Tox/Pharm OSCSE

Question 1

What is Hyperthermia?

Answer 1

Fever - resetting hypothalamus due to cytokines
Hyperthermia - temp > 37.5 with normal hypothalamic set point,despite thermoregulation process - imbalance of heat production and loss
Hyperpyrexia - temp >41

Question 2

Hyperthermia causes

Answer 2

Environmental - exertional and non-exertional heat stroke
Endocrine - hyperthyroid, phaeo
Drug - NMS, Serotonin syndrome, Malignant hyperpyrexia, MDMA/cocaine/ampetamines

Question 3

What is Malignant Hyperthermia? How is it managed?

Answer 3

Rare, AD, variable penetrance
Ryanodine receptor - excessive Ca release causing sustained muscle contraction
S&S: muscle rigidity, met and resp acidosis, increase O2 comsumption, heat prod.
Mx:1 - Recongition
2 - Immediate - help, remove agent, hyperventilate with 100% O2, use non-dep NMB
3 - Treatment - Dantrolene, treat high K, acidosis, DIC, arrhythmias
4 - Monitor - ICU, AKI, genetic counselling

Question 4

What is Neuroleptic Malignant Syndrome

Answer 4

Idiosyncratic reaction to antipsychotics (haloperidol, prochlorperazine)Insidious onset over week or so with altered mental status, autonomic disturbance, pyrexia and muscle rigidity (extrapyramidal signs)Mx - withdrawal, bromocriptine, dantrolene

Question 5

What is Serotonin Syndrome

Answer 5

Caused by: Serotonin agonists: LSD, pethidine breakdown Increase serotonin activity: MDMA
Prevention of reuptake: SSRIs, Tramadol
Prevention of breakdown: MAOi
Rapid onset: altered mental status, autonomic disturbance (fever) and neuromuscular excitability (tremor, clonus)
Mx: withdrawal, benzos, propanolol, dantrolene

Question 6

What is Heat Stroke

Answer 6

Altered mental status, anhydrosis and temp >40.6|
Non-exertional and exertional

Question 7

What is LA toxicity

Answer 7

0.25% = 2.5mg/ml, 1% = 10mg/mlBupivacaine max dose 2mg/kg
Clinical:
1 - Neuro - paraesthesia, visual/auditory disturbance, agitation, seizures, LOC
2 - CVS - blocks fast Na channels - long PR, QRS widening, long QT - VT/arrest
3 - Vascular - low conc cause vasoconstriction, at high conc cause vasodilation
Mx:
ABCDE
Benzos for seizures
Intralipid
Sodium bicarbonate

Question 8

What are the Kings Criteria for Paracetamol OD

Answer 8

Kings criteria:PH < 7.3 after resusOr all 3 of: INR >6.5, Creat >300, enceph 3 or 4

Question 9

What is PRIS

Answer 9

Metabolic acidosis and cardiac dysfunction, mainly bradycardia.
Plus one of:
1 - Rhabdo
2 - High triglycerides
3 - Renal failure

Impaired mitochondrial fatty acid metabolism leading to mitochondrial dysfunction, decreased oxygen use, anaerobic respiration and lactate production. Cardiac and skeletal muscle ischaemia and necrosis.
RF:High dose, young age, brain injury, Low carb/high fat intake (TPN), high catecholamine levels (sepsis), high steroid levels, hypoxia
Mx:
Stop
Alternative
Treat rhabdo
Treat cardiac issues
RRT
Ensure carbohydrate intake
ECMO

Question 10

What are the clinical features of calcium channel blocker overdose?

Answer 10

The presentation of CCB overdose is similar to beta-blocker overdose.
Symptoms:
1 Chest pain
2 Palpitations
3 Weakness
4 Dizziness, syncope, confusion, seizures
5 Diaphoresis, flushing
6 Headache
7 Nausea and vomiting

Signs:
1 Bradycardia (reflex tachycardia may result with peripheral vasodilatation andhypotension)
2 Arrhythmias
3 Heart block, bundle branch block
4 Hypotension
5 Low GCS
6 Weakness
7 Signs of GI dysmotility; may progress to bowel ischaemia +/- perforation if
severe

Question 11

What is the mechanism of CCB toxicity?

Answer 11

L-type calcium channel blockers decrease calcium influx in the cardiac conduction pathway. This leads to an inhibition of the rapid depolarisation in cardiac pacemaker cells and slows the plateau phase in cardiac myocytes and vascular
smooth muscle cells. Myosin and actin binding is diminished and muscle contraction reduced, causing decreased myocardial contractility and peripheral arterial vasodilation.

Cardiovascular effects
1 Peripheral and coronary vasodilatation
2 Negative chronotropy via SA node blockade, causing bradycardia
3 Negative dromotropy via AV blockade, producing conduction abnormalities
4 Negative inotropy, causing myocardial depression

Other effects
1 Suppression of pancreatic insulin release, resulting in hyperglycaemia
2 Decreased utilisation of free fatty acids by myocardium, causing myocardial
depression

Question 12

What is the management of a patient with CCB OD?

Answer 12

1 100% oxygen
2 Activated charcoal may be of use up to 4 hours after ingestion of sustained release preparations
3 Cardiovascular support
– Fluid boluses as required
– Inotropes/vasopressors as required
– Treatment of arrhythmias
– Atropine (often ineffective) +/– isoprenaline +/– pacing may be necessary
– VA ECMO may be considered in refractory cases
4 Calcium therapy
– Calcium chloride is preferred, given slowly via CVC if possible
– Serum calcium levels of 1.5–2 times normal have shown to have beneficial
effect on myocardial contractility
5 Glucagon therapy
– Glucagon promotes calcium entry into cells via a mechanism separate to adrenergic receptors
– Note its action opposes insulin but both can be used in the treatment of
CCB OD
6 High-dose insulin euglycaemic therapy (HIET) – associated with improved survival in animal models
– Positively inotropic, increases intracellular calcium transport and improves CCB-associated vasodilatation
– High doses combined with 50% glucose infusion
– 1–10 units/kg may be required
– Caution: hypokalaemia, hypoglycaemia – careful monitoring of bloods and GCS
– Targets of HIET:
i Improvement in myocardial ejection fraction (LVEF >50%)
ii Adequate heart rate (>60 bpm)
iii Restoration of acid-base balance, normoglycaemia and adequate urine
output (1–2 ml/kg/hour)
iv Reversal of cardiac conduction abnormalities (QRS <120 ms)
v Improved GCS
7 Intralipid (1.5 ml/kg bolus followed by infusion 0.25 ml/kg/hour) – acts as
a lipid sink for lipophilic molecules (e.g. verapamil)
– Used anecdotally with good effect