Term
| what are the tertiary tricyclic antidepressants (decreased 5HT uptake > decreased NE uptake)? |
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Definition
| amitriptyline, amoxapine, clomipramine, doxepin, imipramine, maprotiline, and trimipramine |
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Term
| what are the secondary tricyclic antidepressants (decreased 5HT uptake < decreased NE uptake)? |
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Definition
| desipramine, nortriptyline, protriptyline |
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Term
| what are the selective serotonin reuptake inhibitors (decreased 5HT uptake >>> decreased NE uptake)? |
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Definition
| citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and tianeptine |
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Term
| what are the serotonin norepinephrine reuptake inhibitors? |
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Definition
| desvenlafaxine, duloxetine, mirtazapine, minacipran, and venlafaxine |
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Term
| what are the "other" antidepressants? |
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Definition
| bupropion, nefazodone, reboxetine, trazodone |
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Term
| what are the MAOI antidepressants? |
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Definition
| isocarboxazid, moclobemide, phenelzine, and tranylcypromine |
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Term
| what is the biogenic amine theory of depression? |
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Definition
| early theory: depression results from depletion of central catecholamines (reserpine, an antihypertensive depletes presynaptic NE in blood vessels and pts on it were depressed/depression ceased when drug was d/c'ed + amphetamine/cocaine increase synaptic catecholamines and mood). current theory: depressed pts have upregulated post-synaptic 5-HT (5-HT1A/5-HT2) and/or adrenergic receptors (alpha1/beta). elevated levels of synaptic biogenic amines, as produced by antidepressant drugs eventually induce downregulation of these post-synaptic 5-HT and/or adrenergic receptors (takes 1-4 wks). |
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Term
| what is the major mechanism for TCAs in the adrenergic vs cholinergic systems? |
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Definition
| inactivation of the adrenergic system: reuptake. cholinergic system: enzymatic-break down via acetylcholinesterase |
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Term
| what are possible clinical consequences of blocking NE uptake? |
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Definition
| tremors, tachycardia, erectile/ejaculatory dysfunction, augmentation of pressor effects of sympathomimetic amines |
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Term
| what are possible clinical consequences of blocking serotonin uptake? |
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Definition
| GI disturbances, increase/decrease in anxiety (dose dependent), sexual dysfunction, EPRs, interactions w/tryptophan/MOAI |
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Term
| what are possible clinical consequences of blocking DA uptake? |
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Definition
| psychomotor activation, antiparkinsonian effect, aggravation of psychosis |
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Term
| what are possible clinical consequences of blocking H1 uptake? |
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Definition
| potentiation of central depressant drugs, sedation drowsiness, wt gain, hypotension |
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Term
| what are possible clinical consequences of blocking muscarinic receptors? |
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Definition
| blurred vision, dry mouth, sinus tachycardia, constipation, urinary retention, memory dysfunction |
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Term
| what are possible clinical consequences of blocking alpha 1 adrenergic receptors? |
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Definition
| potentiation of antihypertensive effect of labetalol etc, postural hypotension, dizziness, reflex tachycardia |
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Term
| what are possible clinical consequences of blocking D2 receptors? |
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Definition
| EPRs, endocrine disorders, sexual dysfunction in males |
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Term
| what actions do SSRIs have less of? |
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Definition
| histamine, muscarinic, and alpha-1 blocking action - but these are not necessary to tx depression and the lack thereof may make SSRIs more attractive to some pts. |
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Term
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Definition
| prominent, persistent depressed or dysphoric mood which interferes w/daily functioning (>2 wks). pts may exhibit: appetite changes, fatigue, feelings of guilt/worthlessness, loss of interest in usual activities/decreased sex drive, psychomotor agitation/retardation, sleep changes, slowed thinking/impaired concentration, suicide attempts/ideation. |
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Term
| what are the types of major depressive disorders? |
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Definition
| *primary/endogenous: no clear identifiable cause, occurs at any age, possible genetic factors (25%). *secondary: physical problems (MI/CA), drugs (antiHTNsives), stress (death of a child), psychological disorders (bulimia, OCD, severe anxiety syndrome). *bipolar (manic-depression - 15%). *OCD (esp responsive to SSIs/tertiary TCAs). *pain (best response to TCAs - membrane stabilizing). *enuresis (TCAs - prob due to anticholinergic). *other: fibromyalgia, migraines, IBS, sleep apnea. |
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Term
| what is the effect of TCA administration? |
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Definition
| alpha-1 adrenergic blocking activity, anticholinergic (greater w/tertiary TCAs), blockade of presynaptic reuptake: primarily 5HT for tertiary TCAs and primarily NE for secondary TCAs. |
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Term
| what are the anticholinergic ADRs associated w/TCAs? |
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Definition
| blurred vision, paralysis of accommodation (may precipitate glaucoma attack in pts w/narrow-angle glaucoma), constipation, urinary retention, dry mouth. |
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Term
| what are the CV ADRs associated w/TCAs? |
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Definition
| direct depression of myocardium, prolonged conduction time (may cause ventricular arrhythmias), tachycardia, orthostatic hypotension (alpha-1 ABA) |
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Term
| what are the CNS ADRs associated w/TCAs? |
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Definition
| confusion, delirium, sedation (> 30% in pts >50 y/o - more likely w/tertiary TCAs), dizziness, hypomanic/manic excitement (switch process), seizures (more w/maprotiline), tremors (10%) |
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Term
| what are the "other" ADRs associated w/TCAs? |
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Definition
| agranulocytosis, interference w/orgasm, jaundice, rash, sweating (paradoxical), wt gain (may be related to increased appetite/NS w/fluoxetine) |
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Term
| what are serotonergic disorders? |
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Definition
| eating, impulse control, obsessive compulsive, panic, personality - all indications for SSRIs |
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Term
| how do SSRIs compare to TCAs? |
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Definition
| less anticholinergic activity/sedation. less hypotension (less alpha-1 ABA) no substantial cardiac conduction effects. anorexia w/wt loss. higher incidence of akathisia. |
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Term
| what characterizes fluoxetine? |
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Definition
| this SSRI is a strong inhibitor of 5-HT uptake at the presynaptic membrane and has a t1/2 of 2-3 days. it is biotransformed into norfluoxetine, an equally effective blocker of 5-HT uptake, which has a t1/2 of 7-9 days. both appear to be strong inhibitors of CYP = inhibition of hydroxylation/demethylation, which can cause a significant elevation in TCA blood levels. therefore, if the pt is on both, decrease TCA dosage by 25% and monitor blood levels 1-2x/wk for several months until stability occurs. fluoxetine may interact w/other protein-bound drugs, increasing the t1/2 of diazepam and ADRs of MAOI. dosage should be lowered in liver/kidney damage pts. |
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Term
| what ADRs are associated w/fluoxetine (which may linger after d/c due to long t1/2)? |
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Definition
| CNS (drowsiness, anxiety, agitation, tremor, akathisia), CV (tachycardia, *increased bleeding), GI (constipation, diarrhea - more common than w/TCAs b/c of increased serotonin), and dermatologic (rash, pruritis, alopecia, acne, contact derm, urticaria) |
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Term
| what characterizes the risk of suicide w/antidepressants? |
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Definition
| <24yo had increased cases, while in older pts >25yo had fewer cases. be aware of signs of agitation, irritability, unusual changes in behavior - report them immediately and ensure daily observation by family. |
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Term
| what is serotonin syndrome? |
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Definition
| possibly due to hyperstimulation of the serotonin system: diaphoresis, restlessness, confusion/delirium, shivering/tremor/myoclonus, hyperthermia, tachycardia, acute renal failure, rhabdomyosis, DIC. drugs interactions which may produce serotonin syndrome: tryptophan+MAOI, tryptophan+fluoxetine, MAOI+fluoxetine, MAOI+merperidine, SSRIs+anti-migraine meds and 3,4 methylenedioxymethamphetamine MDMA. tx: 5-HT antagonists - cyproheptadine, methysergide. |
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Term
| what characterizes venlafaxine - an SNRI? |
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Definition
| venlafaxine blocks reuptake of both 5-HT and NE (stronger than TCAs) and is biotransformed by CYP. t1/2: 5 hrs, t1/2 of active metabolite: 11 hrs (t1/2 increased w/cirrhosis + renal impairment). no significant activity at muscarinic, histaminic, alpha-1 ABA, and MAO inhibition. ADRs: sustained HTN (dose-dependent), anorexia, n/v, dizziness, and anxiety. drug interactions: cimetidine (increases t1/2) and MAOI (possibly fatal hyperthermia). |
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Term
| what characterizes duloxetine - an SNRI? |
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Definition
| strong inhibitor of both 5-HT and NE, weak inhibition of DA reuptake, and low affinity for histamine and muscarinic receptors. indicated for depression *and stress urinary incontinence and pain related to DM neuropathy. t1/2: 10-15 hrs. |
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Term
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Definition
| an atypical antidepressant which blocks 5-HT uptake (but weaker than SSRIs). antagonist at 5-HT2A, 5-HT2C, alpha-1 adrenergic and H-1 receptors. sedative effects may result from strong blockade of 5-HT2A & alpha-1 sites and moderate blockade at H-1 receptors. ADRs: priapism rarely. |
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Term
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Definition
| a trazodone analog w/weaker blockade of 5-HT2 receptors, significant inhibition of pre-synaptic uptake of 5-HT, weaker alpha-1 blockade = less orthostatic hypotension, less sedation, dry mouth and nausea |
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Term
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Definition
| weak blockade of dopamine, serotonin and norepinephrine reuptake through unknown MOA. ADRs: seizures. |
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Term
|
Definition
| a SNRI which is an alpha-2 antagonist; dual action: increases NE & 5-HT transmission. enhances 5-HT via 5-HT1 receptors [blocks postsynaptic 5-HT2 and 5-HT3 receptors]. it is a weak anticholinergic and antihistamine. |
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Term
| what are the selectivities of the various MAOI? which MAOI is non-selective? |
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Definition
| MAO-A: preference for 5-HT and NE catabolism (less for DA). MAO-B: preference for DA catabolism. isocarboxazid is a nonselective MAOI, and inhibits both types. |
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Term
| what characterizes the MAO-A inhibitors? |
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Definition
| greater toxicity compared to other psychiatric drugs - reserved for pts not responding to other therapies. the irreversible (hydrazine) MAOI: phenelzine. the reversible (non-hydrazine) MAOI: tranylcypromine. indicated for: depression, narcolepsy, phobic-anxiety. |
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Term
| what ADRs are associated w/the MAOI? |
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Definition
| anticholinergic. CV: hypertensive crisis, orthostatic hypotension. CNS: agitation, dizziness, fatigue, hallucinations, h/a, vertigo. other: constipation, hepatoxicity (can be severe), hyperpyrexia, hyperreflexia, interference w/ejaculation, skin rash. |
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Term
| what is the diet restriction for MAOI pts? |
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Definition
| substances containing tyramine (usually > 10 mg) are likely to cause a rapid/potentially lethal elevation in BP: cheeses, yeast products, anchovies, avocados, bananas, beans, beer, caffeine, caviar, chocolate, cream, canned figs, pickled herring, liqueurs, liver, meat extracts/prepared w/tenderizers, raisins, sherry, snails, soy sauce, sour cream, wine (particularly chianti). |
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Term
| what are possible drug interactions for MAOI pts? |
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Definition
| amphetamine/cocaine/buspirone/L-dopa (increased risk of HTN), meperidine/related narcotics (increased risk of hyperpyrexia), dextromethorphan (increased risk of psychosis), alcohol/anticholinergics/antihistamines (increases peak/duration of effect) |
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