Term
| types of antianxiety drugs |
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Definition
-antidepressants (SSRIs, TCAs, MAOIs)
*Benzodiazepines
-Busirone |
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Term
| pharmacologic actions of benzodiazepines |
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Definition
-relief of anxiety
-drowsiness or sedation
-skeletal muscle relaxation
-anticonvulsive activity
-anterograde amnesia
All from actions in the CNS at GABA-A receptors |
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Term
|
Definition
-has depressant acitivty
-synthesized in the presynaptic terminal, stored in vesicles, and released
-hyperpolarization from influx of chlorine into post-synaptic cell
-formed from a glutamate precursor (which is the primary stimulant int he brain)
-GABA in the primary depressant in the brain |
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Term
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Definition
-ligand gated ion channel for Cl
-antianxiety drugs we use are NOT direct GABA antagonists
-use drugs that POTENTIATE the actions of GABA
-these drugs act on different subunits of the GABA receptor to make GABA work better |
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Term
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Definition
| make GABA work better by keeping Cl channel open for longer |
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Term
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Definition
-makes GABA work better
-act at the interface between two of the receptors different subunits
-open/close the Cl channel rapidly
-shifts GABA dose response curve to the left |
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Term
| CNS depression and antianxiety drugs |
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Definition
-level of CNS depressive effects increases with the relative concentration of drug
-barbituates increase to cause a marked level of CNS depression ultimately leading to death (with euphoria)
-benzo levels off and doesn't have as extreme effects, much safer |
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Term
| absorption, metabolism, excretion |
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Definition
-relative rates of absorption, metabolism, and excretion differ markedly between drugs
-drugs are prescribed based on their pharmacokinetics
**greater lipid solubility leads to greater absorption and more rapid onset of action
**elimination half life is determined by metabolism |
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Term
|
Definition
-more lipophilic drugs get into the CNS very fast, and leave the CNS fast
**limits the duration of action of the drug |
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Term
|
Definition
-Diazepam (valium)
-Lorazepam (Ativan)
-Temazepam
-Triazolam
-Midazolam |
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Term
| lipophilicity of diazepam |
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Definition
-highly lipophilic
-goes right into the brain, but then REDISTRIBUTION
-leaves CNS fast too
-stays around in the body for a while bc it's metabolized into a long acting metabolite that gets stored in fat |
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Term
|
Definition
-drug that enters the brain quickly and LEAVES CNS quickly
*limits the duration of action of the drug
*lipophilic drugs |
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Term
| metabolism of benzodiazepines |
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Definition
Diazepam-->Long lasting active metabolite via P450 in the liver-->conjugation and excretion
Lorazepam-->just right to excretion; no P450 |
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Term
| diazepam pharmacokinetics |
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Definition
-short half life: .5-2 hours
-long elimination half life: 30-60 hours
-very lipid soluble |
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Term
| lorazepam pharmacokinetics |
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Definition
-half life of 1-6 hours
-elimination half life 10-18 hours
-more water soluble, enters brain slowly
used a lot for anxiety |
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Term
| half-life advantages to benzodiazepines |
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Definition
-therapeutic uses depend on half life
LONG half life: anticonvulsants (clonazepam)
SHORT ELIMINATION half life: hypnotics, sleep aids (temazepam)
LONG half life: anti-anxiety (Lorazepam) |
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Term
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Definition
-on the whole, BDZs are safe, but they are CNS depressants
-potentiate effects when in combo with other CNS depressants (ex: alcohol)
-inhibitors or activators of CYP3A4 |
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Term
|
Definition
-lightheadedness, increased reaction time
*hangover effect with long elimination preparations - drowsiness, confusion
-rebound withdrawal effects: rebound anxiety or wakefulness, especially with drugs with short half life or with abrupt discontinuation of the drug (usually the opposite effect of what the drug is intended for) |
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Term
| side effects of high doses of BDZs |
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Definition
-toxic effects at higher doses
-ataxia ("drunken sailor walk"-GABA effect in cerebellum) and nystagmus
-anterograde amnesia
-paradoxical excitement
Dose-dependent |
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Term
| contraindications to BDZ use |
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Definition
-COPD, OSA; BDZ may decrease muscular tone in upper airway
-alcoholics and older patients with liver problems need BDZ that aren't metabolized by a P450 |
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Term
| tolerance, abuse, dependence of BDZ |
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Definition
-some risk of dependence and abuse but much less than with barbiturates
-abuse more prevalent in patients who also abuse other substances
-may be physical dependence after long-term use |
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Term
|
Definition
MANY!
-anxiety
-sleep disorders
-seizures
-skeletal muscle spasms
-alcohol withdrawal
-preanesthetic medication |
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Term
|
Definition
-BDZ receptor ANTAGONIST
-reverses the effects of BDZs
-hastening recovery from BDZ sedation or anesthesia
-only administered IV, in hospital setting |
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Term
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Definition
alpha 1 - sedation (cerebral cortex)
alpha 2 - anxiolytic (limbic region, striatum, cortex) |
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Term
| Z-drugs: effects/uses, pharmacokinetics |
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Definition
ex: Zolpidem (Ambien)
-NON-BDZ that acts at the BDZ receptor (not a 7-membered ring)
-shortens sleep latency, prolongs sleep time
-does NOT treat anxiety
-plasma t1/2=1-3 hours
-can result in wakeful behavior and amnesia at increased doses |
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Term
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Definition
(Zolpidem)
-risk of abuse and tolerance low when used as directed
-few withdrawal reactions (though have been reported)
-no tolerance to therapeutic effects |
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Term
|
Definition
-used to treat generalized anxiety with limited severity
-partial agonist at serotonin receptors
**lacks CHS depressant properties**
-slow onset of action |
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