toxicology

Question 1

What MOA’s does tricyclic antidepressant have?

Answer 1

• Serotonin re-uptake inhibitor
• GABA agonist
• Alpha adrenergic antagonist
• Na+ channel blockers
• Muscirenic receptor antagonist

Question 2

What signs and symptoms with you see with a tricyclic antidepressant toxicity?

Answer 2

hypotension
agitation/coma
tachycardia
QT prolongation
QRS prolongation
Seizures/
Flushing
Fever,
Dry mouth and skin,
Decreased bowel sounds
Hyper-reflexia

Question 3

what are some common tricyclic antidepressants?

Answer 3

Amitriptyline.
Amoxapine.
Desipramine (Norpramin)
Doxepin.
Imipramine (Tofranil)
Nortriptyline (Pamelor)
Protriptyline.
Trimipramine

Question 4

what are some common TCA od ecg findings that suggest Na channel blockage is likely?

Answer 4

Intraventricular conduction delay: - - QRS > 100 ms in lead II
- Terminal R wave > 3 mm in aVR or R/S ratio > 0.7 in aVR
- Patients with tricyclic overdose will also usually demonstrate sinus tachycardia secondary to muscarinic (M1) receptor blockade

Question 5

In tca od What dose is likely going to cause both moderately symptomatic and severe effects?

Answer 5

moderate = >10mg/kg
severe = >20mg/kg

Question 6

when looking at a QRS in a patient who has taken a TCA overdose what may correlate with some symptoms?

Answer 6

QRS > 100ms = high likelihood of seziures.
QRS > 160ms = 50% chance of VT

Question 7

What is SAAS’s stance of management of TCA OD’s?

Answer 7

Consider intubation and hyperventilation if obtunded
- aim for EtCO2 25-30 mmHg in intubated patient.
- Transport and notify receiving facility.

Question 8

What is the benefits and drawbacks of metaraminol combined with adrenaline?

Answer 8

Benefits:
- synergistic effects may result in a reduction of the need for lots of adrenaline.

Drawbacks:
- unfamiliar with the synergistic affects on each other, ? unreliable results.
- not common practice.
- cognitive load may be at capacity with two drug infusions.

Question 9

What is the mechanism of action in organophosphate poisoning?

Answer 9

irreversible inhibition => decreased breakdown of AcH => acetylcholine accumulation => nicotinic and muscarinic receptors stimulation.

ref: Colović MB, Krstić DZ, Lazarević-Pašti TD, Bondžić AM, Vasić VM. Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol. 2013;11(3):315-335. doi:10.2174/1570159X11311030006

Question 10

What does the SLUDGE mnemonic stand for?

Answer 10

S - Salivation
L - Lacrimation
U - Urinary frequency
D - Diaphoresis/diarrhoea
G - Gastrointestinal cramping and pain
E - Emesis

Question 11

What does the dumbels mnemonic stand for?

Answer 11

D - Diarrhea/diaphoresis
U - Urinary frequency
M -Miosis
B - Bronchospasm/bronchorrhea
E - Emesis
L - Lacrimation
S- Salivation

Question 12

What are oximes and how do they work?

Answer 12

Oximes such as pralidoxime have three actions that show benefit in acute cholinergic toxicity.
- Pralidoxime reactivates acetylcholinesterase,
- provides endogenous anticholinergic effects, and
- detoxifies unbound organophosphates.

Oximes are used to work on the nicotinic neuromuscular junction and therefore should be given when there are signs of muscle weakness, especially if the weakness is occurring within the respiratory system.

Question 13

What is the dose and MOA for atropine in Organophosphates for adults?

Answer 13

Dose: IV/IO/IM atropine 1.2 mg aliquots

MOA: Muscirenic receptor antagonist combating the over stimulation of muscirenic receptors.

Note: It doesn’t affect the nicotinic receptors at the neuromuscular junction.

Question 14

What is the paediatric dose of atropine in organophosphate poisoning?

Answer 14

Paediatrics - IV/IO atropine 20 microg/kg
- single max dose 600 microg
- repeat once after 5 mins

Question 15

What are some one pill killers in paediatrics?
Cardiac (5 drugs)
Diabetic (1 drug)
Antidepressants (3 drugs)
Parkinson’s (1 drug)

Answer 15

Amlodipine
Nifedipine
Verapamil
Diltiazem
Clonidine

Gliclazide

Amitryptiline
Diazepam
Temazepam

Selegiline

Question 16

Some Ca+ channel blockers are more weighted towards it’s pump effects and others cardiovascular effects. Can you name some from each category?

Answer 16

Pump:
verapamil, diltiazem.

Cardiovascular:
nifedipine, amlodipine

Question 17

How does glucagon work in bradycardia patients? what is the dose? and what strength of literature is supportive of the tx?

Answer 17

glucagon acts as a back door to cAMP messengers system. This is the same second messenger which is activated by Adrenaline but in this case is independent of the adrenergic receptors.
Evidence is poor
Dose: 0.05mg/kg

Question 18

what are some common beta-blockers:

Answer 18

atenolol (also called Tenormin)
bisoprolol (also called Cardicor or Emcor)
carvedilol
labetalol (also called Trandate)
metoprolol (also called Betaloc or Lopresor)
propranolol (also called Inderal or Angilol)
sotalol

Question 19

What is the mechanism by which alcohol withdrawal may result in seizures.

Answer 19

GABA has binding site for ethanol. Chronic exposure results in regulation of GABA meaning that GABA is down regulated for stimulation.

Ethanol also binds to glutamate rendering it inactive for use as an excitation.

hence withdrawal will result in lower GABA stimulation and increase exocitation.

Question 20

What is the antidote for benzodiazepine OD’s and what is important in its consideration?

Answer 20

Flumazenil is the antidote but…
- it has been closely associated with seizures.
- benzodiazepines are largely associated with hypoventilation which is able to be managed adequately in most scenarios.

Question 21

What is the half-life of methadone and how might it play a role in our care?

Answer 21

With a half-life ranged from 15–207 hour. It’s continual effects are difficult to deal with. With extended wait times and long transportation times it might be important to consider naloxone infusion.

Question 22

what is the toxic dose of paracetamol?

Answer 22

10g or > 200mg/kg

Question 23

What is the drugs involved in and principals for the “triple whammy”?

Answer 23

The nephron of the kidneys are a sensitive to pressure in all aspects. This is why the renal system is able to auto regulate by itself. The balance is in the form of afferent and efferent blood flow as well as renal drainage. Any pathology that affects this has the ability to result in a AKI.

The triple whammy refers to a combination of drugs which may affect this balance:
- ACE inhibitor/ARBs (decrease glomerular filtration by causing vasodilation of the efferent renal arteriole)
- NSAID’s (afferent arteriolar vasoconstriction)
- Diuretics (causing hypovolaemia)

Dehydration, rhabdomyolysis, hyperglycaemia are all factors which should be considered as contributing factors.

Question 24

Quetiapine OD may present with hypotension. What is important to remember in these patients.

Answer 24

Beta 2 agonism in these patients may see paradoxical hypotension. stick with fluids and avoid adrenaline.