Sedatives, Hypnotics, Anxiolytics, and Alcohol Flashcards
General effects of sedative hypnotics
Anti-anxiety/calming effect, sedation, anterograde amnesia, sleep, anesthesia, anticonvulsant, muscle relaxation, effects on respiratory and cardiac function.
Why are benzodiazepines safer than barbiturates?
Because they have a flatter dose response curve, and they increase frequency of GABA a channel opening, but don’t keep the channel open themselves.
What happens when benzo/barbs administered with other CNS depressants?
Additive effects.
Order of effects for benzos/barbs
Anti-anxiety, sedation, hypnosis, anesthesia, coma
Most common GABA a receptor structure
2 alpha 1s
2 beta 2s
1 gamma 1
Where do GABA, Benzos, Barbiturates bind on GABA a receptor?
GABA: Between A and B subunits
Benzos: Between A and G subunits
Barbiturates: many sites
Do sedative hypnotics have a high affinity for the GABA B receptor?
No
Role of A1, A2/3, and A5 subunits in the GABA receptor?
A1- sedation, amnesia, ataxia
A2/3 - anxiolysis, muscle relaxing properties
A5- Memory impairment?
Sedative-hypnotic withdrawal symptoms?
Anxiety/agitation, restlessness, tremor, seizures, hyperactive reflexes
Worst consequence of sudden withdrawal from benzos, barbs, alcohol?
Death
Ultra short acting barbiturate?
Thiopental, no longer available in the US
Immediate acting barbiturates?
Secobarbital, butalbital.
Long acting barbiturate?
Phenobarbital
Pharmocokinetics
AD: rapid
M: Oxidation to form alcohols, acids, and ketones.
E: Renal.
Use of Barbiturates in clinical practice?
Epilepsy, induction of anesthesia, PAS, capital punishment, combination headache remedies.
Barbiturate Toxicit
Small/midpoint pupils, coma, hypertension, decreased myocardial contractivity.
Key group in benzodiazepines?
Carboxamide group
Do barbiturates work anywhere else?
Yes they also depress some of the actions of the AMPA receptor.
Role for benzodiazepines in clinical practice?
Panic, anxiety, phobia disorders. Insomnia, epilepsy, alcohol withdrawal. Etc.
How are benzodiazepines metabolized?
They are all phase I oxidation in the liver except for LORAZEPAM, OXAZEPAM, TEMAZEPAM. Renal excretion.
Which benzos are safest in liver patients?
Lorazepam, Oxazepam, Temazepam
Short acting Benzodiazepines
Midazolam, triazolam, oxazepam
Intermediate Acting Benzos
Temazepam, Alprazolam, Lorazepam, Estazolam
Long acting Benzos
Clonazepam, Diazepam, Chlordiazepoxide
Non-Benzo Hypnotics
Zolpidem, Zaleplon, Eszopiclone
Which non-benzo hypnotics are fast acting, which are slow?
Zolpidem and zaleplon are fast. Eszopiclone is slow.
Effect of Benzodiazepines on Sleep
Decreases REM, increases Stage 2
Effect of new hypnotics on sleep
Zolpidem decreases rem, but doesnt effect other things. Zaleplon doesn’t affect REM.
Flumazenil
Competitive antagonist at benzodiazepine binding site on GABAa receptor, does not block effect of barbs/etoh. Has horrible side effects. R
Ramelteon
Melatonin receptor agonist, doesn’t do much.
Buspirone
Some anxiolytic effects, partial agonist at brain 5-HT1A receptors. Some therapeutic latency (1 week)
Dexmedetomidine
Given IV in ICUs frequently. A2 receptor agonist, sedation by reducing sympathetic activity. Given to respirator patients for sedation. Costs lots. Caution with heart problems.
Sedative hypnotics and pregnancy
All cross blood brain barrier, some risk of terratogenicity, but is disputed.
EtOH metabolism
Zero-order: Rate of oxidation is independent of time and concentration of drug.
Primary metabolism of EtOH
Alcohol dehydrogenase with NAD to turn into acetaldehyde, which is then turned into acetate by aldehyde dehydrogenase. This last step is blocked by disulfiram.
Disulfiram
Blocks oxidation of Acetaldehyde, causes horrible symptoms when drinking.
Ethanol mechanism of action
Enhances action of GABA at GABA A receptors, antagonizes glutamate at NMDA.
Effect of acute alcohol on heart?
Depression of myocardial activity, tachycardia.
Ethanol effect on vessels?
Vasodilator
Effect of chronic alcohol on heart
Dilated cardiomyopathy, CAD, hypertension.
Wernicke-Korsakoff syndrome
Paralysis of external eye muscles, ataxia, confusion, thimine deficiency, chronic disabling memory disorder.
Why is taking tylenol bad on alcohol
Chronic alcohol use leads to the induction of Cyp450 enzymes, which convert acetaminophen to hepatotoxic metabolites
Delirium Tremens
Onset due to alcohol withdrawal, roughly 3 days after. Tachycardia, hypertension, low-grade fever, tremor, delirium,
How to combat alcohol withdrawal?
Benzodiazepine treatment (chlordiazepoxide, diazepam if good hepatic function, lorazepam, oxazepam if poor).
Other drugs to treat alcohol abuse?
Naltrexone, acamprosate (GABA a activator, nmda receptor antagonist), disulfiram
Methanol
Broken down into formaldehyde. Late symptoms of poisoning are really severe. Anion gap metabolic acidosis
Methanol vs ethylene glycol poisoning?
Methanol has visual disturbances, both have anion gap metabolic acidosis.
