Pharmacology of Sedative-Hypnotics and Drug Therapy of Anxiety

Question 1

Contrast sedative and hypnotics.

Answer 1

sedatives (anxiolytics) reduce anxiety with minimal effects on motor or cognitive functions

hypnotics produce drowsiness and promote onset and maintenance of sleep

Question 2

List the 4 major classes of drugs used in treating anxiety disorder and any important features.

Answer 2

benzodiazipines: all about equally efficacious and do not depress respiration although can lead to sedation and are highly teratogenic
anxiolytic: buspirone, has no sedative, anticonvulsant or psychomotor effects

SSRIs: no anticholinergic, a-adrenergic or antihistamine properties

SNRI: similar to SSRIs

Question 3

Contrast BZD and barbiturates.

Answer 3

both can have anticonvulsant effects acting at a common site of action GABAa that result in Cl- channel flux, resulting in hyper polarized neuron

BZD: increase affinity of GABAa receptor and increase frequency of GABA-induced Cl- openings, does not reach clinical anesthesia (safer)

Barbiturates: increase the duration of GABA-induced channel openings, depress respiration

Question 4

List other indications for sedative and hypnotic agents besides as antianlytics.

Answer 4

Adjuncts to anesthesia, tx. seizure disorders, muscle relaxation, alcohol withdrawal

Question 5

Discuss the mechanism, pharmacology and cautions of BZD prototype Diazepam

Answer 5

increases affinity of GABAa and increases frequency of GABA induced Cl- channel opening

most rapidly absorbed BZD PO

caution with depression, hepatic/renal dz, breast feeding and teratogenic

Question 6

Discuss the mechanism, pharmacology and cautions of BZD prototype Lorazepam.

Answer 6

increases affinity of GABAa and increases frequency of GABA induced Cl- channel opening

Metabolized by glucuronidation; “cleaner” less metabolites

caution with depression, breast feeding, or coadministration of valproic or probenicid, teratogenic

DOC for status epilecticus

Question 7

Discuss the salient features of BZD including
alprazolam
clonazepam
midazolam
oxzepam

Answer 7

alprazolam: potent BZD, short half life
clonazepam: potent, long acting BZD (more selective anti seizure med)
midazolam: used in conscious sedation, most rapidly inactivated BZD
oxzepam: cleaner with less metabolites

Question 8

Discuss the mechanism, pharmacology and cautions of BZD antagonist prototype Flumazenil.

Answer 8

IV only short acting, rapid onset BZD, competes for binding at GABAa receptors

used in reversal of BZD overdose/sedation

Caution, reversal last for short time and sedation can reoccur if no readministration, can be pain at injection site, dizziness and headache

Question 9

Discuss the mechanism, pharmacology and cautions of serotonergic anxiolytic Bupirone.

Answer 9

partial agonist at 5-HT receptors with moderate partial agonism of D2 receptors

rapidly absorbed PO and extensive 1st pass metabolism

produces no sedation, anticonvulsant or psychomotor impairment, has significant latency and should not be used with BZD

Question 10

Discuss the mechanism, pharmacology and cautions of hypnotics eszopiclone and zolpidem.

Answer 10

both modulate within the GABAa receptor complex with little/no hang over: possibility of rebound insomnia, avoid alcohol

Zolpidem: should be taken on an empty stomach for short term tx, has been known to cause somnambulism

Eszopiclone: for long term treatment, metallic taste, caution with hepatic dz.