1 / 44

Aches and pains

Aches and pains. Non-opiate analgesics, drugs for arthritis and opiates. This talk. Pain Arthritis osteoarthrosis rheumatoid arthritis gout Analgesics – paracetamol and NSAIDs Drugs for arthritis Opiates. Pain. Somatic inflammation of epithelial surfaces, trauma, sepsis

mandar
Download Presentation

Aches and pains

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Aches and pains Non-opiate analgesics, drugs for arthritis and opiates.

  2. This talk • Pain • Arthritis • osteoarthrosis • rheumatoid arthritis • gout • Analgesics – paracetamol and NSAIDs • Drugs for arthritis • Opiates

  3. Pain • Somatic • inflammation of epithelial surfaces, trauma, sepsis • felt at site of pathology • Visceral • e.g. myocardial ischaemia, colic • poor localisation, often ‘referred’ • Neurogenic • e.g. neuralgia • no response to analgesics

  4. The Ladybird book of arthritis: osteoarthrosis • A disease of cartilage • More common in women than men • Aetiology: • Mechanical insults • Age: osteo. usually a problem in late middle age onwards • Abnormalities of cartilage: genetics

  5. Osteoarthrosis continued • Usually large weight-bearing joints: hips, knees. • Primary familial osteo: distal interphalangeal joints (Heberden’s nodes). • Pain, limited movement, inflammation, crepitus • Joint space narrowing, osteophytes

  6. Heberden’s nodes

  7. Rheumatoid disease • Rd-D affects many tissues other than joints. • A chronic inflammatory condition of unknown cause • Autoantibodies are often present

  8. Rheumatoid disease • Can affect any age group • Insidious onset of inflammation of small joints: hands, feet, neck • In the hands: proximal IPJ and MCPJ • Inflammation, deformity, Rh-D nodules (commonly at the elbow)

  9. Proximal interphalangeal joints Metacarpo-phalangeal joints

  10. Olecrannon bursitis (fluid-filled) Rheumatoid nodule (solid and rubbery)

  11. Gout • Abnormal uric acid metabolism. • Most common in middle-aged males. • Commonest in the first MTPJ of the foot. • But can involve any joint (other than the axial skeleton). • Uric acid may also be deposited in tissues, and may form urinary stones

  12. Gout • Acute gout • sudden onset of severe arthritis • a disease of paroxysms • Chronic tophaceous gout

  13. First metatarso- phalangeal joint

  14. Drugs: overview • Paracetamol • Aspirin • Other NSAIDs • Rh-D ‘disease-modifying’ drugs’ • Drugs specifically for gout

  15. Paracetamol • Mechanism of analgesic activity not fully understood: ?  prostaglandin synthesis in the CNS • Mechanism of antipyretic activity:  PG-E2 in the hypothalamus

  16. Paracetamol • Safe effective analgesic used OTC • analgesia • lowering elevated temperature • it has no anti-inflammatory effect

  17. Dangerous in overdose

  18. Dangerous in overdose saturated

  19. Dangerous in overdose The main problem is hepatotoxicity Takes around 24-36 h to become apparent saturated There is an antidote But you need to use it in the first 24 h The degree of damage correlates with paracetamol conc.

  20. NSAIDs

  21. Phospholipase A2 Arachidonic acid COX-I COX-II Leukotrienes PGs with gastric protective effects PGs with inflammatory effects Membrane phospholipid

  22. steroids X Membrane phospholipid Phospholipase A2 Arachidonic acid COX-I COX-II Leukotrienes PGs with gastric protective effects PGs with inflammatory effects

  23. steroids X Membrane phospholipid Phospholipase A2 Older NSAIDs Arachidonic acid X X COX-I COX-II Leukotrienes PGs with gastric protective effects PGs with inflammatory effects

  24. steroids X Membrane phospholipid Phospholipase A2 Arachidonic acid COX-II inh X COX-I COX-II Leukotrienes PGs with gastric protective effects PGs with inflammatory effects

  25. Aspirin • Acetylsalicylic acid • Analgesic/antipyretic at low dose • Anti-inflammatory at high dose • (Anti-platelet activity at low dose) • Upper GI irritation and bleeding

  26. Aspirin • Partly eliminated unchanged in the urine • Revisit the Henderson-Hasselbach equation and it’s relevance to aspirin OD.

  27. Older NSAIDs • (Ibuprofen: OTC as an analgesic) • Naproxen • Diclofenac • Useful in osteo, rheumatoid and gout • Diminish inflammation • No effect on disease progression in Rh-D

  28. COX-II inhibitors • Rofecoxib • Anti-inflammatory, useful for Rh-D • Much more expensive than older NSAIDs • Reserve for selected patients with PUD or GORD. • Rofecoxib withdrawn because of SAEs - ? A class effect?

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

  30. ‘Disease modifying drugs’ for Rh-D • Gold (sodium aurothiomalate) • Penicillamine • Used to slow disease progression • Do not have immediate impact • Limited by adverse effects: serious and frequent

  31. ‘Disease modifying drugs’ for Rh-D • Gold • rashes • nephritis • blood dyscrasias • Penicillamine • rashes • nephropathy (proteinuria) • loss of taste • blood dyscrasias and haemolysis

  32. Xanthine oxidase Acute and chronic gout • NSAID • Steroid • Allopurinol purines URIC ACID

  33. Xanthine oxidase Acute gout • NSAID • Steroid • Allopurinol purines X URIC ACID

  34. Opiates • Endorphins are endogenous compounds released in the CNS in response to pain. Three receptor sub-types. •  - analgesia and euphoria •  - analgesia •  - dysphoria and hallucination • Opiate analgesics bind to endorphin receptors.

  35. Effects of the opiates • CNS: analgesia, euphoria, sedation (inc. resp depression), cough suppression, nausea. • GI tract: slow transit, constipation, sphincter of Oddi contraction. • CVS: vasodilatation leading to drop in BP and heart work.

  36. Clinical PK of the opiates • All are well absorbed from IM and SC injection. • All subject to first-pass metabolism. • All are terminated by liver metabolism.

  37. Examples • Codeine: relatively low potency • Pethidine: higher potency, short half-life. Less effect on sphincter of Oddi. • Morphine and diamorphine: most potent, longer half-life than pethidine.

  38. Uses • Severe somatic and visceral pain. • No benefit in patients with neurogenic pain. • Pulmonary oedema. • Cough suppression. • Diarrhoea.

  39. Adverse effects and contraindications • ADRs: • Nausea • Constipation • Addiction • Respiratory depression: type-2 resp failure. • Biliary colic. • Contraindications: • Severe respiratory problems • Hepatic impairment • Head injury (resp depression and CO2 retention

  40. Reversal • Naloxone. • Rapid elimination: • Faster than the opiates. • You may be suffering a false sense of security: the patient needs observation. • Dose may need to be repeated. • Infusion may be required.

More Related