ANTIDOTES

2010

ANTIDOTES are agents used to counteract the effects of toxic substances or overdose with drugs. They are used in a wide variety of circumstances and can work in many ways.

First, where the poison works by stimulating, or over-stimulating, a distinct set of pharmacological receptors, treatment is normally straightforward since the use of an appropriate receptor antagonist can be used to reduce or completely block the effects of the poison. For example, naloxone is an opioid receptor ANTAGONIST and can be used as an antidote to an overdose by a wide range of a opioid receptor agonists, including the narcotic analgesics diamorphine (heroin), morphine, methadone and pethidine. It is quick-acting and effectively reverses the respiratory depression, coma or convulsions that result from such an overdose; also, it can be used at the end of operations to reverse respiratory depression caused by narcotic analgesics and in newborn babies.

Second, poisoning by some toxic substances is effectively counteracted by an antidote that binds to the poison, rendering it relatively inert and facilitating its excretion. For example, a CHELATING AGENT can be used as an antidote to metal poisoning, where it has a high affinity for those particular metallic ions. Chelating agents are used to treat too high levels of metals of external origin (accidental or environmental), abnormal metabolism (e.g. high levels of copper in Wilson’s disease; iron-overload in P-thalassaemia), or in disease (rheumatoid arthritis). Examples of useful chelating agents include desferrioxamine (iron overload), dicobalt edetate (cyanide poisoning), dimercaprol (As, Au. Hg; also Lewisite) and sodium calcium edetate (Pb), and penicillamine (Cu, Pb; useful in rheumatoid arthritis and Wilson’s disease).

An overdose with paracetamol can be treated with acetylcysteine and methionine. which act as antidotes to prevent the delayed serious toxic effect on the liver due to active metabolites. A different principle is used in treating ANTICHOLINESTERASE poisoning (insecticides or in chemical warfare). Here pralidoxime is an antidote that acts as a cholinesterase reactivator, and is highly effective (taken with atropine) in preventing irreversible changes to the cholinesterase enzymes. An antivenom is an antidote to the poison in a snakebite, a scorpion’s sting or a bite from any other poisonous creature. Normally, a specific antiserum is used by injection. Similarly, in cardiac glycoside overdose (e.g. digoxin) the proprietary agent Digibind™, which comprises antibody fragments that react with the glycosides, can be used in emergency treatment.