Non-Narcotic Analgesics (NSAID’s) 85Combination of two drugs e.g., paracetamol
- ibuprofen or diclofenac) also used for its
additive effect.
Antipyretic action: Salicylates lower the
elevated body temperature. Hypothalamic
thermoregulatory centre acts as a thermo-
stat of the body which maintains the balance
between heat production and heat loss. Sali-
cylates reset the hypothalamic thermostat
which is disturbed during fever. They do not
affect the heat production but they increase
the heat loss by causing vasodilatation and
sweating. The antipyretic action of salicy-
lates is probably due to the inhibition of PG
synthesis.
Effect on respiratory system: Salicylates
stimulate respiration by increasing the con-
sumption of oxygen primarily by skeletal
muscles and this results in increased pro-
duction of carbon dioxide, which leads to
direct stimulation of the respiratory centre
in the medulla oblongata producing an in-
crease in the depth and to some extent in
the rate of respiration. Toxic doses depress
the respiratory centre.
Antiinflammatory and antirheumatic
action: Salicylates suppress the clinical signs
and symptoms of rheumatoid arthritis and
other related inflammatory disorders by in-
hibiting prostaglandin synthesis, reducing
the capillary permeability and inhibition of
neutrophil aggregation. Salicylates by inhib-
iting the prostaglandin synthesis, prevent
sensitization of the pain receptors to certain
biological amines such as histamine, 5-HT
(serotonin) and bradykinin, the chemical
mediators of inflammation and pain.
Effect on kidney: In low doses, aspirin
inhibits the tubular secretion of uric acid and
can cause uric acid retention while in higher
dose, it also inhibits tubular reabsorption of
uric acid and have beneficial effect in gout
by producing uricosuric action.
Acid-base and electrolyte balance: High
therapeutic dose especially when used in
rheumatic fever, stimulates respiration and
causes respiratory alkalosis. Reduction in
bicarbonate and potassium level reduces the
buffering capacity of the extracellular and
intracellular fluid. Hypokalemia may lead
to dehydration and hypernatremia. They
also interfere with carbohydrate metabolism
resulting in accumulation of pyruvic acid
and lactic acid.
Effect on GIT: Aspirin and related com-
pounds irritate gastric mucosa which may
cause epigastric distress, nausea and vom-
iting as a result of gastric irritation. The sali-
cylates are unionised at the pH of the stom-
ach and can easily enter the mucosal cell
and at the pH of the cell they get ionised
thus unable to cross it and accumulate in-
side the gastric mucosal cell and causing
damage to the gastric mucosa and the dam-
aged mucosa permits back flow of H+ ions
which may damage the endothelium of
submucosal capillaries and gastric bleed-
ing occurs.
Metabolic effects: Salicylates cause un-
coupling of oxidative phosphorylation
which leads to conversion of energy into
heat and may thus produce hyperpyrexia
and increased protein catabolism. Larger
dose produces hyperglycemia and glyco-
suria in normal individual while in diabetic
patient it produces hypoglycemia which
may be due to an enhanced peripheral utili-
zation of glucose and inhibition of