Toxicology Flashcards
Regarding ethylene glycol overdose, which of the following statements is correct?
A It causes formic acid crystals in urine
B It causes metabolic alkalosis
C Toxicity is due to polycyclic hydrocarbon ring structure
D Fomepizole is used as a temporising antidote
D
Explanation
Ethylene glycol toxicity results in a severe metabolic acidosis secondary to the accumulation of glycolic acid and lactate. Calcium oxalate crystals form in the tissues, including the renal tubules, myocardium, muscles and brain. Hypoclacaemia follows and acute renal failure occurs.
Haemodialysis is the definitive treatment.
Metabolism of ethylene glycol into its toxic metabolites can be blocked by inhibiting the enzyme alcohol dehydrogenase with a competing drug-ethanol or fomepizole. Ethanol is harder to achieve a safe and effective blood level
The other toxic metabolite-methanol produces the toxic metabolite formic acid leading to severe metabolic acidosis, coma and blindness
Regarding cocaine, which statement is incorrect?
A It has central and peripheral effects
B It blocks re-uptake of catecholamines
C It inhibits monoamine oxidase
D It has local anaesthetic effects
C
Explanation
Cocaine’s sympathomimetic effects are due to the blockade of presynaptic catecholamine re-uptake. It also has a sodium channel blockade effect and local anaesthetic effect. CNS effects results in excitation, seizure and in severe cases hyperthermia. It is an ester type local anaesthetic.
Note: elevated extracellular calcium partially antagonises the action of local anaesthetics, conversely increased levels of potassium enhances the level of the local effect
Cocaine works in the CNS by inhibiting dopamine reuptake into neurons in the “pleasure centres” of the brain. It produces an amphetamine like psychological effect that is shorter lasting and more intense than amphetamines
Yet another overdose presents to your ED. You examine them and find them to have: blurred vision, urinary retention, dilated pupils and to be very agitated. What have they taken?
A Tricyclic antidepressant
B Morphine
C Cocaine
D MDMA
A
Explanation
Tricyclic antidepressant overdose causes anticholinergic features which are represented in the question. A good way to remember all of them are: blind as a bat- mydriases, mad as a hatter- delirium, red as a beet-flushing and vasodilatation, dry as a chip- anhydrosis”. Other important features are urinary retention and constipation
Regarding methanol intoxication, which of the following statements is correct?
A It is treated in part with activated charcoal
B It is due to formation of oxalic acid
C It can be treated with 4 methylpyrazole
D It is partly due to the inhibition of aldehyde dehydrogenase
C
Explanation
Methanol is metabolized in the liver by alcohol dehydrogenase to formaldehyde, which in turn is metabolized by aldehyde dehydrogenase to formic acid. Ethanol or fomepizole (4-methylpyrazole) competitively inhibits alcohol dehydrogenase so that methanol cannot be metabolized to formaldehyde. GIT decontamination is not recommended
Regarding cannabinoids, which of the following statements is correct?
A They have an antipsychotic action
B They act on a number of non-specific receptors
C They produce tachycardia
D They constrict the pupils
C
Explanation
Cananbinoids are a powerful psychoactive compound (highly lipid soluble). They act on a protein coupled cannabinoid receptor. THC causes disinhibition of dopamine neurons, mainly by the presynaptic inhibition of GABA neurons in the VTA. The most prominent effects are euphoria and relaxation. Two characteristic physiological signs are increased pulse rate and reddening of the conjunctiva. Pupil sizes do not change
Regarding Marijuana, which of the following statements is correct?
A Hydroponic indoor-grown varieties are not more potent than soil grown
B It causes conjunctival hyperaemia and tachycardia
C It causes miosis
D Has antipsychotic properties
B
Explanation
Cananbinoids are a powerful psychoactive compound (highly lipid soluble). They act on a protein coupled cannabinoid receptor. THC causes disinhibition of dopamine neurons; mainly by the presynaptic inhibition of GABA neurons in the VTA. The most prominent effects are euphoria and relaxation. Two characteristic physiological sings are increased pulse rate and reddening of the conjunctiva. Pupil sizes do not change
A 30 year old male patient presents with an acute myocardial infarction. Which drug has most likely caused this?
A Increased adrenalin production due to heroin
B Increased serotonin due to fluoxetine
C Increased noradrenaline effects of cocaine
D Monoamineoxidase inhibition by amphetamine derivative
C
Explanation
The sympathomimetic effects of cocaine are due to the blockade of presynaptic catecholamine re-uptake of noradrenaline (and dopamine).
Increased circulating catecholamine concentrations cause excessive stimulation of alpha- and beta-adrenoceptors and can result in vascular dissection, intracranial haemorrhage and acute cardiomyopathy.
Vasospasm and endothelial fissuring result in acute coronary syndrome
Extra: Use of cocaine may have several consequences:
There is a risk of myocardial infarction, both the subjects with coronary atheroma and those with normal coronary arteries (when it is unclear if the mechanism is thrombosis, embolism, or spasm),
There is a risk of spontaneous cerebral haemorrhage, which may occur even in subjects with normal blood pressure.
This may be a consequence of arterial malformation, ischaemia, arterial vasoconstriction, cerebral vasculitis, cardiac rhythm disturbance, or myocardial infarction
Regarding ethanol metabolism which of the following statements is correct?
A The alcohol dehydrogenase pathway is inducible
B It obeys zero order kinetics
C The MEOS system is the main pathway
D Most alcohol dehydrogenase is found in the stomach
B
Explanation
The main pathway of ethanol metabolism is: alcohol is oxidized by alcohol dehydrogenase to acetaldehyde, which is in turn metabolized by aldehyde dehydrogenase to acetyl CoA. Both steps involve the reduction of NAD to NADH. Metabolism follows zero order kinetic which means that a constant amount is of ethanol is metabolized per unit time. Most of the alcohol dehydrogenase is found in the liver
Extra: for interest only
Kinetics of Alcohol Elimination in-vivo
Alcohol elimination was originally believed to be a zero-order process, meaning that alcohol was removed from the body at a constant rate, independent of the concentration of alcohol. Since the Km of most ADH isozymes for ethanol is low (about 1 mM), ADH is saturated at low concentrations of alcohol, hence, the overall elimination process proceeds at maximal velocity and is independent of the alcohol concentration. However, linearity is not observed at low alcohol concentration since ADH is no longer saturated with ethanol. Alcohol elimination now follows Michaelis-Menten kinetics; the rate of change in the concentration of alcohol depends on the concentration of alcohol and the kinetic constants Km and Vmax
In addition, because the metabolism of alcohol by CYP2E1 and some ADH isozymes, such as ADH4 involves a high Km for alcohol system, a concentration-dependent rate of ethanol elimination can be observed, with higher rates of alcohol elimination at higher blood alcohol concentrations. Because of this concentration dependence, it is not possible to estimate one single rate of alcohol metabolism. Concentration-dependent metabolism of alcohol has been observed in some, but not all studies on alcohol elimination.
Source: alcohol metabolism, clinical liver disease, 2012
The type of metabolism which leads to the accumulation of toxic metabolites in a paracetamol overdose is?
A Sulphation
B Glucuronidation
C Methylation
D Hydroxylation
D
Explanation
Acetaminophen metabolism by hepatocytes by
1. about 90% undergoing glucuronidation/sulfation to inactive metabolites (saturable phase 2 rxns). Glucoronidation and sulfation are adequate for metabolism of therapeutic doses of paracetamol metabolism.
2. About 2% cleared by urine unchanged.
3. In overdose, glucuronidation/sulfation will be exhausted and remaining acetaminophen undergoes CYP oxidation (this is a hydroxylation reaction) to become toxic intermediate NAPQ1- TOXIC 4.. NAPQ1 can either be detoxified by gluthatione to mercapturic acid OR undergo cell death—> Hepatotoxicity.
Acetaminophen is conjugated to harmless glucuronide and sulfate metabolites when it is taken in normal doses. If large overdose is taken, the metabolic pathway gets overwhelmed and a P450 dependent system converts some of the drug to a reactive intermediate NAPQI. If the gluthathione stores are exhausted (in an overdose), NAPQI binds with proteins in the hepatocytes inducing liver damage.
Example of P450-dependent oxidation reactions: hydroxylation, N-dealkylation, O-dealkylation, N-oxidation, S-oxidation and deamination. Other type I reactions: oxidation P450 independent systems, reductions and hydrolyses.
Example of phase II reactions: glucuronidation, acetylation, glutathione conjugation, glycine conjugation, sulfate conjugation and methylation.
Alkalinisation of urine increases the excretion of which drug?
A Quinidine
B Phenobarbitone
C Cocaine
D Amphetamines
B
Explanation
An alkaline urinary pH can result in some drugs being predominantly in an ionised form and unable to be reabsorbed across the tubular epithelium. Phenobarbitone and salicylate are two types of drugs which follow this principle
A young woman presents to the ED with increased temperature, rhabdomyolysis and sweating, which is the likely drug?
A Aspirin
B Heroin
C Amitriptyline
D Methylamphetamine
D
Explanation
Stimulant drugs include illegal ones like amphetamines (MDMA, ecstasy), methamphetamine (cranck), cocaine (crack) as well as legal substances e.g. pseudoephedrine (sudafed) and caffeine (plus other dietary stimulants or fat burners). At low doses euphoria and wakefulness are accompanied by a sense of power and well being. At higher doses, restlessness, agitation and psychosis appear together with tachycardia and hypertension. Prolonged muscular activity may contribute to hyperthermia and rhabdomyolysis. Severe hyperthermia >40C can lead to brain damage and multi-organ failure. Sweating is a classical feature of amphetamine ingestion. The apocrine sweat glands located on the palms of the hands and a few other areas, respond to adrenoceptor stimulants with increased sweat production. Amphetamine is an example of a non catecholamine sympathomimetic drug
A 30yr female presents to the ED 5hrs post ingestion of a drug. She is agitated, hypertensive, febrile and is hyperreflexic with clonus. The most likely causative drug?
A Fluoxetine
B Benztropine
C Prochlorperazine
D Chlorpromazine
A
Explanation
Serotonin syndrome: Sweaty, tachycardic, hot, very increased muscle tone, hyper-reflexia and clonus, dilated pupils, diarrhoea.
Drugs implicated: SSRI/SNRI/TCA/tramadol/amphetamines/St John’s wort.
Rx supportive, cooling and benzos.
What medication is used to decontaminate the body following a toxic iron ingestion?
A Desferioxamine
B EDTA
C Charcoal
D Penicillamine
A
Explanation
Deferoxamine (desferrioxamine), a potent iron-chelating compound, can be given IVI to bind iron that has already been absorbed and to promote its excretion in urine and faeces.
Activated charcoal, a highly effective adsorbent for most toxins, DOES NOT binds iron and thus is ineffective.
EDTA is an IVI chelator indicated in acute lead toxicity.
Penicillamine, succimer, dimercaprol are chelators for mercury poisoning
Which pharmacokinetic property decreases the usefulness of dialysis in treatment of overdose?
A Low molecular weight
B Rapid redistribution from tissues
C Slow endogenous elimination
D High volume of distribution
D
Explanation
The efficiency of dialysis in the overdose situation is a function of the molecular weight, water solubility, protein binding, endogenous clearance, and distribution in the body of the specific toxin.
Toxicological handbook writes that haemodialysis effectively enhances elimination of any drug that is a small molecule, has a small volume of distribution, rapid redistribution from tissues and plasma, slow endogenous elimination and not highly protein bound
What is the principle mechanism of NAC in paracetamol toxicity?
A Conversion of NAPQI to paracetamol
B Indirectly binding to NAPQI
C Increased urinary excretion of NAPQI
D Provision of glutathione
D
Explanation
NAC prevents paracetamol-induced hepatotoxicity by four possible mechanisms:
- Increased glutathione availability (sulfhydryl donor): glutathione substitute
- Direct binding to NAPQI
- Provision of inorganic sulphate
- Reduction of NAPQI back to paracetamol.
Source: https://litfl.com/pharm-101-n-acetyl-cysteine/
A 22-year-old man presents with fever, rigidity, clonus and rhabdomyolysis after ingestion of an unknown substance. Which is the most likely ingested substance?
A Oxycodone
B Paracetamol
C MDMA
D Amitriptyline
C
Explanation
Serotonin syndrome causes hypertonia, hyperthermia, and clonus. Paracetamol causes a silent toxicity initially. Oxycodone causes respiratory and CNS depression. TCAs cause initially antimuscarinic effects, following by agitation, seizures, and coma.
