Toxicology

Question 1

Describe the mechanism of toxicity of Tri–Cyclic antidepressants

Answer 1

1. Na CHANNEL BLOCKADE in a use dependent manner (blockade is higher at faster heart rates):
   CNS toxicity - seizures/altered LOC/coma
   CVS toxicity - Ventricular dysrhythmias

Other
2. M1 blockade –> red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hare, full as a flask
3. H1 blockade –> sedation
4. a1 blockade (peripheral) –> hypotension
5. GABA A blockade –> sedation
6. K channels –> direct myocardial depression

Question 2

What are the clinical features of TCA overdose

Answer 2

CNS: Sedation/Coma/Seizures
CVS: Tachydcardia/Hypotension/Wide complex dysrhythmia
Anticholinergic syndrome

Question 3

What is the most useful investigation to assist with the diagnosis and what are the findings on this?

Answer 3

12 lead ECG
1. QRS > 100 in lead II (>160 associate with dysrhythmia)
2. Dominant secondary R wave > 3mm in aVR or an R/S ration > 0.7 in aVR
- right axis deviation of terminal QRS
3. Tachycardia (M1-)

Question 4

What other agents cause ECG findings typical of TCA overdose

Answer 4

Na blocking agents
1. Type 1a (Quinidine, Procainamide)
2. Type 1c (Flecainide)
3. Local anaesthetics (Bupivacaine, Ropivacaine)
4. Antimalarials (Chloroquine, hydroxychloroquine)
5. Propranolol
6. Carbamazepine
7. Quinine

Question 5

What is the risk assessment for a patient with TCA overdose

Answer 5

> 10mg/kg - potentially life threatening
30 mg/kg - Life threatening

Question 6

Describe the management of TCA overdose

Answer 6

RESUSCITATE (Alkalinize)
OMIG. HHH. ABCDE

1. Hyperventilation
2. NaHCO3 (2mmol/kg bolus) every few minutes while monitoring ECG and HD. Call clinical toxicologist at 6mmol/kg.
   - boluses better –> lead to rapid shifts in concentration of free drug

OPTIMIZE
Target pH: 7.5 - 7.55
Target Na: 155
QRS < 100
Rx seizures (benzos)
Euvolaemia
Decontamination (Activated charcoal) after ETT

If reached maximum NaHCO3 (hypernatraemia, hypokalaemia, severe alkalaemia)
1. NaCl 3%
2. Lidocaine 1 - 1.5 mg/kg IV push then infusion
3. Intralipid
4. VA-ECMO
5. High-dose Insulin Euglycaemic Therapy (HIET)

NB
Contraindications: amiodarone. procainamide, beta-blockers

Question 7

What is the specific antidote used in TCA overdose. What is the mechanism for its effect?

Answer 7

Sodium bicarbonate

Mechanism:
Multifactorial
1. Plasma alkalinization increases TCA plasma protein binding
2. Intracellular alkalosis - displaces TCA from receptor by promoting
3. Sodium load - over-rides Na blockade
4. Correction of metabolic acidosis
5. Volume loading

Question 8

What is the specific management for a BETA BLOCKER overdose and why

Answer 8

1. Glucagon
   - Activates adenylyl cyclase –> increase cAMP which increase Ca available for muscle contration
   - 5mg bolus. Repeat every 3 - 5 mins
   - If success, start infusion 2 - 5 mg/hour
   - Adverse effects: Nausea and Hyperglycaemia
2. Calcium
   - CaCl 1g IV (max 3g) or Gluconate
   - Increase inotropy
3. Vasopressors
   - Stimulate receptors to increase cAMP –> inotropy
   - high doses needed
4. High-dose Euglycaemic Insulin Therapy (HIET)
   - Last resort
5. Haemodialysis
   - May help with atenalol OD
6. Cardiac pacing
7. Intralipid
   - Lipid sink

Question 9

Discuss the treatment of Calcium channel blocker overdose

Answer 9

1. Fluid resuscitation
2. Calcium
   - 20ml 10% CaCl via CVC
   - Repeat x 3
   Consider infusion to keep serum calcium > 2mmol/L
3. Atropine
   - 0.6mg every 2 minutes up to 1.8mg
4. Vasopressors
5. Sodium bicarbonate
   - If severe metabolic acidosis
6. Cardiac pacing
   - Use vetricular pacing to bypass AV node blockade

Question 10

How do organophosphates cause toxicity?

Answer 10

Covalent bonding and inactivation of acetylcholinesterase leading to a cholinergic crisis.

Question 11

What agents often contain organophosphates

Answer 11

Insecticides
Fertilizers
Shampoos (lice)
Pet preparations
Livestock dipping
Crop protection
Fumigation
Nerve agents (sarin)

Question 12

Describe the clinical features of the cholinergic syndrome

Answer 12

Muscarinic: DUMBBELS
Diarrhoea
Urination
Miosis
Bronchorrhoea
Bradycardia
Emesis
Lacrimation
Salivation

Nicotinic
- Muscle fasciculations
- Cramping
- Weakness
- Diaphragmatic failure
- Hypertension
- Tachycardia
- Mydriasis
- Pallor

NB - patients can present with a combination of these findings

Question 13

What investigations can be done to

Answer 13

Acetylcholinesterase activity

Question 14

Discuss management of organophosphate toxicity

Answer 14

RESUSCITATION
OMIG. HHH. ABCDE
Decontamination
- remove contaminated clothes
- wash skin
- activated charcoal if presents < 1 - 2 ours and ETT in place

SPECIFIC THERAPY
Atropine 1 - 2 mg boluses every 5 minutes until bronchorrhoea and oral secretions resolved.
Benzos for seizures
AVOID: succinylcholine (will prolong block)

ICU
- Atropine infusion ± 3mg/hour (titrate up/down)
- Supportive care and wean atropine infusion
- Titrate to secretions nonHR or pupils

Question 15

Describe the management of ethylene glycol/Methanol poisoning

Answer 15

Results in a severe metabolic acidosis with and increased anion gap and osmolar gap

Management
1. IV ethanol
- Ethanol 100mg/ml 10 % diluted into D5W
- Load: 10 ml/kg over 30 minutes
- Maintain: 2 ml/kg/hour
2. Alcohol via NGT
3. Sodium Bicarbonate
4. HAEMODIALYSIS –> treatment of choice