Tox: antidepressants

Question 1

Receptors blocked by TCAs (and the impact of blockade) (6)

Answer 1

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)

Question 2

Symptoms TCA OD

Answer 2

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

Question 3

QRS duration at which seizures, dysrhythmias occur with TCA overdose

Answer 3

> 100ms: seizures

>160ms: wide complex dysrhythmias

Question 4

Typical toxic TCA dose

Answer 4

> 10mg/kg

Question 5

ECG findings in TCA OD

Answer 5

1) Na+ channel blockade signs: 
QRS >100ms
terminal R in aVR >3mm
Rightward deviation of terminal 40ms of QRS 
2) QTc prolongation

Question 6

Examples of Na+ blockade drugs

Answer 6

quinidines, flecainide, propafenone, amantadine, carbamazepine, cocaine, dephenhydramine

Question 7

Other factors that worsen Na+ blockade drugs

Answer 7

Acidosis, hyperkalemia

Question 8

TCA OD treatment

Answer 8

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

Question 9

Medications to avoid in TCA OD

Answer 9

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)

Question 10

Complications of TCA OD

Answer 10

Aspiration
Hypoxic brain injury
Cardiovascular collapse
seizures

Question 11

Symptoms of serotonin syndrome

Answer 11

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

Question 12

Causes of serotonin syndrome

Answer 12

SSRI/SNRIs
Some amphetamines
Tramadol 
St John's wort
MAOis 
TCAs (although Na blockade will kill you first)

Question 13

Hunter criteria for serotonin syndrome

Answer 13

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

Question 14

Tx of serotonin syndrome

Answer 14

Benzos for agitation, seizures 
Consider cyproheptadine (doesn't work that well, only PO, not going to save a life)

Question 15

Examples of MAOIs

Answer 15

MAOI-As: phenelzine (nardil), tranylcypromine (parnate), st. john’s wort.
MAOI-B: used in parkinsons. e.g. selegiline, rasagiline. Much less toxic in overdose.

Question 16

Typical timing of symptom onset with MAOis

Answer 16

6-12 hrs post overdose

Question 17

Foods/meds that interact with MAOIs

Answer 17

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

Question 18

Mxn of MOAIs

Answer 18

Inhibition of monoamine oxidase –> reduced inactivation of biogenic amines (e.g. epi, norepi, serotonin) –> excessive circulating catecholamines

Question 19

Describe tyramine reaction with MAOIs

Answer 19

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.

Question 20

Symptoms of MAOI toxicity

Answer 20

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

Question 21

Tx of MAOI toxicity

Answer 21

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)

Question 22

ECG and lab end points to target when treating TCA OD

Answer 22

QRS<120ms, pH 7.45-7.55

Question 23

If a patient with TCA overdose begins to seize, what drug do you administer and at what dose?

Answer 23

Ativan 2-4mg IV