Very often the college gets lazy and lists a few toxins, with the intention that the candidates can then write down the matching antidotes. It is quick to mark (tick tick tick) and requires little though from the question writers. The candidates also appreciate it; it is easy marks, and having appeared many times in the past papers, the act of matching poisons and their antidotes has become an automatism for many of us. Unfortunately, this specific panel of toxins has not been seen for a few years. Previous examples include the following SAQs:
The question usually looks something like this: "List an antidote (one (1) drug specific to the agent) in the event of an overdose with each of the agents listed below in the table." A table of toxins is then provided. The table below is not from any specific question - it has been concocted from all previous college answers to questions of this form. Some poison-antidote combinations have been added by the author here because they are worth knowing, even if they have never come up in such a question. These errata are italicised so people can tell which are the "canonical" college answers and which are the fevered rant of a madman.
Agent |
Antidote |
Benzodiazepines |
Flumazenil |
Beta blockers |
Glucagon, high dose insulin |
Bupivacaine |
Intralipid |
Cyanide |
Cyanocbalamin/ Sodium thiosulphate |
Digoxin |
Fab |
Ethylene glycol |
Ethyl alcohol, Fomepizole |
Isoniazid |
Pyridoxine |
Methanol |
Ethyl alcohol, Fomepizole |
Methemoglobinemia |
Methylene blue, vitamin C (ascorbic acid) |
Organophosphate |
Atropine, pralidoxime |
Opiates |
Naloxone |
Lead |
Dimercaprol, BAL |
Valproate |
Carnitine |
Iron |
Desferrioxamine |
Heparin |
Protamine |
Warfarin |
Vitamin K |
Calcium channel blockers |
Calcium, glucagon, high dose insulin |
Clonidine |
Naloxone |
Magnesium |
Calcium |
Methotrexate |
Folinic acid |
Antimuscarinic agents |
Physostigmine |
Tricyclic antidepressants |
Sodium bicarbonate |
Class 1 antiarrhythmics |
Sodium bicarbonate |
Paraquat |
Fuller's Earth, bentonite clay |
Dystonic crisis due to classical antipsychotics |
Benztropine |
Serotonin syndrome |
Cyproheptadine |
Carbon monoxide |
Oxygen, potentially even hyperbaric oxygen |
Radioactive heavy metals |
Prussian blue |
In the list provided by the college, there are standard drugs which everyone would know the antidotes for, and non-standard ones which may not be totally familiar to people without a toxicology background.
Pyridoxine is a co-factor in the synthesis of GABA; isoniazid interferes with this synthesis, and causes seizures in overdose. The supplementation of pyridoxine seems to prevent the worst of isoniazid toxicity (it seems the inhibition of lactate metabolism is not such a big deal).
Or so it is thought. The most disturbing aspects of valproate toxicity are valproate-induced hyperammonaemic encephalopathy and hepatotoxicity. Carnitine deficiency is implicated in both, and seems to be caused by chronic valproate administration more so than acute. The reason for the efficacy of carnitine in valproate overdose seems to stem from its central role in beta-oxidation of long chain fatty acids (which is the metabolic pathway taken by valproate). It appears to hasten the resolution of coma, and it seems to protect the liver from necrosis; the mechanism is thought to be the prevention of accumulation of toxic metabolites of valproate. (Incidentally, carnitine is also being considered as a rescue therapy for propofol infusion syndrome)
And mercury, antimony, gold, chrome, cobalt and nickel poisoning. First developed to treat arsenic poisoning during the Second World War, dimercaprol (or British Anti-Lewisite, BAL) is a chelating agent which competes for heavy metal ions with the thiol groups of enzymes, thus preventing the inactivation of those enzymes. The metal-dimercaprol complex is then renally excreted.
Dimercaprol itself is horribly toxic, and its use in heavy metal poisoning is limited to situations where heavy metal levels are high, toxicity is already severe, and water-soluble analogues of dimercaprol (eg. DMPS and DMSA) are not available.
This is more of an aside, used to address the expectations of Question 3 from the first paper of 2022, where "the rationale for use of the pharmacological intervention including the mechanism of action" was expected for the antidotes to digoxin, tricyclics, beta blockers and lignocaine. Beta blocker overdose, digoxin toxicity and tricyclic antidepressant overdose are covered in detail elsewhere, and local anaesthetic toxicity is one of the syllabus items from the First Part exam, making this short summary somewhat redundant; but to collect all these items together here felt like the right thing to do.
Rationale for digoxin-specific Fab fragments in digoxin overdose:
Rationale for sodium bicarbonate in tricyclic antidepressant overdose:
Rationale for high dose insulin euglycaemic therapy in beta-blocker overdose:
Rationale for lipid infusion in local anaesthetic toxicity:
Murakami, K., et al. "Effect of L‐Carnitine Supplementation on Acute Valproate Intoxication." Epilepsia 37.7 (1996): 687-688.
Lheureux, Philippe ER, et al. "Science review: Carnitine in the treatment of valproic acid-induced toxicity–what is the evidence?." Critical care 9.5 (2005): 431.
Kam, P. C. A., and D. Cardone. "Propofol infusion syndrome." Anaesthesia 62.7 (2007): 690-701.
Peters, Rudolph A., Lloyd A. Stocken, and R. H. S. Thompson. "British anti-lewisite (BAL)." Nature 156.Nov. 24 (1945): 616.
There is an indepth entry on dimercaprol in www.inchem.org.