Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
38 Cards in this Set
- Front
- Back
|
What are the relevant pharmacodynamics of TCAs?
|
A - can be delayed secondary to anticholinergic effects
D - lipophilic and protein bound, large Vd, but can be dialyzed M - hepatic, tertiary amines are prodrugs the liver metabolizes to their active secondary amine form |
|
|
What are the pharmacologic effects of TCAs?
|
Thinker
1 - Indirect GABA antagonism (seizures) 2 - Serotonin reuptake inhibition (serotonin syndrome and agitated delirium) 3 - Norepinephrine reuptake inhibition (initial hypertension and agitated delirium) Cardiac 4 - Na channel blockade in phase 0 (wide QRS, impaired inotropy) 5 - K efflux blockade prolonging phase 3 (long QT) 6 - Alpha-1 adrenergic blockade causing vasodilation (hypotension) Anti 7 - Anticholinergic (delirium, seizures, sedation, prolonged gastric emptying) 8 - Antihistamine 9 - Antidepressant |
|
|
What is the best predictor of seizure in TCA OD?
|
QRS >100ms in limb leads (30% develop seizures)
|
|
|
What is the best predictor of dysrhythmia in TCA OD?
|
QRS >160ms in limb leads (50% will develop an arrhythmia)
|
|
|
Why is it essential to monitor ventilation in TCA OD?
|
Respiratory acidosis can occur which would further inhibit conduction through phase 0 fast Na channels and widen QRS
|
|
|
Is physostigmine indicated for TCA OD?
|
No. Physostigmine is associated with seizures, cardiac arrest and death when used to treat TCA OD.
|
|
|
Are gastric lavage and activated charcoal indicated for TCA OD?
|
Yes. Serious ingestion. Decreased gastric emptying secondary to anticholinergic effects. Lack of evidence for better outcomes, but anything could be helpful.
|
|
|
How does NaHCO3 help in a TCA OD?
|
Mechanism is multi-factorial and poorly understood. Rosens states that the sodium load and alkaline pH increase sodium conductance through fast sodium channels in phase 0 of cardiac depolarization.
As per ALiEM: 1. Plasma alkalinization increases TCA plasma protein binding 2. Intracellular alkalosis decreases TCA receptor binding 3. Intracellular hypopolarization (HCO3 into cells, K comes with it, hypopolarized, less Na blockade) 4. Sodium load (Na fights through the block) 5. Correction of metabolic acidosis (may reduce tachycardia and allow use-dependant Na channels to be better accessed) 6. Volume loading (dilutes TCA, resuscitates dehydrated patient) 7. Other pharmacokinetic effects (meh) |
|
|
How would you order HCO3 for use in TCA OD?
|
When unstable give 1-2mEq/kg IV slow push until the QRS narrows to <100
Then consider infusion of 2-3 amps (50mEq/50mL amp) NaHCO3 in 1L D5W to maintain pH 7.5-7.55 and QRS <100. Based on mechanism boluses may be more effective than infusion. Renal compensation may counteract alkalinization. |
|
|
Treatment of TCA OD refractory to HCO3?
|
Bad prognosis
Norepinephrine infusion Consider intralipid |
|
|
Treatment for wide-complex tachycardia in TCA OD
|
HCO3 regardless of SVT with aberrancy vs VT
Type IA (procainamide) and IC (flecainide, propafenone) contraindicated secondary to Na-blockade. Consider transvenous pacing and overdrive pacing for Torsades unresponsive to magnesium |
|
|
Treatment of neurologic complications of TCA OD (agitation, seizures)?
|
Benzo's, benzo's, benzo's
Ideal agents as they have no anticholinergic or cardiac conduction effects If benzo's fail, try phenobarb or propofol, NOT dilantin (Na blockade, ineffective) If all fails, consider neuromuscular blockade with EEG monitoring of seizures. |
|
|
What is the role for hemodialysis/hemoperfusion in TCA OD?
|
Minimal. TCA's have a large Vd and are highly protein bound making them difficult to eliminate renally.
|
|
|
What effects are seen in SSRI OD?
|
<div>Can have GI/CNS/CVS effects</div><div>GI - N/V/abd pain</div>CNS - sedation, agitation, confusion, tremor, hyperreflexia, seizures<div>CVS - flushing, dizzy, bradycardia, tachycardia, hypotension, arrhythmias, prolonged QT, widened QRS</div>
|
|
|
What is unique about fluoxetine and citalopram?
|
They have very long half-lives (35h and 1-4 days) and can have delayed toxicity requiring prolonged monitoring
|
|
|
List common medications associated with serotonin syndrome
|
Stimulants: Amphetamines, cocaine, dextromethorphan<div>Opioids: methadone, meperidine, trazodone</div><div>Antidepressants: SSRI's, TCA's, Lithium</div>
|
|
|
What are the Hunter Serotonin Toxicity Criteria? (Rosen Box)
|
If yes to any then serotonin toxicity:<div>-spontaneous clonus</div><div>-inducible clonus + agitation + diaphoresis</div><div>-ocular clonus + agitation + diaphoresis</div><div>-tremor + hyperreflexia</div><div>-hypertonic + temperature + ocular/inducible clonus</div><div><br /></div><div>If no to all then no serotonin toxicity</div>
|
|
|
What are Sternbach's diagnostic criteria for serotonin syndrome? (Rosen Box)
|
-Addition or dose increase of a serotoninergic agent<div>-Three symptoms*</div><div>-No new/increased neuroleptic</div><div>-R/O infection/intox/metabolic/withdrawal</div><div><br /></div><div>*agitation, ataxia, diaphoresis, diarrhea, hyper-reflexia, hyperthermia, mental status changes, myoclonus, shivering, tremor</div>
|
|
|
Are activated charcoal, gastric lavage or dialysis indicated for SSRI OD?
|
No.<div>AC/GL - rare syndrome even with OD</div><div>Dialysis - largely protein bound with large Vd, hard to dialyze</div>
|
|
|
List some experimental treatments of serotonin syndrome.
|
Cyproheptadine, chlorpromazine, propranolol - all have inconsistent effects.
|
|
|
How is SSRI OD be treated?
|
Benzodiazepines<div>No other treatment is proven.</div><div>Observe OD's for 6 hours except in citalopram (12 horus)</div><div>Admit if signs of serotonin syndrome</div>
|
|
|
What is buproprion?
|
An antidepressant that works by primarily neurotransmitter reuptake. Effects from greatest -> smallest on:<div>depamine, norepinephrine, serotonin</div>
|
|
|
What is bupropion's most significant toxic effect?
|
Seizures! Can occur in OD as well as above the maximal daily dose. Risk of seizures does not correlate with other signs or symptoms.
|
|
|
What are trazodone and nefazodone?
|
Antidepressants that inhibit serotonin reuptake but are NOT SSRI's. Also cause alpha-1 blockade and inhibit norepinephrine reuptake.
|
|
|
How does trazodone overdose present?
|
Similar to SSRI overdose. Most common effect is orthostatic hypotension with lightheaded/diszzy/drowsy/ataxia/N/V.
|
|
|
How should trazodone OD be treated?
|
Similar to SSRI OD with focus on bolused IV crystalloids for orthostatic hypotension.
|
|
|
What is venlafaxine?
|
aka an SNRI - inhibits reuptake of serotonin > norepinephrine > dopamine and can also block Na channels. Think about it like a new TCA.
|
|
|
How does venlafaxine OD present?
|
Between an SSRI and TCA OD. Can get serotonin syndrome and the cardiac effects of TCA's.
|
|
|
What is mirtazipine?
|
An antidepressant that increases the release of serotonin and norepinephrine. It has fewer side effects than TCA's and SSRI's.<div>Isolated OD symptoms are generally mild with somnolence and moderate hypotension being the main features.</div>
|
|
|
How do MAO's work?
|
Monoamine oxidase inhibitors are antidepressants that prevent the breakdown of biogenic amines (epi, norepe & serotonin)
|
|
|
What are the causes of MAO-I toxicity?
|
MAO-I toxicity can be due to:<div>1- OD</div><div>2- Food interaction</div><div>3- Drug interaction</div>
|
|
|
What foods are associated with MAO-I toxicity?
|
Treated/aged meats & fished<div>Aged cheeses</div><div>Beans</div><div>Ripe avocado</div><div>Chocolate</div><div>Undistilled alcoholic beverages</div>
|
|
|
Describe a MAO-I OD
|
Occurs in 4 phases beginning 6-12 hours after OD<div>1 - asymptomatic</div><div>2 - neuromuscular and cardiovascular excitement (seizures, muscular rigidity, agitated delirium, myoclonus, hyperthermia)</div><div>3 - CNS depression and cardiovascular collapse (hypotension, bradycardia)</div><div>4 - Fallout from previous stages</div>
|
|
|
Describe a MAO-I food interaction
|
Sympathetic surge starting in minutes-hours and lasting for only a few hours
|
|
|
Describe a MAO-I drug interaction
|
Sympathetic storm or serotonin syndrome beginning minutes-hours after ingesting the other drug (sympathomimetic, methylxanthine, antidressant, meperidine).<div>-Excessive norepi/serotonin can not be broken down</div><div>-Lasts hours-days</div>
|
|
|
How should a MAO-I reaction be treated?
|
-Difficult situation because sympathetic surge may require sedation and antihypertensive treatment which would be bad once the surge wears off.<div>-Need to use short acting medications. Consider phentolamine and/or nitroprusside infusion for hypertensive emergency.</div>
|
|
|
What is discontinuation syndrome?
|
Syndrome of vague symptoms following discontinuation of an antidepressant. Requires restarting and tapering the agent.
|
|
|
What dose of TCA's is considered life-threatening?
|
10mg/kg or 1G in an adult
Clinical signs of toxicity: anticholinergic toxidrome, decreased LOC, prolonged QRS, >3mm R prime in aVR |
