ANTIDEPRESSANTS-MBBS.pptx by Dr karthiga

ANTIANGINAL DRUGS

1. ANTIDEPRESSANTS Dr M.KARTHIGA M.D., DNB Pharmacology

2. DEPRESSION MOOD Physical and cognitive symptoms NOT JUST BEING SAD !!! >15% The Diagnostic and Statistical Manual of Mental Disorders –DSM - V

3. PATHOGENESIS MONOAMINES THEORY – Noradrenaline, Serotonin, Dopamine NEUROTROPHIC THEORY – Brain derived Neurotrophic factors (BDNF)

4. TRICYCLIC ANTIDEPRESSANTS

5. TRICYCLIC ANTIDEPRESSANTS Neuronal block of SERT/NET/DAT Inhibit the re-uptake of 5HT/NE/DA I ncreased concentration in the synaptic cleft. 3-4 weeks H1 Ach α 2 Adr

6. presynaptic α2 and 5HT1 autoreceptors activated by increased amount of NA/5 HT in the synaptic cleft  decreased firing of locus coeruleus (noradrenergic) and raphe (serotonergic) neurones . After, longterm administration, desensitisation of presynaptic α2 , 5HT1A , 5HT1D autoreceptors  induce other adaptive changes in the number and sensitivity of pre and postsynaptic  net effect of which is enhanced noradrenergic and seroto nergic transmission.

7. In normal individuals – UNPLEASANT - clumsy feeling, tiredness, light headedness, sleepiness, difficulty in concentrating and thinking. In depressed individuals - weeks of continuous treatment, mood is gradually elevated, patients become more communicative and start taking interest in self and surroundings.

8. PHARMACOKINETICS Good but slow highly lipid soluble, Largely bound to tissues and have a relatively long half-life. M - CYP 2D6, 2C19, 3A3/4, 1A2 E- urine for 2 weeks DRUG INTERACTIONS potentiate directly acting sympathomimetic amines (present in cold/asthma remedies). potentiate CNS depressants, including alcohol and antihistaminics . Phenytoin, phenylbutazone, aspirin and CPZ can displace TCAs from protein binding sites and cause transient overdose symptoms. D/t anticholinergic property, delay gastric emptying and retard their own as well as other drug’s absorption.

9. USES Severe major depression

10. T wave suppression or inversion Quinidine-like effects Lower the seizure threshold.

11. MONOAMINE OXIDASE INHIBITORS MAO-A and MAO-B- Phenylethylamine 3 rd line drugs NE, 5HT,DA Tranylcypromine Phenelzine Isocarboxazid . Moclobemide Clorgyline Selegiline

12. M - Acetylation. T1/2 – 24 hrs Effects – 2 weeks USES Moclobemide -Depression unresponsive/ allergic to TCA/elderly/heart No anticholinergic, sedative, cognitive, psychomotor and cardiovascular Selegiline- transdermal patch ADVERSE EFFECTS Hypertensive crisis, Hepatotoxicity, Sexual disturbances, Weight gain Orthostatic hypotension SSRI SNRI TCA

13. SELECTIVE SEROTONIN REUPTAKE INHIBITORS 1st drug fluoxetine available in 1988 Fluoxetine Citalopram Escitalopram Paroxetine Sertraline

14. SSRI Little or no sedation, Do not interfere with cognitive and psychomotor function Devoid of anticholinergic side effects. devoid of α adrenergic blocking action—postural hypo tension does not occur, making them suitable for elderly patients. No seizure precipitating propensity Do not inhibit cardiac conduction—overdose arrhythmias are not a problem

15. Nausea, loose motions nervousness, restlessness, insomnia, anorexia, dyskinesia and headache Epistaxis and echymosis Sexual – dec. libido, erectile dysfunction, anorgasmia, ejaculatory delay – CYP2D6 Inhibitors SEROTONIN SYNDROME  agitation, restlessness, rigidity, hyperthermia, delirium, sweating, twitchings followed by convulsion +TCA/MAOI The SSRIs should not be started until at least 14 days following discontinuation of treatment with an MAOI; this allows for synthesis of the new MAO

16. OCD, PANIC DISORDER, PHOBIA, EATING DISORDER, KLEPTOMANIA

17. SEROTONIN NOREPINEPHRINE REUPTAKE INHIBITORS Duloxetine Venlafaxine Milnacipran Levomilnacipran NO cholinergic, adrenergic or histaminergic receptors or have sedative property

18. VENLAFAXINE – 5(11) HRS DULOXETINE- 12 hrs CYP2D6,3A4 USES Depression,Anxiety , Fibromyalgia and neuropathic pain Off-label Stress urinary incontinence ( duloxetine ) Autism Binge-eating disorders, hot flashes PTSD ( venlafaxine ) ADVERSE EFFECTS Nausea, constipation, insomnia, headaches, sexual dysfunction. DIASTOLIC HYPERTENSION-Venlafaxine BLEEDING- Milnacipran

19. A 51-year-old woman with symptoms of major depression also has angle-closure glaucoma. Which antidepressant should be avoided in this patient? A. Amitriptyline B. Bupropion C. Mirtazapine D. Fluvoxamine

20. ATYPICAL ANTIDEPRESSANTS

21. TRAZADONE, Nefazadone,Vilazadone Less efficiently blocks 5HT uptake, but has prominent α adrenergic and weak 5HT2 antagonistic actions. Metabolite is a strong 5HT2 blocker. M – CYP2D6, 3A4 A/E – Nausea, Inappropriate, prolonged and painful penile erection ( priapism ) Nefazodone - Liver failure The α1 adrenergic blocking property - postural hypotension. Trazodone - depression; associated with insomnia .

22. MIANSERINE MIRTAZAPINE blocks pre synaptic α2 receptors Antagonistic action at 5HT2 , 5HT1c as well as H1 receptors sedative —relieves associated anxiety and suppresses panic attacks seizures in over dose blood dyscrasias and liver dysfunction α2 auto (on NA neurones ) and hetero (on 5HT neurons enhancing both NA and 5HT1 release concurrent blockade of 5HT2 and 5HT3 receptors H1 blocker and moderately strong sedative particularly suitable for those with insomnia Increased weight gain No sexual dysfunction

23. BUPROPION Inhibition of DAT and NET- stimulant activity Hydroxybupropion - Amphetamine like T1/2- 21 hrs CYP2B6 Cautious in renal and hepatic impaired EXTENDED RELEASE

24. BUPROPION ADVERSE EFFECTS Anxiety, mild tachycardia, hypertension, irritability, and tremor. Headache, nausea, dry mouth, constipation, appetite suppression, insomnia, Aggression, impulsivity, and agitation Seizures -dose and Cp, (>450 mg/day) NO SEXUAL DYSFUNCTION . USES Depression Seasonal depressive disorder Smoking cessation treatment ADHD Off label- neuropathic pain and weight loss C/I – Anxiety/eating disorders

25. DEPRESSION Fluoxetine, Sertraline-Juvenile With Antipsychotics-psychotic depression OCD- Kleptomania Body dysmorphic disorder Fluvoxamine(SSRI) Clomipramine Anxiety, phobic disorders, long term treatment of panic attacks and in post traumatic stress disorder (PTSD). Mood swings and hot flashes in menopausal SSRi , SNRI Neuropathic pain –diabetic and postherpetic neuralgia TCA Duloxetine, ADHD Imipramine, nortriptyline and amoxapine Premature ejaculation Clomipramine Dapoxetine Enuresis imipramine Smoking cessation Bupropion Pruritis Doxepin Migraine Amitryptylline

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