Toxicology Flashcards
Describe the mechanism of toxicity of Tri–Cyclic antidepressants
- 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
What are the clinical features of TCA overdose
CNS: Sedation/Coma/Seizures
CVS: Tachydcardia/Hypotension/Wide complex dysrhythmia
Anticholinergic syndrome
What is the most useful investigation to assist with the diagnosis and what are the findings on this?
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-)
What other agents cause ECG findings typical of TCA overdose
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
What is the risk assessment for a patient with TCA overdose
> 10mg/kg - potentially life threatening
30 mg/kg - Life threatening
Describe the management of TCA overdose
RESUSCITATE (Alkalinize)
OMIG. HHH. ABCDE
- Hyperventilation
- 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
What is the specific antidote used in TCA overdose. What is the mechanism for its effect?
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
What is the specific management for a BETA BLOCKER overdose and why
- 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 - Calcium
- CaCl 1g IV (max 3g) or Gluconate
- Increase inotropy - Vasopressors
- Stimulate receptors to increase cAMP –> inotropy
- high doses needed - High-dose Euglycaemic Insulin Therapy (HIET)
- Last resort - Haemodialysis
- May help with atenalol OD - Cardiac pacing
- Intralipid
- Lipid sink
Discuss the treatment of Calcium channel blocker overdose
- Fluid resuscitation
- Calcium
- 20ml 10% CaCl via CVC
- Repeat x 3
Consider infusion to keep serum calcium > 2mmol/L - Atropine
- 0.6mg every 2 minutes up to 1.8mg - Vasopressors
- Sodium bicarbonate
- If severe metabolic acidosis - Cardiac pacing
- Use vetricular pacing to bypass AV node blockade
How do organophosphates cause toxicity?
Covalent bonding and inactivation of acetylcholinesterase leading to a cholinergic crisis.
What agents often contain organophosphates
Insecticides
Fertilizers
Shampoos (lice)
Pet preparations
Livestock dipping
Crop protection
Fumigation
Nerve agents (sarin)
Describe the clinical features of the cholinergic syndrome
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
What investigations can be done to
Acetylcholinesterase activity
Discuss management of organophosphate toxicity
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
Describe the management of ethylene glycol/Methanol poisoning
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