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Biological Therapies

Biological Therapies. SSRIs. Fluoxetine Fluvoxamine Paroxetine Citalopram Sertraline escitalopram. SSRIs. Share no molecular features Half life:20 hours&3days Hepatic metabolism Specific activity in the inhibition of serotonin reuptake No activity on other receptors

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Biological Therapies

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  1. Biological Therapies

  2. SSRIs • Fluoxetine • Fluvoxamine • Paroxetine • Citalopram • Sertraline • escitalopram

  3. SSRIs • Share no molecular features • Half life:20 hours&3days • Hepatic metabolism • Specific activity in the inhibition of serotonin reuptake • No activity on other receptors • Occurring 90% of clinical response at the starting dose

  4. Depression Anxiety dis. Eating dis. PMS Premature ejaculation Paraphilias ADHD Autistic dis. chronic pain syndromes. Psychosomatic conditions SSRIsTherapeutic Indications

  5. SSRIs Adverse Effects • Sexual dysfunction • GI effects • Headache • CNS effects • Antichoinergic effects • Hematologic effects • Electrolyte and glucose disturbances • Endocrine and allergic reactions

  6. Hyperthermia shivering Diarrhea Agitation Hyperreflexia Myoclonus Seizures Rigidity Delirium coma Serotonin syndrome

  7. SSRI withdrawal • Dizziness • Weakness • Nausea • Headache • Rebound depression • Anxiety • Insomnia • Poor concentration

  8. SSRIs • Drug-drug interactions • Dosage and administration

  9. Tertiary amines: Imipramine Amitriptyline Trimipramine Doxepine Clomipramine Secondary amines: Desipramine Nortriptyline Protriptyline Tetracyclic drugs: Maprotiline Amoxapine TCAs

  10. TCAs: • Half life :10-70h(longer HL in Nortriptyline,Maprotiline) • Hepatic metabolism • Blocking of reuptake of serotonin and NE • Antagonism of muscarinic,H1,alfa1,2 • Type A antiarrhytmic effects • 40-fold difference in plasma concentrations in different persons

  11. TCAsTherapeutic Indications • MDD • Panic disorder with Agoraphobia • GAD • OCD • Eating dis. • Pain dis. • Sleep dis.

  12. TCAsAdverse Effects • Psychiatric effects • Anticholinergic effects • Sedation • Autonomic effects • Cardiac effects • Neurological effects • Allergic and hematological effects • Weight gain

  13. TCAsDrug – Drug Interactions • Antihypertensives • Antipsychotics • CNS depressants • Sympathomimetics • OCPs • SSRIs • Lithium • Primidon • Ascorbic Acid

  14. MAOIs • Phenelzine • Isocarboxazid • Tranylcypromine • Selegiline

  15. MAOIsTherapeutic Indications • Panic disorder with agoraphobia • Social phobia • PTSD • Atypical depression • Eating dis. • Pain dis.

  16. MAOIsAdverse Reactions • Or HTN • Insomnia • Weight gain • Edema • Sexual dysfunction • Hypertensive crisis • paresthesia.,myoclonus,muscle pain

  17. Tyramine-Rich Foods • Cheese • Fish • Sausage • Pates • Mortadella • banana

  18. drugs to be avoided • Antiasthmatics • Antihypertensives • Buspirone • Levodopa • Opioids • Sympathomimetics • SSRIs • Clomipramine

  19. Mood Stabilizers • Lithium • Sodium Valproate • Carbamazepine • Lamotrigine • Topiramate • Gabapentin • Calcium Channel Inhibitors

  20. lithium • No binding to plasma proteins • No metabolism • Slow crossing BBB • Half- life : 20 hours • Decreasing of renal clearance in renal insufficiency and puerperium / increasing during pregnancy

  21. Lithiumtherapeutic indications • Bipolar mood disorder • Schizophrenia/schizoaffective disorders • MDD • Aggression • PMS • Bulimia • Binge drinking • BPD • OCD • PTSD • Trichotilomania

  22. Lithiummaintenance treatment • After the second episode of BMD1 • After the first episode in : • Adolescents • High suicide risk • Poor support systems • No percipitating factors • Sudden onset • First episode of mania • FH of BMD1

  23. LITHIUMAdverse effects • Gastrointestinal effects • Neurological effects • Renal effects • Cardiac effects • Thyroid effects • Dermatological effects

  24. Lithium toxicity • Coarse tremor • Dysarthria • Ataxia • GI symptoms • Cardiovascular changes • Renal dysfunction • Fasciculations • Myoclonus • Seizures • coma

  25. DAs Anticonvulsants Thiazids Potassium sparing diuretics NSAIDs ACEIs Calcium channel inhibitors Osmotic diuretics Loop diuretics Xantins Carbonic anhydrase inhibitors LITHIUMDrug interactions

  26. LithiumClinical Guidelines • Initial medical work up • Dosage • Serum concentrations • Discontinuation • Patient education

  27. Sodium valproate • Effects on GABA neurotransmitter system. • Therapeutically effective at serum concentrations above 50 -100 microgr/ml • Half-life : 8-17 hours • Maintaining effective plasma concentrations with dosing 1 to 4 times a day

  28. Sodium ValproateTherapeutic Indications • Bipolar 1Disorder (acute – prophylaxis ) • Schizoaffective Disorder • Behavioral dyscontrol syndromes • Dementia • Organic brain diseases • TBI • Other mental disorders

  29. GI effects Sedation Ataxia Dysarthria Tremor Weight gain Hair loss Elevation of liver transaminases Thrombocytopenia Platelet dysfunction Hyponatremia Hepatotoxicity Pancratitis PCO Sodium Valproate Adverse Reactions

  30. Sodium ValproateDrug interactions • Lithium • Carbamazepin • Antidepressants • SDAs • DAs • Phenytoin • Phenobarbital • BZDs

  31. Sodium ValproateAdministration • R/O liver and pancreatic disease • Dose on the first day : 250 mg • plasma concentrations : 50-100 mg/ml • Daily dose : 1200-1500mg • Mood-stabilizing effects appear between 5-15 days after initiation

  32. Carbamazepine • Steady-state levels in 2-4 days on a steady dosage • Half-life : 12-17 h after 1 month of administration • Metabolized in liver • decreasing synoptic transmission • Reduction of currents through NMDA channels • Antagonism of adenosine A1 receptors

  33. Carbamazepine Therapeutic Indications • Bipolar disorder (manic-depressive episodes) • Schizophrenia and schizoaffective disorder • Impulse-control dis. • PTSD • Alcohol and BZD withdrawal

  34. CarbamazepineAdverse Reactions • Blood Dyscrasias • Hepatitis • Exfoliative dermatitis • GI Effects • CNS Effects • Cardiac Effects • Hyponatremia

  35. SSRIs Anti psychotics Cimetidine Erythromycin Isoniazide Ketoconazole Verapamil allopurinol OCP TCAs Na-valproate Bupropion MAOIs Clomipramine Primidone Phenytoin CarbamazepineDrug Interactions

  36. CarbamazepineTreatment • CBC,LFT,ECG,Serum Electrolytes • Initiate with 200mg to 600-1200mg • Anticonvulsant Blood Concentration : 4-12microgr/ml • Laboratory Monitoring :CBC ,Billirubin,LFT,CBZ Level

  37. CarbamazepineTreatment Discontinuation • WBC<3000/mm3 • Erythrocyte Count < 4000000/mm3 • PMN<1500/mm3 • HCT <32% • HB<11gr/100ml • Reticulocyte Count<0.3 % • Serum Iron Concentration,150mg/100ml

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