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NON STEROID ANTIINFLAMMATORY DRUGS & DRUGS USE IN THE TREATMENT OF GOUT

Siti Suparti
Depart. Of. Pharmacology & Therapy Faculty Of Medicine Padjadjaran University

What is NSAID ?
The antiinflamatory, analgesic, antipyretic drugs are heterogenous group of compounds, often chemically unrelated (most of them are organic acids), which nevertheless share certain therapeutic actions and side effects The prototype is aspirin, named: Aspirin like drugs or NSAIDs

Chemical classification of NSAIDs


Salicylic acid dervatives Para-aminophenol derivatives Indole and Indene acetic acids Heteroaryl acetic acids Anthranilic acids (fenamates) Enolic acids Alkanones

Therapeutic Activities
Analgesic - against pain of low to moderate intensity Chronic post operative pain or pain arising from inflammation => (+) Pain arising from the hollow viscera => (-) Antipyretics - reduce the body temperature in febrile states Anti inflammatory agents - musculosceletal disorder Treatment of primary dysmenorrhea

Side Effects
Induce gastric or intestinal ulceration - erosions, ulcers GI side effects Disturbances in platelet function Prolongation of gestation spontaneous labor Changes in renal function Prolongation of bleeding time Intolerance => to Aspirin = to all NSAIDs

Choice of NSAIDs in varying clinical situation


The choice among NSAIDs for the tretment of arthritides is largely empirical. Choice of the drug, given for a week or more. If the drug is effective => treament should be continued. Mild arthropaties => together with rest and physical therapy. For children: aspirin, naproxen, tolmetin.

Precaution when patients given salicylates or phenylbutazone together with warfarin, sulfonylurea, hypoglycemic agents, methotrexate. If patients can not tolerate NSAIDs => choice the other form of therapy. Gold, hydrochloroquine, penicillamine, imunosuppressive agents and glucocorticoids are another choice. The selection of an NSAIDs for patient according to cost of therapy, Aspirin is very inexpensive.

SALICYLATE
Pharmacological Properties Effects: analgesia, antipyretic, on CNS, respiration, acid base balance and electrolyte pattern, CV, GI, hepatic and renal, uricosuric, the blood, on rheumatic, inflammatory and immunological process, on connective tissue metabolism, on CH, N, fat metabolism, on endocrine, salicylate and pregnancy, local irritant effects.

Absorbtion: orally - absorbed rapidly rectal - absorped slower than orally. Distribution: salicylates is distributed throughout most body tissues and most trancellular fluids. Biotransformation: in many tissues, particularly in the hepatic endoplasmic reticulum and mitochondria. Excretion: renal (GF and proximal tubular secretion)

THERAPEUTIC USE
Systemic uses: antipyresis, analgesia, rheumatoid arthritis. Other uses: in the treatment or prophylaxis of diseases associated with hyperaggregability. Local uses; per rectal, local on skin.

TOXIC EFFECT OF SALICYLATES


=> May be fatal Salicylate intoxication: 10 - 30 g (adult) 4,7 mg methyl salicylate in children. Simptoms and Signs (SALICYLISM) Disturbances in acid balance CNS disturbances Fever

Dehydration GI symptoms Acidosis Toxic encephalopathy. In adult - toxic effects occured by therapeutic dose: Non cardiogenic pulmonary edem Non focal neurologic abnormalities Acid base abnormalities (ketosis)

Aspirin Hypersensitivity
Vasomotor rhinitis Angioedema Generalized urticaria Bronchial asthma Hypotension Shock.

PARA AMINOPHENOL DERIVATIES ACETAMMINOPHEN


An effective alternative to aspirin Available without prescription Acute overdosage causes fatal hepatic damage ( hepetotoxicity ) For Analgesic antipyretic uses, a weak antiinflammatory activity.

INDOMETHACIN
Congener of indomethacin : Sulindac Used in rheumatoid arthritis and related disorder as antiinflamatory drugs, including acute gout. Toxicity often limit its use There is entherohepatic cycling of the conjugate and probably indomethacin used as an antipyretic in Hodgkins disease.

Precaution : In concurrent administration with probenecid, ancoagulant agents, furosemide, thiazide diuretics, Beta adrenergic blocking agents, inhibitor of angiotensin converting enzyme.

Toxic effect of indomethacin


- Most adverse effect are close dependent : GIT complaints Occult blood loss Acute pancreatitis Hepatic abnormalities Severe frontal headache ( CNS effect ) Hemopoietic reaction Hypersensitivity - Contraindication : renal disease, ulcus in GIT

MEFENAMIC ACID
Have antiimflammatory, analgesic and antipyretic properties Inhibit cyclooxygenase Meclofenamic acid may antagonize certain effect of prostaglandis Pharmacokinetic properties : Meclofenamate reaches the peak concentration faster than mefenamic acid 50 % of mefenamic acid excreted in urine 20 % is recovered in the feces

Toxic Effect and Precautions


GIT disorder Hemolytic anemia of an autoimmune type Contraindicated on patients with a history of gastrointestinal diseases Diarrhea or skin rash : drug should be stopped.

NAPROXEN
Fully absorbed. Influenced by food Accelerated by sod.bicarbonate and reduce by Mg oxide or Aluminium hydroxide. Crosses the placenta , 1 % of the material plasma concentration appears in milk of lactating mother GIT effect and CNS effect Ototoxicity Dermatological Problems Other effect

PIROXICAM
Has antiinflammatory, analgesic and antipyretic activity For long term treatment of RA or OA equivalent of aspirin indomethacin or naproxen, be tolerated better T 1 / 2 is long single daily dose For the treatment of AS, acute musculoskeletal disorders, dysmenorrhea, postop.pain and acute gout

PHENYLBUTAZONE
For the treatment of RA etc. In long term therapy serious toxicity Can cause agranulocytosis Sulfinpyrazone much more effective uricosuric agent for chronic gout Can cause edema Death especially caused aplastic anemia and agranulositosis

Do not give drug more than 7 days. Contraindicated in patient with hypertension, cardiac, renal or hepatic dysfuncion, a history of peptic ulcer, blood dyscrasia, or hypersensitivity to the drug Not advisable for elderly persons and not recommended in children under the age of 14

GOLD
Can supress or prevent, but not cure experimental arthritis and synovitis due to a number of infectious and chemical agents The best hypothesis related to the capacity of gold compounds to inhibit maturation and function of mononuclear phagocytes and of T cell supressing immune responsiviness

Aurothioglucose and gold sodium thiomalate : Parenteral and oral Interaction with dimercaprol, penicillamine and N acethylcystein increase the exretion of gold Auranofin : Per oral, par enteral Predominantly exccreated in the feces.

Contraindication Renal disease, hepatic dysfunction, a history of infectious hapatitis, hematological disorders. Pregnancy, breast feeding Concomitant use of antimalarials, immunosupressants, phenylbutazone, oxyphenbutazone Urticaria, eczema, colitis Poorly tolerated by elderly persons

Colchicine
Only againts gouty arthritis dramatic relief of acute attack of gout Effective prophylactic agent An antimitotic agent Inhibit the migration of granulocytes into the inflammed area and a decreased metabolic and phagosytic activity of granulocytes

Allopurinol
Effective for the treatment of : Primary hyperuricemia of gout Secondary to hematological disorders Antineoplastic therapy

Inhibit the terminal step in uric acid biosyntesis Well tolerated by most patients

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