A/26. Non benzodiazepine anxiolytics and non-benzodiazepine hypnotics. Pharmacotherapy of anxiety disorders.

Question 1

Drugs need to know in this topic

Answer 1

zolpidem

zaleplon

melatonin

ramelteon

buspirone

Question 2

Zaleplon
Zolpidem

Answer 2

GABA-A agonist

Oral

*CNS depressant effects can be antagonized by flumazenil
**Do not produce the anxiolytic, muscle relaxant,
or anticonvulsant effects associated with BZ’s

1. Sleep disorders (sleep-onset insomnia → zaleplon, zolpidem;

sleep-maintenance insomnia → eszopiclone)

• *Side effects:**
  1. CNS depression, additive with other CNS depressants
  2. Dependence liability (to lesser extent than BZ’s)

Question 3

Buspirone

Answer 3

5-HT1A partial agonist

Oral

The onset of clinical effect takes 1-2 weeks

1. Generalized anxiety disorders
   Side effects:
2. GI distress
3. Tachycardia
4. Paraesthesia
   *Minimal abuse liability

(inhibitory receptor)

Question 4

Melatonin

Answer 4

Regulation of sleep-wake cycle

Oral

1. Sleep disorders
2. Available as over-the-counter drug

Question 5

Ramelteon

Answer 5

Activates MT1, MT2 receptors in the suprachiasmatic nucleus

Oral

1. Sleep disorders (effective for sleep-onset insomnia)
   Side effects:
2. Dizziness, fatigue
3. Endocrine alterations (testosterone ↓, prolactin ↑)

Question 6

Selective serotonin reuptake inhibitors (SSRI’s)

Answer 6

1. Selective inhibition of 5-HT reuptake; allosterically inhibit the transporter, binding at a site other than that of serotonin
2. Minimal inhibitory effects on NE transporter, cholinergic, and adrenergic receptors

Question 7

Drug’s name of SSRI’s

Answer 7

Fluoxetine

(ES)Citalopram

Sertraline

Question 8

Fluoxetine

(ES)Citalopram

Sertraline

Answer 8

Oral

Inhibitors of cytochrome P450 enzymes (fluoxetine most potent)

1. Major depressive disorders
2. Anxiety disorders (GAD – generalized anxiety disorder)
3. Obsessive compulsive disorder (OCD)
4. Post-traumatic stress disorder (PTSD)
5. Premenopausal dysphoric disorder (PMDD)
6. Panic disorders
7. Bulimia

Question 9

Adverse effects

Answer 9

1.Anxiety, agitation*
2.Sleep disorders
3.Bruxism
4.Sexual dysfunction** (mediated by 5-HT2A receptors) – libido↓, anorgasmia, erectile dysfunction
5.Weight gain
6.SIADH
7.Withdrawal syndrome → flu-like symptoms, dizziness, anxiety, tremor, palpitations
*Benzodiazepines (alprazolam) may be given as adjunct therapy in the first few weeks of SSRI treatment, to control anxiety and agitation symptoms
**Potential off-label use of SSRI’s in the management of premature ejaculation

Question 10

Drug interactions

Answer 10

1. Inhibition of P450 enzymes → increased levels of TCA’s, benzodiazepines, warfarin
2. Serotonin syndrome (with MAO inhibitors, TCA’s, meperidine) → muscle rigidity, myoclonus, hyperthermia, CV instability, ANS instability, seizures
   *Citalopram is the agent least frequently associated with drug-drug interactions