Toxicology Flashcards
In general how do you recognise poisioning?
Non specific symptoms
High index of suspicion
Course that a poison runs - toxidromes
Toxicology screening only helpful in a few
Describe the clinical presentation of anticholinergics
Increased HR, BP, temp
Dilated pupils
Decreased bowel sounds and diaphoresis
Describe the clinical presentation of cholinergics
Constricted pupils
Increased bowel sounds and diaphoresis
Describe the clinical presentation of opioids
Decreased HR, BP, RR, temp, bowel sounds and diaphoresis
Constricted pupils
Describe the clinical presentation of sympathomimetics
Increased HR, BP, temp, bowel sounds and diaphoresis
Dilated pupils
Describe the clinical presentation of sedatives - hypnotics
Decreased HR, RR, BP, temp, bowel sounds and diaphoresis
What is acetyl choline made from?
Choline and acetyl CoA
What happens to acetyl CoA in the synaptic cleft?
Broken down by acetylcholinesterase to choline and acetyl CoA
List some drugs that cause bradycardia
Beta blockers and opiates Anticholinergics Calcium channel blockers Ethanol Digoxin
List some drugs that cause tachycardia
Free base - cocaine
Anticholinergic
Sympathomimetic
Theophylline, thyroid hormones
List some drugs that cause hypothermia
Carbon monoxide Opiates Oral hypoglycaemics, insulin Liquor Sedative hypnotics
List some drugs that cause hyperthermia
Nicotine
Antihistamines
Salicylates, Serotonin syndrome
Anticholinergics and antidepressants
List some drugs that cause hypotension
Clonidine, calcium channel blockers (and beta blockers) Reserpine (other antihypertensives) Antidepressants Sedative-hypnotics Heroin (opiates)
List some drugs that cause hypertension
Cocaine Thyroid supplements Sympathomimetic Caffeine Anticholinergic, amphetamines Nicotine
List some drugs that increase respiratory rate
PCP
ASA, amphetamines
Non-cardiogenic pulmonary oedema
Toxin induced metabolic acidosis
List some drugs that decrease RR
Sedatives, strychnine, snakes
Liqour
Opiates, organophosphates
Weed
Which drugs can we perform lab assessments for?
Paracetamol levels, salicylate levels, alcohol, anti-epileptic drug levels
Which drugs does a urinary drug screen test for?
opiates, barbiturates, benzodiazepines, amphetamines, cocaine
What is a normal anion gap?
Normal 12 ± 4 mEq/L
Which drugs increase the anion gap
Ethylene glycol
Methanol
Salicylate poisoning
What is a normal osmolal gap
Normal 5 ± 7 m osmol/kg
Which drugs increase the osmolal gap?
Ethylene glycol
Methanol
Acetone, ethanol, isopropyl alcohol, propylene glycol
What drugs is an ECG good at detecting
Digoxin toxicity
TCA overdose - sinus tachycardia, QT prolongation, increased QRS
Beta-blockers - conduction abnormalities
What are the goals of toxicology treatment
Reduce absorption of the toxin (xenobiotic)
Enhance elimination
Neutralise toxin
Describe the actions of paracetamol
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
Describe the absorption of paracetamol
Rapidly absorbed from the GI tract
Peak concentration – between 60 and 120 minutes
Peak plasma levels - within 4 hours
Quicker with liquid preparations
Describe the distribution of paracetamol
Approximately 20% plasma protein bound - may increase to 50% in overdose
Has been reported to cross the placenta
Describe paracetamol metabolism
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
Describe paracetamol excretion
metabolic products are excreted by the kidneys
minimal excretion into breast milk
Describe the conjugation of paracetamol
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.
What is the toxic dose of paracetamol
Adults > 150 mg/kg in acute dose
Adults > 7.5 Grams in 24 hours (chronic)
Children (<10 yrs): > 200 mg/kg
Describe phase 1 paracetamol toxicity
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
Describe phase 2 paracetamol toxicity
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
Describe phase 3 paracetamol toxicity
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
Describe phase 4 paracetamol toxicity
Complete resolution or death
What is the antidote for paracetamol toxicity
N-acetylcysteine (NAC/ Parvolex)
glutathione substitute
Describe the mechanism of action of N-acetylcysteine
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
When is a liver transplant needed for a paracetamol overdose patient?
pH < 7.3 after resuscitation INR > 6.5 Creatinine >300mmol/l Lactate > 3 mmol/l after resuscitation encephalopathy grade III/IV)
List some class A drugs
Heroin/ cocaine/ crack/ MDMA (“ecstasy”)/ methamphetamine/ LSD/ psilocybin mushrooms
Name some class B drugs
Amphetamine/ cannabis/ codeine/ methylphenidate
Name some Class C drugs
GHB/ ketamine/ diazepam/ flunitrazepam/ and most other tranquillisers/ sleeping tablets/ benzodiazepine as well as anabolic steroids
Describe sympathomimetic syndrome
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
Describe the management of serotonin syndrome
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
