Drugs Used in Treatment of Affective Disorders PDF

Pharmacology 2, 2024-2025, Prof. Dr. Marwa Safar DRUGS USED IN TREATMENT OF AFFECTIVE DISORDERS (MOOD DISORDERS) Learning Objectives: Demonstrate understanding of the patho...

Pharmacology 2, 2024-2025, Prof. Dr. Marwa Safar DRUGS USED IN TREATMENT OF AFFECTIVE DISORDERS (MOOD DISORDERS) Learning Objectives: Demonstrate understanding of the pathophysiology of depression and mania. Classify antidepressants according to their mechanism of action. Enumerate clinical uses of antidepressants. Compare side effects of various antidepressants. The affective disorders include depression & mania. 1. Uni-polar depression → patient is always in depressed mood; most common. Signs of depression: Emotional symptoms: sadness, hopelessness, frustration, apathy, feeling of low self-esteem, and loss of motivation and interest in usual activities (anhedonia), feeling of guilt and suicidal thoughts. sex drive Biological symptoms (psychosomatic): loss of libido, sleep disturbances, anorexia, chronic pain. an eating disorder characterized by food restrictio 2. Bipolar depression (manic depressive illness) → it is characterized by occurring episodes of elevated & depressed mood. Signs of mania: enthusiasm,  self-confidence, anger, rapid thought and speech patterns (non-stop talk), impaired judgment. Pathophysiology of Depression “Biogenic amine theory; monoamine theory of mental depression” Depression is due to  of monoamines especially NE and/or 5-HT in brain, whereas mania is due to  monoamines in brain.  expression of brain receptors 5HT2A, 5HT2C Neurotrophic and cytokines theory:  brain neurotrophic factor (BDNF), hypothalamus- pituitary axis dysregulation,  proinflammatory cytokines e.g: IL-1; IL-6; TNF-α Genetic (endogenous; major depressive disorder MDD; may not be associated with easily recognized causes) and social factors (exogenous or reactive depression) are involved. Episodes of MDD may occur at intervals throughout one’s lifetime.  Pharmacology 2, 2024-2025, Prof. Dr. Marwa Safar ANTIDEPRESSANT DRUGS Treatment goal = NA and /or  5-HT in brain. Typical antidepressants: NA and /or  5-HT in brain. Atypical antidepressants: work by other mechanisms. 1. MONOAMINE OXIDASE INHIBITORS (MAOIs) Non-selective irreversible MAO inhibitors (blocks MAOA& MAOB) (Phenelzine, Isocarboxazid, Tranylcypromine). Selective MAOB inhibitors: Selegiline (Only antidepressant available as transdermal patch) MOA: MAOIs  inactivate MAO (reversible or irreversible) metabolism of NA, 5-HT, dopamine →  NA & 5-HT & dopamine leakage of greater amounts into synaptic space → activation of NE and 5-HT receptors → antidepressant effect. to appear disappears after and the effect still exists after stopping N.B. Their antidepressant effect is delayed for 2 weeks or more, and it persists for 2-3 weeks after stopping the drug [time taken for regeneration of a new enzyme]. we wait 2 weeks in case of changing the drugs Contraindications and precautions on use: MAOIs should not be taken with indirect acting sympathomimetics including tyramine that is present in aged cheese, yeast products, smoked fish, herring, chicken liver and red wine Why?? Tyramine (Metabolized by MAO in gut and liver)→ release NE→  blood pressure MAOIs →  NE release  blood pressure Tyramine + MAOIs hypertensive crisis Symptoms of hypertensive crisis: occipital headache, stiff neck, tachycardia, nausea, hypertension, cardiac arrhythmias, seizures, and possibly stroke Management of hypertensive crisis: −blockers e.g. phentolamine Certain sympathetic drugs used in the treatment of cold symptoms (decongestants) interact with MAO inhibitors causing the potentiation of the effect of sympathetic agents. Uses: Last line antidepressants in unresponsive patients The use of MAOI is now limited due to dietary restrictions.  Pharmacology 2, 2024-2025, Prof. Dr. Marwa Safar 2. TRICYCLIC ANTI DEPRESSANTS (TCAs); named after their 3 ringed structure Amitriptyline, Clomipramine, Trimipramine, Nortriptyline, Protriptyline, Imipramine, Desipramine, Doxepin MOA TCAs inhibit the neuronal re-uptake of NE and 5-HT→  NE and 5-HT in the Brain.1 → antidepressant action (elevates mood). Effect is delayed for 2-3 weeks. maximum benefit may require up to 12 weeks or more. 2. Muscarinic antagonists, Have strong Anticholinergic activity “Strong Atropine actions”. 3. H1-blocker “Anti-histaminic” Sedative. 4. α1 blocker USES 1. Depression 2. Nocturnal enuresis (especially IMIPRAMINE due to Anticholinergic=Atropine like actions). 3. Panic disorder. 4. Severe chronic pain as diabetic peripheral neuropathy, trigeminal neuralgia. 5. Insomnia. 6. Prevent migraine (particularly Amitriptyline) Adverse effects: 1. Anticholinergic (Atropine) adverse effects; dry mouth, constipation, urine retention (C.I. in Prostatic patients), tachycardia, blurred vision, aggravating glaucoma,..etc. 2. Sedation due to H1 blocking activity (given at night) 3. Orthostatic (postural) hypotension and reflex tachycardia due to 1 blocking activity. 4. Weight gain. Over dose: 3Cs: Coma (excessive sedation), Convulsions, Cardiac arrhythmias (depress cardiac conduction) N.B. Because depressed patients might attempt suicide, the safety of an antidepressant in overdose is an important consideration when selecting a drug for a particular patient. Treatment of Adverse Effects: arrhythmia can be treated by the intravenous administration of sodium bicarbonate. Sodium bicarbonate increases the ratio of nonionized TCA to ionized TCA and thereby decreases the binding to the sodium channel in cardiac membranes. N.B. 1. Tolerance to the Anticholinergic properties and autonomic effects of the TCAs develops within a short time BUT NO tolerance to the antidepressant effect. 2. Therapeutic index: narrow, Monitoring is essential