Toxicology

Question 1

In general how do you recognise poisioning?

Answer 1

Non specific symptoms
High index of suspicion
Course that a poison runs - toxidromes
Toxicology screening only helpful in a few

Question 2

Describe the clinical presentation of anticholinergics

Answer 2

Increased HR, BP, temp
Dilated pupils
Decreased bowel sounds and diaphoresis

Question 3

Describe the clinical presentation of cholinergics

Answer 3

Constricted pupils

Increased bowel sounds and diaphoresis

Question 4

Describe the clinical presentation of opioids

Answer 4

Decreased HR, BP, RR, temp, bowel sounds and diaphoresis

Constricted pupils

Question 5

Describe the clinical presentation of sympathomimetics

Answer 5

Increased HR, BP, temp, bowel sounds and diaphoresis

Dilated pupils

Question 6

Describe the clinical presentation of sedatives - hypnotics

Answer 6

Decreased HR, RR, BP, temp, bowel sounds and diaphoresis

Question 7

What is acetyl choline made from?

Answer 7

Choline and acetyl CoA

Question 8

What happens to acetyl CoA in the synaptic cleft?

Answer 8

Broken down by acetylcholinesterase to choline and acetyl CoA

Question 9

List some drugs that cause bradycardia

Answer 9

Beta blockers and opiates
Anticholinergics 
Calcium channel blockers
Ethanol 
Digoxin

Question 10

List some drugs that cause tachycardia

Answer 10

Free base - cocaine
Anticholinergic
Sympathomimetic
Theophylline, thyroid hormones

Question 11

List some drugs that cause hypothermia

Answer 11

Carbon monoxide 
Opiates 
Oral hypoglycaemics, insulin 
Liquor 
Sedative hypnotics

Question 12

List some drugs that cause hyperthermia

Answer 12

Nicotine
Antihistamines
Salicylates, Serotonin syndrome
Anticholinergics and antidepressants

Question 13

List some drugs that cause hypotension

Answer 13

Clonidine, calcium channel blockers (and beta blockers)
Reserpine (other antihypertensives)
Antidepressants
Sedative-hypnotics
Heroin (opiates)

Question 14

List some drugs that cause hypertension

Answer 14

Cocaine
Thyroid supplements
Sympathomimetic
Caffeine
Anticholinergic, amphetamines
Nicotine

Question 15

List some drugs that increase respiratory rate

Answer 15

PCP
ASA, amphetamines
Non-cardiogenic pulmonary oedema
Toxin induced metabolic acidosis

Question 16

List some drugs that decrease RR

Answer 16

Sedatives, strychnine, snakes
Liqour
Opiates, organophosphates
Weed

Question 17

Which drugs can we perform lab assessments for?

Answer 17

Paracetamol levels, salicylate levels, alcohol, anti-epileptic drug levels

Question 18

Which drugs does a urinary drug screen test for?

Answer 18

opiates, barbiturates, benzodiazepines, amphetamines, cocaine

Question 19

What is a normal anion gap?

Answer 19

Normal 12 ± 4 mEq/L

Question 20

Which drugs increase the anion gap

Answer 20

Ethylene glycol
Methanol
Salicylate poisoning

Question 21

What is a normal osmolal gap

Answer 21

Normal 5 ± 7 m osmol/kg

Question 22

Which drugs increase the osmolal gap?

Answer 22

Ethylene glycol
Methanol
Acetone, ethanol, isopropyl alcohol, propylene glycol

Question 23

What drugs is an ECG good at detecting

Answer 23

Digoxin toxicity
TCA overdose - sinus tachycardia, QT prolongation, increased QRS
Beta-blockers - conduction abnormalities

Question 24

What are the goals of toxicology treatment

Answer 24

Reduce absorption of the toxin (xenobiotic)

Enhance elimination

Neutralise toxin

Question 25

Describe the actions of paracetamol

Answer 25

``` Analgesia Relieves mild to moderate pain Efficacy equivalent to salicylates Inhibits brain prostaglandin synthetase Blocks pain impulses peripherally ``` Antipyrexic Efficacy similar to salicylates Inhibits prostaglandin synthetase in the hypothalamus

Question 26

Describe the absorption of paracetamol

Answer 26

Rapidly absorbed from the GI tract Peak concentration – between 60 and 120 minutes Peak plasma levels - within 4 hours Quicker with liquid preparations

Question 27

Describe the distribution of paracetamol

Answer 27

Approximately 20% plasma protein bound - may increase to 50% in overdose Has been reported to cross the placenta

Question 28

Describe paracetamol metabolism

Answer 28

Occurs via several pathways in the liver 52% by sulfation 42% by glucuronidation 2% excreted unchanged in the urine 4% biotransformed by C-P450 MFO system

Question 29

Describe paracetamol excretion

Answer 29

metabolic products are excreted by the kidneys minimal excretion into breast milk

Question 30

Describe the conjugation of paracetamol

Answer 30

In a healthy individual, about 95% of paracetamol is conjugated with glucuronide and excreted in the urine. Most of the remainder is conjugated with glutathione.

Question 31

What is the toxic dose of paracetamol

Answer 31

Adults > 150 mg/kg in acute dose Adults > 7.5 Grams in 24 hours (chronic) Children (<10 yrs): > 200 mg/kg

Question 32

Describe phase 1 paracetamol toxicity

Answer 32

30mins - 4 hrs Within a few hours after ingestion, patients experience anorexia, nausea, pallor, vomiting, and diaphoresis. Malaise may be present. Patient may appear normal

Question 33

Describe phase 2 paracetamol toxicity

Answer 33

24-48 hrs may seem like a period of recovery right upper quadrant pain may be present due to hepatic damage blood chemistry becomes abnormal with elevations of liver enzymes prothrombin times may be prolonged renal function may begin to deteriorate

Question 34

Describe phase 3 paracetamol toxicity

Answer 34

3-5 days characterized by symptoms of hepatic necrosis coagulation defects/ jaundice/ renal failure hepatic encephalopathy hepatic biopsy - centrilobular necrosis nausea and vomiting may reappear death is due to hepatic failure

Question 35

Describe phase 4 paracetamol toxicity

Answer 35

Complete resolution or death

Question 36

What is the antidote for paracetamol toxicity

Answer 36

N-acetylcysteine (NAC/ Parvolex) glutathione substitute

Question 37

Describe the mechanism of action of N-acetylcysteine

Answer 37

Prevents toxicity if administered in the acute setting Acts as a precursor for the synthesis of glutathione Acts intracellularly as a glutathione substitute Directly binds to NAPQI intracellularly Enhances reduction of NAPQI to a non-toxic substance Modifies toxin induced inflammatory response later in clinical course Increases Nitric Oxide synthesis & EDRF Acts as antioxidant thus improving oxygen delivery and extraction in extrahepatic organs – brain/ heart/ kidney

Question 38

When is a liver transplant needed for a paracetamol overdose patient?

Answer 38

``` pH < 7.3 after resuscitation INR > 6.5 Creatinine >300mmol/l Lactate > 3 mmol/l after resuscitation encephalopathy grade III/IV) ```

Question 39

List some class A drugs

Answer 39

Heroin/ cocaine/ crack/ MDMA ("ecstasy")/ methamphetamine/ LSD/ psilocybin mushrooms

Question 40

Name some class B drugs

Answer 40

Amphetamine/ cannabis/ codeine/ methylphenidate

Question 41

Name some Class C drugs

Answer 41

GHB/ ketamine/ diazepam/ flunitrazepam/ and most other tranquillisers/ sleeping tablets/ benzodiazepine as well as anabolic steroids

Question 42

Describe sympathomimetic syndrome

Answer 42

CVS tachycardia/ hypertension/ chest pain/ MI CNS nistagmus/ tremor/ headache/ seizures Psych. anxiety/ paranoia/ psychosis / hallucinations Resp. tachypnea/ dyspnea Metabolic lactic acidosis/ hyper-K/ hypo-Na/ high CK Ocular mydriasis/ blurred vision/ retinal hemorrhages GI nausea/vomiting/ diarrhoea/ abdominal pain

Question 43

Describe the management of serotonin syndrome

Answer 43

Supportive Cold IV fluids/ other methods of cooling Diazepam for agitation and seizures Metoprolol for Narrow Complex Tachycardia GTN for hypertension Close monitoring of the CK – rhabdomyolysis is common