Antidepressants Flashcards
____ weeks before new MOA A and B are synthesized
2 weeks
What is the mechanism of MOA A inhibitor toxicity
- decreased amine degradation
- amphetamine like effect and increased catecholamine release from intracellular vesicles
- decreased amine reuptake
- increased amine release
- tranylcypromine; GABA antagonism; metabolized to amphetamine
What are the 4 phases of MOA A overdose
- asymptomatic (latent)
- up to 6-12 hours - neuromuscular excitation and sympathetic hyperactivity
- hypertension
- tremor
- hyperreflexia
- hyperthermia
- diaphoresis
- seizures
- rigidity - CNS depression and possible CV collapse
- hypotension - secondary complications for survivors
What is the tx of severe hypertension with MAO overdose
a short acting agent
What is the tx of arrhythmias associated with MAO overdose
standard antiarrhythmics
What is the tx of hypotension associated with MAO overdose?
- direct acting vasopressors- start low
What is the tx of rigidity associated with MAO overdose
benzos, dantrolene, to prevent rhabdomyolysis
What foods should be avoided with MAO inhibitors
- cheese
- alcoholic beverages
- fish
- meat
- fruit (overripe, banana peels)
- yeast extracts
- sauerkraut
- beans
What is the cheese reaction?
- hypertensive crisis (indirect acting amines, direct acting do not require MAO for their metabolism; catabolized by COMT)
What is tyramine?
- a major dietary amine
- indirect acting agonists
Does tyramine cross the BBB
- no
What is the effect of tyramine?
- causes NE release from peripheral noradrenaline neurons
What is the mechanism of action of TCAs?
blocks 5HT and NE reuptake
- also reputes histamine, muscarinic and alpha adrenergic receptors
In usual doses, what is the cardiac effects of TCAs?
- hypertension, tachycardia
- slowed cardiac conduction
- antiarrhythmic properties
- orthostatic hypotension
What are the high risk patients for TCA overdose?
- elderly
- cardiovascular disease
- drug interactions
- overdose cases
What are the central anticholinergic effects of TCAs?
- agitation
- hallucinations
- confusion
- sedation
- coma
- seizures
What are the peripheral anticholinergic effects of TCAs?
- hypertension
- tachycardia
- hyperthermia
- mydriasis
- dry, flushed skin
- decreased GI motility
- urinary retention
What are the cardiovascular specific effects of TCAs?
- intraventricular conduction delay
- sinus tachycardia
- ventricular arrhythmias
- hypotension
What are the CNS effects of TCAs?
- coma
- delirium
- myoclonus
- seizures
What are the risk factors that increase the risk of toxicity of TCAs?
- pre-existing heart condition
- electrolyte abnormalities
- hepatic insufficiency
- stimulant drug use (concomitant stimulant drug use)
- multiple drugs that increase QT intervals
- increase drug dosage
What is the general management strategies for TCA overdose?
- support airways
- cardiac monitoring
- EKG
- if decreased LOC: O2, dextrose, naloxone, thiamine, ABGs
- stomach lavage
- charcoal 50-100 g + cathartic
What is the life threatening dose of TCAs?
- 10-20 mg/kg is considered life threatening
- limit rx to 1 g if pt is suicidal
- sx from as little as 3-4 times daily dose
What is the most common cause of death with TCAs?
- refractory hypotension (due to vasodilation or impaired cardiac contractility)
What is the tx of orthostatic hypotension?
- intravascular volume expansion
- sodium bicarbonate, vasopressors or ionotropes (dopamine)
- correct hyperthermia, acidosis, seizures
What is given as tx for CNS toxic effects?
- supportive tx
- benzos
Coma usually resolves in ______
24 hours
Acidemia from seizures may predispose to _______
arrhythmias
What are seizures usually treated by?
- IV benzos, midazolam infusion(if patients are actively seizing)
What is used for refractory seizures?
- barbiturates or propofol
Are drug levels a good predictor of whether or not someone will have a seizure
NO
What is the most common mechanism of death with cardiac toxicity?
- myocardial depression, ventricular tachycardia, or ventricular fibrillation
What is a good predictor of arrhythmias?
- QRS duration (should be >0.10 s)
_________ has a dramatic effect on narrowing QRS
sodium bicarbonate
this reduces arrhythmias and hypotension
What is the mechanism of cardiac toxicity?
- reductions of extracellular K or increase in extracellular Na
- improves membrane responsiveness and increase conduction velocity
- increase in serum pH may result in reductio of free TCA
- unbound drug correlates with tissue uptake
Describe a lipid rescue- lipid emulsion
- TCAs= highly lipophilic
- indication: refractory cardiotoxicity for overdoses of lipophilic medications
- (TCAs, local anesthetic poisoning)
How long should someone be monitored for in the ICU post TCA OD?
- in the ICU for 12-24 hours after all sx are resolved
What are the s/s of overdose with venlafaxine?
- seizures, hypotension, sinus tachycardia
Serotonin toxicity was _____ common with venlafaxine compared to TCAs
more
Is blood pressure increases dose dependant with venlafaxine?
- YES IT IS (risk increases with increased age)
When is venlafaxine CI’ed in patients?
pre-existing seizures and cardiac diseases
What is the normal half life of venlafaxine, and what can it be extended up to in overdose?
5 hours normally, 15 hours with toxicity
What are the s/s associated with duloxetine overdose?
- somnolence
- serotonin syndrome
- seizures
- vomiting
What is the risk of QRS prolongation and arrhythmias with duloxetine?
- LOW
What are the toxic effects of SSRIs?
- tremor
- sinus tachycardia
- n/v, diarrhea
- obtundation
- seizures
- serotonin syndrome
- mild bradycardia may occur in OD as well
What is the tx of antidepressant overdose?
- charcoal and supportive care
What are some of the causes of serotonin syndrome?
- inhibition of breakdown of 5HT (MAO inhibitors)
- blocking reuptake of 5HT (SSRIs, clomipramine, DM, meperidine, cocaine, venlafaxine)
- 5HT precursors or agonists (lithium, bispirone, LSD)
- enhance 5HT release (MDMA)
What is the treatment 5HT syndrome?
- supportive care
- neuromuscular symptoms (benzos)
- increased temp (tylenol, cooling blankets)
- severe rigidity (dantrolene)
- severe sx: cyproheptadine 4 mg po q4h
What are the s/s of serotonin syndrome?
- agitation
- mental status changes (confusion, hypomania)
- diaphoresis
- diarrhea
- fever
- shivering
- incorporation
- myoclonus
- tremor
- hyperreflexia
When should only 20 mg of citalopram be used?
- 20 mg should only be used in the elderly and in those with hepatic impairment
What is the safety profile of buproprion?
- may cause sinus tachycardia but not usually associated with conduction abnormalities
What is the MOA of mitazipine toxicity?
- increased 5HT and NE + serotonin blocker
- mild-moderate anticholineric
- antihistamine effects
Watch for ________ and ______ effects in overdose of mirtazapine
anticholineric and serotonergic
What are the usual s/s of mirtazapine toxicity?
- decreased LOC
- tachycardia
- hypertension
- no QTc prolongation; no arrhythmias
- NO seizures or serotonin toxicity
