Antidepressants Flashcards
List three categories of antidepressant drugs
uptake inhibitors
monoamine oxidase inhibitors
atypical agents
It is important to screen for _____ before initiating an antidepressant
mania or hypomania
List two early TCAs
imipramine and amitriptyline
List two later TCAs
Desipramine (metabolite of imipramine) and nortryptyline (metabolite of amitriptyline)
Describe the mechanism of action of TCAs
Mixed serotonin and norepinephrine uptake inhibition
List common adverse effects of TCAs (5)
Anticholinergic activity → variety of autonomic effects
Moderate a adrenergic blockade → orthostatic hypotension
Moderate antihistamine activity → sedation
Class IA antiarrhythmic-like activity: blockade of cardiac Na+ channels; extremely dangerous in high doses
Potential serotonin syndrome
Describe the mechanism of action of imipramine
Inhibits 5-HT uptake more than NE uptake
Significant anticholinergic effects: blocks ACh receptors (also used to treat enuresis)
List precautions for imipramine and nortriptyline
Cardiac disease: acute MI, AV block, bundle-branch block, QT prolongation
Ileus
MAO inhibitor therapy
Avoid serotonergic agents e.g. triptans, St. John’s Wort, buspirone
Blood dyscrasias
Hepatic disease- check LFTs
TCAs may sensitize skin to sunburn
Nortriptyline inhibits ____ uptake more than ___ uptake
Norepinephrine more than serotonin
List some adverse reactions of nortriptyline
xerostomia, constipation, lethargy, sedation, orthostatic hypotension, cycloplegia (blocks accommodation at muscarinic receptors)
List five SSRIs
citalopram escitalopram fluoxetine paroxetine sertraline
List two SNRIs
duloxetine
venlafaxine
List one NRI
reboxetine
List some advantages of SSRIs/SNRIs/NRIs over TCAs
little or no anticholinergic activity, a adrenergic blockade, antihistamine activity
Sertraline is a _____ drug and has no significant affinity for adrenergic, cholinergic, GABA, dopaminergic, histaminergic, or serotonergic receptors
SSRI
List precautions for sertraline and venlafaxine
MAO inhibitor therapy
Avoid serotonergic agents e.g. triptans, St. John’s Wort, lorcaserin, buspirone
Avoid sudden DC, taper dosage gradually
Hepatic disease
Venlafixine is a ____ drug that inhibits serotonin uptake more than norepinephrine uptake
SNRI
Iproniazid is a ____ drug that is an isomer of isoniazid (used to treat TB)
MAOI
Describe the mechanism of action of MAOIs
Increase monoamine neurotransmitter activity by inhibiting MAO metabolism of 5-HT, DA, NE
Tranylcypromine is a ____ drug that is second line tx for depression.
MAOI
Describe the mechanism of action of tranylcypromine
Nonselective, irreversible inhibitor of both MAO-A and MAO-B
List adverse reactions seen with tranylcypromien
Sympathomimetic effects: hypertension, agitation, insomnia, tachycardia, mydriasis, diaphoresis, tremor, aggressiveness, urinary retention
List precautions for tranylcypromine
CV: acute MI, angina arrhythmias, heart failure, cerebrovascular disease, hypertension
Hepatic disease, jaundice
Pheochromocytoma
Radiographic contrast administration (MAOIs can precipitate seizures)
Renal disease
Sympathomimetics e.g. local anesthetics containing epinephrine, OTC cold remedies
Diabetes
Selegiline is a ____ drug used in treatment of Parkinsons and off label to treat depression
MAOI
Describe the mechanism of action of selegiline
Noncompetitive, irreversible antagonist of MAO-B, which metabolizes dopamine (decreases dopamine metabolism)
List precautions for use of selegiline
Monoamine uptake inhibitors
Dementia, severe psychosis, tardive dyskinesia, or excessive tremor
Peptic ulcers
Sympathomimetic drugs
____ is an atypical antidepressant; it and its metabolites inhibit 5-HT, NE, and DA uptake and metabolites are amphetamine-like
Bupropion
List precautions for bupropion treatment
MAO inhibitor therapy Seizure disorder Bulimia, anorexia nervosa Sympathomimetic drugs Hepatic disease
Describe the mechanism of action for the atypical antidepressants trazodone and nefazodone
Antagonism at 5-HT2A receptors and a1 receptors, inhibition of 5-HT uptake
Describe the mechanism of action of the atypical antidepressant mirtazapine
Potent antagonist at 5-HT2A, 5-HT2C, 5-HT3, and H1 receptors, also antagonizes presynaptic a2 receptors (↑ NE release), and is a weak antagonist at 5-HT1 receptors
List some other indications for use of antidepressants
Anxiety disorders (SSRIs, TCAs, MAOIs) Pain disorders (SNRIs, TCAs) PMDD (SSRIs) Smoking cessation (bupropion, nortriptyline) Eating disorders (SSRIs) Enuresis (TCAs)
Describe how ketamine acts as an antidepressant
activates the mTOR pathway, leading to increased synaptic signaling proteins and increased number and function of new spine synapses
