A Summary of Toxins and Their Antidotes

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

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 the antidote for isoniazid

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).

Carnitine is the antidote for valproate

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)

Dimercaprol is the antidote for lead poisoning

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.

 

References

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.