A/25. Benzodiazepines

Question 1

Drugs need to know in this topic

Answer 1

Short acting

nitrazepam

midazolam

Intermediate acting

alprazolam

Long- acting

diazepam

clonazepam

flumazenil

Question 2

Mechanism of action

Answer 2

1. Potentiate GABA activity → less GABA is needed to gain the same response (enhanced potency of endogenous GABA)
2. ↑ frequency of Cl- channel opening
3. No GABA mimetic effects – activity of BZ depends on the presence of endogenous GABA
4. Binding of benzodiazepine molecule to BZ receptors (specific binding site on GABAA receptor complex) does not result in channel opening
5. CNS response curve will reach plateau – endogenous GABA levels cannot cause severe medullary suppression and coma

Question 3

Nitrazepam

Answer 3

Oral

Hepatic conjugation
(active metabolite)

Sleep disorders, insomnia

Question 4

Midazolam

Answer 4

Oral, IV

Hepatic conjugation
(active metabolite)

1. Preoperative sedation
2. Anesthesia (IV)

Question 5

Alprazolam

Answer 5

Oral

Hepatic conjugation
(active metabolite)

Anxiety, panic, and phobic disorders

Question 6

Diazepam

Answer 6

Oral, IV

Hepatic conjugation
(active metabolite)

1. Anesthesia (IV)
2. Preoperative sedation
3. Muscle spasticity (centrally-acting skeletal muscle relaxant)
4. Anxiety, panic, and phobic disorders
5. Withdrawal states (ethanol and other sedative-hypnotics)

Question 7

Clonazepam

Answer 7

Oral

Hepatic conjugation
(active metabolite)

1. Anxiety, panic, and phobic disorders
2. Bipolar disorders
3. Seizures

Question 8

Flumazenil

Answer 8

Benzodiazepine antagonists

Antagonist at BZ sites on
GABAA receptor (neutral
allosteric modulator)

IV

1. Benzodiazepine overdose
2. Reverse anesthesia
3. Also affective for terminating the activity of eszopiclone, zaleplon,
   and zolpidem
   *Cannot reverse CNS effects caused by barbiturates and alcohols

Question 9

Adverse effects and toxicity

Answer 9

• *1. Cognitive impairment
  2. Decreased psychomotor skills
  3. Daytime sedation (increased risk in elderly)
  4. Anterograde amnesia (high dose needed)
  5. Cardiovascular and respiratory depression (toxic doses, or as a result of additive drug interaction)**

Question 10

Drug interactions

Answer 10

Additive sedation with other CNS depressants (possible life-threatening respiratory depression):

• *1. Antihistamines (1st gen’)
  2. Anesthetics
  3. Alcohols
  4. Barbiturates
  5. Opioid analgesics
  6. β-blockers
  7. α2-agonists**