Pharmacology of Sedative-Hypnotic Drugs

Question 1

Sedative

Answer 1

calming, anxiolytic effect. ideally with little effect on motor or mental functions

Question 2

hypnotic

Answer 2

induces sleep. more pronounced CNS depression than sedation, can be achieved with most sedative drugs by increasing dose

Question 3

uses of sedative / hypnotic drugs

Answer 3

induce sleep, acute treatment of anxiety disorders, muscle relaxant, anticonvulsant, pre-anesthetic, recreation

Question 4

mechanism of sedative/hypnotic drugs

Answer 4

most bind to some site on GABAa receptor complex and potentiate GABA mediated inhibition. Opens Cl channel, hyperpolarizes cell, inhibiting it.

Question 5

where do benzodiazepines, barbituates, and ethanol bind on GABA receptors?

Answer 5

benzo: binding site between alpha 1 and gamma 2 sub-units
barbituates: bind to alpha or beta sub unit
ethanol: binds to alpha subunit

Question 6

two main family of GABA/Benzo receptor sub-types

Answer 6

BDZ1 = omega 1
BDZ2 = omega 2.  

most clinically used benzos bind to both subtypes

Question 7

properties of diazepam

Answer 7

sedation then hypnosis if heavy dose. muscle relaxation, anticonvulsant activity, anterograde amnesia. very little cardiovascular or respiratory effects

Question 8

what happens if you keep increasing dose of benzos?

Answer 8

ceiling effect. they augment the action of GABA. do not produce respiratory depression, coma, or death! stops at anesthesia

Question 9

what happens if you keep increasing dose of barbituates, alcohol, or general anesthetics?

Answer 9

full CNS depression leading to death. they augment action of GABA, and in high doses can also directly open Cl channel

Question 10

list of benzodiazepines

Answer 10

diazepam, chlorodiazepoxide, lorazepam, flurazepam, alprazolam, midazolam, trazolam.

Question 11

rank benzos based on shortest to longest half life

Answer 11

midazolam, triazolam, alprazolam, lorazepam, chlordiazepoxide, diazepam, flurazepam

Question 12

what metabolizes benzos?

Answer 12

most undergo microsomal oxidation via P450 system and subsequent conjugation

Question 13

what receptor do sleeping pills agonize?

Answer 13

BDZ1 selective aka omega1 agonists

Question 14

BDZ1 agonists

Answer 14

zolpidem (this is ambien). sedation and hypnosis without muscle relaxation or anticonvulsant activity. short half life so little hang over

Question 15

what do you use to reverse overdose of benzos?

Answer 15

flumazenil. benzo anatagonist

Question 16

barbituate metabolism

Answer 16

oxidation at several different P450s. significant P450 enzyme induction. Subsequent glucuronide formation

Question 17

phenobarbitol vs. thiopental

Answer 17

pheno is less lipid soluble so slower onset and slower elimination (anti-epileptic/anti-convulsant). thio is highly lipid soluble, fast on, fast off (induces anesthesia)

Question 18

buspirone

Answer 18

relieves anxiety without marked sedation. no interaction with GABAa receptor complex. may act as partial agonist at 5-HT1A receptors

Question 19

drugs used for calming and anti-anxiety

Answer 19

alpraolam and lorazepam. shorter acting

Question 20

drugs used to induce sleep

Answer 20

triazolam, zolpidem

Question 21

adverse effects of benzos

Answer 21

daytime sedation and drowziness. additive or synergistic depression of CNS with other drugs. significant dose related anterograde amnesia. psychologic and physiologic dependence with chronic use