Toxicology Flashcards

1
Q

Describe the mechanism of toxicity of Tri–Cyclic antidepressants

A
  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

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2
Q

What are the clinical features of TCA overdose

A

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

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3
Q

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

A

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-)

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4
Q

What other agents cause ECG findings typical of TCA overdose

A

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

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5
Q

What is the risk assessment for a patient with TCA overdose

A

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

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6
Q

Describe the management of TCA overdose

A

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

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7
Q

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

A

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

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8
Q

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

A
  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
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9
Q

Discuss the treatment of Calcium channel blocker overdose

A
  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
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10
Q

How do organophosphates cause toxicity?

A

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

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11
Q

What agents often contain organophosphates

A

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

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12
Q

Describe the clinical features of the cholinergic syndrome

A

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

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13
Q

What investigations can be done to

A

Acetylcholinesterase activity

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14
Q

Discuss management of organophosphate toxicity

A

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

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15
Q

Describe the management of ethylene glycol/Methanol poisoning

A

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

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