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Anti Diabetic Agent
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ANTI DIABETIC AGENT (INSULIN & ORAL HYPOGLYCEMIC DRUGS)Wiwik Rahayu, dr., M.KesDepart. of Pharmacology & TherapyMedical Faculty Riau University
It is a heterogeneous group of syndromes all characterized by an elevation of blood glucose caused by a relative or absolute deficiency of insulin.
Symptom:
DMTYPE I (INSULIN DEPENDENT DIABETES MELLITUS, IDDM)Absolute deficiency of insulinCaused by massive -cell lesions or necrosisTreatment: exogenous insulinTYPE II (NON INSULIN DEPENDENT DIABETES MELLITUS, NIDDM)Inability of -cell to produce appropriate quantities of insulinInsulin resistanceOther unknown defectsTreatment: Hypoglycemic oral drugs insulin
PHARMACOKINETICSInsulin p.o degradationsubcutaneousIV: in hyperglycemic emergency
ADVERSE EFFECT & OVERDOSE TOXICITYHypoglycemiaHypoglycemia brain damage !Symptom of hypoglycemiaTachycardiaConfusionVertigoDiaphoresisLipodystrophyHypersensitivity
INDICATIONAll patients with type I DM regardless of agePatient who have ketoacidosis or hyperosmolar comaPatient with type II DM when diet restriction, exercise and oral hypoglycemic agent have failed to maintain satisfactory blood glucose concentrationPatient with type II DM in presence of surgery fever, infections, serious renal or hepatic dysfunction, and other metabolic disturbancesPregnant diabetic women
CONTRAINDICATIONThere are no contraindications if the proper indication exists.Patients must be well educated regarding the role of diet, exercise and illness in modifying their insulin requirements.
INSULIN PREPARATIONSRAPID ACTION INSULIN PREPARATIONZinc insulin: sc iv (in emergencies)B. INTERMEDIATE ACTION INSULIN PREPARATIONSemilente insulin suspensionIsophane insulin suspensionLente insulinInsulin incombinationC. PROLONGED ACTION INSULIN PREPARATION
SULFONILUREASFirst generationTolbutamide, Chlorpropamide, TolazamideSecond generationGlipizide, GlyburideBIGUANIDESMetformin GLUCOSIDASE INHIBITORSAcarboseREPAGLINIDE (?)RepaglinideTHIAZOLIDINEDIONESTroglitazoneORAL HYPOGLYCEMIC AGENTS
SULFONILUREASMechanism of actionStimulation of insulin release from the cellsReduction of serum glucagon levelsIncreased binding of insulin to target tissuesPharmacokineticsOral, bind to serum proteinsMetabolized by liver1st G : inactive, less active, active2nd G: inertExcreted by kidney or liver
Side effectHypoglycemia (especially: chlorpropamide, Glyburide)Contraindication:Renal or hepatic insufficiencyPregnancyElderly
INTERACTIONMeningkatnya kerja obat-obat sulfonilureaBerkurangnya metabolisme hepatik sulfonilureaDikumarol, kloramfenikol, inhibitor mono amin oksidase, fenilbutazonMengganti sulfonil urea dari protein plasmaKlofibrat, fenilbutazon, salisilat, sulfonamidBerkurangnya ekskresi sulfonilureaAlopurinol, Probenesid, fenilbutazon, Salisilat, sulfonamid
ACARBOSEInhibits glucosidase in intestinal
decreased the absorption of disaccharidesTaken with mealsNot cause hypoglycemiaSide effects: flatulence diarrhea abdominal cramping
REPAGLINIDEBinds to the ATP- sensitive potassium channels of cells release of insulinMetabolized inactive
TROGLITAZONEDecreases insulin resistance