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DRUGS USE IN MUSCULOSKELETAL SYTSTEM DISORDERS

DRUGS USE IN MUSCULOSKELETAL SYTSTEM DISORDERS. Assoc. Prof. Dr. Ece Aydoğ PMR. Learning objectives.

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DRUGS USE IN MUSCULOSKELETAL SYTSTEM DISORDERS

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  1. DRUGS USE IN MUSCULOSKELETAL SYTSTEM DISORDERS Assoc. Prof. Dr. Ece Aydoğ PMR

  2. Learning objectives 1.be able to describe action mechanisms and side effects of glucocorticoids and nonsteroiadal anti-inflammatory drugs and enumerate complications and contraindications of local glucocorticoid administration. 2. be able to describe muscle relaxants classification according to their action mechanisms (define antispastic and spasmolytic drugs), and describe clinical usage and side effects.

  3. Non- Streoidal Anti-Inflammatory Drugs (NSAIIDs) Benefical effects: • Analgesia • Antipyresis (inhibits PGs in CNS) • Antiinflammatory • Antiplatelet (prevents thromboxane A2 production)

  4. Mechanism • Inhibiton of the cyclo-oxygenase (COX)Decrease in prostoglandin production • Cox-1: stomach, intestine, platelet, kidney • Cox-2: involved in inflammation • Inhibition of lipoxygenase (sulindac, diclofenac) • Inhibiton of neutrophil adhesion (aspirin, indomethacin) • Inhibition of cytokine production

  5. Salicylates Aspirin Diflunisal Para-aminopheno Acetaminophen Acetic acids Indomethacin Sulindac Etodolac Anthranilic acid Mefenamic acid Sulfananilides Nimesulid Heteroaryl acetic acid Diclofenac Ketolorac Arylpropionic acid Ibuprofen Naproxen Ketoprofen Classification

  6. Enolic acid Piroxicam Meloxicam Alkanones Nabumetone Coxib Celecoxib Etoricoxib Lumiracoxib Cox-2 selective Etodolac Diclofenac Nabumetone Meloxicam Classification

  7. Hepatotoxicity İdiosynchratic hepatit (indomethacin, diclofenac) Cholestasis GİS Dyspepsia GOR Peptic ulcer Hemorrhage Nephrotoxicity Papillary necrosis İncreased sodium retantion Decreasing GFR Acute tubular necrosis Acute intersititial nephritis Side effects

  8. Who is at risk for GD ulcers • Elderly • History of PU • Higher dosage • Chronic diseases • Anticoagulant therapy • Corticosteroid use • Tobacco and alcohol

  9. Protection • Misoprostol (PGE1 analog) • Proton Pump inhibitors

  10. Glucocorticoids(GC) • GC are widely used for the suppression of inflammation in chronic inflammatory diseases such as asthma, RA, inflammatory bowel disease and autoimmune diseases. • GC inhibit the expression of multiple inflammatory genes

  11. Glucocorticoids(GC) • GC increase the syntesis of lipocortin-1, that has inhibitory effect on phospholipas A2 and therefore inhibit the production of lipid mediators as well as inhbit genes coding for COX-2.

  12. Some commonly used glucocoticoids Equivalent oral dose(mg) • Cortisol 20 • Prednisolone 5 • Methylprednisolone 4 • Triamcinolone 4 • Dexamethasone 0.75

  13. Dosing (EULAR) • Low dose up to 7.5 mg/d • Medium dose > 7.5 but ≤ 30 mg/d • High dose >30 but ≤ 100 mg/d

  14. Advers Effects Bone and muscle: Osteoporosis • Mean first- year loss of bone ranging from 1.5-20% at the dose range ≤ 10 mg/d prednisolone. • Addition to GC theraphy Ca and vit D or bisphosphonate should recieve to patient. Osteonecrosis Myopathy

  15. Advers Effects Cardiovascular: • Fluid retention (Hypertension) • Affect lipid profile • Premature atherosclerotic vascular disease • Cardiac arrythmias

  16. Advers Effects Dermatologic and appearance • Skin thinning • Ecchymoses • Cushingoid appearance • Hirsutism • Stria • Impair wound healing • Weight gain

  17. Gastrointestinal Gastritis Ulcers Gastrointestinal bleeding Infectious diseases Ophtalmologic Cataracts Increased intra-ocular pressure Metabolic and endocrine DM HPA insufficiency Neuropsychiatric Imsomnia Memory impairment Depression Psychosis Advers Effects

  18. Injections of steroids These more invasive therapeutic methods are recognized for the treatment of many disorders of the musculoskeletal system. However, except in certain rare cases, their use over a prolonged period is not recommended.

  19. Complications Hemarthrosis, Exacerbation of the inflammation and pain, Infection, Soft tissue atrophy Thinning of the skin Changes in skin pigmentation. The physician should also recommend that the patient not put any undue tension on tendons close to the injection site so as to prevent their possible rupture

  20. Contraindications • Any localized or generalized infectious process, • Fracture, the wearing of a joint brace, • Coagulation problems, • No relief after the first injection.

  21. Muscle relaxants • The effectiveness of these medications is much debated. • But it is particularly important to show prudence when the subjectis elderly, and to write prescriptions that take into account the following adverse side effects: drowsiness, confusion, anticholinergic effects

  22. Classification • Peripherally acting (Neuromuscular blockers) • Centrally acting Baclofen -Diazepam • Direct acting Dantrolene

  23. Spasmolytic agents Spasticity-characteristics • Increased tonic stretch reflexes • Increased flexor muscle spasm • Muscle weakness Clinical conditions of spasticity: • Cerebral palsy, Multiple sclerosis, Stroke Clinical spasticity: • Reflex arc involvement • Higher center affects descending pathways leading to alpha motoneurons hyperexcitability Mechanisms (↓ spasticity) • – Alteration in stretch reflex arc • – Attenuation of excitation-contraction coupling

  24. SPASMOLYTIC DRUGS • (Central effect) • Diazepam • Baclofen • Tizanidine • Dantrolene • Carisoprodol (Soma, Rela) • chlorphenesin (Maolate) • chlorzoxazone (Paraflex) • cyclobenzaprine (Flexeril) • metaxalone (Skelaxin) • methocarbamol (Robaxin) • orphenadrine (Norflex) • Skeletal

  25. There are 2 main categories of skeletal muscle relaxants: antispastic (such as baclofen or dantrolene) for conditions such as cerebral palsy and multiple sclerosis and antispasmodic agents for musculoskeletal conditions. • The most commonly prescribed antispasmodic agents are carisoprodol, cyclobenzaprine, metaxalone, and methocarbamol.

  26. In comparison trials, no single skeletal muscle relaxant has been proven to be superior to another • The most widely studied agent is cyclobenzaprine, with demonstrated efficacy for various musculoskeletal conditions but with significant sedation • Tizanidine, which also causes marked sedation, or cyclobenzaprine may be useful in patients with insomnia because of severe muscle spasms.

  27. All skeletal muscle relaxants are associated with adverse effects including dizziness and drowsiness, • Although methocarbamol and metaxalone are less sedating than tizanidine and cyclobenzaprine, evidence is limited for their efficacy.

  28. A specific skeletal muscle relaxant should be chosen according to consideration of adverse effect profile, patient preference, potential for abuse, and possible interactions with other prescribed medications because comparable efficacy data are limited.

  29. Despite their popularity, skeletal muscle relaxants should not be the primary drug class of choice for musculoskeletal conditions," • The American Pain Society and the American College of Physicians recommend using acetaminophen and...NSAIDs as first-line agents for acute low back pain and reserving skeletal muscle relaxants as an alternative treatment option. • Skeletal muscle relaxants are better than placebo, but not more effective than NSAIDs in patients with acute back pain.

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