A/26. Non benzodiazepine anxiolytics and non-benzodiazepine hypnotics. Pharmacotherapy of anxiety disorders. Flashcards
Drugs need to know in this topic
zolpidem
zaleplon
melatonin
ramelteon
buspirone
Zaleplon
Zolpidem
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
- 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)
Buspirone
5-HT1A partial agonist
Oral
The onset of clinical effect takes 1-2 weeks
- Generalized anxiety disorders
Side effects: - GI distress
- Tachycardia
- Paraesthesia
*Minimal abuse liability
(inhibitory receptor)
Melatonin
Regulation of sleep-wake cycle
Oral
- Sleep disorders
- Available as over-the-counter drug
Ramelteon
Activates MT1, MT2 receptors in the suprachiasmatic nucleus
Oral
- Sleep disorders (effective for sleep-onset insomnia)
Side effects: - Dizziness, fatigue
- Endocrine alterations (testosterone ↓, prolactin ↑)
Selective serotonin reuptake inhibitors (SSRI’s)
- Selective inhibition of 5-HT reuptake; allosterically inhibit the transporter, binding at a site other than that of serotonin
- Minimal inhibitory effects on NE transporter, cholinergic, and adrenergic receptors
Drug’s name of SSRI’s
Fluoxetine
(ES)Citalopram
Sertraline
Fluoxetine
(ES)Citalopram
Sertraline
Oral
Inhibitors of cytochrome P450 enzymes (fluoxetine most potent)
- Major depressive disorders
- Anxiety disorders (GAD – generalized anxiety disorder)
- Obsessive compulsive disorder (OCD)
- Post-traumatic stress disorder (PTSD)
- Premenopausal dysphoric disorder (PMDD)
- Panic disorders
- Bulimia
Adverse effects
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
Drug interactions
- Inhibition of P450 enzymes → increased levels of TCA’s, benzodiazepines, warfarin
-
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