NSAIDS

Analgesics

PGs induce hyperalgesia, NSAIDs block pain sensitizing mechanism induced by

bradykinin, TNF alpha, IL by primarily inhibiting COX-2

Antipyretics

Decrease PGE2- in hypothalamus- decrease set point- reduces fever by promoting heat loss (sweating, cutaneous vasodilation but does not decrease heat production), COX-2 mediated

Anti-

inflammatory

Inhibition of COX-2 mediated suppression of

PGs.

Antiplatelet

aggegatory

Inhibit synthesis of TXA2 which is

proaggregatory, COX-1 mediated

Ductus

arteriosus closure

PGE2 inhibition ,COX-2 mediated, if NSAID

given in pregnancy premature closure occurs, so avoid NSAIDs near term

Labor

Delay labor due to inhibition of PGs

Gastric mucosa

damage

Inhibit COX-1 mediated protective PGs synthesis, decreased bicarbonate secretion,

enhance acid secretion

Renal effect

In hypovolemia, decreased renal perfusion and Sodium loss-> PGs-> vasodilation, NSAIDs can:

• Impair blood flow and reduce GFR

Dysmenorrhea

In dysmenorrhea, PG elevated, NSAID lower

uterine level of PG- Provide relief

Anaphylactoid reactions

Precipitate asthma, Angioneurotic swellings, urticarial: Immunologically mediated

Side effects- at analgesic dose

N, V, Epigastric distress, increased occult blood in stool, gastric mucosal alteration and peptic ulcer

Hypersensitivity and idiosyncrasy

Rashes, FDE, Urticaria, Rhinorrhea, Asthma, Anaphylactoid reaction

Anti-inflammatory dose (3-5 g/day)

Salicylism- Dizziness, tinnitus, vertigo, reversible impairment of hearing and vision, excitement, hyperventilation

Children with RA- Liver damage

Children with viral infection- influenza, varicella- Reye’s syndrome- a rare form of hepatic encephalopathy

Acute salicylate poisoning

At fatal dose– Vomiting, diarrhea, acidotic breath, hyper/ hypoglycemia, restlessness, delirium, hyperpyrexia, convulsion, coma and death due to RF+ CVS collapse

Treatment– Symptomatic and supportive, Gastric lavage, IV fluids with Na, K, HCO3, Glucose

Drug

Dosage

MOA

ADR

USES

Paracetamol (acetaminophen)



• Central analgesic action of PCM is like aspirin i.e. it raises pain threshold
• Good and promptly acting antipyretic
• But has weak peripheral anti- inflammatory component
• Poor inhibitor of PG synthesis in peripheral tissue, but more active on COX in the brain
• Inability to inhibit COX in the presence of peroxides generated at site of inflammation, but are not present in brain
• Does not stimulate respiration or affect AB balance; does not increase cellular metabolism
• GI irritation is insignificant- occur only in overdose
• Does not affect platelet function or clotting factor and not uricosuric

• In isolated antipyretic dose PCM is safe and well tolerated
• N and Rashes occur occasionally, leucopenia is rare

Acute PCM poisoning

• Esp. in small children who have low hepatic glurorinide conjugating ability or if large dose (>150 mg/kg or >10 g in adult) is taken; fatality common with > 250 mg/kg
• Early manifestation– N, V, Abdominal pain, Liver tenderness with impairment of consciousness
• Followed by (12-24 hr.)– Centrilobular hepatic necrosis, Renal tubular necrosis, hypoglycemia that may progress to coma
• Mechanism of toxicity- N-acetyl-p- benzoquinoneimine (NAPQI) is a highly reactive arylating minor metabolite of paracetamol which is detoxified by conjugation with glutathione. When a very large dose of paracetamol is taken, glucuronidation capacity is saturated, more of the minor metabolite is formed—hepatic glutathione is depleted and this metabolite binds covalently to proteins in liver cells (and renal tubules) causing necrosis. Toxicity thus shows a threshold effect manifesting only when glutathione is depleted to a critical point.
• Treatment- gastric lavage, N-acetylcysteine

• Headache
• Mild migraine
• MSK pain
• Dysmenorrhea
• Osteoarthritis- DOC
• Best drug to use as antipyretic– no risk of Reye’s syndrome

Ketorolac

• 15-30 mg IM or IV every 4- 6 hours

• Potent analgesic but modest anti-inflammatory activity
• In PO pain it has equaled the efficacy of morphine but is free of opioid side effects
• Like other NSAIDs it inhibits PG synthesis and relieves pain primarily by peripheral

mechanism

• Nausea, abdominal pain, dyspepsia, ulceration, loose stool
• Drowsiness, headache, dizziness, nervousness
• Pruritus
• Pain at injection site
• Raised serum transaminases
• Fluid retention

• POP pain
• Dental pain
• MSK pain
• Renal colic
• Migraine
• Pain due to bony metastasis
• Orally (10-20 mg 6 hrly.) for short term management of moderate pain
• Topical ketorolac in ocular condition

Ibuprofen



• Weaker anti-inflammatory

• Same as other NSAID

• Analgesic, Antipyretic- as aspirin
• Dysmenorrhea– due to PG synthesis inhibition
• Rheumatoid arthritis
• OA
• MSK disorder
• Soft tissue injuries
• Fracture, vasectomy, tooth extraction
• Postpartum and postoperatively

Nimesulide



• Relatively weak inhibitor of PG synthesis and moderately COX-2 selective

• GI– Epigastralgia, Heart burn, N, loose motions
• Dermatological– Rash, pruritus
• Central– somnolence, dizziness
• Ulcer can occur
• Fulminant hepatic failure can occur- withdrawn in spain, ireland

• Short acting painful inflammatory conditions like:
• Sports injury, dental surgery, sinusitis, ENT disorders, bursitis, low backache, dysmenorrhea, POP pain, OA and fever