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12. antidepressants
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- 2. Classification ● 1. Tricyclicand tetracyclic antidepressants (TCA) ● 2. Selective serotonin reuptake inhibitors (SSRI) ● 3. Monoamine oxidase inhibitors (MAO inhibitors) ● 4. Selective serotonin -norepinephrine reuptake inhibitors (SSNRI) ● 5. Dopamine norepinephrine reuptake inhibitors (DNRI)
- 3. 1. Tricyclic Antidepressants ●Drug ● Amitriptyline ● Clomipramine ● Desipramine ● Doxepin ● Imipramine ● Nortriptyline ● Dose Ranges ● 50-300mg/day ● 50-300mg/day ● 50-300mg/day ● 50-300mg/day ● 50-300mg/day ● 20-150mg/day
- 4. 1. Tricyclic andtetracyclic antidepressants ● Mechanism of action ● Block the reuptake of serotonin and norepinephrine at presynaptic nerve ending ● Also block muscarinic, histaminic and alpha adrenergic receptors ● Metabolized by liver and excreted through kidneys ● Drug levels are increased by drugs that inhibit the cytochrome p450
- 5. 1. Tricyclic andtetracyclic antidepressants ● Indications ● Major depressive disorder ● Panic disorder ● Generalized anxiety disorder ● Post traumatic stress disorder ● Obsessive compulsive disorder ● Panic syndromes
- 6. 1. Tricyclic andtetracyclic antidepressants Adverse Effects ● Peripheral: ● Anticholinergic effects: constipation, urinary hesitancy, dry mouth and blurred vision ● Antihistaminic effects: sedation, weight gain ● Alpha adrenergic effects: orthostatic hypotension and reflex tachycardia ● Cardiac effects:most worrisome : prolong QT interval, flatten T waves, ST segment depression may also increase premature ventricular contractions
- 7. 1. TCA Continue ●Allergic and hematologic: Rashes,agranulocytosis, leukopaenia and eosinophilia ● Central Effects: ● Tremors and lowering of seizure threshold
- 8. 2. Monoamine oxidaseinhibitors ● Drug ● Isocarboxazid ● Phenelzine ● tranylpromine ● Dose Ranges mg/day ● 10-50 ● 15-90 ● 20-90
- 9. 2. Monoamine oxidaseinhibitors ● Mechanism of action ● Monoamine oxidase is an enzyme which degrades serotonin, dopamine, tyramine and norepinephrine ● Block this enzyme ● Two types of mono amine oxidase A and B ● MAO-A brain, liver , gut and sympathetic nerves ● MAO-B brain , liver and platelets
- 10. 2. MAO inhibitorscontinued ● Indications ● Depression with anxiety symptoms ● Panic disorders ● Agoraphobia ● Social phobia PTSD ● Bulimia nervosa ● Atypical depression
- 11. 2. MAO inhibitorscontinued ● Adverse effects ● Anticholinergic ● Antihistaminic ● Alpha adrenergic blockage ● Most worrisome is the ingestion of tyramine containing food concomitantly which may precipitate severe hypertensive crises ● Patients encouraged to avoid such foods ● Patients advised to seek immediate medical attention when symptoms of crisis appear I.e headache,
- 12. 2. MAO Inhibitorscontinue ● Can be treated with nefidipine 10mg tablet or intravenous phentolamine ● The following foods should be avoided: ● Cheese, fish, meat, caviar, salami, sausages, overripe or canned fruits,yeast extracts or fermented products, chocolate, colas, tea, coffee, soya sauce, beer, wine ● Drugs: OTC pain medication,cold and allergy med, cough preparations, decongestants, inhalers, stimulants, diet pills and SSRI
- 13. 3. Selective serotoninreuptake inhibitors ● Drug ● Citalopram ● Escitalopram ● Fluoxetine ● Fluvoxamine ● Paroxetine ● Sertraline ● Dose Ranges mg/day ● 10-60 ● 10-30 ● 20-80 ● 100-300 ● 20-50 ● 50-200
- 14. 3. Selective serotoninreuptake inhibitors ● Mechanism of action ● Selectively inhibit the the reuptake of 5HT at presynaptic neuron ● They lack the side effects of TCA caused by blockage of muscarinic, alpha adrenergic and histaminic ● Therefore they are the most widely prescribed and better tolerated
- 15. 3. SSRI Continued ●Indications ● Major depressive disorder ● Obsessive compulsive disorder ● Social anxiety disorder ● Panic disorder ● Generalized anxiety disorder ● Post traumatic stress disorder
- 16. 3. SSRI Continued ●Premenstrual phosphoric syndrome ● Bulimia nervosa
- 17. 3. SSRI Continued ●Adverse Effects ● Largely dose related ● Central ● Restlessness, anxiety, muscle tension, insomnia and headache ● Sedation, vivid dreams
- 18. 3. SSRI continued ●Peripherally ● GIT: loose bowel movements ● GUT: decrease libido, delay ejaculation and anorgasmia ● Rare cases of serotonin syndrome reported when patients take two or more drugs boosting serotonin levels ● Presents with restlessness, lethargy, mental confusion, flushing, sweating, tremors and myoclonic jerks. Later develop hyperthermia, hypertonicity, rhabdomyolysis, renal failure and
- 19. 3. SSRI continued ●Inhibit cytochrome p450 isoenzyme therefore can lead to increase in drugs metabolized by this system ● Safe to use in pregnancy but should be avoided in breastfeeding ● May not be used concurrently with MAO inhibitors
- 20. 4. Selective serotonin-norepinephrine reuptake inhibitors ● Drugs ● Venlafaxine ● Duloxetine ● Desvenlafaxine ● Dose Ranges mg/day ● 75-350 ● 40-60
- 21. 4. SNRI Continued ●Indications: ● Major depressive disorder ● Generalized anxiety disorder ● Social anxiety ● Panic disorders ● ADHD ● Dual diagnosis of cocaine dependence
- 22. 4. SNRI continued ●Mechanism of action ● Potent inhibitors of serotonin and norepinephrine reuptake ● No activity on other receptors Adverse Effects ● Similar to SSRI
- 23. 5. Dopamine norepinephrinereuptake inhibitors ● Drug ● Bupropion ● Dose range mg/day ● 150-450
- 24. 5. DNRI Continued ●Mechanism of action ● Inhibits the reuptake of dopamine and norepinephrine ● Indications ● Major depressive disorder ● Smoke cessation ● ADHD
- 25. 5. DNRI Continued ●Well tolerated ● Has minimal effects on weight gain, cardiac conduction or sexual dysfunction ● Adverse Effects ● Central ● Headaches, anxiety, tremors, insomnia, sweating, seizures at higher doses.
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