PCC2 Musculoskeletal Drugs

This is effective but this is not selective, which means it can have effects on many body systems. Osteoporosis - HRT - have agonist actions on some tissues and antagonist actions on others Osteoporosis - Selective oestrogen re- - For example, raloxifene has agonist ceptor modulators (SERMs) actions on bone and the cardiovascular system, but antagonist actions on mammary tissue • Increased osteoblast activity in a dose-dependent manner • Reduced activity of osteoclasts. What is the MOA's of Raloxifene? - Increase bone mass by paradoxically stimulating osteoblast numbers and deOsteoporosis - PTH and PTH fragments creasing osteoblast apoptosis. (teriparatide) MOA - Act on PTH-1 receptors (GPCR), activating adenylate cyclase, PLA2, PLC and raise intracellular Ca2+ levels What receptors do PTH and PTH frag- Act on PTH-1 receptors (GPCR), activatments work on and what is activated as ing adenylate cyclase, PLA2, PLC and a result of this? raise intracellular Ca2+ levels How are PTH and PTH fragments administered? Subcutaneously Act on osteoclasts to promote their apopOsteoporosis - Bisphosphonates (alentosis, thereby inhibiting bone reabsorpdronate and risedronate) MOA tion How are Bisphosphonates administered? Orally - accumulate at site of bone mineralisation What can impair the absorption of bisphosphonates? Absorption can be impaired by certain foodstuffs, especially milk 1/5 Osteoarthritis - Paracetamol - often used as an analgesic and antipyretic - It has an indirect inhibitory effect on COX-2 in the CNS by reducing the availability of essential co-substrates. - It has some COX-3 activity but this is not thought to be pharmacologically important. - Paracetamol is not significantly anti-inflammatory and it appears to be able to reduce prostaglandin synthesis in some situations, but not others. - The COX-3 isoform appears to be more sensitive to paracetamol, indicating that COX-3 is not involved with inflammation. Toxicity in overdose which, combined What are the issues associated with the with its ready availability, means it has use of paracetamol? historically been a common method of actual or attempted suicide. Metabolism of paracetamol During its metabolism paracetamol is normally conjugated with glucuronic acid and sulphate. - When toxic doses of paracetamol are taken (10-15g), pathways become saturated, leading to metabolism by cytochrome P450 enzymes (CYP2E1). - This leads to the production of toxic N-acetyl-p-benzoquinone, which can be Describe what happens during a paracinactivated by glutathione. etamol overdose? - Once glutathione is depleted, N-acetyl-p-benzoquinone causes liver and kidney necrosis - irreversible liver damage usually reaches its peak by 72-96 hours 2/5 N-acetylcysteine What drug must be administered 8-10 hrs after the ingestion of paracetamol in overdose? - speeds the replenishment of glutathione What is the current recommendation in the NICE guidelines for the pharmacological treatment of osteoarthritis? Paracetamol and/or topical NSAIDs should be considered ahead of oral NSAIDs, COX-2 inhibitors or stronger analgesics such as opioids. What is topical capsaicin used for? Used as an adjunct to core treatments for knee or hand osteoarthritis. Where paracetamol or topical NSAIDs are ineffective, or provide insufficient What can be prescribed when paracetapain relief in OA, then an oral mol or topical NSAIDs are ineffective in NSAID/COX-2 inhibitor should be conosteoarthritis? sidered and a proton pump inhibitor (PPI) must be co-prescribed. Osteoarthritis - Intra-articular corticosteroid injections They should be considered as an adjunct to core treatments for the relief of moderate to severe pain in people with osteoarthritis. Joint surgery should be considered for people with OA who experience joint When should joint surgery be considered symptoms (pain, stiffness and reduced in patients with osteoarthritis? function) that have a substantial impact on their quality of life and which cannot be managed by non-surgical treatment. Naproxen or other NSAIDs Acute drug treatments for gout Colchicine Acute drug treatments for gout Colchicine Prevents the migration of neutrophils into joints, possibly by binding to tubulin, so microtubules depolymerise. 3/5 Profuse diarrhoea Nausea Vomiting List 3 side effects of Colchicine (high doses)? Corticosteroids are also sometimes used to treat severe cases of gout in people Acute drug treatments for gout - Cortiwho do not respond to other treatment or costeroids are unable to take or cannot tolerate an NSAID or colchicine. - Enzyme xanthine oxidase converts hypoxanthine to uric acid via xanthine - Allopurinol (figure 11) is converted into alloxanthine by xanthine oxidase. Drug treatments for established gout Allopurinol MOA - Alloxanthine then non-competitively inhibits xanthine oxidase, so uric acid production decreases. - The uric acid concentration decreases, which reverses the deposition of crystals - It can exacerbate the acute, painful condition - Rapid reduction of uric acid levels to below the saturation point causes existing 4/5 crystals in the joint cartilage to partially dissolve and become smaller Why is it important to not take Allopurinol during a acute attack of gout? - Smaller crystals can escape or 'shed' into the joint cavity and then inflame the synovium. What happens when smaller crystals shed into the joint cavity? Smaller crystals can escape or 'shed' into the joint cavity and then inflame the synovium. 5/5