33: Antidepressants Flashcards by Elle B

symptoms of major depression

depressed mood

- anhedonia (loss of pleasure) and loss of interest in life

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gold standard treatment for major depression

electroconvulsive therapy

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2 common reasons why chemical antidepressants may not work for people?

delay of therapeutic response (weeks or months of regular dosing to achieve benefit)
side effects can limit usage, especially in elderly

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What are the two hypotheses of depression?

Monoamine/Biogenic Amine hypothesis (abnormalities in 5HT, NE, and DA neurotransmission
Neurotrophic Hypothesis (changes in nerve growth factors BDNF play a role in cell survival and synaptic plasticity)

these two hypotheses are likely not mutually exclusive

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BDNF –>

TRK-B receptors –> increased neuronal survival and growth

antidepressants increase BDNF in the brain: neurotrophic hypothesis

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side effects = GI disturbances, anxiety, sexual dysfunction

5HT reuptake blockade

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side effects = tremors, tachycardia

NE reuptake blockade

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side effects = psychomotor activation, antiparkinsonian effects, psychosis, increased attention and concentration

DA uptake blockade

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side effects = sedation, drowsiness, weight gain, hypotension

H1 receptor blockade

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side effects = blurred vision, dry mouth, sinus tachycardia, constipation, urinary retention, memory dysfunction

Muscarinic Ach receptor blockade

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side effects = postural hypotension, reflex tachycardia, dizziness

a1 receptor blockade (adrenergic)

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MOA MAOIs

increase synaptic availability of NE and 5HT blocking their catabolism via inhibition of MAO enzymes

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MAO-A vs. MAO-B

MAO-A : targets tyramine, NE, 5HT and DA

MAO-B : targets mainly DA

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irreversible MAO-A and MAO-B inhibitors

phenelzine

tranylcypromine

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MOA selegiline

MAO-B inhibitor at low dose, non-selective MAOi at higher dose

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low dose use selegline

parkinson’s disease

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antidepressant use selegline

high dose (patch to prevent first pass effect and tyramine effect)

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tyramine and MAOIs —>

hypertensive crisis

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tyramine and MAOIs —>

hypertensive crisis

amine from tyrosine triggers release of catecholamines in the synapse leading to overwhleming vasoconstriction and a hypertensive crisis

watch out for cheese and chianti wines especially

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current major clinical use for TCAs

chronic pain conditions

used for major deprssion if SSRIs are not effective

MOA TCAs

block reuptake of both 5HT and NE by inhibition of SERT and NET respectively

dirty drugs - also work as agonists at cholinergic, histaminergic and a-adrenergic receptors

which TCA is used to treat enuresis (bedwetting)?

imipraimine

which TCA is more effective at treating neuropathic pain?

desipramine

has stronger NE than 5HT properties

which TCA is known for sedative effects?

amitriptyline

why are TCAs known as "hip breakers" in elderly patients?

antagonist action at alpha1 receptors --> orthostatic hypotension also have dry mouth, constipation, blurred vision, urinary retention and confusion side effects due to antagonist actions at muscarinic receptors

most serious side effect of TCAs

lethal cardiac arrhythmias due to Na/Ca channel blocking properties

3 C overdose of TCAs

convulsion coma cardiac arrhythmia

MOA SSRIs

selectively inhibit SERT and block the reuptake of 5HT into the presynaptic terminal --> increases synaptic 5HT

short term side effects SSRIs = | long term =

short term = nausea, GI upset, diarrhea (1st week) long term = sexual dysfunction

observe: lethargy, restlessness, mental confusion, flushing, diaphoresis, tremor

Serotonin Syndrome -rare side effect of SSRIs due to long half-life that occurs usually when drug combos or switching meds

which SSRIs pose the greatest risk for discontinuation syndrome?

paroxetine and sertraline sudden discontinuation of short half-life SSRIs may cause advers side effects such as dizziness, paresthesias, and anxiety 1-7 days after stopping because of sensitization switch to SSRI with longer half-life and then discontinue if pt is susceptible to this effect

MOA SNRI

selective serotonin-norepinephrine reuptake inhibitors both inhibit serotonin SERT and norepinephrine NET transporters unlike TCAs do not have much affinity for other receptors --> better side effect profile

clinical use venlafaxine

SNRI used for severe depression

clinical use duloxetine

SNRI with increasing use for chronic pain over TCAs

Trazodone is a...

5HT2 antagonist that also blocks H1 receptor --> sedative effects without tolerance or dependence

negative side effect of trazodone

priapism due to peripheral a1 blocking effect

smoking cessation drug

bupropion

MOA bupropion

blocks NE and DA reuptake and increases presynaptic release of catecholamines

MOA mirtazapine

blocks presynpative a2 receptors and increase synaptic release of 5HT and NE - blocks 5HT2 and 5HT2 (antiemetic) blocks H1 receptor --> sedation, weight gain, few sexual side effects

major side effect SNRIs

discontinuation syndrome

what anti-depressants can you combine?

MAOIs, TCAs, and SSRIs should NOT be combined - fatal side effects!

which drugs are potent inhibitors of CYP2D6?

paroxetine fluoxetine fluvoxamine

drug of choice for bipolar disorder

lithium mood-stabilizing. depressive phase requires use of anti-depressants

anticonvulsants used in bipolar disorder treatment

valproic acid and carbamazepine

treatment of acute mania

valproic acid and carbamazepine

MOA lithium

prevents recycling of inositol phosphate (mood dampening) and inhibits release of NE (prevent mania)

4 side effects of lithium

- tremor - hypothyroidism - nephrogenic diabetes insipidus - skin rxn

what drugs interact with lithium?

thiazide and loop diuretics --> diminish Li clearance and can cause toxicity