k - farmakologi obat anti hiperuricemia.pptx
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farmakologiTRANSCRIPT
PHARMACOLOGICAL ASPECT OF ANTI-
HYPERURICEMIC DRUGSDepartment of Pharmacology
Learning objectives
To Explain Classification of the anti hyperuricemic
drugs.Pharmacological Aspect of anti
hyperuricemic drugsPrinciples of clinical Use of anti
hyperuricemic drugs
Uric acidProblems
↑uric acid
level
DRUGS USED IN TEATMENT OF HYPERURICEMIA
Target : lowering the uric acid level below the saturation point (<6 mg/dL), interfering with uric acid synthesis
allopurinol increasing uric acid excretion
Probenecid Sulfinpyrazone Large doses of aspirin
Inhibition of uric acid synthesis
ALLOPURINOL
Mechanism of action
80%-completely absorbed after oral administration.
Metabolized to active metabolite alloxanthine (oxypurinol).
Plasma Half-life allopurinol 2 hour, while oxypurinol 15 hour
Given once daily.Drug & its metabolite are excreted in the feces & urine.
Pharmacokinetics
Gout arthritisChronic tophaceous deposits (reabsorption
is more rapid)High serum uric acid in patients with
impaired renal functionsuric acid stones or nephropathyused to prevent increased uric acid levels
in patients receiving cancer chemotherapy
Clinical Uses
exacerbation of an acute attack of goutHypersensitivity:
Maculopopular skin rashnausea, diarrheaBody : fever, headacheCVS : vasculitisThrombocytopeniaEpistaxis
SIDE EFFECT
With oral anticoagulant: ◦ Potentiates warfarin and dicumarol inhibits their metabolism in
liver With anticancer :
◦ 6-mercaptopurine and azathioprine inhibits their metabolism (doses are reduced up to 75%
With ampicillin : ◦ Increases frequency of skin rash
Prolongs half life of Chlorpropamide• both compete for excretion in renal tubule
DRUG INTERACTION
DRUG INCREASE URIC ACID EXCRETION : Uricosuric
Probenecid SulfinpyrazoneLarge doses of aspirin
Probenesid increases uric acid excretion in the urine
Sulfinpyrazone metabolite of phenylbutazone Metabolized into an active
metabolite in the liver.
URICOSURIC DRUGS
Uricosuric drugs ( probenecid, sulfinpyrazone, large dose of aspirin) block the active transport sites of the proximal tubules(middle segment ) the re-absorption of uric acid is decreased.
Mechanism of action
Should not be started until 2-3 weeks after an acute attack of gout.
In chronic gout when :◦Evidence of tophi appears◦Plasma levels of uric acid are so high that may cause tissue damage
Clinical uses
Urine volume should be maintained at a high level, and urinary pH kept alkaline .
Probenecid is a general inhibitor of the tubular secretion of organic acids , so it is used to prolong action of other weak organic acids as some antibiotics ◦e.g. penicillin.
Clinical uses ( continue)
Probenecid prolong the action of some antibiotics as: penicillin and cephalosporins (result from block tubular secretion)
Probenecid also inhibit excretion of Naproxen, ketoprofen and Indomethacine
DRUG INTERACTIONS
Acute attack of gout Risk of uric acid stone GIT upset Allergic rash Nephrotic syndrome ( probenecid) Aplastic anemia ( not common )
Side effects
History of urinary tract stone
Impaired renal functionRecent acute gouty attackAdministration of low doses of aspirin
Contra-indications
TERIMA KASIH