Term
| pain transduction begins? |
|
Definition
| in the periphery (peripheral nerve) |
|
|
Term
| location of cell bodies for peripheral nerves involved in pain transduction? |
|
Definition
|
|
Term
| 2 routes of pain signaling to the cortex? |
|
Definition
1. direct - through the thalamus
2. indirect - extra synapse in the brain stem |
|
|
Term
| location of voltage gated Na channels? |
|
Definition
| present in excitable cells - neurons, myocytes, cardiac cells |
|
|
Term
| role of voltage gated Na channels? |
|
Definition
| essential for AP generation |
|
|
Term
| are voltage gated Na channels autonomous? |
|
Definition
NO - need 'starter' channels
undergo rapid activation with plasma membrane depolarization |
|
|
Term
| a cell with autonomous voltage gated Na channel is considered what? |
|
Definition
| pacemaker cell - like SA node |
|
|
Term
| can other ions travel through voltage gated Na channels? |
|
Definition
| NO - they are highly selective for Na ions |
|
|
Term
| what things depend on voltage gated Na channels (4)? |
|
Definition
1. sensation
2. emotion
3. thought
4. movement |
|
|
Term
| what blocks voltage gated Na channels? |
|
Definition
|
|
Term
| in response to a stimulus, upstroke of AP is a result of what? |
|
Definition
|
|
Term
| once a cell reaches full depolarization (up to +80 mV), Na channels become ___? |
|
Definition
|
|
Term
| what happens at the peak of an AP? |
|
Definition
Na channels become inactivated
K channels open --> K efflux and repolarization |
|
|
Term
| what cardiac inherited disorders are due to voltage gated Na channels? |
|
Definition
1. congenital long QT syndrome
2. ventricular fibrillation
3. sick sinus syndrome
4. atrial standstill
5. sudden infant death syndrome |
|
|
Term
| composition of each alpha subunit of voltage gated Na channel? |
|
Definition
| 4 hexamers - each with 6 transmembrane segments (S1-6) |
|
|
Term
| location of voltage sensor in voltage gated Na channels? |
|
Definition
| S4 transmembrane segment of each hexamer of the alpha subunit |
|
|
Term
| which segment of the voltage gated Na channel controls its activity? |
|
Definition
|
|
Term
| location of inactivation 'h-gate' in the voltage gated Na channels? |
|
Definition
| between hexamers III and IV |
|
|
Term
| function of inactivation h-gate in voltage gated Na channels? |
|
Definition
| portion of the receptor that closes the channel immediately following activation to effectively inactivate it |
|
|
Term
| location of binding site for local anesthetics in voltage gated Na channels? |
|
Definition
in the carboxy terminus
between F1764 and Y1771 |
|
|
Term
| what is the length of the binding site for local anesthetics on the voltage gated Na channels and why is this important? |
|
Definition
11 amino acids
important because it is the length of most effect local anesthetics |
|
|
Term
| what skeletal muscle inherited disorders are due to voltage gated Na channels? |
|
Definition
1. hyper/hypokalemic periodic paralysis
2. myasthenic syndrome
3. malignant hyperthermia susceptibility |
|
|
Term
| what brain inherited disorders are due to voltage gated Na channels? |
|
Definition
1. epilepsy
2. febrile seizures
3. myoclonic seizures |
|
|
Term
| what peripheral nerve inherited disorder is due to voltage gated Na channels? |
|
Definition
|
|
Term
| what is the most potent toxin on earth? |
|
Definition
| tetrodotoxin - from the puffer fish |
|
|
Term
| saxitonin comes from where? |
|
Definition
|
|
Term
| how do tetrodotoxin and saxitonin work? |
|
Definition
| both act by occluding the pore of the Na channel |
|
|
Term
| where does the brevetoxin come from? |
|
Definition
|
|
Term
| what is the mechanism of action of local anesthetics? |
|
Definition
use-dependent block - differ in what they block in terms of their use
always act on hexamer IV at transmembrane segment 6 of the alpha subunit of the voltage gated Na channel |
|
|
Term
| what are the 2 gates of the voltage gated Na channel? |
|
Definition
|
|
Term
| what is the state of the voltage gated Na channel in the resting state? |
|
Definition
closed
M gate is closed; H gate is open |
|
|
Term
| what is the state of the voltage gated Na channel in the activated state? |
|
Definition
open
M gate open; H gate open |
|
|
Term
| what is the state of the voltage gated Na channel in the inactivated state? |
|
Definition
closed
M gate open; H gate closed |
|
|
Term
| what happens when you use voltage gated Na channels in the presence of local anesthetics? |
|
Definition
| the more you use the channels, the greater the percentage of blocked channels |
|
|
Term
what is 'use-dependent' block of channels?
which channels have this? |
|
Definition
the more the channel is used, the greater the block (ie. the lower the peak current with each new pulse)
unique to voltage gated Na channels |
|
|
Term
| what is the guarded receptor theory of use dependent block of voltage gated Na channels by local anesthetics? |
|
Definition
local anesthetic has to get intracellular to affect the VG Na channel
a conformational change in the VG Na channel leads to change in drug accessibility to receptor
affinity does not change |
|
|
Term
| what is the modulated receptor theory of use dependent block of voltage gated Na channels by local anesthetics? |
|
Definition
| increase use (change in channel state as cycle through) leads to change in receptor affinity for the drug |
|
|
Term
| the guarded receptor theory of use dependent block of voltage gated Na channels by local anesthetics is based on a change in the ____? |
|
Definition
| drug accessibility to the receptor |
|
|
Term
| the modulated receptor theory of use dependent block of voltage gated Na channels by local anesthetics is based on a change in the ____? |
|
Definition
| receptor affinity for the drug |
|
|
Term
| where along the nerve are voltage gated Na channels located? |
|
Definition
|
|
Term
| location of action of local anesthetics in a nerve? |
|
Definition
node of ranvier
location of voltage gated Na channels |
|
|
Term
| why is the node of ranvier the location of action for local anesthetics? |
|
Definition
| there is no myelin but there are voltage gated Na channels |
|
|
Term
| where alone a nerve is the greatest concentration of voltage gated Na channels? |
|
Definition
|
|
Term
| how many nodes of ranvier must be blocked for local anesthetics to work? |
|
Definition
|
|
Term
| what are the 2 main types of pain fibers? |
|
Definition
| A-delta and C-dorsal root |
|
|
Term
| A-delta fibers carry what modalities (3)? |
|
Definition
|
|
Term
| where do A-delta fibers make their synapse? |
|
Definition
| Rexed's lamina I of the dorsal horn |
|
|
Term
| C-dorsal root fibers carry what modalities (4)? |
|
Definition
1. pain
2. temp
3. mechanoreception
4. reflex responses |
|
|
Term
| where do C-dorsal root fibers make their synapse? |
|
Definition
| substantia gelatinosa of the dorsal horn |
|
|
Term
| nerve blockade requires what? |
|
Definition
| a minimal length of fiber exposed to adequate anesthetic concentration |
|
|
Term
| what has be be blocked to induce sufficient anesthesia of a sensory fiber? |
|
Definition
| 3 adjacent nodes of ranvier |
|
|
Term
| which fibers have the greatest internodal distance? |
|
Definition
|
|
Term
| why are B fibers blocked first with local anesthetics? |
|
Definition
|
|
Term
| how does fiber blockade proceed with local anesthetics? |
|
Definition
| from the thinnest (B) fibers to the thickest (A) fibers |
|
|
Term
| the ____ the fiber, the greater the distance between nodes of ranvier |
|
Definition
|
|
Term
| what are the thinnest pain fibers? |
|
Definition
|
|
Term
B fibers are associated with?
local anesthesia at B fibers leads to what? |
|
Definition
autonomic preganglionic fibers
*vasoldilation with associated decrease in BP |
|
|
Term
| what side effect can be seen with local anesthetics before pain blocking and why? |
|
Definition
| *hypotension from blocking B fibers first and causing vasodilation |
|
|
Term
| in what order are the pain fibers blocked by local anesthetics? |
|
Definition
| B > C > A-delta > A-gamma > A-beta > A-alpha |
|
|
Term
| what is the last modality lost with local anesthetics use and what fiber type is it due to? |
|
Definition
motor function
due to A-alpha fibers |
|
|
Term
| which has a greater diameter: C or A-delta fibers? |
|
Definition
A-delta fibers
slow pain (C) is lost prior to losing fast pain (A-delta) with local anesthetics |
|
|
Term
| what channels contribute to repolarization phase of AP? |
|
Definition
|
|
Term
| where are voltage gated K channels located? |
|
Definition
| DRG and dorsal horn neurons |
|
|
Term
| what are 2 drugs that can also bind to voltage gated K channels? |
|
Definition
bupivacaine and lidocaine
bind with lower affinity than to Na channels |
|
|
Term
| where are voltage gated K channels located in the body and why is this important? |
|
Definition
myocardium (heart)
sensitivity to bupivacaine and lidocaine - explains cardiotoxicity of these local anesthetics |
|
|
Term
| why can bupivacaine and lidocaine be cardiotoxic? |
|
Definition
| *due to their secondary effect on voltage gated K channels in the myocardium |
|
|
Term
| are local anesthetics specific to only voltage gated Na channels? |
|
Definition
NO
voltage gated Ca and K channels are also sensitive |
|
|
Term
| what 2 drugs can increase the effects of bupivacaine? |
|
Definition
| nifedipine and nicardipine (L-type voltage gated Ca channel blockers) |
|
|
Term
| what characteristic of local anesthetics makes them short acting and why? |
|
Definition
| having an ester link - makes them susceptible to de-esterification by plasma pseudocholinesterase |
|
|
Term
| what are 2 local anesthetics with ester links in them? |
|
Definition
|
|
Term
| why are lidocaine an bupivacaine long acting local anesthetics? |
|
Definition
| they have an amide link (instead of ester) and are hydrolyzed in hepatocytes by mixed function oxidase |
|
|
Term
| what are 2 local anesthetics with amide linkages in their structures that render them longer acting? |
|
Definition
|
|
Term
| ester local anesthetics (4) |
|
Definition
1. procaine
2. tetracaine
3. benzocaine
4. cocaine |
|
|
Term
|
Definition
|
|
Term
|
Definition
low toxicity
short acting
no topical effect
vasodilation |
|
|
Term
| procaine can interact with what other drugs? |
|
Definition
| antibacterial drugs - sulfonamides |
|
|
Term
| how does procaine interact with sulfonamides? |
|
Definition
| *produces PABA as a metabolite which inhibits sulfonamides |
|
|
Term
| can tetracaine be given in a spinal block? |
|
Definition
|
|
Term
| what has to be given with tetracaine in a spinal block and why? |
|
Definition
10% dextrose
to increase specific gravity of the drug so it can't travel back to the brain and block respiration |
|
|
Term
|
Definition
16
more potent and toxic than procaine |
|
|
Term
| pharmacokinetics of tetracaine? |
|
Definition
| 5 min onset and 2-3 hour duration |
|
|
Term
|
Definition
|
|
Term
| which ester local anesthetics are for topical use only? |
|
Definition
|
|
Term
|
Definition
topical; for the eye
toxic |
|
|
Term
| what is the only local anesthetic that produces vasoconstriction? |
|
Definition
|
|
Term
|
Definition
inhibits reuptake of catecholamines
enhances actions of noradrenaline |
|
|
Term
| what is unique about cocaine compared to other local anesthetics? |
|
Definition
| *it is the only one that produces vasoconstriction |
|
|
Term
| amide local anesthetics (5) |
|
Definition
1. lidocaine
2. mepivacaine
3. bupivacaine
4. ropivacaine
5. prilocaine |
|
|
Term
|
Definition
rapid onset
medium acting
low toxicity
potency = 4 |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| what local anesthetic is used in an epidural for labor? |
|
Definition
|
|
Term
|
Definition
low toxicity
long acting
potency = 16 |
|
|
Term
|
Definition
surgical, post-surgical, and obstetric regional use
effective in orthopedic surgery |
|
|
Term
|
Definition
less toxic
long acting
potency = 16 |
|
|
Term
| what local anesthetic is effective in orthopedic surgery? |
|
Definition
|
|
Term
|
Definition
topical dermal use as Eutectic Mixture of Local Anesthetic (EMLA) Cream for 2-3 hours effect
used under occlusive dressing |
|
|
Term
| what amide local anesthetic is for topical use? |
|
Definition
|
|
Term
| what 2 amide local anesthetics are good for surgery and why? |
|
Definition
bupivacaine and ropivacaine
they are long acting and potent |
|
|
Term
| location of action of topical local anesthetics? |
|
Definition
| nerve endings closest to the skin |
|
|
Term
| administration for local anesthetics involved in infiltration, nerve block, epidural, or spinal blocks? |
|
Definition
|
|
Term
| infiltration mode of local anesthetic administration? |
|
Definition
| tissue are is injected; no specific nerve is targeted |
|
|
Term
| nerve block mode of local anesthetic administration? |
|
Definition
targeting a specific area
usually only done in the lower body to avoid important structures that could paralyze respiration |
|
|
Term
| epidural mode of local anesthetic administration? |
|
Definition
DRG is injected
anesthetic will stay in DRG and not travel. enables lower doses because its effectively localized |
|
|
Term
| spinal block mode of local anesthetic administration? |
|
Definition
injection of anesthetic into the CSF in the spinal cord
can travel throughout the CSF |
|
|
Term
| when will topical anesthetics not be effective? |
|
Definition
|
|
Term
| where are topical anesthetics used? |
|
Definition
surface of wounds, burns, intact mucous membranes, nose, mouth, bronchi, cornea, urinary tract, dental paste, condoms
not effective on intact skin |
|
|
Term
| what drug is given topically for Herpes zoster blisters? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| when do you have to worry about systemic toxicity with topical anesthetics? |
|
Definition
| in high concentrations and large areas of application |
|
|
Term
| when is infiltration mode of administration of local anesthetics used? |
|
Definition
| injected in tissue around incision for minor operations |
|
|
Term
| what drugs are used for infiltration? |
|
Definition
| lidocaine, procaine, bupivacaine |
|
|
Term
| is procaine long or short acting? |
|
Definition
|
|
Term
| what is a good labor and delivery anesthetic? |
|
Definition
|
|
Term
| what is often given with drugs administered by infiltration and why? |
|
Definition
epi
to counter (vasoconstrict) the vasodilatory effects of the local anesthetics |
|
|
Term
| where should epi not be used in addition to local anesthetics administered by infiltration and why? |
|
Definition
fingers, toes, ears, nose, or penis (end-organs)
can get necrosis and gangrene from occlusion of blood supply |
|
|
Term
| when do you have to worry about systemic toxicity with infiltration anesthetics? |
|
Definition
| in high concentrations and large areas of application |
|
|
Term
| IV regional anesthetics must be injected where? |
|
Definition
distal to pressure cuff to arrest blood flow so the anesthetic can't travel upstream
effective until cuff is de-pressurized |
|
|
Term
| IV regional anesthesia use? |
|
Definition
| limb surgeries - amputations, etc |
|
|
Term
| what drugs are used for IV regional anesthesia? |
|
Definition
|
|
Term
| when are IV regional anesthetics useful outside of normal circumstances? |
|
Definition
| in a field hospital or place lacking more specific anesthetics |
|
|
Term
| IV regional anesthesia adverse effects? |
|
Definition
| systemic toxicity when cuff released before 20 mins |
|
|
Term
| a regional nerve block is injected where? |
|
Definition
| near peripheral nerves - accuracy of injection is important |
|
|
Term
| regional nerve block use? |
|
Definition
surgical and dental analgesia
pudendal block for episiotomy during childbirth |
|
|
Term
| what type of administration would be used for a pudendal block for episiotomy? |
|
Definition
|
|
Term
| what are the adverse effects of a regional nerve block? |
|
Definition
slower onset of anesthesia
needs accuracy of injection |
|
|
Term
| spinal administration of local anesthetics is injected where? |
|
Definition
| into CSF - in subarachnoid space to act on spinal cord and spinal roots |
|
|
Term
| when is spinal administration used? |
|
Definition
| surgery of the abdomen, pelvis, leg, and in OB |
|
|
Term
| what drugs can be given by spinal administration? |
|
Definition
|
|
Term
| adverse effects of spinal administration of local anesthetics? |
|
Definition
1. bradycardia, hypotension - due to sympathetic block
2. resp depression - due to phrenic nerve or resp center block
3. urinary retention - due to pelvic parasympathetic block |
|
|
Term
| how do you minimize cranial spread of local anesthetics administered spinally? |
|
Definition
elevate head
use 10% dextrose to increase specific gravity so its heavier than CSF |
|
|
Term
| why do you add 10% dextrose to local anesthetics given by spinal injection? |
|
Definition
to increase the specific gravity and make them heavier than CSF so they don't travel to the brain and cause resp depression or hypotension
also elevate their head |
|
|
Term
| epidurals are injected where? |
|
Definition
| into peridural space to act on nerve roots and spinal roots |
|
|
Term
| epidural administration of local anesthetics use? |
|
Definition
| surgery of abdomen, pelvis, leg, in OB ('painless' childbirth) |
|
|
Term
| what local anesthetics can be given by epidural injection? |
|
Definition
|
|
Term
| what drug is given by epidural injection for use in childbirth? |
|
Definition
|
|
Term
| adverse effects of epidural injections of local anesthetics? |
|
Definition
similar to spinal but less likely because cranial spread is limited - drug stays in DRG
urinary retention - pelvic parasympathetic block |
|
|
Term
| what is the advantage of giving a drug by epidural rather than spinal injection? |
|
Definition
| can give a lower dose epidural because it stays in the DRG |
|
|
Term
| what are the adverse effects (3) common to all local anesthetics? |
|
Definition
1. resp arrest, coma, death
2. decreased myocardial excitability, conduction rate, and contraction force
3. profound hypotension due to vasodilation |
|
|
Term
| what leads to toxicity of local anesthetics? |
|
Definition
|
|
Term
| what are the 2 main types of toxicity seen with OD of local anesthetics? |
|
Definition
cariotoxicity
neurotoxicity |
|
|
Term
| what toxicity occurs at a lower dose? |
|
Definition
| neurotoxicity (lower than cardiac toxicity) |
|
|
Term
| what determines the relative of toxicity of local anesthetics and what does it mean? |
|
Definition
CC:CNS ratio
the number tells the dose difference at which you will get CNS vs. cardiac toxicity
a CC:CNS of 7 = if at 3 mg/kg, get seizures, then at 21 mg/kg, get cardiac arrest |
|
|
Term
| what is the progression of neurotoxicity in a patient? |
|
Definition
1. change in thought process
2. perioral paresthesia
3. whole body flushing feeling
4. tinnitus
5. generalized seizures |
|
|
Term
| what is the first clinical sign of neurotoxicity with local anesthetics? |
|
Definition
start with a change in thought processes
culminates in generalized seizures |
|
|
Term
| what are the 2 phases of neurotoxicity with local anesthetics? |
|
Definition
excitation phase - numbness, tinnitus, nystagmus, dizziness, excitability, restlessness, tremor, convulsions
depression phase - coma, resp and cardiac arrest |
|
|
Term
| what is the first sign of local anesthetic neurotoxicity? |
|
Definition
| *logorrhea or total silence |
|
|
Term
|
Definition
| excessive talkativeness, especially when the words are uncontrolled or incoherent |
|
|
Term
| what is the OR rule of local anesthesia? |
|
Definition
| *keep the patient talking while the anesthetic is administered |
|
|
Term
| what happens in cardiotoxicity of local anesthetics? |
|
Definition
1. peripheral vasodilation --> hypotension
2. inhibition of Ca channels --> decreased myocardial contractility
3. increase in refractory period, firing threshold, and conduction time lead to: bradycardia with long PR interval, wide QRS complex, increased QT, dysrhythmias (blocks, re-entry, ventricular ectopics) |
|
|
Term
| what are the heme side effects of local anesthetics? |
|
Definition
|
|
Term
| what local anesthetics can have methemoglobinemia as a side effect? |
|
Definition
prilocaine
lidocaine
benzocaine |
|
|
Term
| how do local anesthetics lead to methemoglobinemia? |
|
Definition
| prilocaine is metabolized to O-toluidine in the liver --> this metabolite is a potent oxidizer of Hb to metHB |
|
|
Term
| symptoms of methemoglobinemia? |
|
Definition
*1. cyanosis
2. cutanous discoloration - gray
3. tachypnea
4. dyspnea
5. exercise intolerance
6. fatigue
7. dizziness and syncope
8. weakness |
|
|
