14- Sedative-Hypnotics/Anti-anxiety Agents

Question 1

zolpidem (Ambien)

Answer 1

non-benzodiazepine
act between alpha or gamma site on GABAa receptor
-enhance GABA effect by increasing Cl- influx and increase frequency of GABA receptor opening
-plasma levels peak within 1-2 hours
-1/2 life 1.5-3 hours
-Metabolized by CYP3A4

Question 2

zaleplon (Sonata)

Answer 2

non-benzodiazepine
act between alpha & gamma site on GABA receptor
-enhance GABA effect by increasing Cl- influx and increase frequency of GABA receptor opening
-plasma levels peak within 1-2 hours
-1/2 life 1.5-3 hours
-Metabolized by CYP3A4

Question 3

eszopiclone (Lunesta)

Answer 3

non-benzodiazepine
act between alpha & gamma site on GABA receptor
-enhance GABA effect by increasing Cl- influx and increase frequency of GABA receptor opening
-plasma levels peak within 1-2 hours
-1/2 life 1.5-3 hours
-Metabolized by CYP3A4

Question 4

diazepam (Valium)

Answer 4

Benzodiazepine

• bind between alpha and gamma subunit of GABAa receptors in limbic system to enhance GABA inhibition (produces anxiolytic effects)
• inc. FREQUNCY of GABA channel opening leading to greater Cl- influx and hyperpolarization
• BDZs cannot open GABAa receptor in the absence of GABA
• Prodrug metabolized to desmethyldiazepam which has active effects (extensive CYP metabolism)
• short onset (1-2 hrs), long half-life (30-60 hrs)

Question 5

chlordiazepoxide (Librium)

Answer 5

Benzodiazepine

• bind between alpha & gamma subunit of GABAa receptors in limbic system to enhance GABA inhibition (produces anxiolytic effects)
• inc. FREQUNCY of GABA channel opening leading to greater Cl- influx and hyperpolarization
• BDZs cannot open GABAa receptor in the absence of GABA
• Prodrug metabolized to active form via phase 1 metabolism
• Extensive CYP metabolism

Question 6

alprazolam (Xanax)

Answer 6

Benzodiazepine

• bind between alpha & gamma subunit of GABAa receptors in limbic system to enhance GABA inhibition (produces anxiolytic effects)
• inc. FREQUNCY of GABA channel opening leading to greater Cl- influx and hyperpolarization
• BDZs cannot open GABAa receptor in the absence of GABA
• Prodrug metabolized to active alpha-hydroxy metabolites via Phase 1 metabolism (extensive CYP metabolism)
• short onset (1-2 hrs); short half-life (12-15 hrs)

Question 7

lorazepam (Ativan)

Answer 7

Benzodiazepine

• bind between alpha & gamma subunit of GABAa receptors in limbic system to enhance GABA inhibition (produces anxiolytic effects)
• inc. FREQUNCY of GABA channel opening leading to greater Cl- influx and hyperpolarization
• BDZs cannot open GABAa receptor in the absence of GABA
• onset 1-6 hrs; intermediate half-life (10-18 hrs)

Question 8

midazolam (Versed)

Answer 8

Benzodiazepine

• bind between alpha & gamma subunit of GABAa receptors in limbic system to enhance GABA inhibition (produces anxiolytic effects)
• inc. FREQUNCY of GABA channel opening leading to greater Cl- influx and hyperpolarization
• BDZs cannot open GABAa receptor in the absence of GABA
• Extensive CYP metabolism
• Rapid onset (0.2-1 hr); ultra-short half-life (2-5 hrs)

Question 9

flumazenil (Romazicon)

Answer 9

Benzodiazepine Antagonist

• blocks the effects of GABA agonists
• competitive inhibition of BZD binding site (gamma subunit)
• used to reverse s/fx of BZDs
• may need to be redosed because half-life is shorter than BZDs

Question 10

pentobarbital (Nembutal)

Answer 10

GABA-A receptor agonist
-binds beta subunit on GABAa receptor in RAS and cortex
+increase open time of receptor and leads to hyperpolarization.
+at high concentrations it acts as GABAnergic (it can open channel without GABA).
-Works in the reticular formation (pons and medulla) which controls: somatic motor control, CV control, pain modulation, sleep and consciousness.
-Quick onset (0.5-1H); t1/2 elimination 15-50’
- used for preoperative sedation.
-metabolized by CYP’s and induces CYP metabolism
-more severe S/E, withdraw,and dependence than benzo
-potent respiratory depressant

Question 11

phenobarbital (Luminal)

Answer 11

GABA-A receptor agonist
-binds beta subunit on GABAa receptor in RAS and cortex
+increase open time of receptor and leads to hyperpolarization.
+at high concentrations it acts as GABAnergic (it can open channel without GABA).
-Works in the reticular formation (pons and medulla) which controls: somatic motor control, CV control, pain modulation, sleep and consciousness.
- used as anticonvulsant.
-metabolized by CYP’s and induces CYP metabolism
-more severe S/E, withdraw,and dependence than benzo
-potent respiratory depressant

Question 12

propranolol (Inderal)

Answer 12

miscellaneous antianxiety

• beta-receptor blocker
• blocks effects of epi which dec. HR, BP, sweating and shaking
• useful for disabling situational anxiety

Question 13

buspirone (Buspar)

Answer 13

miscellaneous antianxiety

• partial agonist for serotonin 1A (5HT) receptor
• produces only anxiolytic effects, no CNS depression
• no issues with dependence or withdrawal and no additive depression with ETOH
• Onset takes 1-3 weeks limiting its use