Sedatives, Hypnotics, Anxiolytics, and Alcohol

Question 1

General effects of sedative hypnotics

Answer 1

Anti-anxiety/calming effect, sedation, anterograde amnesia, sleep, anesthesia, anticonvulsant, muscle relaxation, effects on respiratory and cardiac function.

Question 2

Why are benzodiazepines safer than barbiturates?

Answer 2

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.

Question 3

What happens when benzo/barbs administered with other CNS depressants?

Answer 3

Additive effects.

Question 4

Order of effects for benzos/barbs

Answer 4

Anti-anxiety, sedation, hypnosis, anesthesia, coma

Question 5

Most common GABA a receptor structure

Answer 5

2 alpha 1s
2 beta 2s
1 gamma 1

Question 6

Where do GABA, Benzos, Barbiturates bind on GABA a receptor?

Answer 6

GABA: Between A and B subunits
Benzos: Between A and G subunits
Barbiturates: many sites

Question 7

Do sedative hypnotics have a high affinity for the GABA B receptor?

Answer 7

No

Question 8

Role of A1, A2/3, and A5 subunits in the GABA receptor?

Answer 8

A1- sedation, amnesia, ataxia
A2/3 - anxiolysis, muscle relaxing properties
A5- Memory impairment?

Question 9

Sedative-hypnotic withdrawal symptoms?

Answer 9

Anxiety/agitation, restlessness, tremor, seizures, hyperactive reflexes

Question 10

Worst consequence of sudden withdrawal from benzos, barbs, alcohol?

Answer 10

Death

Question 11

Ultra short acting barbiturate?

Answer 11

Thiopental, no longer available in the US

Question 12

Immediate acting barbiturates?

Answer 12

Secobarbital, butalbital.

Question 13

Long acting barbiturate?

Answer 13

Phenobarbital

Question 14

Pharmocokinetics

Answer 14

AD: rapid
M: Oxidation to form alcohols, acids, and ketones.
E: Renal.

Question 15

Use of Barbiturates in clinical practice?

Answer 15

Epilepsy, induction of anesthesia, PAS, capital punishment, combination headache remedies.

Question 16

Barbiturate Toxicit

Answer 16

Small/midpoint pupils, coma, hypertension, decreased myocardial contractivity.

Question 17

Key group in benzodiazepines?

Answer 17

Carboxamide group

Question 18

Do barbiturates work anywhere else?

Answer 18

Yes they also depress some of the actions of the AMPA receptor.

Question 19

Role for benzodiazepines in clinical practice?

Answer 19

Panic, anxiety, phobia disorders. Insomnia, epilepsy, alcohol withdrawal. Etc.

Question 20

How are benzodiazepines metabolized?

Answer 20

They are all phase I oxidation in the liver except for LORAZEPAM, OXAZEPAM, TEMAZEPAM. Renal excretion.

Question 21

Which benzos are safest in liver patients?

Answer 21

Lorazepam, Oxazepam, Temazepam

Question 22

Short acting Benzodiazepines

Answer 22

Midazolam, triazolam, oxazepam

Question 23

Intermediate Acting Benzos

Answer 23

Temazepam, Alprazolam, Lorazepam, Estazolam

Question 24

Long acting Benzos

Answer 24

Clonazepam, Diazepam, Chlordiazepoxide

Question 25

Non-Benzo Hypnotics

Answer 25

Zolpidem, Zaleplon, Eszopiclone

Question 26

Which non-benzo hypnotics are fast acting, which are slow?

Answer 26

Zolpidem and zaleplon are fast. Eszopiclone is slow.

Question 27

Effect of Benzodiazepines on Sleep

Answer 27

Decreases REM, increases Stage 2

Question 28

Effect of new hypnotics on sleep

Answer 28

Zolpidem decreases rem, but doesnt effect other things. Zaleplon doesn't affect REM.

Question 29

Flumazenil

Answer 29

Competitive antagonist at benzodiazepine binding site on GABAa receptor, does not block effect of barbs/etoh. Has horrible side effects. R

Question 30

Ramelteon

Answer 30

Melatonin receptor agonist, doesn't do much.

Question 31

Buspirone

Answer 31

Some anxiolytic effects, partial agonist at brain 5-HT1A receptors. Some therapeutic latency (1 week)

Question 32

Dexmedetomidine

Answer 32

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.

Question 33

Sedative hypnotics and pregnancy

Answer 33

All cross blood brain barrier, some risk of terratogenicity, but is disputed.

Question 34

EtOH metabolism

Answer 34

Zero-order: Rate of oxidation is independent of time and concentration of drug.

Question 35

Primary metabolism of EtOH

Answer 35

Alcohol dehydrogenase with NAD to turn into acetaldehyde, which is then turned into acetate by aldehyde dehydrogenase. This last step is blocked by disulfiram.

Question 36

Disulfiram

Answer 36

Blocks oxidation of Acetaldehyde, causes horrible symptoms when drinking.

Question 37

Ethanol mechanism of action

Answer 37

Enhances action of GABA at GABA A receptors, antagonizes glutamate at NMDA.

Question 38

Effect of acute alcohol on heart?

Answer 38

Depression of myocardial activity, tachycardia.

Question 39

Ethanol effect on vessels?

Answer 39

Vasodilator

Question 40

Effect of chronic alcohol on heart

Answer 40

Dilated cardiomyopathy, CAD, hypertension.

Question 41

Wernicke-Korsakoff syndrome

Answer 41

Paralysis of external eye muscles, ataxia, confusion, thimine deficiency, chronic disabling memory disorder.

Question 42

Why is taking tylenol bad on alcohol

Answer 42

Chronic alcohol use leads to the induction of Cyp450 enzymes, which convert acetaminophen to hepatotoxic metabolites

Question 43

Delirium Tremens

Answer 43

Onset due to alcohol withdrawal, roughly 3 days after. Tachycardia, hypertension, low-grade fever, tremor, delirium,

Question 44

How to combat alcohol withdrawal?

Answer 44

Benzodiazepine treatment (chlordiazepoxide, diazepam if good hepatic function, lorazepam, oxazepam if poor).

Question 45

Other drugs to treat alcohol abuse?

Answer 45

Naltrexone, acamprosate (GABA a activator, nmda receptor antagonist), disulfiram

Question 46

Methanol

Answer 46

Broken down into formaldehyde. Late symptoms of poisoning are really severe. Anion gap metabolic acidosis

Question 47

Methanol vs ethylene glycol poisoning?

Answer 47

Methanol has visual disturbances, both have anion gap metabolic acidosis.