Antidepressants Flashcards
Biogenic amine hypothesis of mood disorders
- Patients treated with reserpine developed DEPRESSION
- Thought that biogenic amines were depleted due to reserpine
Ultimately: depression = too little CNS NE and/or 5-HT
Antidepressant drugs tend to block
reupatke of both NE and 5HT, but to VARYING degrees
Pharm effect of antidepressants happens in; clinical improvement happens in
minutes to hours; weeks or months (6-8 wks);
For very severe depression, how are meds viewed relative to placebo?
Thought to be BENEFICIAL for patients with severe depression
Tranylcypromine (Parnate)
Class: MAOI
Mech: Irreversibly inhibit both MAOa (oxidizes mainly NE, 5HT, tyramine) and MAOb (oxidizes DA, phenylethylamine)
Thera: Depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism
Important SE’s: Hypertensive crisis (with tyramine-rich foods) since liver MAO is inhibited and lose first-pass metabolism; serotonin syndrome (MAOI + SSRI) with hyperthermia, muscle rigidity, myoclonus, rapid changes in mental status and vital signs; agitation (rare), delerium –> seizures
Other SE’s: Anticholinergic, orthostatic hypotension, sexual dysfunction, weight gain, sedation
Phenelzine (Nardil)
Class: MAOI
Mech: Irreversibly inhibit both MAOa and MAOb
Thera: Depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism
Important SE’s: Hypertensive crisis (with tyramine-rich foods); serotonin syndrome (MAOI + SSRI); agitation (rare), delerium –> seizures
Other SE’s: Anticholinergic, orthostatic hypotension, sexual dysfunction, weight gain, sedation
Desipramine (Norpramin)
Class: Tricyclic
Mech: Block reuptake of NE or 5-HT at varying potencies and selectivity; use N-demethylation followed by P450 oxidation and then glucuronide conjugation; also variably block muscarinic, a-adrenergic, dopamine, and histamine receptors
Thera: Depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism
Important SE’s: Sympathomimetic with tremor and insomnia (cardiac arrhythmias and conduction defects, especially at OD)
Other SE’s: Antimuscarinic like blurred vision and constipation, orthostatic hypotension, sedation (additive with alcohol), seizures
Misc: Not very safe; rarely used anymore; high protein binding and relatively high lipid solubility and thus a LARGE Vd; active metabolite of imipramine; half life 22 hr
Imipramine (Tofranil)
Same as desipramine, but makes active metabolite that is desipramine; half life of 12 hr
Amitriptyline (Elavil)
Same as desipramine, but makes active metabolite nortriptyline; half life of 21 hr
Nortriptyline (Pamelor)
Half life 31 hr; same as amitriptyline but active metabolite of amitriptyline
Fluoxetine (Prozac)
Class: SSRI
Mech: Inhibit reuptake of 5-HT (and NE to lesser extent)
Thera: Depression, anxiety (GAD, panic, OCD), PTSD, chronic pain, enuresis, bulimia, alcoholism; pre-menstrual dystrophic disorder
Important SE’s: Serotonin syndrom (with MAOIs)
Other SE’s: Fewer than tricyclics with no seizures or cardiac arrhythmia; mostly nausea, decreased sexual function
Misc: Potent P450 inhibitor; forms active metabolite (norfluoxetine)
Paroxetine (Paxil)
Just that there is no thera for pre-menstrual dystrophic disorder; potent P450 inhibitor
Sertraline (Zoloft)
no thera for pre-menstrual dystrophic disorder
Escitalopram (Lexapro)
no thera for pre-menstrual dystrophic disorder
Citalopram (Celexa)
no thera for pre-menstrual dystrophic disorder
Duloxetine (Cymbalta)
Class: SNRI
Venlafaxine (Effexor)
Class: SNRI
Bupropion (Wellbutrin)
Class: Atypical
Mech: Blocks DA (notable selectivity for DAT) and NE reuptake
Thera: Depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism; maintain nicotine abstinence in quitting smokers
Important SE’s: Lowers seizure threshold
Mirtazapine (Remeron)
Class: Atypical
Mech: 5HT2a antagonists; also inhibit 5HT reuptake
Thera: Depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism
Lithium
Mech: Unknown; lithium depletes secondary messengers IP3 and DAG, important in a-adrenergic and muscarinic-cholinergic transmission
Thera: Anti-manic/mood-stabilizing (bipolar); long-term cluster headache prevention
Important SE’s: If elevated levels: neurotoxicity, cardiac toxicity, renal dysfunction
Other SE’s: Drowsiness, weight gain, tremor, polydipsia, polyuria
Misc: Nausea and vomiting early sign of lithium OD; indomethacin and Na-depleting diuretics should be avoided (increase [Li])
Depressive phase of mania often requires what?
concurrent use of antidepressant, usually maoi, with lithium/carbamazepine/valproate (TCA’s might precipitate mania);
LI onset can be slow, so use
benzos; if severe, add benzos or ANTIPSYCHOTIC drugs (pine, done, aripiprazole)
