Tricyclic Mechanism, Pkin/DDI,

M: Tertiary: Imipramine, Comipramine, amitriptyline - inhibit amine reuptake 5-HT>NE

Secondary: Nortriptyline, desipramine - inhibit amine reuptake NE>>5-HT

PKin/DDI: Big first pass effect, active metabolites, elim via glucuronidation & renal elim, inhibitor + substrate of many CYP450, serotonin syndrome if combined

Tricyclic Adverse Effects

Affect several different receptors

Na: AV Blocks, arrhythmias

M: Vomiting, dry mouth, constipation, urinary retention, blurred vision

Adren-blck: orthost. hypot, reflex tachy

5-HT block: sedation, weight gain

D-blck: akathisia, parkinsonism

Endo: impaired sex fxn, mania in bipolar

OD: Seizures, coma, arrhythmias, death

Amitriptyline>imipramine>desipramine

1. Clomipramine - OCD
2. Anxiety
3. Enuresis
4. Chronic Pain
5. ADHD (Atomoxetine [Straterra])
6. Smoking Cessation

SSRI Mechanisms, Pkin/DDI

Fluoxetine, Paroxetine, Sertraline, Escitalopram, Fluvoxamine, Citalopram

M: Inhibit amine reuptake - 5-HT

Pkin/DDI: Fluoxetine acive metabolite, T_1/2 7-9 days.

-Inhibition of CYP450

-Serotonin syndrome - SSRI + amphetamines, buspirone, cocaine, dextromethorphan, lithium, MAOI, meperidine, St. John's Wort, tryptophan - Seizures, CV instability, hyperthermia, myoclonus

-Insomnia, anxiety, diarrhea, nausea, impaired sexual dysfxn

-antiplatelet

-weight changes

-hyponatremia in elderly

-increased suicide in teens

-switch to mania in bipolar patients

-OD - fatalities rare if solo

-Seizure rare and only for fluoxetine

-fluvoxamine and paroxetine are sedating

1. PMDD - fluoxetine
2. OCD - fluoxetine, fluvoxamine
3. GAD & Phobia - paroxetine
4. Bulimia Nervosa - fluoxetine
5. Discontinuation - grip of side effects for 1-several weeks

Bupropion (Wellbutrin)

Mechanism, adverse, pkin/ddi, other uses

M: unknown, NE/dopa reuptake inhibitor

Adverse: nausea, weight loss, sweating, shaking, seizures, retlessness, LEAST sex dysfxn, OD: seizures, arrhythmias

PKin/DDI: CYP2B6 (?)

Other uses: smoking cessation, SAD, ADHD

MAOI - phenelzine

Mech./adverse/pkin/ddi/other uses

M: inhibit MAO A and MAO B (NE, 5-HT, tyramine, dopamine [B])

A: headache, drowsiness, dry mouth, weight gain, postural hypotension, sexual disturbances, potential excess tyramine, OD: agitation, delirium, seizures, shock, hyperthermia

Pkin/DDI: acetylated, effect continues for 2-3 wks after d/c, serotonin syndrome (w/SSRI, cold meds)

Other: MAO-B inhibitor Selegiline used in Parkinson's

Trazodone, nefazodone

Mech/adverse/pkin/ddi/other

M:presynaptic 5-HT receptor antagonist, histamine antagonist, weak 5-HT reuptake inhibitor

A: strong hypnotic, priapism, limited sex dysfxn, OD: hypotension, excessive sedation, seizure for nefazodone

Pkin/DDI: Short t1/2, substrate/inhibitor of CYP

Other: trazodone best to induce sleep,

Nefazodone effective as SSRIs, less sexual dysfxn, more hypnotic

Venlafaxine

Mech/adverse/pkin/other

M: 5-HT reuptake inhibitor, NE reuptake @ higher dose

P: short T1/2

A: hypertension, sweating, dizziness, nausea, impotence, hyponatremia, bleeding, mydriasis (bad for glaucoma pts), OD: agitation, convulsions, drowsiness, extreme tiredness or weakness, fast heartbeat, tingling, burning, trembling

Duloxetine

mech, pkin/ddi, other uses

Mech: 5-HT & NE reuptake inhibitor

Pkin/DDI: CYP metabolism, renal excretion, dose adjust in renal/hepatic dysfxn

Other uses: diabetic peripheral neuropathic pain, generalized anxiety disorder

Nausea, insomnia, loss of appetite/weight, sweating, sexual dysfxn

Increased BP - 2mmHG

Mydriasis - bad in narrow-angle glaucoma

OD: serotonin syndrome, somnolence, comiting, seizures - deaths rare

Mirtazapine

mech, pkin/ddi, other uses

Mech: presynaptic "inhibition of inhibion" of 5-HT release via block of 5-HT_1,2 presyn. alpha-2 antagonist, histamine H₁ antagonist

Pkin/ddi: CYP elimination

Other: add-on med to enhance effectiveness of other agents in severe depression.  LESS sexual dysfxn

Mirtazapine

adverse effects

Sedation (H₁-mediated)

increased appetite/weight

occasional ortho hypo (alpha-1 block peripherally)

OD: safe

Serotonin Syndrome

causes, sx

Cause: too much serotonin due to combo of SSRIs/tricyclics with other drugs, St. John's Wort

Sx: Seizures, CV instability, hyperthermia, myoclonus