Lecture 10 - Antidepressants Flashcards
MAOIs:
___ weeks before new enzyme is synthesized
2
Describe the mechanism of MAO A inhibitor toxicity
- decreased amine degradation
- amphetamine-like effect + increased catecholamine release from intracellular vesicles
- decreased amine reuptake
- increased amine release
- tranylcypromine; GABA antagonism; metabolized to amphetamine
List the 4 phases of MAOI overdose
1) asymptomatic (latent) period
2) neuromuscular excitation and sympathetic hyperactivity
3) CNS depression and possible CV collapse
4) secondary complications for survivors
Describe:
1) Asymptomatic period
- delayed toxicity
- up to 6-12 hours
- monitor for 24 hours post ingestion
Describe:
2) Neuromuscular excitation and sympathetic hyperactivity
- hypertension
- hyperreflexia
- hyperthermia
- diaphoresis (sweating)
- tremor
- myoclonus
- seizures
- rigidity
- agitation
*when treating HTN, treat with short-acting agents so you can readily reverse if they suddenly become hypotensive
Describe:
3) CNS depression and possible CV collapse
hypotension
What is the treatment for MAOi overdose?
Severe hypertension: use a short acting agent
Arrhythmias: use standard antiarrhythmics
Hypotension: DIRECT acting vasopressors; start low
Charcoal
Hyperthermia: treat aggressively
Rigidity: benzos, dantrolene, to prevent rhabdomyolysis
What foods do you want to avoid with MAOi inhibitors?
Foods with high tyramine content:
- all aged cheese
- alcohol
- fish
- meat
- ripe fruit
- yeast extracts
- sauerkraut
- beans
Describe the cheese reaction
Hypertensive crisis:
- indirect acting amines
- direct acting do not require MAO for their metabolism
- catabolized by COMT
Tyramine: a major dietary amine; indirect acting agonist
Peripheral effects (doesn’t cross BBB)
Causes NE release from peripheral noradrenergic neurons
Normally, little absorbed
-dietary amine is metabolized by GI MAO-A
How do TCAs work?
- Block serotonin and NE reuptake
- Block histamine, muscarinic, and alpha adrenergic receptors
List some cardiac effects of TCAs
- hypertension, tachycardia
- slowed cardiac conduction
- antiarrhythmic properties
- orthostatic hypotension
What patients are at a higher risk for CV effects when taking TCAs?
- elderly
- CV disease
- drug interactions that cause increased levels
- overdose
What are central anticholinergic side effects of TCAs?
- agitation
- hallucinations
- confusion
- sedation
- coma
- seizures
What are some peripheral anticholinergic side effects of TCAs?
- hypertension
- tachycardia
- hyperthermia
- mydriasis (dilated pupils)
- dry, flushed skin
- decreased GI motility (constipation)
- urinary retention
What are CV toxic effects of TCAs?
- intraventricular conduction delay (QRS prolongation)
- sinus tachycardia
- ventricular arrhythmias
- hypotension
What are CNS toxic effects of TCAs?
- coma
- delerium
- myoclonus
- seizures
What are other toxic effects of TCAs?
- hyperthermia
- ileus (lack of movement in intestines that can lead to blockage which means no food, liquid, or gas can get through)
- urinary retention
What are risk factors that will increase the risk of TCA toxicity?
- pre-existing heart condition
- electrolyte abnormalities (particularly K+)
- hepatic insufficiency
- stimulant drug use
- multiple drugs that increase QT intervals
- increase dosage
Describe the general management of TCA overdose?
- Airway if needed; IV line; cardiac monitoring, EKG
- Decreased LOC; O2, dextrose, naloxone, thiamine, order ABGs
- Stomach lavage
- Charcoal 50-100 g + cathartic
What dose of TCAs are usually considered life-threatening?
10-20mg/kg
Limit Rx of TCA to ___ if patient is suicidal
1 gram
symptoms of TCA can occur from as little as ____ times their daily dose
3-4 times
most common cause of death in TCA overdose?
refractory hypotension
What is Tx for orthostatic hypotension?
- intravascular volume expansion
- sodium bicarbonate, vasopressors (NE) or isotropes (dopamine)
- correct hyperthermia, acidosis, seizures
How do you treat the confusion, agitation or hallucinations of TCA toxicity?
- supportive therapy
- benzos
Coma in TCA toxicity usually resolve in ___ hours
24
Describe the characteristics and treatment of seizures due to TCA toxicity?
Seizures are usually brief but often occur immediately before cardiac arrest.
- acidemia from seizures may predispose to arrhythmias
- usually responsive to IV benzos; midazolam infusion
- refractory: barbiturates or propofol
- phenytoin no longer recommended; pro arrhythmic, limited efficacy
________ are contraindicated in TCA toxicity
antiarrhythmics
TCAs are highly ______
lipophilic
How does a lipid rescue or lipid emulsion work in TCA toxicity or local anesthetic poisoning?
Lipid sink: sequesters TCA into blood and it doesn’t reach the receptors to produce an effect
How long should you treat for in an OD situation?
at least 2 half lives
Which TCA is the worse for fatal toxicity?
Amitriptyline
Venlafaxine (SNRI):
What overdose symptoms have been reported?
- seizures (all with seizures ingested equal to or greater than 900mg)
- hypotension
- sinus tachycardia
compare venlafaxine toxicity to TCA toxicity
- more seizures in Venlafaxine Toxicity
- Velafaxine NOT less likely to prolong QRS than TCAs
- coma was less likely with venlafaxine
- serotonin toxicity more common with venlafaxine
- TCA overdoses are more likely to be unconscious and require ICU admission
List 3 things for safety points regarding venlafaxine
- Seizures in overdoses
- Serotonin syndrome (MAOIs, SSRIs, triptans)
- BP increases (dose-dependent and usually reversible)
What type of patients is venlafaxine CI in ?
Relatively CI in patients:
- high risk of OD
- with pre-existing seizures and cardiac disease
What type of patients should you watch venlafaxine in?
- subjects who are poor CYP 2D6 metabolizers
- concomitant drugs which inhibit CYP 2D6
What is the active metabolize of venlafaxine?
desmethylvenlafaxine
Describe toxicity of desmethylvenlafaxine (Pristiq)
- minor effects with mild hypertension and tachycardia
- risk of seizures or serotonin toxicity is low
- generalized seizures occurred in 5%
- none had abnormal QT or QRS
Signs and symptoms of duloxetine (SNRI) toxicity
- somnolence
- serotonin syndrome
- seizures
- vomiting
- risk of QRS prolongation + arrhythmias is low
What are SSRI toxic effects?
- tremor
- sinus tachycardia
- n/v/d
- obtundation (altered level of consciousness)
- seizures
- serotonin syndrome
- mild bradycardia can occurring OD
Treatment of SSRI toxicity
charcoal + supportive care
Treatment of serotonin syndrome
- supportive care
- use benzos for neuromuscular symptoms
- use tylenol and cooling blankets for increased temp
- dantrolene for severe rigidity
For severe symptoms:
- cyproheptadine
- 5-HT antagonism
- watch anticholinergic and antihistaminic properties
Describe the presentation of serotonin syndrome
- agitation
- confusion
- hypomania
- diaphoresis
- diarrhea
- fever
- shivering
- incoordination
- tremor
- hyperreflexia
- myoclonus
Describe the cardiac toxicity related to citalopram
- dose-related QT prolongation (high-risk in metabolic disturbance and pre-existing cardiac disease)
- potential increased risk of tornadoes de pointes
What is the max dose?
40mg/day
*20mg/day in elderly or hepatic impairment
Bupropion may cause _____ or _______
tachycardia or seizures
How does mirtazapine work?
- increased serotonin and NE + serotonin blocker
- mild-moderate anticholinergic
- antihistamine effects
Does mirtazapine cause cardiac probs?
- no cardiac effects
- no QTc prolongation
- no seizures
- no serotonin toxicity
