A Textbook of Clinical Pharmacology and Therapeutics

Table 54.5: Antidotes and other specific measures.
Overdose drug Antidote/other specific
measures
Paracetamol Acetylcysteine i.v.
Methionine p. o.
Iron Desferrioxamine
Cyanide Oxygen, dicobalt edetate
i.v. or sodium nitrite i.v.
followed by sodium
thiosulphate i.v.
Benzodiazepines Flumazenil i.v.
Beta-blockers Atropine
Glucagon
Isoprenaline
Carbon monoxide Oxygen
Hyperbaric oxygen
Methanol/ethylene glycol Ethanol, Fomepizole
Lead (inorganic) Sodium EDTA i.v.
Penicillamine p.o.
Dimercaptosuccinic acid (DMSA)
i.v. or p.o.
Mercury Dimercaptopropane sulphonate
(DMPS)
Dimercaptosuccinic acid (DMSA)
Dimercaprol
Penicillamine
Opioids Naloxone
Organophosphorus Atropine, pralidoxime
insecticides
Digoxin Digoxin-specific fab antibody
fragments
Calcium-channel blockers Calcium chloride or gluconate i.v.
Insulin 20% dextrose i.v.
Glucagon i.v. or i.m.
Note: DMSA, DMPS and 4-methyl-pyrazole are not licensed in the UK.
overdoses of 7.5 g or more may cause hepatic failure, less commonly
renal failure, and death (for discussion of the mechanism
involved see Chapter 5). The patient is usually asymptomatic
at the time of presentation, but may complain of nausea and
sweating. Right hypochondrial pain and anorexia may precede
the development of hepatic failure. Coma is rare unless a sedative
or opioid has been taken as well.
If a potentially toxic overdose is suspected, the stomach
should be emptied if within one hour of ingestion. The antidote
should be administered and blood taken for determination
of paracetamol concentration, prothrombin time (INR),
creatinine and liver enzymes. The decision to stop or continue
the antidote can be made at a later time. The plasma paracetamol
Plasma paracetamol concentration (mg/L)
1000
200
100
INTENTIONAL SELF-POISONING 447
Treatment line for
patients who are
malnourished or taking
enzyme-inducing drugs,
including alcohol
Usual treatment line
10
4 6 8 10 12 14 16
Time after ingestion (h)
Figure 54.1: Treatment graph for paracetamol overdose. The
graph provides guidance on the need for acetylcysteine
treatment. The time (in hours) after ingestion is often uncertain.
If in doubt – treat.
concentration should be obtained urgently and related to the
graph shown in Figure 54.1, which plots time from ingestion
against plasma paracetamol concentration and probability of
liver damage. A more precise treatment graph is printed in the
British National Formulary (it is unreliable for staggered overdoses).
If doubt exists concerning the time of ingestion it is
better to err on the side of caution and give the antidote.
Intravenous acetylcysteine and/or oral methionine are
potentially life-saving antidotes and are most effective if given
within eight hours of ingestion; benefit is obtained up to 24
hours after ingestion. For serious paracetamol overdoses seen
greater than 24 hours after ingestion, advice should be sought
from poisons or liver specialists. Acetylcysteine is administered
as an intravenous infusion. In approximately 5% of
patients, pseudoallergic reactions occur, which are usually
mild. If hypotension or wheezing occurs, it is recommended
that the infusion be stopped and an antihistamine administered
parenterally. If the reaction has completely resolved,
acetylcysteine may be restarted at a lower infusion rate.
Alternatively, methionine may be used (see below).
Patients who are taking enzyme-inducing drugs (e.g.
phenytoin, carbamazepine) and chronic alcoholics are at a
higher risk of hepatic necrosis following paracetamol overdose.
The INR is the first indicator of hepatic damage. If the
INR and serum creatinine are normal when repeated at least
24 hours after the overdose, significant hepatic or renal damage
is unlikely.