e&m farmakologi^hypoglycemic agent^

7/30/2019 E&M Farmakologi^Hypoglycemic Agent^

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Hypoglycemic Agent

Prof. DR. dr. Hadyanto Lim, M.Kes,SpFK,FESC,FIBADept. of Pharmacology, Faculty of Medicine,

Methodist University of Indonesia-Medan


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Tekanan

Darah

KolesterolLDL

KencingManis

Merokok

S

TRESS

OKSID

ATIF

Kerusakan Pemb. Darah

Peradangan

NYER

I

DA

DA

Dzau VJ. Hypertension 2001; 37: 1047-52Ross, R. N Eng J Med 1999; 340: 115-126


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Patel A. et al. The ADVANCE collaborative Group N Engl J Med 2008; 358: 2560-72

Cumulative Incidences of Events, According to Glucose-Control Strategy


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Diabetes ? Classification of DM

The Regulation and Dysregulation of Blood Glucose

Clinical Features of Type I and Type DM

Criteria of DM Pathophysiological Basis of the Symptoms and

Signs of Diabetes

Complications of DM

Drugs Used in Controlling DM

Evidence-based medicine on DM


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A clinical syndrome characterized by

hyperglycemia due to absolute or relativedeficiency of insulin.


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Type 1 diabetes (results from -cell destruction, usually leading to

absolute insulin deficiency)

Type 2 diabetes (results from a progressive insulin secretorydefect on the background of insulin resistance)

Other specific types of diabetes due to other causes, e.g., geneticdefects in -cell function, genetic defects in insulin action, diseasesof the exocrine pancreas (such as cystic fibrosis), and drug orchemical-induced diabetes (such as in the treatment of AIDS or

after organ transplantation)

Gestational diabetes mellitus (GDM) (diabetes diagnosed duringpregnancy)

The classification of diabetes

American Diabetes Association 2010


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Etiologic Classification of Diabetes Mellitus


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Normal Glucose Metabolism


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1. A1C 6.5%. OR

2. FPG 126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intakefor at least 8 h. OR

3. Two-hour plasma glucose 200 mg/dl (11.1 mmol/l) during anOGTT.

The test should be performed as described by the World Health

Organization, using a glucose load containing the equivalent of 75 g

anhydrous glucose dissolved in water. OR

4. In a patient with classic symptoms of hyperglycemia orhyperglycemic crisis, a random plasma glucose 200 mg/dl (11.1mmol/l).

American Diabetes Association 2010


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Pathophysiological Basis of the Symptoms and Signs of Diabetes


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Acute : Diabetic Ketoacidosis


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Chronic :

Macrovascular Disease (Coronary, Cerebral and

Peripheral vascular disease)

Microvascular Disease ( Diabetic microangiopathy)

: Diabetic Nephropathy, Diabetic Retinopathy,

Diabetic Neuropathy


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Insulin ResistanceHyperinsulinemiaand Atherosclerosis


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19/33Libby, P. et al. Circulation 2005;111:3481-3488


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Drugs Used in Controlling Diabetes


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The Characteristics of Type I and Type II DM,Classified by National Diabetes Data Group in 1979

HLA, Human Leucocyte Antigen


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Insulin

Oral Antidiabetic


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Pharmacokinetic Profiles of Insulin


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Hypoglycemic Drugs

- Sulfonylurea drugs- Meglitinide drugs

- Rapaglinide (Prandin)

- Nateglinide (Starlix)

Antiglycemic Drugs

- Metformin- Thiazolidinediones

- Pioglitazone (Actos)

- Rosiglitazone (Avandia)

-Glucosidase Inhibitors- Acarbose (Precose) ,

- Miglitol (Glyset)


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Mechanism of Action of Oral Hypoglycemic Agents


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Pharmacologic Properties of Oral Antidiabeic Drugs


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FPG, Fasting Plasma Glucose Concentration

PPG, Postprandial glucose concentration HBA1c , Glycosylated hemoglobin conc.

Effects of Oral Antidiabetic Drugs


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Diet

Exercise

Drugs Education


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The Role of Amyloidogenic Islet Amyloid Polypeptide in the

Pathogenesis of type 2 Diabetes Mellitus

Prevalence of retinopathy by deciles of the distribution of


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Prevalence of retinopathy by deciles of the distribution ofPG, 2hrPPG and HbAlc in 40- to 74-year-old participants inthe National Health and Nutritional Epidemiologic Survey

(NHANES III).

x-axis ,the lower limit of each decile group. FPG=fasting plasma glucose;2hrPG=two-hour postprandial plasma glucose; HbA1c=glycosylated hemoglobin)

Pooled relative risk and risk difference (per 1000 patients over 5 years of treatment) estimates


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ofsevere hypoglycemia, by trial, early and more recent trial subgroups, and overall.ACCORD= Action to Control Cardiovascular Risk in Diabetes (12); ADVANCE = Action in Diabetes and

Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (13);UKPDS = United Kingdom Prospective Diabetes Study (8, 11); VADT = Veterans Affairs

Diabetes Trial (14).

Kelly T N et al. Ann Intern Med 2009;151:394-403

e&m farmakologi^hypoglycemic agent^

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