Term
Selective anxiolytic effect
Relieve anxiety without sedative effects. |
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Definition
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Term
| Were once extensively used for antianxiety and sedation, but have been largely replaced by the benzodiazepines |
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Definition
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Term
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Definition
Sedative-Hypnotic: treat insomnia
Anxiolytic (antianxiety): Anxiety (panic, obsessive compulsive disorders, phobias)
Muscle Relaxant: spasticity, dystonias
Anticonvulsant: absence, status epilepticus, and generalized seizures (rapid tolerance develops)
Other Uses:
Pre-operative medication & endoscopic procedures
Withdrawal from chronic use of ethanol and other CNS depressants. |
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Term
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Definition
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Term
| Which BZD when given as I.V. has anesthetic actions |
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Definition
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Term
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Definition
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Term
| THE LIMBIC SYSTEM IS COMPOSED OF |
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Definition
| the limbic system (amygdala, septum, hippocampus) |
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Term
| Area of the brain involved in sleep, ataxia, and muscle relaxation |
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Definition
Sleep involves the ascending reticular formation
Muscle relaxation involves the medulla
Ataxia involves the cerebellum |
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Term
| GABA-A Receptor structure and subunits |
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Definition
| Pentameric structure composed of alpha, beta, delta, and gamma subunits |
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Term
| Binding sites on GABA-A Receptor and actions associated with binding |
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Definition
•GABA site (there are 2, between A-1 and B2))
Increase GCl-
Hyperpolarization
Inhibition
•Barbiturate site
Increase GABA effect
•Benzodiazepine site (Between A-1 and Gamma 2)
Increase GABA effect
•Picrotoxin site
Block Cl- channel |
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Term
Actions at the GABA-A Receptor
Agonists: GABA |
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Definition
GABA binds to GABAA receptors which increases Cl-conductance and hyperpolarizes neurons
Neuronal activity is inhibited by GABA |
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Term
Actions at the GABA-A Receptor
Antagonists: Bicuculline |
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Definition
Competitive block of GABA binding
Reduces inhibition and produces convulsions |
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Term
Actions at the GABA-A Receptor
Antagonists: Picrotoxin |
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Definition
Non-competitive block of GABA actions
Blocks the chloride channel
Reduces inhibition and produces convulsions |
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Term
| Actions of Benzodiazepines at the GABAA Receptor |
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Definition
BZs bind to a site on GABAA receptor (ionotropic Cl- channel).
Enhance inhibitory effect of GABA by increasing Cl- influx (hyperpolarization).
BZ’s increase FREQUENCY of Cl- channel opening in the presence of GABA.
BZ’s alone (without GABA) don’t affect Cl-channel function. |
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Term
| Sedative Hypnotics & Antianxiety Agents general definitions |
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Definition
Sedative: Depress the CNS-Calm down, treat agitation
Hypnotic: Induce sleep
go to sleep fast, feel refreshed tomorrow !!!
Anxiolytic: Reduce anxiety
physical, emotional, cognitive |
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Term
| Actions of Other Agents at the Benzodiazepine Receptor: INVERSE AGONISTS (Beta-carbolines) |
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Definition
Produce the opposite effects at the BZ binding site
Decrease chloride conductance
Anxiety, irritability, agitation, delirium, convulsions
No therapeutic uses |
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Term
| What are BZD-R Inverse agonists |
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Definition
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Term
| Noncompetitive BZD antagonists |
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Definition
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Term
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Definition
BZD receptor antagonist
Blocks both agonist & inverse agonist; Have no biological effect ; Can precipitate withdrawal in dependent persons
High Ist pass metabolism
Only i.v.
Used to reverse BZD anesthesia
BZD over dose
0.2mg/mt→If does not respond suspect other drugs along with BZD like alcohol |
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Term
| competitive BZD antagonists |
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Definition
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Term
| Chlordiazepoxide (Librax, Librium) |
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Definition
Chlordiazepoxide (Librax or Librium)
Has a medium to long half life, but its active metabolite has a very long half life.
Has amnestic, anxiolytic, hypnotic and skeletal muscle relaxant properties.
Used for short term treatment of anxiety for 2-4 weeks & management of acute alcohol withdrawal syndrome
Similar to Phenobarbital in its anticonvulsant properties. However, it lacks the hypnotic effects of Barbiturates |
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Term
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Definition
alprazolam= Xanax
oxazepam= Serax
midazolam= Versed
triazolam = Halcion
temazepam= Restoril |
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Term
| Actions of Other Agents at the Benzodiazepine Receptor: Non-BZD Agonists |
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Definition
| Act at BZ receptor to produce pharmacological actions similar to BZDs. |
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Term
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Definition
lorazepam= Ativan
estazolam= ProSom
temazepam= Restoril |
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Term
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Definition
chlordiazepoxide= Librium
clonazepam= Klonopin
clorazepate=Tranxene
diazepam= Valium
flurazepam= Dalmane *widely used for primary insomnia and other sleep disorders
temazepam= Restor |
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Term
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Definition
Lipid-soluble: fast cross blood-brain-barrier: rapid onset of action.
Persist longer in high fat-to-lean body mass
obese, elderly
Abuse liability (Valium)
Biotransformation & Half-Life:
Hepatic oxidation: long-t1/2, active metabolites
Glucuronidation: short-t1/2, no active metabolite |
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Term
| What determines the use of BZD and Barbs |
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Definition
| Dose and Plasma Half Life |
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Term
| BZDs with T1/2=>24hr(long) are usually used for? |
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Definition
| Anxiety, Withdrawal, Muscle Relaxant |
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Term
| BZDs with T1/2=6-24hr(intermediate) are usually used for? |
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Definition
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Term
| BZDs with T1/2=2-6hr(short) are usually used for? |
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Definition
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Term
| BZDs with T1/2=<2hr(ultra-short) are usually used for? |
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Definition
| Pre-anesthetic Medication |
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Term
| Therapeutic Index of BZD are? |
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Definition
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Term
| Benzodiazepines: Acute Toxicity Treatment |
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Definition
TREATMENT:
Support respiration & blood pressure
Gastric lavage, activated charcoal, cathartic (Sorbitol)
Give antagonist: Flumazenil (Romazicon)
Short acting (~2 hr)
Injected IV, quickly reverses BZ-induced respiratory depression. |
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Term
| Which is safer BZDs or BARBS |
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Definition
| BZDs safer. Barbs increased risk of respiratory depression --> coma -->death |
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Term
| Acquisition of tolerance relative to BZD uses |
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Definition
| Anticonvulsant > Sedation >> Muscle Relaxant > Antianxiety |
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Term
| What type of dependence may result from BZDs |
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Definition
Physical and/or psychological dependence may develop
Physical dependence is present when withdrawal symptoms occur. |
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Term
| Benzodiazepines: Drug Interactions |
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Definition
Minimal induction of liver drug metabolizing enzymes, therefore few drug interactions are produced.
Additive CNS effects
Severe CNS depression and coma can result from BZs taken with other CNS depressants such as ethanol
Death from BZ overdose is usually associated with ingestion of a CNS depressant |
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Term
| Benzodiazepines Overdose Adverse Effects |
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Definition
Somnolence (difficulty staying awake)
Mental confusion
Hypotension
Hypoventilation
Impaired motor functions
Impaired reflexes
Impaired coordination
Impaired balance
Dizziness
Muscle weakness
Coma |
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Term
| Increasing doses of BZDs produce |
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Definition
| sedation, hypnosis, and stupor NOT anesthesia |
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Term
| Antagonist that blocks the Cl- channel |
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Definition
| Picrotoxin (Noncompetitive) |
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Term
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Definition
| NO only in the presence of GABA |
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Term
| BZD Antagonist that is only given I.V.? Why? |
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Definition
Flamazenil (Romazicon)
HIGH First pass effect |
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Term
| If Pt. does not responds to Flumazenil it is likely |
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Definition
| to suspect other CNS depressant drugs along with BZD |
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Term
| BZD(s) with *greater efficacy for panic and phobic disorders |
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Definition
| Alprazolam (Xanax, Clonazepam (Klonopin) |
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Term
| BZD(s)widely used for primary insomnia and other sleep disorders |
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Definition
| Triazolam (Halcion), Estazolam (ProSom), Flurazepam (Dalmane) |
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Term
| BZD(s) *used for management of withdrawal states in physiologically dependent on ethanol and other sedative-hypnotics |
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Definition
| Chlordiazepoxide (Librax, Librium) |
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Term
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Definition
Barbiturates are effective and relatively inexpensive
Barbiturates have been extensively studied and there is a vast amount of information available related to side effects and toxicity |
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Term
| Therapeutic uses of Barbs |
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Definition
IV anesthesia: Thiopental (Pentothal) and Methohexital (Brevital)
Convulsions: emergency treatment (eclampsia, tetanus, status epilepticus), but benzodiazepines are preferable.
Epilepsy
Rarely used as a sedative due to the availability of safer benzodiazepine agents. |
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Term
| Peripheral effects of BARB |
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Definition
Respiration: depression with increasing doses
Cardiovascular: decreased BP and HR at sedative-hypnotic doses
Liver: bind cytochrome P450
Induce drug metabolizing and other enzymes
Increases metabolism of steroids, vitamins K/D, cholesterol and bile salts. |
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Term
| General & Specific MOA of Barbs |
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Definition
General Mechanisms
Potently depress the activity of neurons in the reticular formation (pons, medulla) and cortex.
Specific Mechanisms
Bind to a site on GABAA receptors while inhibiting excitatory AMPA receptors.
AMPA receptors are the subtype of glutamate receptors sensitive to kainate or quisqualate.
Increase the open time of Cl- channels in the presence of GABA.
Increases Cl- influx
Enhances the inhibitory effects of GABA
At high concentrations directly increase Cl- conductance in the absence of GABA (act as GABAmimetics). |
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Term
| At high concentrations can directly increase Cl- conductance in the ABSENCE of GABA |
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Definition
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Term
| Barb with the highest lipid solubility that is used as an inducting agent in anesthesia |
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Definition
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Term
How are MOST barbs with the exception os Phenobarbital (Luminal) metabolized?
How is Luminal metabolized? |
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Definition
With the exception of Phenobarbital, which is excreted partly unchanged in the urine, the BARBs are extensively metabolized via oxidation at the C5 position.
Most barbiturates are dealkylated
Conjugation by glucuronidation
Renal excretion |
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Term
| Barbs with T1/2=80-120hr (long) are usually used for? |
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Definition
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Term
| Barbs with T1/2=15-50 or ~10hr (Intermediate-short) are usually used for? |
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Definition
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Term
| Barbs with T1/2=>3-10hr (ultra-short) are usually used for? |
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Definition
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Term
| Common side effects & Contraindications of BARBS |
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Definition
SIDE EFFECTS:
Common Effects: Sedation & confusion
CONTRAINDICATIONS:
Pain: can increase sensitivity to painful situation resulting in restlessness, excitement and delirium.
Pulmonary insufficiency: respiratory depression. |
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Term
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Definition
Enhance CNS depressive effects of:
Antipsychotics, antihistamines, ethanol, and tricyclic antidepressants.
Accelerate metabolism of:
Beta-blockers, Ca2+-channel blockers, corticosteroids, estrogens, phenothiazines, valproic acid and theophylline. |
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Term
| What kind of dependence is common with Barbs? |
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Definition
| Physical manifested by withdrawal symptoms |
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Term
| Newer NonBZD/NonBarb Hypnotic Agents |
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Definition
| Zolpidem (Ambien), Eszopiclone (Lunesta), Zaleplon (Sonata) |
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Term
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Definition
Used for the short-term treatment of Insomnia and as a sedative before minor medical or pediatric dentistry for diagnostic imaging procedures
Today, it is commonly used as an ingredient in the veterinary anesthetic Equithesin (mixture of chloral hydrate, magnesium sulfate and pentobarbital sodium) |
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Term
| Metabolic produces of chloral hydrate |
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Definition
| trichloroethanol and trichloroacetic acid |
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Term
| Discontinued Hypnotic agents |
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Definition
| Ethanol, barbs (avoided), Meprobamate (Equanil) |
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Term
| BZDs commonly used for the management of generalized anxiety disorders? |
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Definition
Chlordiazepoxide (Librium)
Diazepam (Valium)
Oxazepam (Serax)
Clorazepate (Tranxene)
Lorazepam (Ativan)
Alprazolam (Xanax)
Halazepam (Paxipam) |
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Term
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Definition
Miscellaneous Anxiolytic agent
Buspirone
Has selective affinity of 5-HT1A (mixed agonist antagonist activity), is a relatively new anxiolytic.
Seems most effective in mild and generalized anxiety and is not effective compared to benzodiazepines and certain antidepressant agents in treatment of panic disorder.
Does not exhibit cross-tolerance with benzodiazepines or other sedative-hypnotics. No physical dependence. No sedation or impaired cognition occurs with this drug.
No anticonvulsant activity, will not protect from withdrawal symptoms
Start 5 mg tid, max 60 mg/day. Onset of action is 1 to 3 weeks; limits it usefulness.
No additive depression with ethanol |
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Term
| If Pt. cannot give up alcohol and is sufferring from anxiety which anxiolytic agent would you suggest? |
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Definition
Buspirone (BuSpar)
-No additive depression with ethanol |
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Term
| Antihistamines used to tx anxiety & insomnia |
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Definition
Diphenhydramine [Benadryl]
25-100 mg hs sleep OR 10-25 mgr prn anxiety
Hydroxyzine [Atarax]
25-100 mg hs sleep
10-25 mg 1-4 times/day |
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Term
| Beta-Blocker useful to tx anxiety (esp. performance anxiety) |
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Definition
Physiologic component of anxiety:
tachycardia, palpitations, tremor, sweating
No CNS depression
non-addicting, no drowsiness
Do not use in asthma, diabetes, CHF
monitor BP and pulse
Helpful for performance anxiety:
Propranolol 10 mg prn |
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Term
| Class of drugs that are preferable used as:1. Sedatives, 2. Hypnotics and 3. Anxiolytics |
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Definition
Sedatives
Benzodiazepines
Antipsychotics
Hypnotics (Non-pharmacological 1st)
Antihistamines
Zolpidem
Benzodiazepines (rapid onset, short t1/2)
Anxiolytics
Benzodiazepines (acute)
Antidepressants (chronic) |
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