Sedative/Hypnotic Drugs

Question 1

3 Classes of S/H Drugs

Answer 1

Barbiturates
Benzodiazepines
Newer non-BDZ GABA agonists

Question 2

Main R for S/H Drugs

Answer 2

GABAa

Question 3

GABAa 2 Subunit Locations for Drugs and 2 Subunit Types for Effects

Answer 3

Alpha/gamma: BDZs and most other things
Alpha/beta: Barbs
Alpha1 sub for hypnosis and alpha2 for anxiolysis

Question 4

BDZ Effect

Answer 4

Increase GABA-mediated currents by increasing frequency. Doesn’t have own activity

Question 5

Barbiturates Effect

Answer 5

Have own effect to activate R, and also facilitate GABA signaling but by increasing duration of opening, not time

Question 6

S/H Comparison of Increasing Dose

Answer 6

Bc Barbs have independent effect, can keep increasing effect higher and higher linearly until get cardiac failure
BDZs tail off at certain level, so safer but might not reach anesthetic level

Question 7

BDZs Use

Answer 7

Anxiety and insomnia

Question 8

BDZs 4 Benefits

Answer 8

High TI
Low drug interactions
Low risk of dependence
Effects mainly limited to CNS

Question 9

BDZ Pharmacokinetics (3)

Answer 9

Lipid soluble so easily absorbed orally and get to brain rapidly
Metabolized by hepatic microsomes but have active metabolites that can last longer/be more effective than actual drug, so its own half life doesn’t really determine
Drug choice determined by differences in elimination rate

Question 10

2 Long Acting BDZs (and use)

Answer 10

Desirable for anxiolytic action (less sleep inducing)
Diazepam (Valium) - has more active metabolites, so longer t1/2 and some sleep effects
Alprazolam (Xanax) - faster acting, more anxiolytic selective

Question 11

Short Acting BDZ (and use)

Answer 11

For insomnia, triazolam (Halcion)

Question 12

Anxiety Treatment (2)

Answer 12

Short term: BDZs (bc develop tolerance)

Long term: Treat cause/antideps/Buspirone

Question 13

Flumazenil ((Romazicon)

Answer 13

Competitive antagonist of GABA Rs, so good for BDZ overdose. Can have unwanted effects so usually administered in hospital

Question 14

Barbs Problem

Answer 14

Not as selective, so depress excitability of all tissues and can depress respiration/CV

Question 15

2 Uses of Barbs

Answer 15

Induce anesthesia/preanesthetic sedation

Anti-convulsant

Question 16

Thiopental (Pentothal) (what its for and notable metabolism point)

Answer 16

Barb to induce anesthesia. Lipid soluble so quick, but effects terminated by redistribution and not metabolism so predictable

Question 17

Phenobarbital (Luminal) (what it is/for and notable metabolism point)

Answer 17

Selective anti-convulsant barb

Anywhere from 25-30% excreted unchanged

Question 18

3 Barbiturate Interactions

Answer 18

Potentiate CNS depressants like EtOH
Accelerate microsomal metabolism of a bunch of shit like TCA, warfarin, OCs, etc and reduces their bioavailability as well as its own
MAOIs inhibit metabolism of barbs and increases their bioavailability

Question 19

Buspirone

Answer 19

Excellent selective anxiolytic, just takes time to work