Tox: antidepressants Flashcards
Receptors blocked by TCAs (and the impact of blockade) (6)
1) Histamine (sedation/coma)
2) Muscarinic (anti-cholinergic)
3) Alpha-adrenergic (hypoTN, reflex +HR)
4) GABA (seizures)
5) Na+ channel/prolongation of phase 0/depolarization phase of cardiac AP (QRS widening, wide complex dysrhythmias)
6) K+ channel antagonism (QTc prolongation, dysrhythmias)
Symptoms TCA OD
Early: +HR, +BP, rapid mumbled speech, urinary retention, ALOC
Late: myocardial depression, -BP, seizures, wide complex dysrhythmias
May deteriorate rapidly
Symptoms typically occur within 1-2hrs
QRS duration at which seizures, dysrhythmias occur with TCA overdose
> 100ms: seizures
>160ms: wide complex dysrhythmias
Typical toxic TCA dose
> 10mg/kg
ECG findings in TCA OD
1) Na+ channel blockade signs: QRS >100ms terminal R in aVR >3mm Rightward deviation of terminal 40ms of QRS 2) QTc prolongation
Examples of Na+ blockade drugs
quinidines, flecainide, propafenone, amantadine, carbamazepine, cocaine, dephenhydramine
Other factors that worsen Na+ blockade drugs
Acidosis, hyperkalemia
TCA OD treatment
Decontam: AC if w/in 1hr ingestion Na bicarb if: - QRS>120ms - Ventricular dysrhythmias - Hypotension unresponsive to fluids - Give boluses of 1-2mEq/kg until QRS narrows
Supportive tx: Early intubation to avoid respiratory acidosis (worsens Na blockade) Benzos for seizures IVF/bicarb for hypoTN but levophed prn MgSO4 for torsades
**Target QRS <120-100, pH 7.5
Medications to avoid in TCA OD
Physostigmine has no benefit, may cause adverse effects.
Class 1a/1c antidysrhythmics (Na channel blockade, e.g. procainamide, flecainamide, propafenone)
Class III antidysrhythmics (K channel blockade, e.g. amiodarone)
Anti-seizure drugs (e.g. phenytoin)
Complications of TCA OD
Aspiration
Hypoxic brain injury
Cardiovascular collapse
seizures
Symptoms of serotonin syndrome
Triad: ALOC, auto dysfxn, neuromuscular activity
ALOC/CNS dysfunction inc. agitation
Autonomic dysf: hyperthermia, tachy, diaphoresis
Neuro: nystamus, myoclonus, ocular clonus, hyperreflexia, muscular rigidity (mainly LE), tremors, seizures
Other: n/v/d, abdo pain
Causes of serotonin syndrome
SSRI/SNRIs Some amphetamines Tramadol St John's wort MAOis TCAs (although Na blockade will kill you first)
Hunter criteria for serotonin syndrome
Diagnose if any of:
1) Spontaneous clonus
2) Inducible clonus with agitation and/or diaphoresis
3) Ocular clonus w/ agitation or diaphoresis
4) Tremor, hyperreflexia
5) Hypertonia, temperature >38*C and ocular or inducible clonus
Tx of serotonin syndrome
Benzos for agitation, seizures Consider cyproheptadine (doesn't work that well, only PO, not going to save a life)
Examples of MAOIs
MAOI-As: phenelzine (nardil), tranylcypromine (parnate), st. john’s wort.
MAOI-B: used in parkinsons. e.g. selegiline, rasagiline. Much less toxic in overdose.
Typical timing of symptom onset with MAOis
6-12 hrs post overdose
Foods/meds that interact with MAOIs
Tyramine containing foods: cured/processed meats, fermented foods, sauces (soy, fish, teriyaki, miso), alcohol, aged/strong cheese, dried fruit.
Drugs: any serotonergic agent (trigger SS), stimulants (e.g. methylphenidate), phenylephrine
Mxn of MOAIs
Inhibition of monoamine oxidase –> reduced inactivation of biogenic amines (e.g. epi, norepi, serotonin) –> excessive circulating catecholamines
Describe tyramine reaction with MAOIs
Pt takes MAOI (inc at therapeutic levels) and ingests tyramine containing food (e.g. red wine, cheese, etc).
‘hypertensive crisis.’
Will develop HTN, headache, diaphoresis, palpitations, neuromuscular excitation. Lasts for several hours.
Tx: phentolamine is drug of choice. BBs contraindicated.
Symptoms of MAOI toxicity
Excessive sympathetic activity. Similar to serotonin syndrome (may be serotonin syndrome).
CVD: +HR, +BP, +temp
MSK: rigidity, hyperreflexia, myoclonus, rhabdo
CNS: seizure, coma, agitation, mydriasis
Tx of MAOI toxicity
Supportive with aggressive tx of agitation, rigidity, seizures, tachycardia and hyperthermia with BENZOS.
If severe HTN: nitrprusside, phentolamine.
AVOID: BB (get unopposed alpha-adrenergic stim), all indirect sympathomimetics (e.g. dopamine)
ECG and lab end points to target when treating TCA OD
QRS<120ms, pH 7.45-7.55
If a patient with TCA overdose begins to seize, what drug do you administer and at what dose?
Ativan 2-4mg IV
