Hypnotics & Anxiolytics

Question 1

Name 3 BZDs (benzodiazepine)

Answer 1

1. diazepam
2. lorazepam
3. midazolam

Question 2

BZD MOA

Answer 2

• acts on midbrain ascending reticular formation (wakefulness)
• limbic system (thought and mental function)
• increase GABA inhibitory transmission in CNS
  1. enhance GABA binding
  2. increase chloride influx thru GABAa receptor - allosteric modulation in presence of GABA (by increase Cl- channel opening frequency)

Question 3

Name uses of BZD

Answer 3

1. selective CNS depressants - sedation/ anxiolytics/ hypnosis
2. suppress seizures - IV diazepam for status epilepticus
3. muscle relaxant

Question 4

Pharmacokinetics of BZD

Answer 4

1. metabolized in liver by CYP450
2. cross placenta, secrete in milk

Question 5

State use and action of SSRIs and SNRIs

Answer 5

• act only after chronic treatment
• used extensively in chronic anxiety disorders (not good for acute)

Question 6

Interaction of BZD

Answer 6

• cimetidine, isonazid, oral contraceptive -> retard its metabolism
• synergise other CNS depressants

Question 7

Adverse effects of BZD

Answer 7

1. tolerance to sedative effects
2. overdosing not fatal -> treated with flumazenil (BZD antagonist)
3. long term use -> potential for addiction
   -> limit duration, taper doses
   -> switch to other drugs for long term treatment

Question 8

Tolerance leads to BZD withdrawal symptoms
- state the symptoms

Answer 8

• insomnia
• ANS hyperactivity: sweating, tachycardia
• Tremor
• Hallucination

Question 9

Z drugs (non BZD hypnotics) MOA

Answer 9

• agonist of a1 subunit of GABA receptors/ BZD receptors

Question 10

Name use of Z drugs

Answer 10

• hypnotic-amnesic effect
• weak antianxiety
• short term treatment of insomnia
• lower abuse potential than BZDs

Question 11

Name drug to treat Z drugs overdose toxicity

Answer 11

BZD antagonist - flumazenil

Question 12

Name side effect for Z drugs

Answer 12

1. metallic or bitter after taste
2. impaired judgement& alertness
3. Dry mouth

Question 13

Buspirone MOA

Answer 13

• presynaptic 5HT1a autoinhibitory receptor partial agonist
  -> bind to 5HT1a receptorn in dorsal raphe
  -> inhibit exocytosis of 5HT vesicles
• weak affinity for 5HT2 receptors
  *act only after chronic treatment

Question 14

Pharmacokinetics of buspirone

Answer 14

• extensive first pass metabolism

Question 15

Buspirone side effects

Answer 15

minor:
- dizziness
- nausea
- abdominal discomfort

*caution for operating machines/ vehicles

Question 16

State B-adrenergic blocker and its MOA

Answer 16

• propranolol/ other non selective blockers
• relieve somatic symptoms of anxiety
  e.g. palpitation, rise in BP, tremor, GI hurrying
  -> performance/ situation anxiety
  -> adjuvant to BZD

Question 17

Name two Z drugs

Answer 17

zolpidem, zopiclone

Question 18

Name the anti-epileptic drug that can also be used as sedative hypnotics

Answer 18

Pregabalin