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Flashcards in Antidepressants Deck (25):

What medications can cause serotonin syndrome

1. MAOIs (block serotonin brkdn)
2. SSRIs (blk serotonin reuptake)
3. Opiates (blk serotonin reuptake)
a. meperidine (demerol)
b. methadone
4. Stimulants
a. cocaine (enhance release and inhibit brkdn)
b. dextromethorphan
c. MDMA (enhance release)
d. PMMA (enhance release)
5. Mirtazipine
6. Lithium
7. LSD


Which non-TCA/MAOI antidepressants are associated with seizures?

- Citalopram
- Escitalopram
- Buroprion
- Duloxetine
- Reboxetine


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:
1. Spontaneous clonus
2. Inducible clonus and agitation/diaphoresis
3. tremor AND hyperreflexia
4. 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

1. Na channel blockade
2. K channel blockade
3. NE and 5HT reuptake inhibition
4. GABA antagonism
5. Alpha blockade
6. Histamine receptor blockade
7. Muscarininc receptor blockade
8. 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 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


What is the DDx of serotonin syndrome?

- 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:

1. MAOI od
2. MAOI-food or beverage interactions
MAOI drug interactions


When does the onset of MAOI-food or –beverage interactions occur?

Within minutes


How are MAOI ODs managed

1. decon: AC +/- lavage
2. Supportive: cooling, BZD, fluids
3. HTN crisis: Nitroglycerine or nitroprusside. BB c/i b/c BP can be very labile