Analgesic Drugs

28.4.06

Not covered:
• Opiates.
• Disease-modifying drugs for rheumatoid arthritis.
• Drugs for neuralgic pain.

Pain
• Somatic.
-Inflammation of epithelial surfaces, trauma, sepsis.
-Felt at site of pathology.
• Visceral.
-Eg. myocardial ischaemia, colic.
-Poor localisation, often "referred."
• Neurogenic.
-Eg. neuralgia.
-No response to analgesics.

Osteoarthritis
• Common.
• Disease of cartilage.
• Big weight-bearing joints: knees and hips.
• More likely if there is joint insult eg. trauma.
• Congenital component: "primary familial osteoarthritis."
• Heberden's nodes, distal interphalangeal joints.

Rheumatoid arthritis
• Common.
• May commence at any age.
• Inflammatory condition: joints commonest "tissues" involved, but also inflames arteries etc.
• Small joints: hands and feet.
• Hands: metacarpal phalangeal joints and primary interphalangeal joints.

Gout
• Common.
• Paroxysmal arthritis, with quiet joints between attacks.
• Any joint, excepting axial skeleton.
• Uric acid crystals in joint fluid.
• Most commonly, first metatarsal phalangeal joint.

Ankylosing spondylitis
• Less common.
• Around 20% people with HLA B27.
• Low back pain in early 20s, leading to variable degrees of spinal deformity.
• Also, arthritis of hips and knees.
• Other tissues: iritis.

DRUGS
Paracetemol
• Mechanism pf analgesic activity not fully understood: ? decreased prostaglandin synthesis in CNS.
• Mechanism of antipyretic activity: decreased PG-E2 in hypothalamus.
• Safe, effective analgesic used OTC:
-Analgesia.
-Lowering elevated temperature.
-No anti-inflammatory effect.
• Dangerous in overdose.
• Main problem: hepatotoxicity.
• Takes around 24-36 hours to become apparent.
• Antidote: n-acetyl cysteine, but use in first 24 hours.
• Damage correlates with paracetemol concentration.
• Measure concentration - no earlier than 4 hours.

NSAIDs
Aspirin
• Acetylsalicyclic acid.
• Analgesic/antipyretic at low dose.
• Anti-inflammatory at high dose.
• [Anti-platelet activity at low dose.]
• Upper GI irritation and bleeding.

Aspirin overdose
• Partly eliminated unchanged in urine.
• Strong acid, lipid soluble at acid pH (remember Henderson-Hasselbach).
• "Alkaline diuresis": iv bicarbonate to yield alkaline urine.
• Hence, water soluble aspiring and higher aspirin clearance.
• Dialysis in most serious cases.

Other NSAIDs
• [Ibuprofen: OTC as analgesic.]
• Naproxen.
• Diclofenac.
• Useful in inflammatory arthritis.
• Use adjunct to opiates in terminal care.

COX-II inhibitors
• Anti-inflammatory, useful for Rh-D.
• Much more expensive than older NSAIDs.
• Reserve for selected patients with PUD or GORD.
• Rofecoxib withdrawn for SAEs - may prove to be class effect.

NSAID adverse effects
• GI.
• Salt and water retention.
• Renal impairment.
• Asthma may be precipitated.

DRUGS FOR GOUT
Acute gout
• Commonly precipitated by diuretics (especially thiazides).
• May be very severe and resemble septic arthritis.

Treatment
• Rest.
• NSAID until arthritis settles.
• Worst cases merit prednisolone.
• If prophylactic drug (eg. allopurinol) to be used, then NSAID "cover."

Allopurinol
• Purine bases metabolised via xanthines to uric acid.
• Xanthines water soluble.
• Uric acid pretty insoluble.
• Allopurinol inhibits xanthine oxidase.
• Used to decrease frequency of paroxysms.
• May precipitate acute gout when first started: NSAID "cover."

Acute drug reactions and interactions
• GI upset.
• Rash.
• Azathioprine - potentiated.
• Warfarin - potentiated.