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I) Tricyclic Antidepressents:TCA:
- 3ry amines; old generation more selective to 5HT reuptake inhibition are: imipramine, trimipramine, clomipramine, amitriptyline, and doxepin( potent H1 blocking agent).
- 2ry amines; new generation more selective to NE reuptake inhibition are: nortriptyline, protriptyline, maprotiline, desipramine, and amoxapine(can block DA receptor causing Park-like effect).
MOA: they block NE and 5HT reuptake, thus increase their levels. Plus they inhibit histaminergic, cholinergic, alpha adrenergic receptors.
It requires weeks to give antidepressent effect. And alpha blocking effect will subside withing few weeks.
It is used in; enursis, tics, neuropathic pain, ADHD, and depression.
Avoid adrupt D/C, taper down 25% of dose every week.
Side effects: Must monitor since NTR
Anticholinergic, CV due to NE reuptake inhibition, sedation due to H1 blocking effect thuse give at bed time, OH and reflex tachycardia due to alpha inhibition, Wt gain, skin rashes and leukopenia.

Drugs; citalopram-escitalopram(least DDI), paroxetine(sedative give at bed time), fluoxetine(wt loss &only approved for pediatrics)-fluvoxamine(most DDI), and sertraline.
MOA: it inhibits 5HT reuptake and stimulate 5HT1-2A for antidepressent effect. It needs 80% of receptor to be bound for effect.
Used in OCD, panic, and depression.
We need a washout period btw SSRI and TCA about 2 weeks, and between SSRI-MAOI about 4-6 weeks to avoid Serotonin syndrome.
Serotonin Syndrome: muscle twitches, hyperreflexia, sweating, penile erection, shivering, tremors, seizure, and coma. Once occuring D/C drugs causing it. ( with ergots, triptans, maoi, buspirone.......)
Side effects: due to 5HT3 -2C
N&V, HA, rash, sexual dysfunction, insomnia, suicidal attempts, and SIADH(dilutional hypoNa).
Treatment is for 6 months.

Drugs; phenelzine, isocarboxazid(hepatic damage), and tranylcypromine.
MOA: inhibit mono aminase oxidase, thus inhibit breakdown of NE, 5HT, and DA. Irreversible and non-selective.
Used in atypical and refractory depression. Washout periods are required.
Side effects: OH, wt gain, edema, and sexual dysfunction. drowsiness, blurred vision, mouth dryness, constipation, and dysuria.
HTN CRISIS: due to tyramine+ MAOI interaction; HA, tachycardia, HTN, N&V, neck stiffeness, photophobia and nose bleeds. Treat with alpha 1 blocker.
Food with tyramine: aged cheese, soya beans, smoked fish or meat, wine, fava beans and some drugs that cause constriction.

Drugs: venlafaxine, desvenlafaxine, and duloxetine.
MOA: inhibits 5 HT, and NE reuptake. NE reuptake inhibition is weak at first and as we increase the dose it increases.
SR formulations are present.
Uses: depression after failure of first line, diabetic neuropathy, GAD, fibromalgia, chronic fatigue syndrome.
SE: nausea, HA, anixety, dry mouth, sweating, sexual dysfunction, HTN.

Drugs:trazodone, nefazodone
MOA: trazodone increases 5 HT release and decrease its uptake unclearly, plus it blocks alpha 1 and histamine receptors. And nefazodone increase sertonin by antognistic activity against 5HT2.
Uses in post partum depression, resistant depression, and severe depression.
SE: sedation less with nefa, OH less with nefa, sexual dysfn less with nefa, N&V& C, and hepatotoxicity with nefa.
Those increase with high doses.
Drugs: bupropion
MOA: inhibit reuptake of NE, DA and maybe 5HT. SR formulation present but with multiple doses.
Used in depression and smoking cessation, contraindicated in seizure, bulimia and aneroxia
SE: seizure at high doses, sweating, dizz, tremor and dry mouth.

VII) Mirtazapine:
MOA: inhibits alpha 2 presynapticly , blocks histamine and 5 HT2C but avoids 5HT2/3 rec so less SE.
Adjust in hepatic and renal.
SE: somlenace, dizz, dry mouth, constipation, and weight gain.…...

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