A Textbook of Clinical Pharmacology and Therapeutics

INTENTIONALSELF-POISONING 447

overdoses of 7.5 g or more may cause hepatic failure, less com-
monly 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 seda-
tive 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 anti-
dote should be administered and blood taken for determina-
tion of paracetamolconcentration, 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

concentration should be obtained urgently and related to the

graph shown in Figure 54.1, which plots time from ingestion

against plasma paracetamolconcentration and probability of

liver damage. A more precise treatment graph is printed in the

British National Formulary (it is unreliable for staggered over-

doses). If doubt exists concerning the time of ingestion it is

better to err on the side of caution and give the antidote.

Intravenousacetylcysteineand/or oral methionineare

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 paracetamoloverdoses seen

greater than 24 hours after ingestion, advice should be sought

from poisons or liver specialists. Acetylcysteineis adminis-

tered 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 adminis-

tered parenterally. If the reaction has completely resolved,

acetylcysteine may be restarted at a lower infusion rate.

Alternatively, methioninemay 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 paracetamolover-

dose. 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 dam-

age is unlikely.

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.

Usual treatment line

Treatment line for

patients who are

malnourished or taking

enzyme-inducing drugs,

including alcohol

Plasma paracetamol concentration (mg/L)

200

1000

100

10

46 810121416

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.