86 Section 2/ Drugs Acting on CNSneoglucogenesis induced by salicylates and
related compounds. Chronic use can also
lead to negative nitrogen balance by in-
creased conversion of protein to carbohy-
drate.
Effect on blood: Platelets are the
important factors in thrombus formation
and aspirin has been shown to inhibit plate-
let aggregation. They reduce the blood
prothrombin level by inhibition of pro-
thrombin synthesis and prothrombin time
is prolonged. The aspirin suppresses the
synthesis of thromboxane (TXA 2 ) in the
platelets. They also prolong the bleeding
time due to prevention of platelet aggrega-
tion which may be due to inhibition of re-
lease of adenosine diphosphate (ADP) from
the platelets by salicylates.
Effect of CVS: In therapeutic doses, as-
pirin has no direct effect on CVS but in larger
doses, it can lead to increase in cardiac out-
put to meet increased peripheral oxygen
demand and can cause direct vasodilatation.
Endocrine effects: Salicylates decrease
the plasma protein bound iodine due to dis-
placement of thyroxine from prealbumin
and stimulation of central sympathetic cen-
tre causes release of adrenaline from the
adrenal medulla.
Pharmacokinetics
Salicylates are well absorbed after oral
administration. They are absorbed from the
stomach and largely from the upper part of
small intestine. After oral administration,
appreciable plasma concentrations are
found within half an hour, peak plasma level
is achieved within two hours and approxi-
mately 50 percent of the drug is eliminated
within 24 hours and plasma half life is two
to eight hours. After absorption, about 80
percent of salicylate is bound to plasma pro-
tein (mainly albumin) and rapidly distrib-
uted in the tissues. Aspirin is deacetylated
to salicylic acid which is the major circulat-
ing and active form. Salicylates are mainly
metabolized in the liver and excreted in
urine in the form of conjugates with glycine
(mainly) and glucuronic acid.Adverse Effects
These include nausea, vomiting, gastric
irritation and occult blood in stool.
Allergic reactions include urticaria, skin
rash, rhinorrhoea, asthmatic attack and ana-
phylactic reactions.
Prolonged administration of salicylates
cause a syndrome called ‘salicylism’ which
is characterized by headache, dizziness, tin-
nitus, vertigo, difficulty in hearing, dimness
of vision, mental confusion, drowsiness,
lethargy, hyperventilation and electrolyte
imbalance.
Overdose/acute salicylate poisoning is
characterized by salicylism which consists
of tinnitus, vertigo and deafness, hyperther-
mia, toxic encephalopathy (agitation, con-
fusion and convulsions followed by coma),
dehydration (due to hyperpyrexia, sweating
and vomiting), disturbances of acid base
balance and petechial haemorrhages.Treatment of Overdose/Toxicity (Salicy-
late Poisoning)
i. Gastric lavage.
ii. Intravenous fluid to correct dehydration.
iii. Cold water/alcohol sponges for hyper-
thermia.