Sedative Hypnotics

Question 1

What drugs are classified as sedative hypnotics?

Answer 1

• Barbiturates
• Benzodiazepines
• Nonbenzodiazepines (Z-drugs)
• Others (Buspirone)

Question 2

Where on the GABA receptor do Benzodiazepines bind?

Answer 2

• Between α₁ and γ₂ subunits
• Benzodos increase the frequency of Cl^{<strong>-</strong>} channel opening (results in hyperpolarization)

Question 3

Where on the GABA receptor do Barbiturates bind?

Answer 3

• Different site than Benzodiazepines and Z-drugs (Flumazenil, Zolpidem)
• Increase the duration of Cl^-channel opening (results in hyperpolarization)

Question 4

What are the GABA_A-α1 selective agonists?

Answer 4

• Zolpidem
• Zaleplon
• Eszopiclone

More receptor specific

May lose specificity if you take a lot of them (dependence)

Question 5

What are the other drugs that bind at a site on the GABA receptor close to where benzodiazepines bind?

Answer 5

• Z-Drugs (α1 agonist; AKA BZ1 subtype receptor of GABA)
  
  • Zolpidem.
• Flumazenil (Benzodiazepine antagonist)

Question 6

Why are benzodiazepines less lethal than barbiturates?

Answer 6

• Barbiturates cause greater CNS effects with greater doses (causes decreased respiration)
  
  • Especially if mixed with alcohol and/or opiates (other depressants)
  • Barbiturates have low therapeutic index
  • Barbiturates induce CYP450 so they have many drug interactions
• CNS effects are lower for benzodiazepines (never reach respiratory decreasing levels)

Question 7

What benzodiazepines don’t require oxidative metabolism? Which patients would this be ideal for?

Answer 7

• Oxazepam
• Temazepam (sleep medication)
• Lorazepam

Easy On The Liver

• Good for patients with impaired liver function
• They are only conjugated and don’t have active metabolites

Question 8

What is the mechanism of action for Flumazenil?

Answer 8

• Competitive antagonist for BZ binding site (blocks action of benzodiazepines and Z-drugs)
  
  • But not barbiturates, ethanol, opioids, anesthetics (used for problems with anesthesia)

Question 9

What are some adverse effects of Flumazenil? What drug is used more than Flumazenil?

Answer 9

• Can cause precipitated withdrawal symptoms (including seizures) in benzodiazepine-dependent patients
• Naloxone is used more (safer and more likely to act on the respiratory depression caused by opioids)

Question 10

What is the half-life of Flumazenil?

Answer 10

• Short (30-60 minutes)
  
  • Shortest of all BZDs so there may be need for frequent dosing

Question 11

What patients are barbiturates contraindicated in?

Answer 11

Patients with acute intermittent porphyria or porphyria variegate

Question 12

What is the mechanism of action for Buspirone? What is the onset?

Answer 12

• 5-HT_1A Partial agonist
• Slow onset (2-6 weeks)

Question 13

What is Buspirone used for clinically?

Answer 13

• Generalized anxiety disorder (GAD)
  
  • No abuse potential

Question 14

What is the mechanism of action for Ramelteon?

Answer 14

Agonist at MT₁ and MT₂ melatonin receptors (located in the suprachiasmatic nuclei of the brain)

Question 15

What is Ramelteon used for clinically?

Answer 15

• Insomnia
  
  • No abuse potential

Question 16

Barbiturates (increase/decrease) the production of porphyrins.

Answer 16

Increase