (from A or B) present for 6+ months to a point that is disruptive & inappropriate for developmental level
A) List of inattention Sx
B) List of Hyperactive/inpulsive Sx |
|
|
Term
| How effective are stimulants are Tx of ADHD? |
|
Definition
| so much so that combined CBT is not needed |
|
|
Term
| What are the 5 amphetamines? |
|
Definition
1) Amphetamine
2) DA
3) Methamphetamine
4) Methylphenidate
5) Dextroamphetamine |
|
|
Term
|
Definition
| release monoamines thru non-exocytotic mechanism |
|
|
Term
| What form of stimulants have been developed for stable effect throughout the day? |
|
Definition
|
|
Term
|
Definition
1) ADHD
2) excessive daytime sleepiness (narcolepsy, sleep apnea, etc)
3) appetite suppressants (historically) |
|
|
Term
|
Definition
headaches that are:
1) unilateral
2) pulsatile/throbbing
3) associated with N/V
4) sufficient intensity to interrupt daily activities
5) last 4-72 hrs if untreated |
|
|
Term
| Who is affected by migranes? |
|
Definition
|
|
Term
| What tends to be the triggers for mirgranes? |
|
Definition
|
|
Term
|
Definition
|
|
Term
Tx
migranes
(not severe, no vomiting) |
|
Definition
|
|
Term
|
Definition
1) Triptans
2) Dihydroergotamine |
|
|
Term
|
Definition
| 5-HT1B/1D receptor agonists => inhibition of neurotransmitter release |
|
|
Term
| When in combination with what do triptans seen to be most effective in treating migranes? |
|
Definition
| NSAIDs (may be given in combination with antiemetics as well) |
|
|
Term
|
Definition
|
|
Term
| When in the migrane course should triptans be administered? |
|
Definition
| as early as possible (early intervention is important) |
|
|
Term
| Why shouldn't triptans be given as monotherapy? |
|
Definition
| Alone, not much better than NSAIDs & have a high cost |
|
|
Term
|
Definition
1) sumatriptan
2) fovatriptan |
|
|
Term
|
Definition
1) β blockers (propanolol, timolol, metoprolol)
2) AED (valproate, topiramate)
3) TCAs
4) Behavioral therapies |
|
|
Term
|
Definition
|
|
Term
def
positive Sx
Schizophrenia |
|
Definition
| paychotic episodes: loss of reality, delusions, disordered thinking & memory, hallucinations |
|
|
Term
def
negative Sx
Schizophrenia |
|
Definition
| prodromal Sx: social isolation/withdrawl, poverty of speech, odd behavior/ideas, blunted affect, lack of motivation |
|
|
Term
| Is poorer schizophrenia prognosis asociated with positive or negative Sx? |
|
Definition
|
|
Term
| What biological findings are seen to be esp. associated with negative schizophrenic Sx? |
|
Definition
1)decreased frontal lobe BF
2) decreased BF to caudate during working tasks
3) reduced hippocampanl & medial temporal lobe volume
4) enlarged ventricles |
|
|
Term
| Ho much of the population is affected by schizophrenia? |
|
Definition
|
|
Term
| What increases risk of developing schizophrenia? |
|
Definition
|
|
Term
| What monoamines seems to be present in high amounts in schizophrenics? |
|
Definition
DA (i.e. DA agonists induce/exacerbate psychosis)
there also seems to be an increase in DA receptors => less DA = greater effect |
|
|
Term
MOA
all clinically effective antipsychotics? |
|
Definition
|
|
Term
| What type of receptors are DA receptors D1-D5? |
|
Definition
|
|
Term
| What 2 DA receptors predominate? |
|
Definition
|
|
Term
| Where are D3 receptors found? |
|
Definition
|
|
Term
| Where are D4 receptors found? |
|
Definition
|
|
Term
Which DA receptors are part of the D1 family?
D2 family? |
|
Definition
|
|
Term
|
Definition
| increase cAMP => increase PIP2 hydrolysis => PKC activation => Ca2+ mobilization |
|
|
Term
|
Definition
| decreased cAMP => increase K+ currents & decrease voltage gated Ca2+ currents |
|
|
Term
| Where is 80% of DA found? |
|
Definition
|
|
Term
|
Definition
| modulate movement & learned habits |
|
|
Term
|
Definition
| modulated motivation, goal-directed thinking, affect, & reward |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
Function
Area postrema DA (outside BBB) |
|
Definition
|
|
Term
Sx
overactive mesolimbic/cortical DA |
|
Definition
|
|
Term
Sx
hypofunction mesocortical DA |
|
Definition
|
|
Term
Sx
abnormal nigrostriatal DA |
|
Definition
| extrapyramidal (motor) SE, tardive dyskinesia |
|
|
Term
Sx
abnormal hypothalamic DA |
|
Definition
|
|
Term
| Which DA receptor blockage coorelates with clinical efficacy in schizophrenia? |
|
Definition
|
|
Term
| Which atypical antipsychotic was a weak D2 blocker with decreased neurological SE & increased efficacy? |
|
Definition
|
|
Term
What are the profiles of atypical antipsychotics?
Why? |
|
Definition
| "D2 +"
b/c clozapine blocked D2 weakly + had affinity for 5-HT2A |
|
|
Term
|
Definition
|
|
Term
|
Definition
1) Olanzapine
2) Clozapine
3) Risperidine
4) Quetiapine
5) Aripiprazole
6) Ziprasidone |
|
|
Term
| How do typical APDs differ from atypical APDs in affinity for receptors? |
|
Definition
| FGAs: (risk of EPS) occupy forst striatal D2 receptors
SGAs: occupy lower proportion of D2 receptors, but more cortical 5-HT2A receptors |
|
|
Term
| What is the only antipsychotic that doesn't affect D4 in cortex? |
|
Definition
|
|
Term
|
Definition
| immediate blockage, but delayed clinical effects (same as antidepressants) |
|
|
Term
|
Definition
| not well understood, but commonality = D2 receptor block |
|
|
Term
|
Definition
readily, but incompletely absorbed
long duration relative to plasma half life, though protein-bound due to high lipid solubility |
|
|
Term
|
Definition
Significant 1st pass metabolism by P450
Conjugation for urinary excretion |
|
|
Term
|
Definition
|
|
Term
|
Definition
autonomic: muscarinic & α block (dry mouth, urinary retention, constipation, orthostatic hypotension, impotence)
CV: increased HR, abnormal ECG, QT prolongation (SGAs, esp. ziprasidone), 2x risk sudde cardiac death (dose-dependent)
hyperprolactinemia => amenorrhea-galactorrhea, infertility, impotence
Neurological effects
EPS (extrapyramidal sydrome)
weight gain (SGAs esp. clozapine & olanzapine) |
|
|
Term
| What causes the adverse neurological effects with APDs? |
|
Definition
|
|
Term
Sx
Early Neurological SE APDs |
|
Definition
1) acute dystonic rxn - face/back (NOT seizures/hysteria)
2) akathisia (restlessness)
3) parkinsonism
4) neuroleptic malignant syndrome (extreme & rare) |
|
|
Term
Tx
acute dytonic rxn, akathisia, parkisonism due to APDs |
|
Definition
| reduce dose of APD or administer an anti-muscarinic |
|
|
Term
Tx
neuroleptic malignant syndrome due to APD |
|
Definition
| bromocriptine, dantrolene |
|
|
Term
Sx
Late occuring neurological SE APD |
|
Definition
|
|
Term
| Why is early recognition of tardive dyskinesia due to APD important? |
|
Definition
| advanced cases difficult to reverse, can be masked by increased APD dose (worsen upon withdrawl) |
|
|
Term
| What has the SE tardive dyskinesia done to the pharm inductry? |
|
Definition
| driven the search for atypicals |
|
|
Term
| How severe are EPS Sx seen in APD? |
|
Definition
| in proportion to D2 receptor affininty - some short-term & limiting, others long-term & irreversible |
|
|
Term
| What causes weight gain with atpyical APDs? |
|
Definition
|
|
Term
| What does weight gain with SGAs lead to? |
|
Definition
| weight-related insulin resistance, diabetes |
|
|
Term
|
Definition
seizures
agranulocytosis (potentially fatal, but reversible if caught => regular blood counts) |
|
|
Term
|
Definition
| study to compare/contrast FGA & SGAs |
|
|
Term
|
Definition
Olanzapine showed modest advantage to FGAs in terms of duration & Sx relief, but had substantial weight-related SE.
Other SGAs had no advantage over FGAs
Patients are more likely to continue SGAs than FGAs
Clozapine is significantly more effective & patients stay on it longer |
|
|
Term
|
Definition
| UK follow up to CATIE study |
|
|
Term
|
Definition
~ in quality of life, efficacy, & SE
Clozapine = better in managing Sx than other SGAs in treatment resistant patietns, overall QOL better |
|
|
Term
|
Definition
| follow up to CATIE via study of early onset schizophrenia (8-19 y/o) |
|
|
Term
|
Definition
~ equivalent
Olanzapine had weight gain w/ increased cholesterol & other metabolic disturbances |
|
|
Term
| What drives drug choice for APDs? |
|
Definition
1) Cost (SGA > FGA)
2) SE (FGZ vs SGA, long term vs short term)
3) compliance (depot, drug change)
4) True treatment resistance |
|
|
Term
Advantage/Disadvantage
Chlorpromazine (FGA) |
|
Definition
Ad: generic (inexpensive)
Dis: SE profile - autonomic, EPS risk, TD |
|
|
Term
Advantage/Disadvantage
Haloperidol (FGA) |
|
Definition
Ad: generic, parenteral form, less autonomic effects
Dis: strong D2 block => higher risk of EPS & TD |
|
|
Term
Advantage/Disadvantage
Risperidone |
|
Definition
Ad: depot & generic, "borderline atypical" => less 5-HT related SE (weight gain), very tolerable
Dis: "borderline atypical" => more DA related SE (hyperprolactinemia, EPS) |
|
|
Term
Advantage/Disadvantage
Olanzapine |
|
Definition
Ad: less risk of EPS & TD, more tolerable, somewhat more effective
Dis: expensive, SE- weight gain, diabetes, other metabolic risks |
|
|
Term
| What other SGA drug does olanzapine's structure resemble? |
|
Definition
|
|
Term
Advanage/Disadvantage
Clozapine |
|
Definition
Ad: most efficacious
Dis: expensive, eight gain/diabetes, more serious effects (agranulocytosis, seizures) |
|
|
Term
|
Definition
1) Schizophrenia (primary indication)
2) Schizoaffective disorders (schizophrenia + a mood disorder)
3) neuroleptoanesthesia
4) pre-op
5) Mood disorders
6) AD/dementia aggressive behavior
7) Pediatrics for aggressive behavior |
|
|
Term
Tx
schizoaffective disorder |
|
Definition
| combo APD + antidepressants, Li, or valproate |
|
|
Term
|
Definition
| droperidol (short acting, highly sedating) + fentanyl |
|
|
Term
| Which APDs are used pre-op? |
|
Definition
|
|
Term
| Why are APDs used pre-op? |
|
Definition
| strong antiemetic effects, sedation, relief of pruitis |
|
|
Term
| Why are APDs the top selling calls of drugs? |
|
Definition
1) use in mood disorders
2) use in AD/dementia with agiation (CI due to increased death due to CV accidents & infections)
3) Pediatrics for aggressive behavior |
|
|
Term
| How are APDs used in AD/dementia? |
|
Definition
| calming sedative properties for patient control |
|
|
Term
| How are APDs used in pediatrics? |
|
Definition
1) autistic children with aggressive, self-injurous behavior
2) bipolar
3) ADHD |
|
|
Term
After an acute psychotic episode, a 19 y/o male is Dx with schizophrenia. He is slightly overweight & has a family Hx of DMII. What drug should be perscribed?
Why? |
|
Definition
| Risperidone is a good choice. You don't want to go with a full SGA (esp. clozapine or olanzapine) due to weight, DM risk. You don't want to go with a full FGA due to EPS & TD risk. Split the difference with Risperidone. |
|
|
Term
Sx
Parkinson's Disease (PD) |
|
Definition
1) bradykinesia
2) muscular rigidity
3) resting (pill rolling) tremor
4) impairment of postural stability
(early - may present as weakness/fatigue, weak voice, micrographia, olfactory loss) |
|
|
Term
| What other illnesses are comorbid with PD? |
|
Definition
|
|
Term
Course duration
PD
(onset to death) |
|
Definition
~15 yrs
Sx progressivly worsen, til postural instability causes more complication
death due to general wasting/complications of immobility |
|
|
Term
|
Definition
1) loss of midbrain DA-producing neuron, particularly nigrostriatal DA neurons (need >80% loss of nigrostriatal DA neurons before Sx will occur)
2) presence of Lewy bodies
(other cells & other regions are also impacted, tho to lesser extent & more variable) |
|
|
Term
|
Definition
| inclusion with radiating fibrils |
|
|
Term
| What holds 80% of all DA? |
|
Definition
|
|
Term
|
Definition
| modulates learning & execution of complex, purposeful motor patterns, learned behavior |
|
|
Term
|
Definition
| modulates motivation, goal-directed thinking, affect, & reward |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
Function
Area postrema (DA receptors outside BBB) |
|
Definition
|
|
Term
| From where does DA modulate exicatory information? |
|
Definition
|
|
Term
| How does Basal ganglia send information back to the cortex after DA excitation? |
|
Definition
| via excitation from thalamus |
|
|
Term
Function
BG direct pathway |
|
Definition
|
|
Term
Function
BG indirect pathway |
|
Definition
|
|
Term
Effect
>80% nigrostriatal loss of DA (i.e. PD) |
|
Definition
| decreased excitation of cortex |
|
|
Term
| What are the potential causes of PD? |
|
Definition
1) idiopathic (environmental/multigenic)
2) Environmental toxins
3) infection
4) oxidative stress
5) mitochonrial defects
6) rare genetic forms |
|
|
Term
|
Definition
1) L-Dopa (Levodopa)
2) DA agonist
3) MAO-B Inhibitors
4) Catechol-O-methyltransferase inhibitors (COMT inhibitors)
5) Amantadine
6) Amtimuscarinics
7) Surgery |
|
|
Term
|
Definition
|
|
Term
| What affects absorption od L DOPA? |
|
Definition
|
|
Term
|
Definition
| decarboxylated peripherally, so <1% reaches the brain |
|
|
Term
| What is L DOPA given in combination with? |
|
Definition
peripheral aromatic aa decarboxylase inhibitor (carbidopa)
can be given atypical antipsychotics if psychotic SE |
|
|
Term
| When in PD is L DOPA effective? |
|
Definition
early on, for bradykinesia > tremor
over time(2-5 yr), reduced efficacy => on-off phenomenon & dyskinesias |
|
|
Term
|
Definition
early: anorexia, nausea, hypotension
chronic: hallucination, delusions, agitation, insomnia, pathological gambling, hypersexuality |
|
|
Term
| What are the 2 types of DA agonists? |
|
Definition
|
|
Term
| What are the 2 ergots for PD? |
|
Definition
1) bromocriptine (not used due to SE)
2) pergolide (not used due to cardiac valve regurgitation) |
|
|
Term
| Why are non-ergots DA direct agonists used? |
|
Definition
|
|
Term
| What are the 4 non-ergots? |
|
Definition
1) pramipexole
2) ropinirole
3) apomorphine
4) rotigotine |
|
|
Term
| How does pramipexole & ropinirole compare to L DOPA? |
|
Definition
| slightly less effective, but with fewer SE |
|
|
Term
SOA
pramipexole & ropinirole |
|
Definition
Adjunct or First line for PD
Restless Leg Syndrome |
|
|
Term
SE
pramipexole & ropinirole |
|
Definition
| nausea, edema, hypotension, pathological gambling, other compulsions, somnolence |
|
|
Term
SOA
injectible apomorphine |
|
Definition
|
|
Term
|
Definition
N/V
yawning & hypersexuality |
|
|
Term
| How is rotigotine administered? |
|
Definition
| once daily transdermal patch |
|
|
Term
| How does rotigotine compare to other non-ergots in PD Tx? |
|
Definition
| ~ to other non-ergots, just more convenient |
|
|
Term
| What 2 MAOI-Bs are used in PD? |
|
Definition
1) Selegiline
2) Rasagiline |
|
|
Term
|
Definition
| irreversible MAO-B inhibitor => inhibited DA metabolism |
|
|
Term
| Can selegiline be used in combo with L DPOA for PD? |
|
Definition
| yes, since there's not much peripheral MAO |
|
|
Term
|
Definition
| newer irreversible MAO-B inhibitor |
|
|
Term
|
Definition
| nausea, orthostatic hypotension |
|
|
Term
| Effectivity of MOAI-Bs in PD? |
|
Definition
modest benefits, possilbe neuroprotection
rasagiline is effective in clinical trials for early PD or as adjunct in advanced PD |
|
|
Term
| What catechol-o-methyltransferase inhibitor(newer) (COMTI) is used for PD? |
|
Definition
|
|
Term
|
Definition
| increase dopa levels by blunting metabolism in periphery & brain |
|
|
Term
|
Definition
| l-dopa + carbidopa + entacapone |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
Efficacy
amantadine for PD |
|
Definition
| modest & transient, but may be better for tremor |
|
|
Term
|
Definition
Typical SE + livedo reticularis
psychosis rare |
|
|
Term
| What 4 antimuscarinics are used in PD Tx? |
|
Definition
1) Bentropine
2) trihexyphenidyl
3) procyclidine
4) biperiden |
|
|
Term
MOA
antimuscarinics for PD |
|
Definition
| offsets neurochemical imbalance in STR created by DA loss |
|
|
Term
Efficacy
antimuscarinics for PD |
|
Definition
| early onset tremor, rigidity, drooling (not bradykinesia) |
|
|
Term
|
Definition
| lots of CNS & PNS effects (impaired memory, drowsiness, confusion, delusions, dry mouth, blurred vision, urinary retention, tachycardia) |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| cholinesterase inhibitors + PT & exercise |
|
|
Term
| What 4 surgical procedures can be used with PD who have dyskinesias & clinical fluctuation on dopa? |
|
Definition
1) DA cell replacement
2) Ablations
3) DBS (deep brain stimulation)
4) rescue of sick cells |
|
|
Term
| What cells are replaced in DA cell replacement? |
|
Definition
| adrenals, carotid bodies, fetal cells (from humans, pigs, stem cells) |
|
|
Term
|
Definition
|
|
Term
|
Definition
| help tremor, bradykinesia, med response (irreversible, non adjustable) |
|
|
Term
| What is the safer, reversible, adjustable, more effective with fewer complications version of ablation? |
|
Definition
| DBS (& can be done bilaterally) |
|
|
Term
| What patients are candidates for DBS? |
|
Definition
| refractory to med Tx with significant duskinesia and/or fluctuations on dopa, but with intact cognition |
|
|
Term
| What nerves are stimulated by DBS? |
|
Definition
| subthalamic > g.pallidus > thalamus |
|
|
Term
MOA
reduce sick cells (neurorestoration) in PD |
|
Definition
1) infusion of trophic factor GDNF => no efficacy + SE
2) injection of AAV-GDNF-like factor, AAV-GAD => promising
3) injections of transgenes through receptor-mediated uptake |
|
|
Term
|
Definition
1) Delay Tx until necessary
2) consider trial of antimuscarinics or MAOI-Bs alone
3) initiate DA therapy when necessary
4) Add sinemet if necessary (carbidopa)
5) add COMTI in long term L DOPA complications
6) Apomorphine for rescue during "off" periods
7) add anticholinergics for tremor or drooling
8) consider DBS if Tx fails |
|
|
Term
| What is actually treated in PD? |
|
Definition
| Sx, not the cause => long term goal is neuroprotective/neurorestoration |
|
|
Term
| What is the most common neurological disorder among adults? |
|
Definition
|
|
Term
|
Definition
1) crescendo tremor
a) primarily: action or kinetic tremor in both upper limbs
b) less common head, tongue, & lower limbs
2) aggravated emotions, hunger, fatigue, temp. extremes |
|
|
Term
Disease Course
essential tremor |
|
Definition
| doesn't shorten lifespan, only affects QOL |
|
|
Term
Pathophysiology
essential tremor |
|
Definition
| unknown, possible abnormal oscillations within thalamocortical & olivocerebellar loops |
|
|
Term
| When are patients at an incrased risk for essential tremor? |
|
Definition
| when first degree relative Dx (seems autosomal dominant) |
|
|
Term
|
Definition
primary: propranolol (or metaprolol, other beta blockers), low dose of AED primadone, topiramate
secondary: (refractory patients) ventralis intermedius thalmotomy or DBS |
|
|
Term
Efficacy
Tx of essential tremor |
|
Definition
>50% respond to initial Tx
>80% of refractory patients respond to secondary Tx |
|
|
Term
65 y/o man with PD was successfully treated with Sinemet (carbidopa) is brought in by his wife. He's experiencing a severe headache & elevated BP. Wife admits to giving him her tranylcypromine b/c it helped her & he seemed depressed.
What is the course of action? |
|
Definition
1) Stop MAOI
2) administer an anti-hypertensive
3) possibly cut back on carbidopa for a while (b/c MAOI is irreversible) |
|
|
Term
|
Definition
1) Gut
2) Blood
3) Brain
4) Metabolism in GI
5) Peripheral tissues ( toxicity) |
|
|
Term
|
Definition
1) drug administration
2) drug distribution
3) drug metabolism/excretion |
|
|
Term
|
Definition
1) cellular receptors
2) drug concentration & effect |
|
|
Term
What are the 5 most commonly used drug classes for typical anesthetics in balanced anesthesia?
Why are each one used? |
|
Definition
1) benzos (anmesia)
2) opioids (analgesia)
3) induction agents (sedation/unconsciousness)
4) neuromuscular blockers (paralysis)
5) sympathomimetics (hemodynamic control) |
|
|
Term
| What functions of the body may be affected depending on the depth of the sedation? |
|
Definition
|
|
Term
| What are the 5 steps that must be completed pre-op? |
|
Definition
1) Hx
2) PE
3) Lab data
4) Summary of physical status
5) Plan: informed consent & monitoring |
|
|
Term
27 y/o female presents for nail removal of right fifth digit. She did not tolerate the procedure in the primary care physician's office.
As an anesthesiologist, what do you need to know? |
|
Definition
1) Hx
-ROS, mood, NOS?
2) PE
-BMI, vital signs, Mallampti class, cardiopulmonary check
3) Lab Data
-What lab tests are appropriate? (none in this case)
4) Summary
-Classification according to ASA (American Society of Anesthesiologists)
5) Plan
-Informed consent, and normal standard of care monitoring needed |
|
|
Term
|
Definition
| Nil Per Os = no food or drink for at least 8 hrs prior to procedure |
|
|
Term
def
mallampati classification |
|
Definition
| Class I-IV, depends on how much tongue/back throat is seen when asked to say "ah." This coorelates with how easy a patient will be to intubate |
|
|
Term
| What are the 6 summary classifications according to ASA? |
|
Definition
I: normal healthy patient
VI: declared brain-dead patient
(E: Emergency procedure) |
|
|
Term
| What is the intraoperative monitored anesthesia care? |
|
Definition
1) Sedation (benzo + analgestic)
2) Local anesthesia (infiltration, digital block, solution, additives) |
|
|
Term
| What benzos can be used in sedation? |
|
Definition
Midazolam
Diazepam
Lorazepam |
|
|
Term
|
Definition
sedation
anxiolysis
amnesia
anticonvulsant |
|
|
Term
|
Definition
| enhancing GABA transmission |
|
|
Term
| Do benzos provide analgesia? |
|
Definition
|
|
Term
|
Definition
| long acting in large doses |
|
|
Term
| How is midazolam administered? |
|
Definition
|
|
Term
|
Definition
| resp. depression, loss of balance, prolonged emergence |
|
|
Term
| Why fors 1-2 mg dose of midazolam last for 20-30 min? |
|
Definition
| redistribution, eliminiation hald life of 3 hrs |
|
|
Term
|
Definition
| mimic endogenous endorphins on mu, kappa, delta receptors in the brain & SC => neurotransmitter inhibition via inhibition of Ach & substance P release |
|
|
Term
|
Definition
| intra-op & post-op pain control |
|
|
Term
| What varies b/w opioids s.a. morphine, fentanyl, and its derivatives? |
|
Definition
| dose, time to peak effect, duration of analgesia |
|
|
Term
|
Definition
resp. depression
sedation
GI slowing
dependence
mood
blunt stress response |
|
|
Term
| What derivative of fentanyl is used for infusion? |
|
Definition
|
|
Term
| What metabolizes remifentanil? |
|
Definition
|
|
Term
| Is fentanyl or morphine more potent? |
|
Definition
| fentanyl is 100x more potent |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| How fast until morphine reaches it's peak concentration? |
|
Definition
|
|
Term
| **What is the toxic dose of lidocaine? |
|
Definition
|
|
Term
| What happens when Epi is added to lidocaine? |
|
Definition
| prolong block (+ allows 7 mg/kg dose) |
|
|
Term
| What happens when you add bicarbonate to lidocaine? |
|
Definition
| speed up the onset of the block |
|
|
Term
| When shouldn't Epi ever be added to lidocaine? |
|
Definition
| fingers, toes, penis, nose, ears |
|
|
Term
|
Definition
| anesthetic technique requiring drug delivery to very precise locations along the body's neural transmission |
|
|
Term
| What are the 2 types of regional anesthesia? |
|
Definition
1) epidural
2) intrathecal (spinal or subdural) |
|
|
Term
Which local anesthetics should be used to provide labor analgesia?
A) Bupivicaine .0625% solution
B) Bupivicaine 2% solution
C) Lidocaine .0625% solution
D) Lidocaine 2% |
|
Definition
|
|
Term
| What does nerve block depend on? |
|
Definition
| size, proximity within neural bundle, myelin presence |
|
|
Term
|
Definition
| bind preferentially to Ns channels in the open/inactivated state => makes membranes unable to generate AP |
|
|
Term
| What is the preferred method for C-section delivery anesthesia? |
|
Definition
|
|
Term
| What agents can be used for GA induction? |
|
Definition
| any IV agent, so drug must be chosen based on SE & matched to patient & case |
|
|
Term
| What is the most common GA induction agent? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| rapid onset, short duration |
|
|
Term
|
Definition
potent resp. & CV depressant
pain on injection |
|
|
Term
|
Definition
GA - induction
antiemetic
antipruritic |
|
|
Term
|
Definition
|
|
Term
|
Definition
| sympathomimetic & analgestic |
|
|
Term
|
Definition
| CV stability & adrenal suppression |
|
|
Term
| What, besides athesthesia maintenance, in managed by the anesthesiologist intraoperatively? |
|
Definition
| Airway management (bag mask ventilation, endotracheal tube) |
|
|
Term
| What are the 2 ways anesthesia can be administed intraoperatively? |
|
Definition
1) IV
2) inhalation
(chosen on patient's comorbidities) |
|
|
Term
| What are the 2 IV GA agents? |
|
Definition
|
|
Term
| What are the 4 inhalation agents? |
|
Definition
isoflurane
sevoflurane
desflurane
NO |
|
|
Term
| What can be added to the GA regimen intraoperatively as needed? |
|
Definition
1) narcostic
2) muscle relaxant
3) sympathomimetics
4) reversal agents |
|
|
Term
| What 4 things need to be done post-op prior to discharge from recovery room to floor or home?? |
|
Definition
1) ensure reversal
2) ensure adequate resp. & extubate
3) provide pain relief
4) awaken |
|
|
Term
|
Definition
| loss of memory & other intellectual abilities serious enough to interfere with daily life |
|
|
Term
| How much of dementia is accounted for by Alzheimer's Disease (AD)? |
|
Definition
|
|
Term
| What are the types of dementia? |
|
Definition
1) AD
2) Vascular
3) Mixed
4) Lewy Body
5) PD, FTD, CJD, HD, & other neurological diseases |
|
|
Term
| What occupation seems to increase risk of dementia? |
|
Definition
| professional sports (anywhere where head trauma is eminent) |
|
|
Term
def
MCI (mild cognitive impairment) |
|
Definition
| cognitive decline greater than expected for one's age that may or may not interfere with activities of daily living |
|
|
Term
|
Definition
| number of cognitive scales |
|
|
Term
|
Definition
| it is associated with increased risk...it may be pre-dementia or transitional state of AD |
|
|
Term
|
Definition
| few Tx, but AD Tx may be beneficial |
|
|
Term
|
Definition
progressive & fatal
gradual onset
short-term memory impairment => impairment in other cognitive abilities => very advanced stage - effect on distant memories, alterness, motor function |
|
|
Term
|
Definition
| complications of immobility (6-12 years after onset) |
|
|
Term
| What is the pathophysiology of AD? |
|
Definition
1) marked atrophy of cerebral cortex
2) uneven loss of cortical & subcortical neurons innervating the cortex
3) appearance of plaques & tangles in hippocampus & associative cortex
4) senile plaques accompanied by degenerating neuronal processes
5) neurofibrillary tangles |
|
|
Term
| What does an abundance of plaques & tangles coorelate with in AD? |
|
Definition
|
|
Term
| What are the causes of AD? |
|
Definition
1) idopathic
2) genetic (APP, PS1, PS2, APOE-4)
PS1 & PS2 are APP processing proteins |
|
|
Term
|
Definition
1) cholinesterase inhibitors
2) NMDA receptor antagonist |
|
|
Term
Function
cholinesterase inhibitors |
|
Definition
|
|
Term
| What are the 4 cholinesterase inhibitors used in AD Tx? |
|
Definition
1) donepezil
2) tacrine (not used anymore - hepatotoxicity)
3) rivastigmine
4) galantamine
(Don'T foRGet) |
|
|
Term
|
Definition
mild, moderate, severe AD
MCI
PD w/ dementia
LBD (Lewy Body Dementia)
vascular dementia |
|
|
Term
|
Definition
| reversible acetylcholinesterase inhibitor |
|
|
Term
| Why is once-daily dosing allowed for donepezil? |
|
Definition
|
|
Term
|
Definition
GI & muscle cramps
bradycardia
urinary incontinance
(tend to decrease over time) |
|
|
Term
|
Definition
| CYP2D6 & CYP3A4 => many DDIs |
|
|
Term
|
Definition
mild, moderate AD
PD dementia
LBD |
|
|
Term
|
Definition
| reversible, noncompetitive inhibitor of AchE (& butyrylcholinesterase) |
|
|
Term
| How is rivastigmine dosing different from donepezil? |
|
Definition
| shorter half life => BID dosing, but there is a transdermal patch available |
|
|
Term
|
Definition
|
|
Term
|
Definition
| ChE hydrolysis => NO DDIs |
|
|
Term
|
Definition
mild, moderate AD
vascular dementia |
|
|
Term
|
Definition
| reversible competitive inhibitor or AchE (& binds allosterically to nAchR) |
|
|
Term
| How is galantamine dosed differently from donepezil? |
|
Definition
| BID dosing, but now comes in ER formula |
|
|
Term
Metabolism/Excretion
Galantamine |
|
Definition
Both:
metabolized by CYP3A4 & CYP2D6
AND
excreted unchanged |
|
|
Term
|
Definition
|
|
Term
| Do cholinesterase inhibitors slow the progression from MCI to AD? |
|
Definition
|
|
Term
| What is the NMDA receptor antagonist used in AD? |
|
Definition
|
|
Term
|
Definition
moderate, severe AD (when you're really sick you want your mommy)
vascular dementia |
|
|
Term
|
Definition
| noncompetitive NMDA receptor antagonist |
|
|
Term
| What is the rationale behind NMDA receptor antagonists in AD? |
|
Definition
| use-dependent blockade of overly active NDMA receptors that pass calcium & may lead to excitotoxicity |
|
|
Term
| How effective is memantine compared to the cholinesterase inhibitors? |
|
Definition
| ~effective + may control aggression/agitation (better alternative to antipsychotics => increased risk of death) |
|
|
Term
|
Definition
|
|
Term
|
Definition
generally well tolerated & safe
headache
dizziness
confusion |
|
|
Term
Metabolism/Excretion
memantine |
|
Definition
| no metabolism, excreted unchanged into urine |
|
|
Term
| What is memantine often combined with? |
|
Definition
|
|
Term
| What psychotic Sx can be seen in AD? |
|
Definition
| outbursts, emotional distress, restlessness, shredding things, hallucinations, delusions |
|
|
Term
|
Definition
1) off-label (CAUTION)
a) antidepressants
b) anxiolytics
2) antipsychotics (CAUTION due to increased risk of death...esp. in LBD => VERY HIGH risk ∴ use clozapine if needed or ChEI) |
|
|
Term
|
Definition
| sudden state of confusion accopanied by hallucinations, agitation |
|
|
Term
| What causes hospital delirium? |
|
Definition
| unclear - possible triggers: infection, surgery, pneumonia, catheter insertion, medication, sleep interruption, lack of clear sensorium due to loss of eyeglasses, hearing aids or dentures |
|
|
Term
| What are early stage predictors of AD? |
|
Definition
| combination of memory tests, PET scans, & CSF amyloid |
|
|
Term
| What amyloid type is a problem in AD? |
|
Definition
|
|
Term
| What anti-amyloid therapeutics are being used for AD disease modification? |
|
Definition
1) increase Aβ clearance via immunotherapy
2) decrease Aβ generation thru inhibition of BACE1 or γ-secretase
3) decrease amyloid aggregation
4) anti-tau/tangle therapy |
|
|
Term
|
Definition
|
|
Term
| Why is it doubtful that γ secretase inhibitors will work now on AD? |
|
Definition
semagacestat => dose-dependent DECREASE of cognitive function & daily living abilities
though there is new hopw due to novel targeting of γ secretase |
|
|
Term
| What amyloid-targeting has shown promise in clinical benefit & decreased CSF amyloid? |
|
Definition
|
|
Term
|
Definition
| stabilizes neuronal microtubles in axons |
|
|
Term
| What happens to tau protein to disrput axons? |
|
Definition
| hyperphosphorylation => paired helical filaments |
|
|
Term
| What 3 drugs are being developed for anti-tau/tangle therapies? |
|
Definition
1) AL-108 aka NAP
2) mehtylthionium chloride
3) lithium & valproic acid |
|
|
Term
MOA
Li & Valproic Acid as an anti-tau/tangle therapy |
|
Definition
| inhibit glycogen synthase kinase 3 (GSK 3) which may be involed in tau hyperphosphorylation |
|
|
Term
| What are the risks modifiable & unmodifiable for AD? |
|
Definition
Unmodifiable: Age, genetics, head injury
Modifiable: midlife obesity, DM HTN, hypercholesterolemia, EtOH, smoking |
|
|
Term
| What are the protective factors of AD? |
|
Definition
1) cognitive reserve (education, occupation, mental activites)
2) physical activity
(no benefit obsevered yet of antihypertensives, statins, B vitamins, omega-3, ginko biloba, antioxidants, cognitive interventions) |
|
|
Term
| What does early identification of AD allow? |
|
Definition
|
|
Term
| What lifestyle & non-pharmacological interventions are being used in early AD Tx? |
|
Definition
| brighter lights, modified physical layouts of spaces, use activities & food with positive emotional content (persists even with memory impairment) |
|
|
Term
| What helps decrease ChEI GI SE? |
|
Definition
|
|
Term
73 y/o patient with moderate AD has been on donepezil for several months. He comes in with severe diarrhea, nausea, & muscle cramps. The family doctor has recently perscribed the patient citalopram to treat increasing irritability, sleeplessness, & flat affect.
What is the likely cause of the new Sx?
What action should be taken? |
|
Definition
SSRI is metabolized by same P450 enzymes.
Several options:
1) Remove SSRI
2) Switch anti-depressant to one not metabolized by same P450
3) Switch donepezil to rivastigine or memantine since neither are metabolized by P450 |
|
|
Term
|
Definition
| a hydrophilic molecule formed by decarboxylation of L-histadine |
|
|
Term
| What enzyme decarboxylates L-histadine to histamine? |
|
Definition
|
|
Term
| What cofactor does histadine decarboxylase require? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| What happens to histamine immediately after it's formation? |
|
Definition
|
|
Term
| Does histamine tend to work in a local or systemic fashion? |
|
Definition
|
|
Term
def
autacoids (local hormones) |
|
Definition
| histamine, prostaglandins, leukotrienes, serotonin, & certain endogenous peptides (angiotensin II, bradykinin, substance P, etc) collectively |
|
|
Term
|
Definition
1)immediate allergic responses (rhinitis)
2)immediate hypersensitivity
3)***promotes vasodilation, smooth muscle contraction, increased vascular permeability, & gastric secretion
4)***involved in platelet aggregation, complement activation, mucous secretion, & chemotactant for inflammatory cells
5) Edema-urticaria (hives)
6) neurotransmission/neuromodulation |
|
|
Term
| Where in the bosy is histamine found? |
|
Definition
virtually all tissues in:
1) mostly mast cells
2) basophils in blood
3) enterochromaffin-like cells of fundus of stomach
4) brain |
|
|
Term
| Where within mast cells & basophils is histamine stored? |
|
Definition
| within metachromatic secretory granules |
|
|
Term
| In storage, is histamine active or inactive? |
|
Definition
|
|
Term
| Whas histamine complexed with to facilitate inactivation in storage granules? |
|
Definition
1)specific proteases
2)heparin
3)chrondroitin sulfate proteoglycans |
|
|
Term
| Is histamine turnover in secretory granules fast or slow? |
|
Definition
|
|
Term
Function
histamine in enterochromaffin-like cells of the fundus of the stomach |
|
Definition
| involved in gastric secretion |
|
|
Term
Function
histamine in brain |
|
Definition
| involved in neurotransmission/neuromodulation |
|
|
Term
| Is histamine turnover fast or slow in sites outside of mast cell secretory granules? |
|
Definition
|
|
Term
| What happens to histamine once released? |
|
Definition
| degraded, mostly in liver by histamine (or imidazole) N-methyltransferase & then MOA |
|
|
Term
| What does histamine N-methyltransferase convert histamine to? |
|
Definition
|
|
Term
| What does histamine N-methyltransferase in conjunction with MOA convert histamine to? |
|
Definition
| N-methylimidazole acetic acid (MIAA) |
|
|
Term
| What is the major excreted metabolite of histamine? |
|
Definition
|
|
Term
| What can catalyze the direct covesion of histamine directly to imidazole acetic acid? |
|
Definition
| diamine oxidase (~histaminase) |
|
|
Term
| How much of histamine is excreted unchanged? |
|
Definition
|
|
Term
| What are the 3 types of causes that can induce histamine release? |
|
Definition
1) immunological
2) mechanical
3) chemical |
|
|
Term
|
Definition
| immediate hypersensitivity following sensitization to an allergen |
|
|
Term
| What causes mast cell degranulation? |
|
Definition
|
|
Term
Effect
mast cell degranulation |
|
Definition
| vasodilation, smooth muscle contraction, increased vascular permiability, gastric secretion, platelet aggregation, complement activation, mucous secretion |
|
|
Term
| What disease states are seen as a result of mast cell degranulation? |
|
Definition
asthma
hay fever
skin rashes
anaphylaxis |
|
|
Term
| What mechanical causes can induce mast cell degranulation? |
|
Definition
| scratches, crushes, exposure to extreme hot or cold, & sunlight, etc |
|
|
Term
| What mediates mast cell degranulation? |
|
Definition
|
|
Term
| What chemical cause can induce mast cell degranulation? |
|
Definition
| modulation of Ca2+ => modulation of histamine release |
|
|
Term
| What modulates calcium & therefore histamine? |
|
Definition
1) Cromolyn sodium
2) Nedocramil
3) Compound 48/80
4) polymxin B
5) organic bases, morphine, Abx, radiocontrast dyes |
|
|
Term
Function
cromolyn sodium & nedocramil |
|
Definition
| block influx of divalent ions (including Ca2+ & histamine) |
|
|
Term
|
Definition
|
|
Term
Function
compound 48/80 & polymyxin B |
|
Definition
| act as ionophores => influx of Ca2+ & histamine release |
|
|
Term
Effect on Histamine
therapeutic compounds s.a. organic bases, morphine, turbocurarine, Abx, & radiocontrast dyes |
|
Definition
|
|
Term
MOA
therapeutic compounds s.a. organic bases, morphine, turbocurarine, Abx, & radiocontrast dyes |
|
Definition
| dissociation of histamine from heparin-bound complex inside granules |
|
|
Term
| What vancomycin SE is due to histamine release? |
|
Definition
Red Man Syndrome
(Vanocomycin looks like Vancouver => Red Man's Syndrome) |
|
|
Term
| What are the 4 types of histamine receptors? |
|
Definition
|
|
Term
| What is common among all 4 histamine receptors? |
|
Definition
| all are GPCR, 7 transmembrane-containing proteins, exist on cell surface |
|
|
Term
| Where are H1 receptors found? |
|
Definition
| smooth muscle of gut & bronchi, endothelium, and brain |
|
|
Term
|
Definition
| elicit effects thru second messangers IP3, DAG, Ca2+, & NFKB |
|
|
Term
| Where are H2 receptors found? |
|
Definition
| gastric mucosa (parietal cells), cardiac muscle cells, mast cells, & the brain |
|
|
Term
|
Definition
|
|
Term
| Where are H3 receptors found? |
|
Definition
|
|
Term
| Where are H4 receptors found? |
|
Definition
| eosinophils, neutrophils, CD4 T cells |
|
|
Term
| Which histamine receptor is involved in gastric secretions? |
|
Definition
|
|
Term
| Which histamine receptor is involved in neurotransmission? |
|
Definition
|
|
Term
| Where (again) does histamine exert powerful effects? |
|
Definition
| smooth muscle (bronchi/gut), endothelial cells, nerve cells, heart, & gastric muscosa |
|
|
Term
What 2 histamine receptors affect the cardiovascular system?
What are their effects? |
|
Definition
| H1: decreased BP
H2: increased HR |
|
|
Term
| Why does histamine cause decreased blood pressure? |
|
Definition
| vasodilation effects on arterioles & precapillary sphincters |
|
|
Term
|
Definition
"flushed" feeling
headache
sense of being "warm" |
|
|
Term
What histamine receptor is in the GI smooth muscle?
What's it's effect? |
|
Definition
| H1: contracts smooth muscle |
|
|
Term
What histamine receptor is on bronchiolar smooth muscle?
What's it's effect? |
|
Definition
| H1: contraction, tho normally minimal unless asthmatic |
|
|
Term
| How can histamine be used to detect asthma? |
|
Definition
| Since it's only a powerful bronchial contrictor in asthmatics, it's used as a provocative test of broncial hyper-reactivity |
|
|
Term
What histamine receptor is in the lungs, uterus, ureters, & urinary bladder?
What's it's effect? |
|
Definition
|
|
Term
What does histamine induce as a result of post-capillary vessels?
Why? |
|
Definition
edema since increased permeability => trasudation of fluids & molecules.
When severe => urticaria (hives) |
|
|
Term
What histamine receptor is in nerve endings?
What are the effects? |
|
Definition
| H1: itching due to receptor mediated stimulation of sensory nerve endings (think insect stings) |
|
|
Term
What histamine receptor is in the gastric mucosa?
What are the effects? |
|
Definition
| H2: secretes gastric acid |
|
|
Term
| Where does histamine exert ionotropic & chronotropic effects? |
|
Definition
|
|
Term
| How can histamine's actions be blocked pharmacologically? |
|
Definition
1) antagonist
2) modulate release
3) inverse agonists |
|
|
Term
| What drug is used to counteract histamine's response in systemic anaphylaxis? |
|
Definition
|
|
Term
| What is epinephrine to histamine? |
|
Definition
|
|
Term
| What are allergy pills & sleep aids? |
|
Definition
|
|
Term
MOA
histamine inverse agonists |
|
Definition
| block histamine receptors |
|
|
Term
|
Definition
rhinitis
urticaria
conjunctivitis
(NOT for the common cold, though) |
|
|
Term
| What are the 2 types of H1 inverse agonists? |
|
Definition
1) First Generation
2) Second Generation |
|
|
Term
| What is the difference b/w first generation & second generation H1 inverse agonists? |
|
Definition
| sedative effects (since histamine stimulates wakefulness) |
|
|
Term
| Whaat are the 2 first generation H1 blockers (inverse agonists) of choice? |
|
Definition
Benadryl (diphenhydramine)
Chlor-Trimeton (chlorpheniramine) |
|
|
Term
Effects
diphenhydramine & chlorpheniramine |
|
Definition
reduce Sx of allergy, allergic rhinitis, & urticaria
sedation (put people to sleep) |
|
|
Term
| What is the second generation H1 blocker of choice? |
|
Definition
|
|
Term
| Why do second generation H1 blockers lack a sedative effect? |
|
Definition
| don't distribute well to CNS |
|
|
Term
def
dramamine (dimenhydrinate) |
|
Definition
| H1 blocker used to antimotion sickness property |
|
|
Term
|
Definition
| acts at synpatic relay b/w inner ear & brain stem |
|
|
Term
|
Definition
| diminish gastric secretion |
|
|
Term
|
Definition
duodenal ulcers
gastritis
reflux espohagitis |
|
|
Term
| What are the 2 H2 blockers of choice? |
|
Definition
Tagamet (cimetidine)
Zantac (ranitidine)
(tho not referred to as anti-histamines) |
|
|
Term
| What are the 6 first generation anihistamines? |
|
Definition
1) Chlorpheniramine maleate
2) Hydroxyzine HCl
3) Meclizine HCl
4) Promethazine HCl
5) Diphenhydramine HCl
6) Dimenhydrinate
(CHoMP on DDs) |
|
|
Term
| What are the 6 second generation antihistamines? |
|
Definition
1) Cetirizine
2) Acrivastine
3) Loratadine
4) Levocabastine
5) Fexofenadine
6) Desloratadine
(Can't ALL Fall Down) |
|
|
Term
|
Definition
| polypeptide hormine secreted from the mucosa of gastric antrum in response to eating or alkanization of stomach |
|
|
Term
|
Definition
| cause gastric secretion of pepsin & HCl & promotes growth of GI mucosa |
|
|
Term
|
Definition
| the proteinase of gastric juice derived from pepsinogen and elaborated & secreted by chief cells of gastric mucosa |
|
|
Term
| What are the 5 acid-peptic diseases? |
|
Definition
1) Gastritis
2) Gastric/duodenal peptic ulcers
3) Gastroesophageal reflux disease (GERD)
4) Gastric pyrosis (heartburn)
5) Pathological hypersecretion (Zollinger-Ellison Syndrome: gastrin secreting tumor) |
|
|
Term
| What are the possible pathogeneses of acid-peptic disease? |
|
Definition
1) gastric acid/pepsin secretion
2) mucosal resistance
3) h. pylori
4) NSAIDs |
|
|
Term
| How does mucosal resistance contribute to the pathogenesis of acid-peptic disease? |
|
Definition
| secretion of bicarb by epithelial cells (inherent property of surface/mucous) |
|
|
Term
| How can NSAIDs contribute to the pathogenesis of acid-peptic disease? |
|
Definition
1) exacerbate peptide ulcers
2) cause dyspepsia |
|
|
Term
| What 2 pathogenic factors cause over 99% of peptic ulcers? |
|
Definition
|
|
Term
Tx
ulcerative & inflammatory GI diseases |
|
Definition
1) Neutralize acid
2) reduce gastric acid secretion
3) enahnce mucosal defenses thru cytoprotective or anti-microbial intervention |
|
|
Term
| What are used to neutralize the acid? |
|
Definition
|
|
Term
|
Definition
| weak bases that inactivate HCl & confer mucosal protection thru stimulation of mucosal prostaglandin production |
|
|
Term
| What are most antacuds composed of? |
|
Definition
| either Mg(OH)2 or Al(OH)3 (alone or in comination) sometimes along with sodium bicarb or a calcium salt |
|
|
Term
|
Definition
1) Sodium bicard (baking soda)
2) Magnesium hydroxide
3) Magnesium trisilicate
4) Aluminum hydroxide
5) Calcium carbonate (tums)
(SMMACk) |
|
|
Term
| What should be considered before an antacid is chosen? |
|
Definition
palatability
price
potency
SE (Al => constipation, Mg => diarrhea) |
|
|
Term
| What does the effectiveness of the antacid depend on? |
|
Definition
1) how much acid
2) how fast emptied
3) potency of antacid |
|
|
Term
|
Definition
neutralize acid
cytoprotective (more so, since doses too low to neutralize gastric acid) |
|
|
Term
| How are antacids cytoprotective? |
|
Definition
| binding irritating compounds (possibly) |
|
|
Term
| What are the 4 compounds that can be used to reduce gastric acid secretion? |
|
Definition
1) antihistamines
2) antimuscarinics
3) proton pump inhibitors
4) somatostatin analogs |
|
|
Term
| What 3 agonists control gastric acid secretion? |
|
Definition
1) histamine
2) Ach
3) gastrin |
|
|
Term
| What antihisatmines are used to reduce gastric acid secretion? |
|
Definition
|
|
Term
| Why are H2 antagonists used to reduce gastric acid secretion? |
|
Definition
| effective in promoting healing of gastric & duodenal ulcers |
|
|
Term
| Is combination of antihistamines with antacids more effective? |
|
Definition
|
|
Term
| What 4 antihistamines are used to reduce gastric acid secretion? |
|
Definition
1) Cimetidine
2) Famotidine
3) Ranitidine
4) Nizatidine |
|
|
Term
| How do antimuscarinics decrease gastric acid sectretion? |
|
Definition
| depress smooth muscle motility & PS mediated release of HCl. |
|
|
Term
| When are antimuscarinics used to reduce gastric acis secretion? |
|
Definition
| when a patient is refractory to H2 antagonists |
|
|
Term
| What are the 4 proton pump inhibitors? |
|
Definition
1) Pantoprazole
2) Omeprazole
3) Lansoprazole
4) Esomeprazole
(POLE - prazoles) |
|
|
Term
|
Definition
| irreversibly inhibits the gastric parietal cell proton pump |
|
|
Term
| What activated omeprazole? |
|
Definition
| secretory canaliculus of the parietal cell in acid environment |
|
|
Term
|
Definition
gastric & duodenal ulcers
severe gastroesophageal disease
Zollinger-Ellison Syndrome |
|
|
Term
| How many doses of proton pump inhibitors are needed for 100% reduction of gastric acid secretion? |
|
Definition
|
|
Term
| What somatostatin analog is used to decrease gastric acid secretion? |
|
Definition
|
|
Term
|
Definition
| parenteral administration required |
|
|
Term
|
Definition
| suppress nocturnal acid secretion |
|
|
Term
| For whom is intractability (no response to H2 antagonists) frequently seen? |
|
Definition
|
|
Term
| What happens if a gastric secretion reducer becomes intractible? |
|
Definition
| try another H2 antagonist, proton pump inhibitor, or try to possibly Tx h. pylori infection |
|
|
Term
| How can you enhance mucosal defenses? |
|
Definition
1) Mechanical barrier protection (infrequently used)
2) GI motility |
|
|
Term
MOA
mechanical barrier protection |
|
Definition
| forms protective coating on ulcer crater that will remain for several hourse |
|
|
Term
| What 3 drugs use mechanical barrier protection? |
|
Definition
1) Sucralfate
2) Bismuth subsaicylate (peto-Bismol)
3) Prostaglandins |
|
|
Term
|
Definition
| aluminum salt of sulfated disaccharide |
|
|
Term
|
Definition
| directly inhibits pepsin & blie action w/o changing pH of stomach (tho NOT an antacid) |
|
|
Term
| What is needed for activation of sucralfate? |
|
Definition
|
|
Term
|
Definition
| polymerizes & selectively binds to necrotic ulcer tissue, forming barrier to acid, pepsin, & blie |
|
|
Term
| When is bismuth subsalicylate especially useful? |
|
Definition
| in combination with Abx for h. pylori |
|
|
Term
|
Definition
| binding to the ulcer, coating, & protection from acid & pepsin |
|
|
Term
| Why are prostaglandins Tx for peptic ulcers? |
|
Definition
| prevent gastric acid secretion by blocking histamine stimulated cAMP production |
|
|
Term
DOC
prostaglandin for peptic ulcers |
|
Definition
|
|
Term
|
Definition
|
|
Term
| What neurotransmitter system controls gastric motility? |
|
Definition
|
|
Term
| What cholinomimetic is used to stimulate GI motility with a peptic ulcer (w/o increasing gastric, biliary, or pancreatic secretions)? |
|
Definition
|
|
Term
| Why is metoclopramide useful in reflux esophagitis? |
|
Definition
| increases resting tone of lower esophageal sphincter |
|
|
Term
|
Definition
1) increases resting tone of lower esophageal sphincter
2) hasten esophageal clearance
3) accelerates gastric emptying
4) shortens bowel time
5) antiemetic properties |
|
|
Term
| Why does metoclopramide have antiemetic properties? |
|
Definition
|
|
Term
|
Definition
| 2 Abx(Amoxicillin & Clarithromycin)
+ proton pump inhibitor
Regimen alternative (cheaper):
bismuth
2 Abx (metronidazole, tetracycline)
H2 blocker |
|
|
Term
|
Definition
| emetic center located in the reticular portion of the medulla |
|
|
Term
| What are the 3 basic steps involved in naussea/vomiting? |
|
Definition
1) Sensor excitation
2) Emetic center recives stimulation
3) Emetic center coordinates series of physiological effects that first promote nausea => vomiting |
|
|
Term
| What are the possible sensors that can initiate N/V? |
|
Definition
1) Cerebrum (psychic vomiting)
2) semicurcular cancels & labyrinth (motion sickness)
3) pharynx (gagging)
4) irritation to stomach/intestinal lining
5) irritation of mesentary or peritoneum (peritonitis)
6) thorasic pain |
|
|
Term
| What does the emetic center recieve stimulation from? |
|
Definition
| CTZ (chemoreceptor trigger zone) on the floor of the 4th ventricle, the vestibular apparatus, etc. |
|
|
Term
| What is contained in CTZ? |
|
Definition
| DA receptors => increased motor drive to emetic center |
|
|
Term
| What medications can promote vomiting? |
|
Definition
| potent dopaminergic agonists (s.a. apomorphine) |
|
|
Term
Effects
Emetic Center stimulation |
|
Definition
1) increase HR, salivation, mydriasis, seating & pallor
2) contraction of pylorus & relaxation of gastric smooth muscle
3) intermittent tensing of the abdominal & intercostal muscles (increased abdominal pressure)
4) reverse peristalsis @ lower esophagus => ejection of gastric contents |
|
|
Term
| hat ae the after effects of vomiting? |
|
Definition
| reflex slowing of heart, fall in blood pressure, faintness, & pallor |
|
|
Term
| What are the 2 types of emetic agents? |
|
Definition
1) locally acting
2) central acting |
|
|
Term
| What is a locally acting emetic? |
|
Definition
|
|
Term
| Where does ipecac syrup come from? |
|
Definition
| extract of dried root of Brazillian plant |
|
|
Term
| What mediates the emetic action of ipecac syrup? |
|
Definition
| emetine & cephaeline (2 alkaloids) => irritant action directly on stomach & CTZ |
|
|
Term
|
Definition
|
|
Term
| What is the centrally acting emetic? |
|
Definition
|
|
Term
| How does apomorphine induce vomiting? |
|
Definition
| the acid modified morphine acts primarily on the CTZ thru DA receptors as an agonist |
|
|
Term
|
Definition
|
|
Term
| What are the 5 antiemetics? |
|
Definition
1) Prochlorperazine
2) Metochlopramide
3) Trimethobenzmide
4) Ondansetron
5) Clorpromazine
(Pros Meet & Tri On Clothes) |
|
|
Term
MOA
anti-motion sickness agents |
|
Definition
| block H1 receptors => blocking of synpatic relay along CNVIII => decreased N/V (doesn't block other pathways to CTZ) |
|
|
Term
| What is the anti-motion sickness agent? |
|
Definition
|
|
Term
|
Definition
| agents that soften/hasten evacuation of fecal material from colon |
|
|
Term
| What are the 3 types of laxatives? |
|
Definition
1) Irritants/stimulants
2) Bulking laxatives
3) Stool softeners |
|
|
Term
Effect
chronic use of laxatives |
|
Definition
| serious atonic hypomotility of colon |
|
|
Term
| What are the 3 irritant/stimulant laxatives? |
|
Definition
1) castor oil
2) emodin alkaloids
3) diphenylmethanes |
|
|
Term
| What happens to castor oil when taken PO? |
|
Definition
| hydrolyzed to ricinoleic acid by lipases secreted from pancreas => acid stimulated the GI tract motility => promotes evacuation |
|
|
Term
|
Definition
|
|
Term
|
Definition
| pregnancy, esp. 3rd trimester (can induce premature labor) |
|
|
Term
| How can the emodin alkaloids (cascara, senna, & aloes) induce GI motility? |
|
Definition
| metabolized by bacteria to yield an active compound => peristalsis |
|
|
Term
|
Definition
|
|
Term
| What are the 2 types of bulking laxatives? |
|
Definition
1) osmotic laxatives
2) fiber laxatives |
|
|
Term
| What are included as osmotic laxatives? |
|
Definition
1) magnedium sulfate (epsom salt)
2) magnesium hydroxide (milk of magnesia - also an antacid) |
|
|
Term
|
Definition
| hold water by osmotic force => distension of bowels |
|
|
Term
| What are included as fiber bulk laxatives? |
|
Definition
1) hyrophilic colloids (most natural physiological laxation)
2) psyllium seed (metamucil) |
|
|
Term
|
Definition
inability of digestive processes to break down cellulose => formation of gelatinous mass that retains more fluid => distension of bowels
(also promote soften stool & more fecal matter) |
|
|
Term
| What are used as stool softeners? |
|
Definition
1) lubricants s.a. mineral oil
2) glycerin |
|
|
Term
MOA
lubricants s.a. mineral oil |
|
Definition
| coating & lubricating fecal matter => prevention of normal absorption of water |
|
|
Term
| How is glycerin usally administered? |
|
Definition
|
|
Term
|
Definition
| lubricating & produces local irritation of rectum => initiation of defecation reflex |
|
|
Term
|
Definition
constipation
poisoning
anthelminthics (destroy intestinal worms)
pre-op, pre-radiological exam, pre-protological exam
anorectal diseases (to prevent straining)
opioid Tx |
|
|
Term
| How long does acute diarrhea last? |
|
Definition
|
|
Term
| When can acute diarrhea be life threatening? |
|
Definition
| young children (dehydration & electrolyte imbalance) |
|
|
Term
|
Definition
| physiological defense mech. aimed at expelling infective agent from GI |
|
|
Term
| What can cause chronic diarrhea? |
|
Definition
| manifestation of some other possible serious organic disease |
|
|
Term
| Why must care be taken prior to anti-diarrhea agents Rx? |
|
Definition
1) acute diarrhea (may increase host exposure time to toxins of infection)
2) chronic diarrhea (may mask Sx & delay Dx/Tx of a disease) |
|
|
Term
| What are the 2 types of anti-diarrheal agents? |
|
Definition
1) affect motility
2) absorptive of water (absorbent powders) |
|
|
Term
| What are the 3 anti-diarrheal agents that affect motility? |
|
Definition
1) opiates
2) diphenoxylate & atropine
3) loperamide |
|
|
Term
|
Definition
| promote sustained contraction of GI & interrupt normal organized sequence of peristaltic contractions |
|
|
Term
|
Definition
| inhibition of Ach release from presynaptic opioid receptors in enteric nervous system |
|
|
Term
|
Definition
| absorb water (& toxins) to provide protective coating to inflamed intestine |
|
|
Term
| What are the aborbent powder drugs? |
|
Definition
1) Kaolin
2) Pectin
3) Bismuth subsalicylate (also enhances mucoal protection)
4) Combination products s.a.
a) Kaolin magma + belladonna alkaloids
b) Kaolin magma + pectin |
|
|
Term
|
Definition
long chain fatty acids that act as autocrine or paracrine agents.
include:
prostaglandins, prostacyclin, thromboxanes, leukotrienes |
|
|
Term
| What is the usual precursor of eicosanoids? |
|
Definition
|
|
Term
| Where does arachidonic acid come from? |
|
Definition
| released from membrane phospholipids by phospholipase A2 |
|
|
Term
| What is another possible substrate for eicosanoids (other than the usual arachidonic acid)? |
|
Definition
| fatty acids s.a eicosapentanoic acid (found in fatty fishes), but yield different eicosanoid products |
|
|
Term
|
Definition
1) reduce cholesterol, triglycerides in recovery from acute coronary disease
2) increase tachycardia/fibrillation/cardiac death in chronic coronary disease
3) reduce Sx of inflammation in RA & psoriasis |
|
|
Term
| What do COX1 & COX2 catalyze? |
|
Definition
| 2 step reaction (oxygenation & peroxidation) => prostaglandin PGH2 formation |
|
|
Term
|
Definition
| constitutive form in stomach, platelets, & other tissue |
|
|
Term
|
Definition
1) inducible form in inflammatory tissues
2) constitutive form in kidney & vascular endothelium |
|
|
Term
| What eicosanoid product(s) predominate in the stomach? |
|
Definition
|
|
Term
| What eicosanoid product(s) predominate in platelets? |
|
Definition
|
|
Term
| What eicosanoid product(s) predominate in vascular endothelium? |
|
Definition
|
|
Term
| How are COX products released? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| minutes (very short half lives) |
|
|
Term
| What inactivates eicosanoids? |
|
Definition
| specific enzymes by fatty acid oxidation |
|
|
Term
| What eicosanoid products do not come from the precursor PGH2? |
|
Definition
|
|
Term
| What eicosanoid products are found in the kidney? |
|
Definition
| PGE2 & PGI2
TXA2 (very little) |
|
|
Term
| Function
PGE2 & PGI2 in kidney |
|
Definition
1) increase release of renin from juxtaglomerulat apparatus (JMA)
2) vasodilation => increase GFR
3) reduce effects of ADH in collecting duct |
|
|
Term
| Effect
PGE2 & PGI2 in kidney |
|
Definition
| increase sodium & water clearance |
|
|
Term
| What synthesizes TXA2 during infiltration of inflammatory cells? |
|
Definition
|
|
Term
|
Definition
| vasoconstriction & decline in renal function |
|
|
Term
| What is the only vasoconstrictor eicosanoid (in humans)? |
|
Definition
|
|
Term
| What eicosanoids are produced by vascular endothelial cells? |
|
Definition
| PGI2 (main source) & PGE2 (in microcirculation) |
|
|
Term
| Effect
PGI2 & PGE2 on blood vessels |
|
Definition
| vasodilation (=> hypotension & reflex tachycardia if IV injection of prostacyclin PGI2) |
|
|
Term
Effect
prostaglandins & thromboxanes on GI smooth muscle |
|
Definition
|
|
Term
| What eicosanoids are produced by COX1 in the stomach? |
|
Definition
|
|
Term
| Function
PGE2 & PGI2 in stomach |
|
Definition
| cytoprotective by maintaining secretion of mucins & limiting pepsin & acid secretion |
|
|
Term
| What happens to GI if COX1 is inhibited? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| What happens to GI if COX2 is inhibited? |
|
Definition
|
|
Term
| What is the major COX1 eicosanoid product of platelets? |
|
Definition
|
|
Term
|
Definition
1) vasoconstrictor
2) potent platelet aggregator
3) increase effects of thrombin & other aggregators |
|
|
Term
| What can counteract TXA2 effects? |
|
Definition
| 1) prostacyclin (COX2 systnesis in vascular endothelium)
2) PGD2 |
|
|
Term
| What eicosanoids relax bronchiolar & tracheal muscle? |
|
Definition
| prostacyclin (PGI2) & PGE2 |
|
|
Term
| What eicosanoids constrict bronchiolar & tracheal muscle? |
|
Definition
| TXA2 & other prostaglandins |
|
|
Term
| What can induce PGE2 synthesis in the nervous system? |
|
Definition
| pyrogenes => IL-1 induced synthesis of PGE2 |
|
|
Term
|
Definition
1) fever
2) transmission of pain fibers in SC |
|
|
Term
| What 2 eicosanoids sensitize nerve endings of pain fibers in the periphery? |
|
Definition
|
|
Term
| What eicosanoids can cause uterine contraction? |
|
Definition
| 1) TXA2
2) PGF2α
3) low doses of PGE2 |
|
|
Term
| What effect does COX1 & COX2 inhibition have on inflammation? |
|
Definition
| palliative relief from inflammation (inspite of the fact that prostaglandins & prostacyclin has anti-inflammatory effects) |
|
|
Term
| How is PGE2 anti-inflammatory? |
|
Definition
1) inhibits differentiation of B-lymphocytes into plasma cells
2) inhibits mitogen induced proliferation & lymphokine release by T lymphocytes |
|
|
Term
| How is TXA2 pro-inflammatory? |
|
Definition
1) promotes cloncal expansion of T lymphocytes
2) stimulates IL & IL receptor synthesis |
|
|
Term
| What is the most likely explanation for the anti-inflammatory effect of COX inhibitors? |
|
Definition
| diminished eicosanoid effects on vasodilation & sensitization of nociceptive nerves |
|
|
Term
|
Definition
| PGE1 used for:
1) vasodilating effect in Tx of impotence when injected directly into corpora cavernosa
2) maintain patent ductus arterosus prior to cardiac surgery |
|
|
Term
|
Definition
| PGE11 derivative used:
1) with mifepristone in terminating pregnancies
2) for protection against peptic ulcer |
|
|
Term
| What eicosanoids are used with oxytocin to induce labor? |
|
Definition
|
|
Term
| What eicosanoid is used to treat pulmonary & portopulmonary HTNs? |
|
Definition
|
|
Term
|
Definition
| family of enzymes that can catalyze oxygenation of arachadonic acid to hyperoxides |
|
|
Term
| Where is 5-LOX isoform found? |
|
Definition
| PMNs, basophils, mast cells, eosinophils, & macrophages |
|
|
Term
| What physiological processes are associated with 5-LOX products? |
|
Definition
| asthma, anaphylactic shock, & CVD |
|
|
Term
| What leads to the release of arachidonate & association of 5-LOX with FLAP on the nuclear membrane? |
|
Definition
| activation of 5-LOX containing cells |
|
|
Term
|
Definition
|
|
Term
| What is arachidonate oxygenated & dehydrated by 5-LOX to produce? |
|
Definition
| unstable leukotriene LTA4 |
|
|
Term
| What happens to the unstable LTA4 produced by 5-LOX? |
|
Definition
| 1) hydrated to LTB4
or
2) conjugated to LTC4 by a thiol bond to the tripeptide, glutathione |
|
|
Term
|
Definition
| sequentially degraded by extracellular enzymes to LTD4 & LTE4 |
|
|
Term
| Where is 12-LOX isoform found? |
|
Definition
| platelets + all inflammatory cells containing 5-LOX |
|
|
Term
|
Definition
| coverts arachidonic acid directly to stereoisomers 12S-HETE & 12R-HETE |
|
|
Term
| What happens to LTA4 when exposed to 12-LOX? |
|
Definition
| coverted to lipoxins A & B |
|
|
Term
| What shares the same receptor as LTB4? |
|
Definition
| 12-HETEs (the conjugated leukotrienes bind to another class of receptors) |
|
|
Term
| What happens to LTB4 & LTC4? |
|
Definition
| actively transported out of the cell |
|
|
Term
Duration
leukotrienes & HETEs |
|
Definition
|
|
Term
|
Definition
| CYP4F P450 family in leukocytes |
|
|
Term
| Where are the conjugated leukotrienes degraded? |
|
Definition
|
|
Term
|
Definition
| chemoattractant for PMNs, eosinophils, & monocytes |
|
|
Term
|
Definition
1) attract eosinophils
2) vasoconstrict (=> depression of cornonary & myocardium blood flow)
3) increase vascular permeability (=> mucus secretion & plama exudation in airways)
4) airway: Slow Reacting Substance of Anaphylaxis (SRS-A) secreted in anaphylaxis & asthma => bronchoconstriction |
|
|
Term
| Which leukotriene is screted by colonic epithelial cells & are therefore high in inflammatory bowel disease? |
|
Definition
|
|
Term
|
Definition
| mediate angiotensin II's release of aldosterone (not ACTH's) |
|
|
Term
SOA
5-LOX & LT receptor antagonists |
|
Definition
asthma
(not generalized inflammation s.a. RA) |
|
|
Term
Effect
Non-Steroidal Anti-inflammatory Drugs (NSAIDs) |
|
Definition
1) reduce inflammation
2) analgestic
3) antipyretic |
|
|
Term
| Why are NSAIDs a mainstay in the management of various inflammatory diseases? |
|
Definition
| reduce inflammation without affecting underlying disease processes |
|
|
Term
|
Definition
| inhibit COX (not 5-LOX or leukotriene synthesis) => inhibition of PGs, TXAs, & prostacyclin |
|
|
Term
Compare/Contrast
COX1 & COX2 |
|
Definition
Catalyze same reactions, but have different distribution
COX1: stomach, platelets, & other tissues
COX2: localized to cells in inflammation, vascular endothelium & renal juxtaglomerular apparatus |
|
|
Term
|
Definition
| acetyl salicylic acid (ASA) is an organic acid that is readily absorbed from the stomach |
|
|
Term
| What happens to the majority of ASA once absorbed from the stomach into the stomch lining? |
|
Definition
| hydrolyzed to salicyclic acid & accumulates |
|
|
Term
| What happens to absorbed aspirin? |
|
Definition
| widely distributed & hetabolized (hydrolysis, conjugation) in liver |
|
|
Term
| Is aspirin elimination 1st order or zero order in OD? |
|
Definition
| zero (b/c metabolism is saturable) |
|
|
Term
| What does aspirin displace from their binding sites on serum albumin? |
|
Definition
1) methotrexate
2) phenetoin
3) coumarins
4) sulfonylurea hypoglycemics |
|
|
Term
|
Definition
| via kidney where it competes for secretion with uric acid in proximal tubule |
|
|
Term
| What does aspirin irreversibly inhibit? |
|
Definition
| COX1 & COX2, but has higher affinity for COX1 |
|
|
Term
| Why is aspirin inhibition of COX irreversible? |
|
Definition
| aspirin acetylates active site of the enzymes |
|
|
Term
|
Definition
1) analgesia
2) antipyresis
3) anti-inflammation
4) antithrombotic |
|
|
Term
| How does aspirin exert it's analgestic effects? |
|
Definition
| PGs are moderators of nervous activity in PNS & CNS. Aspirin decreases PGs peripherally => mild/moderate pain relief |
|
|
Term
| How does aspirin exert it's antipyresis effects? |
|
Definition
| blocks pyrogen induced PG synthesis in hypothalamus to lower febrile (but not basal body) temp. |
|
|
Term
| How does aspirin exert it's anti-inflammatory effects? |
|
Definition
| reduces heat, pain, & swelling (contributes to analgestic property) |
|
|
Term
| How can aspirin exert it's antithrombotic effect? |
|
Definition
| low doses aspirin => selective inhibition of COX1 on platelets with little effect on COX2 on endothelial cells => mild increase in clotting time |
|
|
Term
| Why does aspirin inhibit COX1 for the life of the platelets? |
|
Definition
| non-nucleated, so can't create new COX |
|
|
Term
| When is increase in clotting time dangerous? |
|
Definition
| hemophilia & with other anticoagulants |
|
|
Term
|
Definition
1) gastric irritation, bleeding, ativation of peptic ulcers (due to inhibition of gastric COX1 & corrosive properties of salicylate)
2) precipitate gouty attacks
3) Reye's syndrome in children
4) exacerbate existing renal disease
5) bronchospasm due to hypersensitivity |
|
|
Term
| When is aspirin OD common? |
|
Definition
|
|
Term
|
Definition
| central effects s.a. tinnitus, vertigo & hyperventilation => resp. alkalosis => metabolic acidosis & CNS mediated hyperthermia & resp. depresion => resp. & vasomotor collapse |
|
|
Term
|
Definition
gastric lavage
fluids
alkalinization of urine
correction of acid/base defects |
|
|
Term
|
Definition
| non-specific COX inhibitor (NOT an NSAID) |
|
|
Term
|
Definition
1) analgestic
2) antipyretic
(NOT anti-inflammatory or anti-coagulant, nor does it cause stomach irritation) |
|
|
Term
| Where is APAP metabolized? |
|
Definition
|
|
Term
| What can metabolites of APAP cause in OD? |
|
Definition
| irriversible & fatal hepatotoxicity & renal toxicity |
|
|
Term
|
Definition
|
|
Term
| What are the 6 NSAIDs that are non-selective reversible COX inhibitors? |
|
Definition
1) Phenylpropionic acid derivatives s.a. Ibuprofen, naproxen (fenprofen, ketoprofen & others)
2) indomethacin
3) meclofenamate
4) diclofenate
5) sulindac
6) phenylbutazone |
|
|
Term
Effect
NSAID reversible non-specific COX inhibitor |
|
Definition
1) anti-inflammatory
2) analgestic
3) antipyretic
(not anticoagulant) |
|
|
Term
| How do pehnylpropionic acid derivatives s.a. ibuprofen (advil) & naproxen (aleve) compare to aspirin? |
|
Definition
| more potent, more expensive, with milder GI effects |
|
|
Term
Duration?metabolism
ibuprofen & naproxen |
|
Definition
| variable hepatic metabolism & duration (naproxen has a loner half life) |
|
|
Term
|
Definition
well tolerated
can have serious hematological & renal SE
chronic use of ibuprofen can antagonize cardioprotection of aspirin |
|
|
Term
|
Definition
severe gastric effects
severe headache
thrombocytopenia
aplastic anemia
coronary artery constriction
hyperkalemia & others
(very powerful NSAID, but serious SE) |
|
|
Term
|
Definition
| short term under special circumstances in gout, ankylosing spondylitis, pericarditis & pleurisy |
|
|
Term
|
Definition
| children (except patent ductus arteriosis) |
|
|
Term
| How does meclofenamate compare to aspirin? |
|
Definition
| ~ to w/ less gastric effects |
|
|
Term
|
Definition
| potent NSAID with high incidence of gastric effects |
|
|
Term
|
Definition
ointment for osteoarthritis
patch for pain due to minor injury
(systemic exposure less after topical doses) |
|
|
Term
|
Definition
| NSAID prodrug where the hepatic metabolite undergoes enterohepatic cycling to prolong duration of action |
|
|
Term
|
Definition
| seldom used except in actue gouty attacks (due to powerfulness => SE) |
|
|
Term
| What is the NSAID selective reversible COX2 inhibitor? |
|
Definition
|
|
Term
| Is Celecoxib more or less effective as an anti-inflammatory? |
|
Definition
| neither, about equal (but more expensive) |
|
|
Term
| Why would someone use celecoxib if it's more expensive and as effective? |
|
Definition
|
|
Term
| Does celecoxib have the same anticoagulant effect of COX1 inhibitors? |
|
Definition
| no, but they do interact with coumarins to increase PT time |
|
|
Term
| What can increase gastric side effects of COX2 inhibitors? |
|
Definition
| cardioprotective doses of aspirin |
|
|
Term
|
Definition
| allergic rxn in patients allergic to sulfonamindes |
|
|
Term
| What can reduce NSAID related dyspepsia? |
|
Definition
| H2 receptor antagonists, proton pumps (+ ulceration reduction, but short term) - tho neither can prevent long term protection of reactivation of peptic ulcers |
|
|
Term
| Can APAP be sed in GI protection? |
|
Definition
| effective against pain, but it's anti-inflammatory |
|
|
Term
| In combination with what can misoprostol (synthetic prostaglandin) prevent gastric ulcers? |
|
Definition
non-selective NSAID
(misoprostol can cause severe diarrhea & can't be used in pregnancy) |
|
|
Term
SE
ALL NSAIDs (including celecoxib) |
|
Definition
1) inhibit renal PG synthesis
2) decrease renal blood flow
3) cause fluid retention
(sometimes renal failure)
4) CNS effects s.a. dizziness, drowsiness, anxiety, & confusion |
|
|
Term
| What can increase the risk of renal failure in NSAID use? |
|
Definition
| diruetics, cirrhosis, CHF |
|
|
Term
| For what drugs do NSAIDs decrease the effectiveness of? |
|
Definition
1) diuretics
2) beta blockers
3) ACE inhibitors |
|
|
Term
| For what drugs do NSAIDs increase the toxicity of? |
|
Definition
|
|
Term
Effect
DMARDs (Disease Modifying Anti-Rheumatic Drugs) |
|
Definition
supress proliferatio & activity of lymphocytes & PMNs by a variety of mechanisms =>
1) reduction of inflammation
2) joint destruction
3) slow/stop progress of RA |
|
|
Term
|
Definition
1) Adalimumab
2) Leflunomide
3) Imfliximab
4) Etanercept
5) Sulfasalazine
6) Abatacept
7) Hydroxychloroquine
8) Methotrexate
9) Azathioprine
10) Rituximab
(Adam LIES About His dMARd's) |
|
|
Term
| Which drug is the standard of care for DMARD therapy? |
|
Definition
|
|
Term
|
Definition
1) lymphocytes: decreased proliferation, decreased cytokine production
2) PMNs: decreased chemotaxis, decreased free radical formation
3) thyamine deficiency |
|
|
Term
|
Definition
| ihibition of DHFR (dihydrofolate reductase) |
|
|
Term
| When does imporvemt occur in methotrxate therapy? |
|
Definition
|
|
Term
|
Definition
lose doses: well tolerated
GI, hematological, hepatic effects |
|
|
Term
| Which 3 DMAARDs are teratogenic? |
|
Definition
Methotrexate
Leflunomide
Azathiprine
(MAL = bad in french) |
|
|
Term
SE
methotrexate + leflunomide |
|
Definition
|
|
Term
|
Definition
RA
malaria
ameba infestation |
|
|
Term
|
Definition
malaria/ameba: partitions into the acidic vacuole of the organisms
PMNs: accumulation in lysosomes |
|
|
Term
|
Definition
PMNs:
reduces chemotaxis
phagocytosis
superoxide production |
|
|
Term
| How long before RA effects take place with hydroxychloroquine? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| Which 2 DMARDs are contraindicated in individuals with G6P DH deficiency (& probably shouldn't be given to pregnant women either)? |
|
Definition
Hydroxycloroquine
Sulfasalazine |
|
|
Term
|
Definition
RA
inflammatory bowel disease |
|
|
Term
| How is sulfasalazine absorbed? |
|
Definition
| It's split by the enteric flora to 5-aminosalicylic acid (active agent in inflammatory bowel disease) & sulapyridine (absorbed & => antirheumatic effect) |
|
|
Term
|
Definition
rashes
dizziness
GI upset
photosensitivity
neutropenia (rare) |
|
|
Term
|
Definition
| hepatic metabolism to active compund => inhibition of dihydroorotate dehydrogenase => pyrimadine deficiency produces effects similar to methotrexate |
|
|
Term
|
Definition
diarrhea
hair loss
hepatic damage |
|
|
Term
| What DDIs are caused by leflunomide? |
|
Definition
| CYP2C9 inhibition => many DDIs (including NSAIDs) |
|
|
Term
|
Definition
| converted to 6-mercaptopurine => inhibits several steps in purine interconversions => inhibits DNA synthesis |
|
|
Term
|
Definition
| ~methotrxate, tho may increase risk of lymphoma |
|
|
Term
MOA
injectible gold salts, gold sodium thomalate & gola thioglucose in RA |
|
Definition
| unclear but may induce complete remission |
|
|
Term
|
Definition
stomatitisrash
proteinuria
leukopenia
thrombocytopenia
enterocolitis & aplastic anemia - rare, but fatal |
|
|
Term
| What does long term use of cyclophosphamine is RA cause? |
|
Definition
|
|
Term
| When is thalidomide (well known teratogen) used in RA? |
|
Definition
| refractory cases (with SE of sedation) |
|
|
Term
| What produces TNFα in RA? |
|
Definition
| macrophages & T cells in synovium |
|
|
Term
|
Definition
| recruitment of inflammatory cells, angiogenesis, & tissue distruction |
|
|
Term
| Are TNFα inhibitors more or less effective than methotrexate in RA Tx? |
|
Definition
|
|
Term
| What are the 3 TNFα inhibitors? |
|
Definition
1) Adalimumab
2) Etanercept
3) Imfliximab
(AEIou or .F.AI.N.T.Ed) |
|
|
Term
| What is etanercept composed of? |
|
Definition
| fusion protein consisting of TNF receptor & Fc fragment of IgG |
|
|
Term
|
Definition
|
|
Term
|
Definition
| inactivates TNF via mouse anti-TNF |
|
|
Term
|
Definition
| inactivates TNF via human Ab |
|
|
Term
|
Definition
RA
anklosing spondylitis
psoriasis
ulcerative colitis |
|
|
Term
|
Definition
opportunistic infections
multiple sclerosis
heart failure
lymphomas
lupus erythmatosis
injection site rxns
auto-Ab |
|
|
Term
|
Definition
| IL-1 receptor competitive antagonist |
|
|
Term
| What is abatacept composed of? |
|
Definition
| extracellular portion od T lymphocyte-associated-antigen 4 fused to modified FC fragment |
|
|
Term
|
Definition
| inhibit T cell activation by binding CD80 & CD86 on APCs to prevent binding of T-cell CD28. |
|
|
Term
|
Definition
|
|
Term
|
Definition
infection (increased risk when given with TNF inhibitors)
pulmonary effects (in patients with COPD) |
|
|
Term
|
Definition
| chimeric monocolonal Ab that targets B cell antigen CD20, binding => cell death by apoptosis |
|
|
Term
|
Definition
hemtological neoplasms
w/ methotrxate for autoimmune diseases s.a. RA resistant to TNF inhibitors |
|
|
Term
|
Definition
severe (even fatal) infusion reaction
activation of hep B & other viral inf.
other serious inf. |
|
|
Term
| Where is uric acid synthesized from? |
|
Definition
| xanthine via hypoxantine, catalyzed by xanthine oxidase |
|
|
Term
|
Definition
| high levels of uric acid that crystallize in joings => engulfment by synoviocytes & recruitment of other inflammatory cells |
|
|
Term
Tx
acute inflammation due to gout |
|
Definition
|
|
Term
| What are the 3 drugs used in gout Tx? |
|
Definition
1) Cholchicine
2) Allopurinol
3) Probenecid |
|
|
Term
|
Definition
| binds to tubulin in leukocytes & reduces motility & ability to undergo phagocytosis |
|
|
Term
|
Definition
acute attacks of gout for short periods
(esp. useful when gouty attacks aren't controlled by NSAIDs) |
|
|
Term
|
Definition
GI disturbances (diarrhea)
hair loss
marrow depression
peripheral neuropathy
myopathy
etc |
|
|
Term
|
Definition
| inhibitor of xanthine oxidase => inhibition of both steps of synthesis or urate => less urate & more xanthine & hypoxanthine accumulate |
|
|
Term
|
Definition
chronically to prevent attacks of gout
(no value to relieving actue gouty attacks...may precipitate an attack when first administered) |
|
|
Term
| When can be given in an acute gouty attack? |
|
Definition
1) NSAID
2) colchincine
3) uricosuric acid (s.a. probenecid) |
|
|
Term
|
Definition
allergic skin rxn
GI disturbances
marrow depression
peripheral neuritis |
|
|
Term
|
Definition
| azathioprine (6-mercaptopurine) is metabolized by xanthine oxidase => exacerbation of marrow depression |
|
|
Term
| What happens to urate in proximal tubule? |
|
Definition
| actively excreted & reaccumulated |
|
|
Term
| What enhances reaccumulation of urate by proximal tubules? |
|
Definition
| thiazide & loop diuretics |
|
|
Term
|
Definition
| inhibits both active excretion & reaccumulation of urate in proximal tubles => net loss of urate |
|
|
Term
| Why can aspirin precipitate an acute gouty attack? |
|
Definition
| only inhibits urate excretion |
|
|
Term
|
Definition
| chronically to prevent attacks |
|
|
Term
|
Definition
well tolerated
allergic dermatitis
rare- aplastic anemia |
|
|
Term
|
Definition
| can inhibit proximal tubular secretion of other drugs s.a. penicillins & NSAIDs |
|
|
Term
| What is the most prominent naturally occuring glucocorticoid in humans? |
|
Definition
|
|
Term
| What controls the secretion of cortisol? |
|
Definition
| ACTH (ant. pituitary hormone) |
|
|
Term
|
Definition
1) provokes secretion of adrenal steroids
2) trophic hormone for adrenal cortex |
|
|
Term
| What stimulates ACTH secretion? |
|
Definition
| CRF (secreted from median eminence of yhypothalamus) |
|
|
Term
| What is used for feedback inhibition on both ACTH & CRF? |
|
Definition
|
|
Term
|
Definition
| binding to cytoplasmic receptor that exists in a complex with Hsp 90 & other proteins => activated receptor enters nucleus & binds to DNA sequences GREs (glucocorticoid receptive elements) => activation/inhibition of mRNA transcription & appropriate consequences |
|
|
Term
| What are the 3 general categories of glucocorticoid effects? |
|
Definition
1) metabolic
2) anti-inflammatory
3) sodium retentive (aldosterone-like) |
|
|
Term
| When are the anti-inflammatory & sodium retentive effects of glucocorticoids (GCs) most evident? |
|
Definition
|
|
Term
MOA
anti-inhibitory effect of GCs |
|
Definition
| 1) inhibition of effernet limb of immune system (decreased IL & TNFα synthesis, decreased neutrophil, monocyte, & macrophage chemotaxis/activation, decreased T cell proliferation, etc)
2) depression of the inflammatory response (decreased synthesis of COX2, phospholipase A2 & NOS, increased lipocortin synthesis, etc) |
|
|
Term
SOA
anti-inflammatory effects of GCs |
|
Definition
| acute & severe allergic, autoimmune, & inflammatory conditions |
|
|
Term
| How much higher is the pharmacological dose of GCs for anti-inflammatory effects than physiological doses? |
|
Definition
|
|
Term
SE
GCs pharmacological dose |
|
Definition
increased metabolic & sodium retentive effects => (time & dose dependent, so short course is well tolerated)
1) cataracts
2) hyperglycermia/DM
3) thinning of skin
4) Edema
5) Peptic ulcer
6) Osteoporosis
7) Atherosclerosis
8) Psychosis
9) impaired wound healing
10) susceptibility to infection
11) iatrogenic Cushingoid state
12) atrophy of adrenal gland
13) lymphocytopenia |
|
|
Term
| What causes atrophy of adrenal gland in chronic GC therapy? |
|
Definition
| inhibition of ACTH secretion by high doses of cortisol (therefore cannot abruptly stop GC therapy & must be tapered for several months until gland regenerates) |
|
|
Term
| Why do pharmacological doses of GC have modified structure? |
|
Definition
| to reduce sodium retaining properties & increase potency of anti-inflammatory effect of GCs (tho metabolic properties annot be separated from the anti-inflammatory effects) |
|
|
Term
| What are the synthetic GC anti-inflammatory drugs? |
|
Definition
1) Prednisolone
2) Prednisone
3) Dexamethasone |
|
|
Term
| How are cortisol & dexamethasone administered? |
|
Definition
| any route (PO, parenteral, topical) |
|
|
Term
| How are prednisolone & presnisone administered? |
|
Definition
| usually PO, but other routes are available |
|
|
Term
| What do GCs bind to in blood? |
|
Definition
physiological levels: CBG or transcortin (corticosteroid binding globulin)
pharmacological levels: albumin or free |
|
|
Term
| How can you avoid systemic concentrations of GCs? |
|
Definition
| local administration when possible |
|
|
Term
|
Definition
anti-inflammatory:
insect bites
bronchial asthma
RA (pain mitigation prior to DMARD efficacy)
diseased joints (use intraarticular injections)
osetoarthritis (local injections)
anti-leukrmic effects:
acute leukemia
lymphoma
myeloma
breast cancer
metabolic effects:
Addison's
immunosuppression |
|
|
Term
| How does a high dose of GCs cause lymphocytopenia? |
|
Definition
1) sequester lymphocytes to the spleen (& then they're released)
2) detroy certain leukemic lymphocytes |
|
|
Term
| What does the cytotoxic effect of the GCs depend on? |
|
Definition
|
|
Term
Function
Immune Suppression Drugs |
|
Definition
| suppress the immune system to Tx rejection or organ transplants/tissue grafts, graft-vs-host hisease, autoimmune idseases, & certain allergic rxns. |
|
|
Term
| What has traditionally been the major problem of immunosuppressive agents? |
|
Definition
|
|
Term
| What are the 4 classes of immune system drugs? |
|
Definition
1) glucocorticoids
2) immunophilin ligands
3) cytotoxic agents
4) Ab/biologics |
|
|
Term
| What are the 2 types on immunophilin ligands? |
|
Definition
1) calcineurin inhibitors
2) mammalian target of rapamycin inhibitor |
|
|
Term
| What are the 2 types of cytotoxic agents? |
|
Definition
1) anti-metabolites
2) alkylating agent |
|
|
Term
| What are the 2 types of Ab/biologics? |
|
Definition
1) Polyclonal
2) Monoclonal |
|
|
Term
| What powerful immunosuppresive agents also have broad anti-inflammatory effects? |
|
Definition
|
|
Term
| Why is it easy to assume there should be SE with glucocorticoid immuno suppressive therapy? |
|
Definition
| glucocorticoid receptors are on virtually all mammalian cells |
|
|
Term
|
Definition
| Steroids bound to CBG (corticosteroid-binding globulin) => enterance of soluble sterois into cell (w/o CBG) => cytosolic steroid receptor complexes 2 molecules of hsp90 & a number of other "stabilizers" => release of molecules upon binding => active receptor dimer enters nucleus => receptor binds to GRE (glucose response elements) in promoter enhancer regoins => modulation of transcription |
|
|
Term
| What does the glucocorticoid ligand receptor also modulates the activity of? |
|
Definition
| pro-inflammatory transcription factors AP1 & NF-ϰB |
|
|
Term
Overall Effect
glucocorticoids |
|
Definition
anti-growth
anti-inflammation
immunosuppression |
|
|
Term
| What 5 actions do glucocorticoids use to exert their effects? |
|
Definition
1) reduce cytokine-induced inflammation
2) inhibit T cell proliferative response to Ag, induce lymphocyte/eosinophil apoptosis
3) inhibito monocyte/macrophage activation, chemotaxis, & ability to recognize/respond to Ag & mitogens
4) decreased emigration of leukocytes from vessels
5) suppressed production of pro-inflammatory PGs, LTs, TXAs, & PAF |
|
|
Term
| How do glucocorticoids reduce cytokine-induced inflammation? |
|
Definition
| inhibit production of IL-1, IL-2, IL-4 & TNFα |
|
|
Term
| How does glucocorticoids decrease emigration of leukocytes from vessels? |
|
Definition
| inhibit neutrophil chemotaxis & adhesion to endothelium |
|
|
Term
| How do glucocorticoids suppress production of pro-inflammatory PGs, LTs, TXAs, & PAF? |
|
Definition
| inhibit phospholipase A2 & COX2 |
|
|
Term
| What is the most widely perscribed steroid? |
|
Definition
|
|
Term
|
Definition
| liver to active form: prednisolone |
|
|
Term
| When might prednisone & prednisolone NOT be considered equivalent? |
|
Definition
|
|
Term
|
Definition
idopathic throbocytopenic purpura
RA
asthma
inflammatory bowel disease
allergic rxns (inc. allergic rhinitis)
inflammatory skin disease
*initial Tx to induce requisite immunosuppression assoiciated with solid organ & hematopoieticc stem cell transplants
*graft-vs-host disease
(* relavent to this lecture) |
|
|
Term
| When can glucocorticoid toxicity be seen? |
|
Definition
| chronic use (average & cumulative dose, low dose) |
|
|
Term
| What is the problem with glucocorticoid toxicity effects? |
|
Definition
| many of them are asymptomatic until they are advanced s.a. cataracts, osteoporosis & atherosclerotic disease |
|
|
Term
Sx
glucocorticoid toxicity |
|
Definition
1) skin/soft tissue: thining, purpura, Cushing's, alopecia, acne, hirsutism, poor wound healing
2) Ocular: cataracts, increased ocular pressure/glaucoma
3) Vascular: accelerated atherosclerosis, hyperlipidemia, HTN
4) GI: gastritis, peptic ulcer disease, GI bleeding
5) Musculoskeletal: osteoporosis, osteonecrosis, myopathy
6) Neurological: psychosis, euphoria, memory impairment (esp. elderly), pesudo-tremor cerebri, increased ICP (insomnia > euphoria > depression)
7) Opportunistic Infections
8) Endocrine: DM/hyperglycemia, hyperlipidemia, increased appetite/wt. gain, growth inhibition/delay onset of puberty
9) GU: amenorrhea/anovulation/infertility |
|
|
Term
| Why do glucocorticoids cause osteoporosis? |
|
Definition
1) osteoblast function is inhibited => impaired bone formation
2) decreased calcium absorption from gut
3) increased excretion of calcium in urine |
|
|
Term
| Why are there usually no warnings of an opportunistic infection in glucocorticoid use? |
|
Definition
| reduction in inflammatory & febrile responses can mask the warning signs |
|
|
Term
MOA
immunophilin binding agents |
|
Definition
| binding to innumophilins (intracellular proteins) => selectively block production of IL-2 & other sytokines in CD4 T cells |
|
|
Term
| What have innumophilin binding agents dramatically improved? |
|
Definition
| long-term survival of transplanted organs |
|
|
Term
SOA
immunophilin binding agents |
|
Definition
transplants
hematopoietic stemm cell transplant
RA
psoriasis
atopic dermatitis
exzema
chronic dry eyes (secondary to ocular inflammation) |
|
|
Term
| What are the 2 calcineurin-inhibiting agents? |
|
Definition
| cyclosporine & tacrolimus |
|
|
Term
|
Definition
| lipophilic cyclic decapeptide |
|
|
Term
|
Definition
| lipophilic non-Abx macrolide |
|
|
Term
| How are both cycosporine & tacrolimus derived? |
|
Definition
|
|
Term
| What immunophilin do cyclosporines bind? |
|
Definition
|
|
Term
| What immunophilin does tacrolimus bind? |
|
Definition
| FKBPs (FK Binding Proteins) |
|
|
Term
MOA
calcineuriun-inhibiting agents |
|
Definition
| immunophilin-drug complex bind to & inhibit calcineurin => recduced transcription of early cytokine genes IL-2 (most important), IL-3, IL-4, TNFα, IFNγ, & GM-CSF => dose-dependent inhibition of lymphocyte production after TcR-CD3 receptors bound |
|
|
Term
|
Definition
| calcium-calmodulin dependent serine/threonine phosphatase |
|
|
Term
| What is the limitation os alcineurin-inhibiting agents? |
|
Definition
| not effective in halting amplification of immune response AFTER activation |
|
|
Term
| What cells do cyclosporine & tacrolimus primarily act on? |
|
Definition
| T helper cells cytokine production (=> inhibition of T cell dependent B cells, T suppressor & T cytotoxic functions) |
|
|
Term
| Are cyclosporine & tacrolimus cytotoxic or myelotoxic? |
|
Definition
|
|
Term
| Why must blood levels be monitored for both cyclosporine & tacrolimus? |
|
Definition
| extremely variable bioavailability |
|
|
Term
Elminiation
calcineurin inhibitors |
|
Definition
| CYP3A4 (=> DDIs that could alter blood levels) |
|
|
Term
Which calcineurin inhibitor is preferred for liver transplant?
Why? |
|
Definition
| tacrolimus b/c cyclosporeine is partially dependent on bile salts for absorption |
|
|
Term
| Can hemodialysis remove cyclosporine or tacrolimus? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| What can prolong the half life of both tacrolimus & cyclosporine? |
|
Definition
|
|
Term
|
Definition
1) nephrotoxicity: (occurs at therapeutic & low doses) renal injury, progressive renal failure, tubular dysfunction (=> hyperkalemia, hypophosphatemia, hyperuricemia, hypeomagnesemia)
2) HTN (due to sodium rentntion & vasoconstriction)
3) neurotoxicity: benign tumor common & improves with dose alteration, headaches, visual disturbances, sleep disorders, seizures, cerebral edema, encephalopathy, coma (more common with tacrolimus)
4) Metabloism: glucose itolerance, DM, bine loss, hyperlipidemia, hyperurcemia, gynecomastemia
5) Malignancy: several, inc. non-Hodgekin's lymphoma, skin cancers
6) Gingival hyperplasia
7) Hirsutism
8) Alopecia |
|
|
Term
| Why is HTN a problem with calcineurin inhibitors? |
|
Definition
Difficult to treat:
1) calcium channcel blockers have no effect on chronic toxicity
2) ACEIs can potentiate acotemia & hyperkalemia
3) diuretics can worsen hyperuricemia & predispose gout |
|
|
Term
|
Definition
| non-Abx macrolide produced by fungus & binds to immunophilins (like tacrolimus, but isn't a calcineurin-inhibitor) |
|
|
Term
|
Definition
| intereferes with signal transduction pathways elicited by IL-2
binds FKBPs (like tacrolimus), esp. FKBP12 => mTOR inhibition (mammalian Target of Rapamycin) => T cell arrest in G1 |
|
|
Term
| What is sirolimus commonly combined with? |
|
Definition
|
|
Term
| Can sirolimus be combined with tacrolimus? |
|
Definition
| yes bc FKBP12 is present in such large amounts that sacrolimus doens't rate-limit tacrolimus |
|
|
Term
|
Definition
wound healing
lymphoceles
dyslipidemia
thrombocytopenia
decreased proliferation of vascular smooth muscle
synergistic nephrotoxicity when combined with calcineurin inhibitor |
|
|
Term
|
Definition
| CYP3A4 => same DDIs as calcineurin inhibitors |
|
|
Term
| What are the 4 anti-metabolite cytotoxic agents? |
|
Definition
1) azathioprine
2) methotrexate
3) mycophenolate mofetil
4) leflunomide |
|
|
Term
|
Definition
| nitroimidazole derivative of 6-mercaptopurine (6-MP) |
|
|
Term
|
Definition
serum: 30 min
biological: 24 hr |
|
|
Term
|
Definition
1) coverted to 6-MP by GSH in RBCs
2) in liver by xanthine oxidase & thiopurine methyltransferase |
|
|
Term
|
Definition
| intracellular by hypoxanthine guanine phosphoribosyltransferase (HGPRT) to thioinosinic acid & thioguanylic acid |
|
|
Term
|
Definition
| thioinosinic acid & thioguanylic acid suppress intracellular inosinic acid => suppression of adenine & guanine synthesis => decreased RNA production => decreased B& T cells, Ig production, IL-2 secretion |
|
|
Term
|
Definition
maintenance for organ transplant
autoimmune disorders |
|
|
Term
|
Definition
bone marrow suppression
anemia
alopecia
GI Sx
liver disease (rare) |
|
|
Term
|
Definition
| allopurinal = lethal interaction since allopurinol blocks metabolism of azathioprine by xanthine oxidase |
|
|
Term
|
Definition
RA
psoriasis
tissue vs graft host disease |
|
|
Term
|
Definition
| structural analog of folic acid |
|
|
Term
|
Definition
| competitively & irreversibly binds to DHFR => decreased FH4 => affected purine & pyrimidine metabolism |
|
|
Term
Metabolism/Excretion
methotrexate |
|
Definition
| 80-90% unchanged in urine |
|
|
Term
|
Definition
| other folate depleteing drugs s.a. bactram or probenecid |
|
|
Term
|
Definition
GI upset
stomatitis
alopecia
macrocytosis
CNS: fatigue, headaches, loss of concentration
fevers
opportunistic infections
hematologic malignancies s.s B cell lymphoproliferative disorder
bone marrow toxicity => pancytopenia
interstitial lung disease
hepatotoxicity
(SE can be severe/fatal) |
|
|
Term
|
Definition
| lymphocyte specific agent used to treat refractory renal or other solid organ transplant rejection episodes |
|
|
Term
|
Definition
| inhibits IMPD (inosine monophosphate dehydrogenase) => decrease production of GMP => depletion of guanosine nuclotides & excess of adenosine nucleotides => lymphocyte proliferation & response to antigenic or mutagenic stimulation is depressed |
|
|
Term
Metabolism/Excretion
mycophenolate mofetil |
|
Definition
hydrolyzed to acive form mycophenolic acid in liver & GI.
principle metabolite is glucuronide form that is inactive & excreted in urine/bile |
|
|
Term
| Why are neutrophils spared (i.e. phagocytosis & bacterial killing) with mycophenolic acid? |
|
Definition
| decreased GTP pools in lymphocytes & monocytes only |
|
|
Term
|
Definition
| GI - ileus, diarrhea, gastritis, N/V |
|
|
Term
|
Definition
| inhibits pyrimidine (not purine) synthesis |
|
|
Term
|
Definition
RA
psoriatic arthritis
autoimmune skin disorders
allograft rejection |
|
|
Term
|
Definition
diarrhea
GIliver damage
kidney impairment
teratogenic effects |
|
|
Term
| What is the cytotoxic alkylating agent? |
|
Definition
|
|
Term
|
Definition
| severe, life-threatening autoimmune diseases & inflammatory diseases s.a SLE, Wegener's granulomatosis, vasculitis, refractory RA |
|
|
Term
Metabolism
cyclophosphamide |
|
Definition
| in liver to 4-hydroxyxyxlophosphamide & aldophosphoramine => active metabolite phosphoramide mustard & non-alkylating bladder toxic metabolite acrolein |
|
|
Term
|
Definition
| 2 armed dichlorethyl moieties of phosphoramide mustard metabolite attach to nucleic acid chains or enzyme macromolecules & interfere with functions |
|
|
Term
| Where are the active metabolites of cyclophosphamide found? |
|
Definition
| lipophilic, so protein bound & in tissue |
|
|
Term
Excretion
cyclophosphamide |
|
Definition
| inactive metabolites excreted in urine (renal failure dose adjustment) |
|
|
Term
|
Definition
1) drugs that alter hepatic microsomal enzyme activity
2) succinylcholine => prolonged neuromuscular blockade thru reduction of PChE
3) TCAs & other anticholinergic agents => decrease bladder emptying => prolonged bladder exposure to acrolein |
|
|
Term
|
Definition
alopecia
N/V
anorexia
diarrhea
atomatitis
mucositis
sterility
gonodal suppression
myelosuppression
anemia
acute hemorrhagic cystitis
congestive heart failure
pulmonary toxicity |
|
|
Term
| What name indicates humanized monoclonal Abs? |
|
Definition
|
|
Term
| What name indicated chimeric Abs? |
|
Definition
|
|
Term
| What are the 6 drug types seen in Ab/biologics? |
|
Definition
| 1) Lymphocyte Immune Globulin
2) Antithymocyte Globulin
3) Muromonab-CD3
4) RH0(D)-Immune Globulin
5) Anti-TNFα Agents
6) Anti-Cytokine Abs |
|
|
Term
SOA
antithymocyte globulin |
|
Definition
organ transplant
transplant rejection |
|
|
Term
def
antithymocyte globulin |
|
Definition
| polyclonal Abs in human lymphoid cells |
|
|
Term
|
Definition
infection
fever
headache
lymphoma
malignancies (esp. when combined with other immunosuppressives) |
|
|
Term
|
Definition
| anti-CD3 monoclonal Ab aka OKT3 |
|
|
Term
|
Definition
| organ transplant (esp. kidney & esp. during rejection periods) |
|
|
Term
|
Definition
| inactivate, deplete, & destroy T cells |
|
|
Term
|
Definition
| cytokine release syndrome: fever, headache, HTN |
|
|
Term
| SOA
RhL0(D) immune globin |
|
Definition
| to passively immunize Rh- mothers against Rh Ag on baby's RBCs => prevents erythroblastosis fetalis in subsequent pregnancies if administered within 1-3 days post birth |
|
|
Term
|
Definition
| autoimmune dieases s.a. RA, psoriasis, & Crohn's |
|
|
Term
| What are the 3 anti-TNFα drugs? |
|
Definition
1) Adalimumab (humanized monoclonal Ab)
2) infliximab (chimeric monoclonal Ab)
3) Etanercept |
|
|
Term
| What are the 2 anti-cytokine Abs? |
|
Definition
1) Daclizumab (humanized monoclonal Ab)
2) Basiliximab (chimeric monoclonal Ab) |
|
|
Term
|
Definition
| bind CD25 (on IL-2 receptor on T cells) |
|
|
Term
|
Definition
|
|
Term
|
Definition
| wheezing & SOB due to narrowing of airway |
|
|
Term
| What triggers the majority of asthma? |
|
Definition
| allergen-induced immuno-responses |
|
|
Term
|
Definition
| chronic airway obstruction in elderly patients primarily due to long-term cigarette smoking |
|
|
Term
|
Definition
1) bronchodilation to reverse airway constriction
2) anti-inflammation to reverse airway mucosal thickening caused by edema & cellular infiltration |
|
|
Term
| What 3 features contribute to airway narrowing in asthma? |
|
Definition
1) spasm of smooth muscle surrounding airway
2) excessive secretion of mucus
3) mucosal inflammation & swelling |
|
|
Term
| What causes early onset asthma? |
|
Definition
| abnormal response associated with allergy |
|
|
Term
| When can late onset asthma occur? |
|
Definition
| at age, tho majority of patients are adults |
|
|
Term
| Do external allergens play a role in the pathogenesis of late onset asthma? |
|
Definition
|
|
Term
| What provokes last onset asthma? |
|
Definition
| non-specific factors s.a. cold air, perfume, paint, tobacco smoke, stress, infection, severe exhertion, etc. |
|
|
Term
|
Definition
|
|
Term
MOA
mast cell degranulation |
|
Definition
| Ag bound to IgE binds to mast cell => influx of Ca2+ => degranulation & release of histamine, 5-HT, & LTs |
|
|
Term
|
Definition
unknown, possibly:
1) increased cholinergic response
2) reduced β-adrenergic response |
|
|
Term
MOA
normal bronchial β2 adrenergic response |
|
Definition
| β2 receptor agonist => activated Gs protein => increased AC => increased cAMP => inactivation of activated MLCK => no MLC phosphorylation => relaxation |
|
|
Term
MOA
normal bronchial M cholinergic response |
|
Definition
| M receptor agonist => activated Gq => increased Phospholipase C => increased IP3 (& DAG => increased PKC) => influx of cytosolic ca2+ from ER => Ca2+-calmodulin formation => activation of MLCK => phosphorylation of MLC => contraction when actin is added to MlC-PO4 |
|
|
Term
| What are the 5 stages of asthma? |
|
Definition
I: little obstruction
II: moderate obstruction
III severe obstruction
IV: marked hypoxemia
V: resp. acidosis |
|
|
Term
| What is the preferred administration route for Tx of COPD & asthma? |
|
Definition
| aerosol => faster/safer due to lower dose required |
|
|
Term
| What are the 4 types of bronchodilators? |
|
Definition
1) β2 non-selective agonists
2) β2 selective agonists
3) Anticholinergic agents
4) Xanthines |
|
|
Term
| What are the 3 ways β2 non-selective agonists Tx COPD/asthma? |
|
Definition
1) bronchial muscle relaxation (per previous MOA)
2) inhibit allergens-induced bronchospasm
3) decrease congestion & edema |
|
|
Term
| How do β2 non-selective agonists inhibit allergens-induced bronchospasm & mucosal edema? |
|
Definition
| β2 agonist => increased AC => increased cAMP => inhibition of exocytosis of mediators of mast cells & basophils => inhibition of allergen-induced bronchospasm & mucosal edema |
|
|
Term
| How do β2 non-selective agonists decrease congestion & edema? |
|
Definition
| β2 non-selective agonist activates α receptor => constriction of bronchial mucosal vessel & decrease blood flow => prevention of mucosal gland from overacting => decreased congestion & edema |
|
|
Term
| What 3 β2 non-selective agonists can be used as bronchodilators? |
|
Definition
1) epinephrine
2) ephedrine
3) isoproterenol |
|
|
Term
| What is epinephrine an agonist for? |
|
Definition
|
|
Term
SOA
epinephrine as a bronchodilator |
|
Definition
| manage severe acute attack (rapid effects) |
|
|
Term
SE
epinephrine as a bronchodilator |
|
Definition
|
|
Term
| What receptors is ephedrine an agonist for? |
|
Definition
|
|
Term
SE
ephedrine as a broncodilator |
|
Definition
1) cardiac stimulation since high affinity for β1
2) tremor due to CNS stimulation |
|
|
Term
| What receptors are isoproteerenol an agonist for? |
|
Definition
|
|
Term
| How fast is the response to inhaled isoproterenol? |
|
Definition
|
|
Term
|
Definition
| ~30 min (longer than epinephrine) |
|
|
Term
|
Definition
| cardiac stimulation due to β1 |
|
|
Term
SE
β2 non-specific agonists |
|
Definition
nervousness
anxiety
palpitations |
|
|
Term
CI
non-selective β2 agonist |
|
Definition
coronary artery disease & HTN since
1) increased HR & contraction => increased BP & tachycardia
2) α agonists => vasoconstriction => increased vascular resistance => increased BP |
|
|
Term
| What are the 3 short acting β2 selective agonists? |
|
Definition
1) albuterol
2) levalbuterol
3) pirbuterol |
|
|
Term
| What are teh 2 long acting β2 selective agonists? |
|
Definition
1) formoterol
2) salmeterol |
|
|
Term
| What are the advantages of β2 selective agonists over β2 non-selective agonists? |
|
Definition
1) bronchodilation with fewer cardiac effects
2) longer duration (~5 hrs copmpared to ~30 min) |
|
|
Term
|
Definition
| patients on non-selective β blockers => decreased brochodilation |
|
|
Term
Effects
vagus n. activation |
|
Definition
brochoconstriction
mucus secretion
bronchial vasodilation |
|
|
Term
| What anti-cholinergic is no longer used as a bronchodilator due to it's other anticholinergic SE since β2 agonists have emerged? |
|
Definition
|
|
Term
| What 2 anti-cholinergics are used for bronchodilation currently? |
|
Definition
1) Ipratopium bromide
2) Tiotropium bromide |
|
|
Term
|
Definition
| short-acting bronchodilator for chronic bronchitis & COPD |
|
|
Term
|
Definition
long acting bronchodilator for once-daily maintenance of bronchospasms associated with COPD
(may be added to a corticosteroid regimen for those who can't handle a β2 agonist or must take a β blocker for CVD) |
|
|
Term
|
Definition
| inhibit phosphodiesterase => no coversion of cAMP to 5'AMP ∴ increased cAMP => bronchial muscle relaxation & inhibition of mast cell degranulation => decreased mucosal secretion & edema |
|
|
Term
|
Definition
| co-administered with β2 agonist for Tx in prolonged asthma or COPD attack |
|
|
Term
| Which xanthine also has a modest anti-inflammatory effect which contributes to its efficacy? |
|
Definition
|
|
Term
|
Definition
| N/V (from action in CNS, mech. unclear) |
|
|
Term
|
Definition
seizure
cardiac stimulation: arrythmia, hypotension, cardiac arrest
(can be lethal & low therapuetic levle => monitor plasma levels closely) |
|
|
Term
|
Definition
barbituates => increased speed of elimination
caffeine => competition with common metabolic enzymes => augmented CNS/CV effects |
|
|
Term
| What 2 anti-inflammatory drug types maybe given in COPD/asthma? |
|
Definition
1) cortocosteroids
2) cromolyn sodium |
|
|
Term
| Why are anti-inflammatories s.a. corticosteriods critical to COPD/asthma Tx? |
|
Definition
| they are chronic inflammatory diseases |
|
|
Term
| What 6 inhaled corticosterioids can be used is Tx of asthma/COPD? |
|
Definition
1) Beclomethasone
2) Triamcinolone
3) Budesonide
4) Mometasone furoate
5) Flunisolide
6) Fluticasone
(Becky Tried Bud & her Mom developed a UNIlateral TIC) |
|
|
Term
| Why are fluticasone & budesonide the currently preferred inhaled corticosteroid agents? |
|
Definition
long duration
high local potency
less systemic effects |
|
|
Term
| Do aerosol corticosteroids have immediate effect like bronchdilators? |
|
Definition
| no ∴ aren't effective in relief of an acute episode |
|
|
Term
| What is the new combination drug for asthma? |
|
Definition
| fluticason propionate + salmeterol (inhaled corticosteroid + β2 agonist) - CI in children < 12y |
|
|
Term
| When might a patient use a high dose systemic corticosteroid in asthma/COPD? |
|
Definition
| severe acute asthma w/ no rapid response to bronchodilator |
|
|
Term
| What 2 systemic corticosteroids might be given to Tx asthma/COPD? |
|
Definition
|
|
Term
Effect
prednisone/prednisolone in asthma/COPD |
|
Definition
| dramatic relief in severe asthma (stage III & IV) |
|
|
Term
| Does prednisone/prednisolone inhibit IgE mediated release? |
|
Definition
|
|
Term
MOA
prednisone/prednisolone in asthma/COPD Tx |
|
Definition
| unknown - maybe biomembrane stabilization, inhibition of inflammatory rxn, enhance response of β receptor |
|
|
Term
SE
prednisone/prednisolone |
|
Definition
1) suppression of hypothalamic-pituitary-adrenal (HPA) function (∴ can't abruptly cease Tx)
2) Cushing's
3) growth retardation
4) other corticosteroid SE
(more prevalent with systemic than local aerosol administration) |
|
|
Term
|
Definition
| stabilize mast cell membrane via Ca2+ channel blocker, inhibiting Ca2+ influx => prevents release of mediators
(Not: doesn't not stop IgE from binding mast cells & doesn't relax smooth muscle directly) |
|
|
Term
|
Definition
prophylactic Tx of mild/moderate asthma
(NEVER for acute bronchospasm) |
|
|
Term
Absorption/Metabolism/Excretion
cromolyn sodium |
|
Definition
not absorbed orally, thus must be given via inhalation (given with a powder since unstable in water)
excreted unchanged |
|
|
Term
|
Definition
well tolerated/safe
sore throat
dry mouth
skin rash
headache
dizziness |
|
|
Term
| What agents can theoretically be used to relax airway smooth muscle, but are only in experimental stages? |
|
Definition
|
|
Term
| What 3 drugs modulate allergic reactions upstream of the inflammatory cascasde & are used in the Tx of asthma? |
|
Definition
1) LT synthesis inhibitor
2) LT receptor blocker
3) IgE Ab |
|
|
Term
| Why would drugs that modulate the allergic reaction upstream of the inflammatory cascade be used to treat asthma? |
|
Definition
| airway inflammation caused by allergens, viral resp. infections, or other stimuli may lead to bronchial hyper-responsiveness & obstruction of airflow (does NOT apply to COPD) |
|
|
Term
| Why did the LT synthesis inhibitor Zileuton fall out of favor? |
|
Definition
|
|
Term
| What was the first LT receptor blocker? |
|
Definition
|
|
Term
| Why isn't Zafirleukast used as frequently anymore? |
|
Definition
| interactions b/w drug & food in stomach |
|
|
Term
| What LT receptor blocker has replaced Zafirleukast? |
|
Definition
|
|
Term
| What IgE Ab is currently used in Tx of asthma? |
|
Definition
|
|
Term
|
Definition
| humanized monoclonal Ab that bings to IgE |
|
|
Term
|
Definition
| > 12y. with moderate/severe & persistant asthma not adequately controlled by an inhaled corticosteroid |
|
|
Term
Tx
mild, infrequent asthma |
|
Definition
| intermittent (as needed) inhaled, short acting β2 agonist |
|
|
Term
| What indicated need for an anti-inflammatory Tx with asthma? |
|
Definition
| use of short-acting β2 agonist more than 2x weekly (not for exercise induced bronchospasm) |
|
|
Term
| What are the most effective anti-inflammatory agents in asthma? |
|
Definition
|
|
Term
| When should a long-acting β2 agonist be used in asthma Tx? |
|
Definition
| if regular use of low dose corticosteroid + short acting β2 agonist doesn't improve Sx |
|
|
Term
| When should dose of cortocosteroid be raised in asthma Tx? |
|
Definition
adding a second drug is more effective
but may be needed if it's a stage IV or V asthmatic attack & is unresponsive to bronchodilator |
|
|
Term
| What 2 drugs should not be given to stage I asthmatics? |
|
Definition
|
|
Term
| What drug should not be given to stage II asthmatics? |
|
Definition
|
|
Term
| What 3 drugs should not be given to stage II, IV, or V asthmatics? |
|
Definition
1) cromolyn sodium
2) montelukast
3) IgE Ab |
|
|
Term
| What other drug (besides Cromolyn sodium, montelukast, & IgE Ab) should not be given to stage Iv & V asthmatics? |
|
Definition
|
|
Term
|
Definition
stop smoking!
mild, intermittent: short acting bronchodilator
severe, persistant: long acting bronchodilators (may add inhaled corticosteroid) |
|
|
Term
| When can a β2 agonist be used in coombination with a anticholinergic for CPOD Tx? |
|
Definition
|
|
Term
| What is given with COPD patients with severe hypoxemia? |
|
Definition
|
|
Term
Patient is a 27 y/o hispanic female treated for narcolepsy with fluoxetine (SSRI) for 3 years. At an office visit for an URTI, her BP is 160/95, a significant elevation over previous values. Patient explains she's just taken an OTC cold/flu remedy known to contain caffeine, pseudoephedrine & scopolamine.
Explain her reactions & action to be taken. |
|
Definition
Pseudoephedrine releases NE => vasoconstriction
Caffeine potentiates the pressor effects of pseudoephedrine via weak NE releaser & blocks presynaptic alpha receptor => blocked feedback inhibition (ask how much other caffeine she's consumed)
Scopolamine causes tachycardia (antimuscarinic) due to autonomic imbalance of heart (potentiated by caffeine as well)
Tx: Discontinue cold meds |
|
|
Term
| For the previous patient, what if she were on an amphetamine or an MAOI instead of an SSRI? |
|
Definition
| would have had exaggurated adrenergic effects => severe HTN & hypertensive crisis |
|
|
Term
Patient is a 27 y/o AA female treated for bipolar depression with Li. She has HTN, so she was started on the diuretic hydrochlorothiazide. She now complains of a tremor along with excessive frequency of urination & thirst.
Explain her reactions & action to be taken. |
|
Definition
Li is cleared by the kidney & handled ~ to sodium (elimination thru glomerular filtration & passively reabsorbed in renal tubule)
Diuretics decrease Li excreition => Li toxicity
Tx: stop diuretic & switch to another anti-hypertensive (don't want to switch Li if it's working) |
|
|
Term
Patient is a 47 y/o white male with DMII that WAS controlled with glipizide. After being diagnosed HIV+, he began Tx with HIV-protease inhibitor ritonavir + 2 nucleoside inhibitors of reverse transcriptase. Now he's hyperglycemic with hyperlipidemia.
Explain his reactions & action to be taken. |
|
Definition
HIV protease inhibitors inhibit GLUT4 => hyperglycemia
Ritonavir induces CYP2C9 => faster metabolism of glipizide => less effective
Tx: switch to another anti-DM medication (maybe insulin, maybe metformin) |
|
|
Term
Patient is a 72 y/o male taking oxybutynin to treat urinary incontinence & labetelol for HTN. He has been diagnosed with mild AD & has been taking rivastigmine for 2 months. He has not shown any clinical response in his AD & his wife is now complaining that incontinence has become a major problem again. He also complains of abdominal pains probably attributable to recurrance of previous problems with a peptic ulcer.
Explain his reactions & action to be taken. |
|
Definition
oxybutynin is a muscarinic antagonist => lowered smooth muscle tone in bladder.
Rivastigmine is a ChEI.
Oxybutynin can cross BB & antagonize rivastigmine & Rivastigmine will antagonize the bladder effects of oxybutynin.
Tx: switch to a incontinence agent that wont cross the BBB or switch rivastigmine to mimantine |
|
|
Term
| A 50 y/o female is being treated for hyperthyroidism with methimazole & propranolol. She complains of urticaria probably brought on by the methimazole. Benadryl did not relieve the uticaria. She was then treated with subcutaneous epinephrine. After 5 minutes, she started shouting that her head was going to explode. Her BP was 250/150. Treatment with IV clevidipine brought her BP back to acceptible levels. |
|
Definition
Since she's on propranolol (a non-specific β blocker) all of her β2 receptors are full. When administered epi, instead of being able to counteract itself soem by binding to β2 first selectively, there are only α receptors for it to bind to, enhacing the vasoconstriction.
Tx: use another antihistamine (one of the more potent ones) & possibly an anti-inflammatory |
|
|
Term
| What happens if you supplement inadequate intake of calcium & Vit D with calcium supplements? |
|
Definition
| decrease risk of BMD loss |
|
|
Term
| What do all the bisphosphonate drugs end in? |
|
Definition
|
|
Term
|
Definition
| bind to active site on bone remodeling & inhibiting osteoclasts |
|
|
Term
|
Definition
heartburn, esophageal irritation, esophagitis, abdominal pain, diarrhea and other adverse GI effects, esophageal cancer
Severe bone, joint and muscle pain
Osteonecrosis of the jaw (ONJ) has been described with chronic use of bisphosphonates
renal failure requiring dialysis and deaths in patients with decreased renal function treated with zoledronic acid |
|
|
Term
| What SERM (selective estrogen receptor modulator) is used to Tx & prevent osteroporosis? |
|
Definition
|
|
Term
|
Definition
Hot flashes, leg cramps and peripheral edema
Like estogen: throboembolic events |
|
|
Term
| Why is estrogen no longer used for osteoporosis prevention? |
|
Definition
|
|
Term
|
Definition
| Estrogen plus a progestin has been associated with an increased incidence of coronary events (cardiac death or myocardial infarction), stroke, pulmonary emboli and breast cancer. Long-term use of estrogen may also increase the risk of ovarian cancer. |
|
|
Term
| What 2 other hormones may be used in Tx/prevention of osteoporosis? |
|
Definition
|
|
Term
|
Definition
| stimulates bone formation |
|
|
Term
|
Definition
| nausea, headache, dizziness and muscle cramps, hypercalcemia, osteosarcoma |
|
|
Term
|
Definition
| decreases bone resorption by inhibiting osteoclast function (may have analgestic effect) |
|
|
Term
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Definition
| Rhinitis and occasional epistaxis have occurred with intranasal calcitonin. Nausea and flushing can occur with the parenteral formulations. Serious allergic reactions including anaphylaxis |
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