ADVERSE EFFECTS AND

CONTRAINDICATIONS OF NSAIDs
ADVERSE
EFFECTS
 SALICYLATES
• Nausea, vomiting, epigastric
distress.
• Gastric mucosal damage and
peptic ulceration
• Hypersensitivity and
idiosyncrasy: includes rashes,
fixed drug eruption, urticaria,
rhinorrhoea, angioedema,
asthma, anaphylactoid
reaction.
 SALICYLISM
• At anti-inflammatory dose (3-5gm/day) of aspirin,
a syndrome called salicylism is seen.
• There is hyperpnoea due to direct stimulation of
respiratory centre, Pco2 levels get decreased and
leads to respiratory alkalosis.
• Renal mechanisms compensate for the
respiratory alkalosis by increasing the excretion of
HCO3 from the kidney.
• It can also be treated with systemic acidifying
agents like ascorbic acid or ammonium chloride.
 SYMPTOMS OF SALICYLISM
• Headache
• Vertigo
• Tinnitus
• Hyperventilation
• Nausea and vomiting
 REYE’S SYNDROME
• There is an association between aspirin intake
and reye’s syndrome which is rare and at
times fatal disorder in children. It is
characterised by liver damage and
encephalopathy which occurs when they are
recovering from febrile viral infection. Hence
paracetamol and not aspirin, should be
preferred in fever of unknown origin in
children below 12 years
 ACUTE
SALICYLATE
POISONING
 ACUTE SALICYLATE POISONING
• It is more common in children.
• Fatal dose in adults is 15-30gms but is considerably lower in
children.
• Serious toxicity is seen at serum salicylate levels >50mg/dl.
• Characterized by: hyper/hypoglycaemia, petechial
haemorrhages, restlessness, delirium, hallucinations,
convulsions, coma and death due to respiratory failure +
cardiovascular collapse.
 TREATMENT
• External cooling and i.v. fluid with Na , K and
HCO3 and glucose
• Gastric lavage
• Alkaline diuresis or haemodialysis
• Blood transfusion and vitamin K if bleeding
occurs.
 PROPIONIC ACID DERIVATIVES
• Gastric discomfort
• Nausea and vomiting
• CNS side effects: headache, dizziness, blurring
of vision, tinnitus and depression.
• Rashes, itching and other hypersensitivity
reactions are infrequent.
 FENAMATE
• Diarrhoea
• Epigastric distress
• Skin rashes
• Dizziness
• Other CNS manifestations
• Haemolytic anaemia is rare
 ENOLIC ACID DERIVATIVES
• GI side effects are more than ibuprofen
• Rashes and pruritus in <1% patients.
• Edema and reversible azothemia
 ACETIC ACID DERIVATIVES
KETOROLAC
• Nausea, abdominal pain,
dyspepsia, ulceration, loose
stools
• Drowsiness, headache,
dizziness, nervousness
• Rise in serum transaminase
INDOMETHACIN
• Gastric irritation , nausea,
anorexia, gastric bleeding
and diarrhoea
• Frontal headache, mental
confusion, hallucination,
depression, psychosis.
• Leukopenia hypersensitivity
 DICLOFENAC
• Epigastric pain, nausea, headache ,dizziness,
rashes
• Increases risk of heart attack and stroke
• Reversible elevation of serum amino
transferases
• Kidney damage is rare
PARA-AMINOPHENOL DERIVATIVES
ACUTE PARACETAMOL POISONING
ACUTE PARACETAMOL POISONING
• Occurs in small children with low hepatic
glucoronide conjugating ability.
• >150mg/kg or >10gm in an adult causes
serious toxicity
• More than 250mg/kg is fatal
 MANIFESTATIONS
• Nausea ,vomiting, abdominal pain, liver
tenderness.
• After 12-18 hours, centrilobular hepatic
necrosis can occur and it may be accompanied
by renal tubular necrosis and hypoglycaemia
-> may progress to coma.
• Jaundice starts after 2 days.
• Hepatic failure and death.
 MECHANISM OF TOXICITY
• N-acetyl-p-benzoquinoneimine is detoxified by
conjugation with glutathione
• Glucuronidation capacity is saturated with large dose
of paracetamol, and more of the minor metabolite is
formed, this decreases hepatic glutathione
• Metabolite thus binds to proteins in liver cells causing
necrosis
 Chronic alcoholics (5-6gm/day) results in hepatotoxicity
 Paracetamol is not recommended in premature infants
(<2kg)
CONTRAINDICATIONS
 ASPIRIN
• Peptic ulcers, bleeding tendencies, children suffering
from chicken pox or influenza
• Cautious use in chronic liver disease (hepatic necrosis)
• Avoided in diabetics, juvenile rheumatoid arthritis
• Stopped before elective surgery
• If given during pregnancy,
o Low birth weight babies
o Delayed or prolonged labour
o Greater postpartum blood loss
o Premature closure of ductus arteriosus
• Avoided by breast feeding mothers
• Avoid in G-6PD deficient individuals
 OTHER NSAIDs

• Propionic acid derivatives are contraindicated in

pregnant women and in peptic ulcer patients
• Acetic acid derivatives are not to be given to
patients on anti-coagulants
• Indomethacin is contraindicated in machinery
operators, drivers, psychiatric patients, epileptics,
kidney disease, pregnant women and in children
• Paracetamol is not recomended in premature
infants (<2kg) for fear of hepatotoxicities