Antidepressants Flashcards
What medications can cause serotonin syndrome
- MAOIs (block serotonin brkdn)
- SSRIs (blk serotonin reuptake)
- Opiates (blk serotonin reuptake)
a. meperidine (demerol)
b. methadone - Stimulants
a. cocaine (enhance release and inhibit brkdn)
b. dextromethorphan
c. MDMA (enhance release)
d. PMMA (enhance release) - Mirtazipine
- Lithium
- LSD
Which non-TCA/MAOI antidepressants are associated with seizures?
- Citalopram
- Escitalopram
- Buroprion
- Duloxetine
- Reboxetine
Venlafaxine
Which non-TCA/MAOI antidepressants are associated with QT prolongation?
- Citalopram
- Escitalopram
- Buroprion
- Venlafaxine
Which non-TCA/MAOI antidepressants are associated with QRS prolonation?
- All SSRI’s mild prolongation in LARGE ingestions
- Buproprion
- Mirtazapine
- Venlafaxine
What are 2 complications of trazadone ingestions?
- Pripaism :due to alpha-antagonism, can occur at therapeutic levels
- Disproportionate number of cases!
- Orthostatic hypotension (alpha blockade)
What is unique about Citalopram / Escitalopram ingestions?
- Cause the most QT prolongation (at >400mg)
- Require prolonged observation for late onset Sz and ECG changes (up to 36hrs)
- If nothing by 6 hrs, will not likely have any delayed toxicity (Mark Yarema)
What are the clinical features of serotonin syndrome?
- Classic triad: “CAN”
o C - Cognitive change
o A - Autonomic instability
o N - Neuromuscular symptoms - Hunter Serotonin Toxicity Criteria best diagnosis of SSS
o Myoclonus, hyperreflexia, hypertonicity
o Agitation, diaphoresis, fever
What is the Hunter criteriaa for dx of serotonin syndrome
Ingestion of serotonergic agent and 1 of:
- Spontaneous clonus
- Inducible clonus and agitation/diaphoresis
- tremor AND hyperreflexia
- Hypertonia PLUS temperature above 38ºC PLUS ocular clonus or inducible clonus
How do TCAs cause ECG changes?
Block fast Na channels: delay phase 0 depolarisation/ Leads to QRS widening and RBBB pattern with RAD and terminal R wave in aVR
List 6 false positives for urine TCAs
- Diphenhydramine
- Carbemazepine
- Gravol
- Quetiapine
- Cyproheptadine
- Flexeril
- MOST anticholinergics
- Cyclobenzaprine
List 8 receptor systems affected by TCAs
- Na channel blockade
- K channel blockade
- NE and 5HT reuptake inhibition
- GABA antagonism
- Alpha blockade
- Histamine receptor blockade
- Muscarininc receptor blockade
- MAO-I
List 6 EKG findings of acute TCA toxicity
- Dysrhythmias: o ST most common o WCT à abberantly conducted ST most common, difficult to differentiate from VT o Degenerates into VT (4% cases) - Intraventricular conduction delay o RBB longer refractory period, affected more than other conductive tissue. o RBBB o Extreme RAD (120-270) o Rightward deviation of the terminal 40ms of QRS in aVR § R in aVR > 3mm § R/S > 0.7 § S in I and aVL o QRS prolongation - Interval widening: o PR, Qt prolongation - Brugada type pattern à Can unmask a subclinical type I Brugada - Toursades
How does the QRS duration correlate with clinical presentation, and serve as an indicator of toxicity?
- QRS > 100ms in limb leads = 30% sz, 15% dysrhythmias
o Assocaited with serious toxicity: coma, intubation, hypotension
o R aVr R>0.3, R:S>0.7 as predictive as QRS >100 for Sz and dysrhythmias - QRS > 160 = 50% dysrhythmias
List 5 things in TCA overdose that predisposes the development of VT?
- Hypoxia
- Acidosis
- Sz
- Hyperthermia
B-adrenergic agonists
What is the most common cause of death from TCA toxicity?
- Refractory hypotension due to myocardial depression
- Hypotension exacerbated by hypoxia, metabolic acidosis, volume depletion, seizures, or concomitant ingestions of other cardiodepressant drugs
- Cyclical nature of acidosis induced hypotension (acid à more TCA binding à more acidosis….)
In TCA OD If NaHCO3 fails to stop WCT, which antidysrhythmic therapies are recommended?
- Lidocaine
o Class Ib – don’t affect NaCh the same way as Class 1a
o Safer to use
o Doesn’t cause widened QRS b/c it doesn’t bind at the same phases in the AP as the other classesPhenytoin
Why is lidocaine OK to use for WCT in TCA overdose
It is a Ib antiarrhythmic so block different sodium channels than the TCA therefore doesn’t contribute to wide QRS
List 4 drugs to avoid in TCA cardiotoxicity:
- Phenytoin: worsening cardiovascular effects, fails to terminate seizures
- Class Ia: Na channel blockers
o Quinidine, procainamide
o Worsening NaC blockade - Class III: K channel blockers
o Amiodarone, sotalol
o May prolong the QTc, not well studied - BB, CB, psysostigmine: hypotension and death
List 15 medications that can induce or contribute to SSS
- Inhibition of Serotonin Breakdown o Linezolid o Methylene blue o MAOI’s (phenelzine, moclobemide, clorygline) o Harmine and harmaline – psychoactive drinks in Amazon river - Enhancers of serotonin release o Amphetamines, esp MDMA o Cocaine o Lithium o mirtazapine - Blockade of Serotonin reuptake o SSRI’s (citalopram, excitalopram, fluoxetine, paroxetine, sertraline) o Buproprion o Venlafaxine o Chloripramine o Cocaine o Dextromethorphan o Fentanyl o Meperidine o Pentazocine o Tramadol o Trazadone - Seratonin Precursors or agonists o L-tryptophan o LSD
What is the DDx of serotonin syndrome?
- SSS
- NMS
- Anticholinergic
- Sympathomimetics
- SH w/d
- Strychnine poisoning
- CNS infection/sepsis
- Metabolic ie thyroid storm
How can seizures be treated in serotonin syndrome
Olanzapine is a 5HT antagonist. Can be used in severe Serotoni syndrome
BZD are indirect GABA agonist so need some endogenous GABA present in order to stop seizures
Propofol is a direct GABA agonist so it work even in GABA deplete pts
Where do MAOIs work
Work to reduce presynaptic degradation of MAO causing greater availability for release.
List the 3 contexts that MAOI toxicity is encountered:
- MAOI od
- MAOI-food or beverage interactions
MAOI drug interactions
- MAOI-food or beverage interactions
When does the onset of MAOI-food or –beverage interactions occur?
Within minutes
How are MAOI ODs managed
- decon: AC +/- lavage
- Supportive: cooling, BZD, fluids
- HTN crisis: Nitroglycerine or nitroprusside. BB c/i b/c BP can be very labile
