Toxicology

Toxicology
IS the science which deals with the investigations of a
poisoned patient.
Poisoning could be by:-(1)Foods.
(2)Drugs.
(3)To committee suicide (Drinking of hair dye).
Important tests that should be performed on the
patient with suspeccted poisoning include:-(A)Serum
urea.
(B)Electrolytes(K+ , Na+).

(C)Blood glucose.
(D)Liver function tests.
(E)Blood gases & pH.
Common drugs which may cause poisoning:-

(1)Paracetamol

It is essential to measure plasma drug concentrations

in suspected paracetamol poisoning because:(A)A metabolite of paracetamol is hepatotoxic ; the
patient may die of liver failure despite recovery from
the immediate effects.
Approximately 80% of ingested paracetampl is
converted in the liver to a toxic metabolite , N-acetyl-pbenzoquinoneimine (NABQI) , which is usually
detoxified by conjugation with glutathione.

If large amounts of paracetamol are taken , the hepatic

stores of glutathione become depleted , and NABQI
binds irreversibly to proteins within the hepatocyte ,
producing centriole necrosis.
In some cases , renal damage is also produced by a
similar mechanism.
(B)A specific antidote to the hepatotoxic effect is
available.

(C)The antidote is only useful if given within a defined

period of time and if defined plasma concentrations are
reached.
(D)The likelihood of hepatotoxicity cannot be
predicated from the clinical picture at presentation.
N-acetylcysteine , cysteamine and methionine are all
relatively effective antidotes , because they enable
paracetamol to be converted to non-toxic metabolites.
N-acetylcysteine is the least toxic and is most often
used.

Cysteamine may cause nausea , vomiting , abdominal

pain and cardiac arrhythmias.
Methionine , although less toxic , may cause
vomiting.
N-acetylcysteine is only effective in clearly defined
circumstances and should only be given after the
following factors have been taken into account:-

(A)Timing of the specimen

Plasma concentrations of the drug cannot be
interpretd and should not be measured , until
absorption and distribution are nearly complete , at
about four hours after ingestion.
If treatment is to be effective it should be started as
soon as possible following ingestion and is probably
ineffective after about 20 hours.
Concentrations should be measured on specimens
taken as early as possible between four and 20 hours
after ingestion.

(B)Plasma paracetamol concentrations

As a rough guide , treatment is indicted if the plasma
paracetamol concentration is 200mg/l(1300mol/l) or
more at 15 hours after the dose and falls above the solid
line in below fig.

Results of serial measurement of plasma transaminase

activities and prothrombin time may indicate liver
involvement , which may become apparent about three
days after ingestion.

(2)Salicylates

Patients often present with nausea , vomiting and

increased rate of respiration.
Dehydration , due to vomiting , is often severe.
Acid-base disturbances are common-usually a mixed
respiratory alkalosis and metabolic acidosis-but if
vomiting is severe , a metabolic alkalosis can develop.
The diagnosis is confirmed by measuring
plasma[salicylate].
Blood-gas analysis may also be indicated.

In patients with plasma[salicylate] above

3.6mmol/l(500mg/dl) ,or in children < 5 years plasma
[saicylate] above 2.5mmol/l(350mg/dl) , treatment
with repeated oral administration of activated charcoal
and IV infusion of sodium bicarbonate is often used to
increase the excretion of the drug into urine.
Haemodialysis may also be required in the severely
poisoned patient[saicylate] aove 5.1mmol/l(700mg/dl)
or if renal function is impaired.

(3)Digoxin

Digoxin toxicity is a poisoning that occurs when

excess doses of digoxin.

Classification
Digoxin toxicity is often divided into acute or chronic.
The therapeutic level for digoxin is 0.5-2 ng/mL.
Low serum potassium increases the risk of digoxin
toxicity and cardiac dysrhythmias.
The classic arrhythmia is a paroxysmal atrial
tachycardia with block.

Digoxin toxicity occurs because it is very easy to

overdose.
Overdose commonly occurs because its therapeutic
effect works only within a very narrow window.
The most common source of digoxin is from the
Foxglove plant.

Symptoms
Symptoms include hypersalivation, fatigue,
nausea/vomiting, changes in heart rate and rhythm,
loss of appetite (anorexia), diarrhea, visual disturbances
(yellow or green halos around objects), confusion,
dizziness, nightmares, agitation, and/or depression, as
well as a higher acute sense of sensual activities.

Investigation
(1)Concetration of digoxin in blood
(2)Serum potassium.

Treatment
The primary treatment of digoxin toxicity is digoxin
immune Fab.
Digoxin should not be given if the apical heart rate is
below 60 BPM (beats per minute).

Other treatment that may be tried to treat lifethreatening arrhythmias, until digoxin Immune Fab is
acquired are magnesium, phenytoin, and lidocaine.

(4)Theophylline

May be useful , especially in acute asthmatic attacks

that are not responding clinically , results may help to
ensure that the poor response is not due to
underdosage , and , if it is not , that increasing the
dosage will not lead to toxic plasma levels.
Theophylline and its active metabolite caffeine are
used in the mangement of recurrent apnoea in the
newborn ; at this age their clearance is slow and
theophylline is partially metabolized to caffine.

Both plasma theophylline and caffeine concentrations

may need to be assayed if theophylline has been given ,
in order to assess if theophylline or toxic effects.
Samples for theophylline assays should be taken at
between two and four hours after the last dose.

(7)Iron overdosage

Is commonest in children who may mistake the

tablets for sweets.
Desferrioxamine chelates iron and the chelate is
excreted in the urine.
The concentration of plasma iron at which treatment
is indicated have not been clearly defined , but
concentrations above 90mol/l(500g/dl) in young
children and above 150mol/l(840g/dl) in adults are
said to be definite indications for treatment.
If there is an doubt desferrioxamine should be given.

(8)Insulin

(5)Ethanol

The acute effects of over-indulgence in ethanol

sometimes lead to admission to hospitals.
If the diagnosis is in doubt , plasma[ethanol] should
be measured.
Patients taking a deliberate drug over-dose frequently
take alcohol with the drug.
Some patients may have drunk methylated spirits
rather than ethanol , and rapid identification of both
methanol and ethanol is then needed.

(6)Methanol & ethylene glycol

Methanol is metabolised to formaldehyde and formic
acid , while ethylene glycol is metabolised to a number
of protects including glycoaldehyde , glycoxylic and
oxalic acids.

Many of these are toxic and also give rise to metabolic

acidosis.
Sever methanol poisoning frequently leads to
permanent visual impairment or complete blindness.
Hypocalcaemia occurs with ethylene glycol poisoning.
As little as 10ml of methanol can cause blindness.
Lethal doses can be as little as 30ml for methanol and
100ml for ethylene glycol.

Urgent measurement of plasma concentrations of

these substances is required if poisoning is suspected ,
but it may be difficult to get such measurements done
out of normal laboratory hours.
Measurement of the osmolar gap (i.e. the difference
between the measured and calculated osmolality) is
useful in all suspecyted cases of methanol/ethylene
glycolin gestion if the patient presents early after the
overdose.

An osmolar gap >10mos/Kg is widely regarded as

being indicative of an abnormality but others have
suggested that a value >6mos/Kg should be regarded as
abnormal.
The osmolality must be measured using freezing
point depression and not vapour pressure as the latter
will produce falsely low results.
A number of formulae have been published for the
calculation of osmolality , for example 2X[Na++K+]+
[Urea]+[Glucose].

The osmolar gap may only be present early in the

poisoning while a high anion gap may only occur late
in the presentation when the ingested poisons have
been metabolised to the acidic products.
Treatment consists of giving ethanol or fomepizole
to inhibit the metabolism of the methanol or ethylene
glycol to their toxic metabolites.
The metabolic acidosis and hypocalcaemia must also
be corrected.
Haemodialysis is also indicated.