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بسم الله الرحمن الرحیم Antidepressants Range  Tricyclics  Tetracyclics  SSRI  SNRI  MAOI  Oddities  Adjuvants.

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Presentation on theme: "بسم الله الرحمن الرحیم Antidepressants Range  Tricyclics  Tetracyclics  SSRI  SNRI  MAOI  Oddities  Adjuvants."— Presentation transcript:

1

2 بسم الله الرحمن الرحیم

3 Antidepressants

4 Range  Tricyclics  Tetracyclics  SSRI  SNRI  MAOI  Oddities  Adjuvants

5 Factors Influencing Choice  Features of illness, e.g. agitation, hypersomia  Suicide risk  Other therapy  Other illness.  Side effects  Cost  Special problems e.g. Age, driving, pregnancy

6 Drug Failure  Non compliance.  Inadequate dosage.  Other drugs e.g. alcohol, caffeine.  Unresolved outside problems.  Up to 25% failure even if above don’t apply.

7 Tricyclics & tetracyclics TCAS

8 Imipramine Imipramine Amitriptyline Amitriptyline Tertiary amines Tertiary amines trimipramin trimipramin TCAS Cloimpramine TCAS Cloimpramine Secondary Amines Desipramine Secondary Amines Desipramine Nortriptyline Nortriptyline Tetracyclic Amoxpine Tetracyclic Amoxpine Maprotiline Maprotiline

9 Pharmacokinetics Pharmacokinetics Peak plasma 2-8hr Peak plasma 2-8hr Half- lives hr Half- lives hr P 450 enzyme system P 450 enzyme system

10 Pharmacodynamics Pharmacodynamics Block the reuptake NE Block the reuptake NE 5HT 5HT Antagonists at: Antagonists at: Muscarinic Ach Muscarinic Ach Histamine H1 Histamine H1 alfa 1 adrenergic alfa 1 adrenergic alfa 2 adrenrgic alfa 2 adrenrgic

11 Indications Indications Major depressive dis Major depressive dis Secondary depression Medical dis Secondary depression Medical dis Movement dis Movement dis Dementia Dementia

12 Panic dis ( Imipramine) Panic dis ( Imipramine) Generalized anxiety dis (doxepine) Generalized anxiety dis (doxepine) Obsessive – compulsive dis Obsessive – compulsive dis Clomipramine Clomipramine SSRIs SSRIs Eating dis (imipramine,desipramine) Eating dis (imipramine,desipramine) Pain dis Pain dis Enuresis (Imipramine) Enuresis (Imipramine) Peptic ulcer (doxepin) Peptic ulcer (doxepin) Narcolepsy Narcolepsy

13 Premature Ejaculation ( clomipramine) Premature Ejaculation ( clomipramine) Nightmare Nightmare PTSD PTSD ADHD ADHD Sleepwalking dis Sleepwalking dis Separation anxiety dis Separation anxiety dis Sleep terror Sleep terror

14 Adverse reactions Adverse reactions

15 Psychiatric: Mania Psychiatric: Mania Psychosis Psychosis

16 Anticholinergics: Anticholinergics: Dry mouth ( Gum) Dry mouth ( Gum) Constipation (laxative) Constipation (laxative) Blurred vision Blurred vision Urinary retention (Bethanechol) Urinary retention (Bethanechol) Impotence ( “ ) Impotence ( “ ) Narrow angle glaucoma (mioitc agent) Narrow angle glaucoma (mioitc agent)

17 CNS antichcoli: CNS antichcoli: Confusion ( physostigmine) Confusion ( physostigmine) delirium delirium

18 Sedation Sedation serotonergic serotonergic Cholinergic Cholinergic Histaminergic Histaminergic

19 Autonomic effects Autonomic effects Orthostatic hypotension Orthostatic hypotension (fludrocortisone 0—05mg X2) (fludrocortisone 0—05mg X2) Sweating Sweating Palpitations Palpitations Blood pressure Blood pressure

20 Cardiac effects Cardiac effects Tachycardia Tachycardia Flattened T waves Flattened T waves Prolonged QT Prolonged QT S.T S.T Quinidinelike effect PVC Quinidinelike effect PVC

21 At high plasma concentrations At high plasma concentrations arrhythmogenic arrhythmogenic Hypertensive episodes during surgery Hypertensive episodes during surgery

22 Neurological effects Neurological effects Sedation Sedation Delirium Delirium Psychomotor stimulation Psychomotor stimulation Myoclonic twitches Myoclonic twitches Speech blockage Speech blockage Paresthesia Paresthesia Peroneal palsies Peroneal palsies Ataxia Ataxia Seizure ( maprotiline) Seizure ( maprotiline) Lower the seizure threshold (Clomipramine – Amoxapin) Lower the seizure threshold (Clomipramine – Amoxapin)

23 Allergic effects Allergic effects Exanthematous 4-5%( marprotiline ) Exanthematous 4-5%( marprotiline ) Jaundice Jaundice

24 Hematological effects Hematological effects Agranulocytosis Agranulocytosis Leukocytosis Leukocytosis Leukopenia Leukopenia Eosinophilia Eosinophilia

25 Sore throat CBC Sore throat CBC

26 Other adverse effects Other adverse effects Weight gain Weight gain Impotence Impotence Gynecomastia Gynecomastia Amenorrhea Amenorrhea SIADH SIADH Hepatitis Hepatitis

27 Drug – Drug Interactions Drug – Drug Interactions

28 TCAS Block: propranolol TCAS Block: propranolol Clonidine Clonidine Guanethidine Guanethidine

29 TCAS increas : Antipsychotics level TCAS increas : Antipsychotics level

30 TCAS+ sympathomimetics serious TCAS+ sympathomimetics serious Cardiovascular Cardiovascular effects effects

31 Oral contraceptives TCA Oral contraceptives TCA

32 Acetazolamide Acetazolamide Aspirin Aspirin Cimetidine TCA Cimetidine TCA Thiazide Thiazide Fluoxetine Fluoxetine Sodium bicarbonate Sodium bicarbonate

33 Ascorbic acid Ascorbic acid Ammonium chlorid Ammonium chlorid Barbiturates Barbiturates Cigarette smoking TCA Cigarette smoking TCA Chloral hydrate Chloral hydrate Lithium Lithium Primidone Primidone

34 TCAS additive effects: TCAS additive effects: Opioids Opioids Alcohol Alcohol Anxiolytics Anxiolytics Hypnotics Hypnotics Over – the – counter cold Over – the – counter cold

35 Guidelines Guidelines CBC CBC LFT LFT Electrolytes Electrolytes ECG ECG

36 Dosage Dosage TCAS: mg TCAS: mg Nortriptyl : mg Nortriptyl : mg

37 Overdose Attempts Agitation Agitation Delirium Delirium Convulsions Convulsions Hyperactive deep tendon reflex's Hyperactive deep tendon reflex's Bowel and bladder paralysis Bowel and bladder paralysis Dysregulation of (BP) and temperature Dysregulation of (BP) and temperature Mydriasis Mydriasis Coma Coma Respiratory depression Respiratory depression Cardiac arrhythmias (3-4days) Cardiac arrhythmias (3-4days)

38 Treatment – resistant Depression Treatment – resistant Depression Lithium ( mg) Lithium ( mg) Liothyronine( T3 ) ( mg) Liothyronine( T3 ) ( mg) T4 T4

39  Selective Serotonin reuptake Inhibitors  SSRIs

40  SSRIs Fluoxetine  Fluvoxamine  Paroxetine  Sertraline  Citalopram  Escitalopram

41  Indication  Depression Sertraline Fluoxetine  Obsessive – Compulsive Disorder  (OCD) Floxentine  Panic dis citalopram  Eating dis Bulimia Fluoxetine  Anorexia Fluoxetine  B.P.D  Social phobia Paroxetine  PTSD  PMS  Premataure EjaculationFluoxtine  Sertraline

42  Sexual obsessions  ADHD  Autistic dis Fluoxetine  Neuropathic pain  Fibromyalgia  Headache  Psychosomatic conditions Fluoxetine  Syncope sertraline  CopD sertraline

43  Pharmacokinetics  half life = 1-3 days  metabolized : liver  P4 5O – Cyp 2D6

44  Pharmacodynamics   Inhibition of serotonin Reuptake

45  Augmentation Strategies

46  Pregnancy   Fluoxetine IQ  Language delays  Behavioral problems  Neonatal Jitteriness  Tachypnea

47 Depression in Mechicallyill Dression in Mechicallyill Treatment of Depression Excessive Physical morbidity Myocardial Infarction Prolonged hospitalization Death  Depression in Medically ill

48  Fluoxetine mg  Sertraline mg  Paroxetine mg  Citalopram mg  Fluvoxamine mg

49  Adverse Reactions  ¾ no side effects  10-15% no tolerate

50  Sexual dysfunction  Inhibited orgasm  Decreased libido  Bupropion  Yohimbine  Cyproheptadine  Bromocriptine  Amantadine  Sildenafil  Amphetamine(5mg) 

51  Gastrointestinal adverse effects  Nausea  Diarrhea  Anorexia  Vomiting  Dyspepsia

52 Weight gain  Paroxetine

53  Headaches  18-20%  Fluoxetine

54  Anxiety  Fluoxetine

55  Insomnia  Fluoxetine  Benzodiazepines  Trazodone

56 –Sedation Citalopram – Paroxetine –Bupropion

57  Vivid Dreams

58  Seizures – %  Fluoxetine >100mg

59  Extrapyramidal symptoms  Tremor 5-10% – Akathisia  Dystonia  Cogwheel rigidity  Torticollis  Opisthotonos  Gait dis  Bradykinesia  Tardive Dyskinesia  Bruxism (Buspirone)

60  Anticholinergic effects  Paroxetine  Dry mouth  Constipation  Sedation

61  Hematological adverse effects  Paroxetine  Fluoxetine  Increase Bruisability  Neutropenia

62  Electrolyte  Glucose concentration  Hyponatremia  Secretion of inappropriate antidiuretic  Hormone ( SIADH)

63  Endocrine  Prolactin mammoplasia Galactorrhea

64  Allergic reactions  Rashes  Pulmonary system(fibrotic)  Dyspnea

65  Serotonin syndrome  MAOIS  L-tryptophan  Lithium  Diarrhea  Restlessness  Extreme agitation  Hyperreflexia  Autonomic instability

66  Myoclonus  Seizures  Hyperthermia  Shivering  Rigidity  Delirium  Coma  Status epilepticus  Cardiovascular collaps  Death

67 Supportive care Nitrvoglycerine Cyproheptadine Methysergide Cooling blankets Chlorpromazine Dantrolene Benzodiazepines Articonvulsants Mechanical ventilation Paralyzing agents

68 SSRI Withdrawal Dizziness Weakness Nausea Headache Anxiety Insomnia Poor concentration Upper respiratory symptoms Paresthesia Migrain like symptome

69  Drug – Drug interactions

70  Fluoxetine Carbamazepine Antineoplastic A. Diazepam Phenytoin Warfarin

71  Sertraline PT

72  Paroxetine PT CPP 2D6 Antidepressants Phenothiazines Antiarrhythmic d.

73  Fluvoxamine  Most Risk for interactions

74

75  venlafexine, Effexor®  1st available as IR, not well tolerated  Approval of XR resulted in better tolerance at higher doses better efficacy  Available in mg caps  Dose range in XR form  Half life 5 hours steady state in 3 days, longer with XR preparation  Very effective with comorbid depression and anxiety, OCD, panic

76  Anti-anxiety effect present at higher doses >150mg QD  No weight gain  Rare sedation  Dizziness, lightheaded, restless, disturbed sleep more common  Sweating, headaches  Side effects are usually transient at onset of treatment

77  Duloxitine, Cymbalta®  Newest addition to SSRI/SNRI group  Available mg caps  Dose range mg QD  Marketed as effective for patients with somatic/pain issues  More efficacious SNRI mg for mg than venlafexine

78  Very useful in the elderly with chronic pain, discomfort  Effective with FMS  As effective as venlafexine in anxiety, panic  Not as efficacious as venlafexine in OCD, by experience  Well tolerated, no sedation, weight gain  Dry mouth, headaches, restless, insomnia dose related

79  buproprion, Wellbutrin SR, XL®  SNRI & dopamine reuptake inhibitor  Available SR, IR, XL, tabs  Dosage range mg QD rarely exceeds 300mg QD  Half life 20 hours, steady state 2-4 weeks  Effective for depression with low mood, energy and motivation, (anhedonia)

80  Effective at addressing cognitive symptoms associated with mood disorders.  Improves attention and concentration and mental energy.  Well tolerated no sedation, weight gain, no sexual dysfunction  Headaches, restless, rare agitation, insomnia

81 Venlafaxine  Selective Serotonin and noradrenaline reuptake inhibitor – like amitryptyline.  Few other effects – unlike amitryptyline.  mg / day minimum  Dry mouth, somnolence, high BP, nausea, headache and dizziness.

82  The old ones block peripheral MAOI ( B ) and central MAOI (A) so a low tyramine diet is needed. ? Obsolete. Moclobemide.  Only MAOI-A.  ? Role.  ? Special place in anxiety disorder.  mg / day.

83 Trazodone.  Unique structure.  Low cardiotoxicity, few anticholinergic side effects.  Drowsiness +.  Nausea.  150 mg /day.


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