بسم الله الرحمن الرحيم

1. بسم الله الرحمن الرحيم ِAnti-depressants

3. Tricyclic antidepressants • Mixed serotonin & norepinephrine reuptake inhibitors. Tertiary amines • Amitriptyline, Imipramine. Secondary amines • Desipramine, Nortriptyline. • the potency and selectivity of TCAs for the inhibition of reuptake of NE and 5-HT vary greatly among these agents. • affect other receptor systems including the anticholinergic, neurologic, and cardiovascular systems, adverse events are reported frequently during TCA therapy.

4. Parmacokinetics: • absorbed rapidly after oral administration. • Bioavailability is low (30% to 70% for most TCAs) due to the first-pass effect, which shows great interindividual variation. • They are bound extensively and strongly to plasma proteins. • Metabolized in the liver by CYP450.

5. A.E: • Adverse effects of any TCA would be additive with those of other drugs with similar pharmacologic effects (e.g., anticholinergic, sedative, or hypotensive drugs).

6. Drugs Interactions:

8. SELECTIVE SEROTONIN REUPTAKE INHIBITORS: • The efficacy of SSRIs to equal to the TCAs in treating patients with major depression. • Have a low affinity for histaminic, á1-adrenergic, and muscarinic receptors, so fewer adverse effects than the TCAs, and are not associated with weight gain. • E.g. Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine.

9. A.E: • Gastrointestinal symptoms (i.e., nausea, vomiting, and diarrhea). • Sexual dysfunction in both males and females. • Headache, insomnia and fatigue. • Increase in anxiety symptoms or agitation early in treatment.

10. Pharmacokinetics: • Different chemical structures & p.kinetic profile. • Escitalopram, and citalopram, are extensively bound to plasma proteins (94% to 99%) except fluvoxamine. • extensively distributed to the tissues. • May have a nonlinear pattern of drug accumulation with long-term administration (except citalopram). • Metabolized through cytochrome P450 system, 2D6 and 3A4. • Liver & renal impairment.

11. Drug interactions:

13. MONOAMINE OXIDASE INHIBITORS: • MAOIs inhibit the MAO enzyme increasing the concentrations of NE, 5-HT, and DA within the neuronal synapse. • Phenelzine and tranylcypromine, are nonselective inhibitors of MAO A and MAO B.

14. A.E: • most common adverse effect of MAOIs is postural hypotension (espphenelzine) minimized through divided dosage scheduling. • Anticholinergic side effects, especially dry mouth and constipation. • Sedation & insomnia. • Hypertensive crisis with tyramine containing foods (occipital headache, stiff neck, nausea, vomiting, sweating, and sharply elevated blood pressure.

16. Refractory Patients. • No adequate response in 6-8 weeks.

17. Bipolar disorders • acute mania in bipolar I, Lithium, divalproex sodium) and olanzapine Administration (FDA) for the treatment of disorder, and lithium and lamotrigine are approved for the maintenance treatment. • Lithium is the drug of choice for classic bipolar disorder, whereas valproate has better efficacy for mixed states and rapid cycling compared to lithium. • Carbamazepine and oxcarbazepine are not approved for bipolar disorder, but an alternative treatments (or adjunctive agents) for acute mania and maintenance therapy.