Anxiolytics

Question 1

What is the difference between a sedative and a hypnotic drug?

Answer 1

Sedative = calming/anxiolytic effect ideally with little effect on motor or mental functions

Hypnotic = sleep inducing (more pronounced CNS depression than sedation; can be achieved by most sedative drugs simply by increasing dose)

Question 2

How do most sedative-hypnotic drugs act on GABA-A receptors?

Answer 2

they open the chloride channel, hyperpolarize the cell and thus inhibit the cell; they POTENTIATE GABA-mediated inhibition

Question 3

What are the parts of the GABA-A transmembrane receptor complex?

Answer 3

1) Cl- channel core
2) pentameric structure
3) endogenous agonist GABA binds alpha or beta subunits

**note that where GABA binds is NOT where Benzos and Barbs etc bind (they bind elsewhere to potentiate GABA’s action)

Question 4

What part of the GABA subunit do Benzodiazepenes, Barbiturates, and Ethanol bind to?

Answer 4

Benzos: between alpha1-gamma2
Barbs: alpha or beta
Ethanol: alpha

Question 5

What are the two main GABA-A receptor sub-types and which do benzos bind to?

Answer 5

BDZ1 = omega1; BDZ2 = omega2; diazepam (and most benzos) bind to both!

Question 6

What are some of the properties of diazepam and most benzodiazepines?

Answer 6

sedation, hypnosis, muscle relaxation, anticonvulsant activity, anterograde amnesia

Question 7

Benzos vs Barbs: which produce a “ceiling effect” and which produce a linear dose-response?

Answer 7

Benzos have a ceiling effect (no respiratory depression, coma, or death; merely augmenting action of GABA)

Barbs (&alcohol) have full a linear dose-response with CNS depression leading to death because not only do they augment GABA action, but they DIRECTLY open Cl- channels

**Benzos much safer

Question 8

What are the names of all the Benzodiazepines we need to know for testing purposes?

Answer 8

Diazepam, Chlordiazepoxide, Lorazepam, Flurazepam, Alprazolam, Midazolam, Triazolam

Question 9

How are the benzos metabolized? What causes unwanted daytime sedation related to this metabolism pathway?

Answer 9

Most undergo microsomal oxidation (Phase I via P450 with only modest P450 induction) and subsequent conjugation.

Daytime sedation is related to production of Phase I metabolites which are active w/long half lives

Question 10

Name the benzos that don’t produce active metabolites as well as their respective half lives

Answer 10

Midazolam (1.9hr), Triazolam (2.9hr), Alprazolam (12hr), Lorazepam (14hr)

Question 11

Name the benzos with active metabolites and their respective half lives

Answer 11

Chlordiazepoxide (10hr); Diazepam (43hr); Flurazepam (74 hr); all have active metabolites up to 100hr

Question 12

What types of drugs are selective for the BDZ1 (ormega1) receptor?

Answer 12

sleeping pills (Zolpidem)

Question 13

What are the therapeutics of Zolpidem and potential side effects?

Answer 13

Therapeutics: sedation and hypnosis w/out muscle relaxation or anticonvulsant activity with a short 2hr half life

Side Effects: sleep-walking, next morning impairment

Question 14

What is the name of the benzodiazepine antagonist used to treat overdose of benzos?

Answer 14

Flumazenil

Question 15

What are some of the drawbacks to Flumazenil?

Answer 15

possible life-threatening withdrawal; seizures in mixed overdoses and non uniform reversals of respiratory depression

Question 16

How are the Barbiturates metabolized?

Answer 16

Phase I: oxidation (P450) with significant enzyme induction

Phase II: glucuronide formation

Question 17

What type of drug is Phenobarbital, what is it used to treat, and is it fast or slow onset/elimination?

Answer 17

1) Barbiturate (binds a or b subunit of GABA-a)
2) Antiepileptic/Anticonvulsant
3) Less lipid soluble thus slower onset, slower elimination

Question 18

What type of drug is Thiopental, what is it used to treat, and is it fast or slow onset/elimination?

Answer 18

1) Barbiturate (binds a or b subunit of GABA-a)
2) Induces anesthesia
3) Highly lipid soluble thus fast on/fast off due to tissue redistribution

Question 19

What is the order or redistribution of Thiopental in the body?

Answer 19

brain–>muscle–>fat (metabolized by liver; dosed based on lean body mass)

Question 20

What are the side effects of the barbiturates?

Answer 20

daytime sedation/drowsiness, dose-dependent depression of CNS, psychologic and physiologic dependence w/chronic use, and abrupt withdrawal life-threatening

Question 21

What would you use to treat acute anxiety versus generalized anxiety?

Answer 21

Acute: benzodiazepines

GAD: antidepressants and/or benzodiazepenes

Question 22

What is the name of the anti-anxiety medication that does not cause sedation? How does it act?

Answer 22

Buspirone; doesn’t have interaction with GABA-A; instead it may be a partial agonist at 5HT1A receptors

Question 23

What do you use to treat Panic Disorder? OCD? PTSD?

Answer 23

Panic: SSRIs or benzos
OCD: SSRIs
PTSD: various antidepressants

Question 24

Which of the benzodiazepines treat short term depression, and bipolar disease?

Answer 24

All of them except for Midazolam!

Question 25

What does Midazolam used for?

Answer 25

Anesthesia (calming effects, produces anterograde amnesia)

Question 26

Which benzodiazepine also induces sleep?

Answer 26

Triazolam

Question 27

Which benzodiazepine also causes sedation?

Answer 27

Alprazolam and Lorazepam

Question 28

Which benzodiazepine acts as anticonvulsant?

Answer 28

Lorazepam and Diazepam

Question 29

Which benzodiazepine acts as a muscle relaxant?

Answer 29

Diazepam (by inhibitory effects on polysynaptic reflexes and interneuron transmissions)

Question 30

What are the adverse effects of sedative hypnotics?

Answer 30

drowsiness and “hangover”, falls (in the elderly), dose-related CNS depression w/other drugs, tolerance, psychological and physiologic dependence with chronic use, anterograde amnesia