ANTI DIABETIK A

ORAL

dr. Theodorus, MMedSc

Staf Bagian Farmakologi
FK Unsri
• Stimulate insulin secretion
• Cause hypoglycaemia  stimulate appetite
and leads to weight gain
• Only effective if β-cells are functional
• Block ATP-sensitive K + channels in β-cells
Mechanism of Insulin Secretion
K
ATP
Glucose Channel
ATP

+ - -
Metabolism Binding
Sulfonylurea
- Voltage

Insulin
Ca trigger Ca Passive
i Ca
Secretion flux
+ + Channel

Sulfonylurea
K VDCC K VDCC
ATP or ATP
Ca2+
 ATP
K+ Depolarization

Resting celll Stimulated cell

3 Pancreas : Insulin secretion
Sulfonylureas  Insulin secretion
 SULFONILUREA
1. Generasi I :
Carbutamide
Tolbutamide
Chlorpropamide
2. Generasi II :
Glyburide
Glipizide
gliklasid
3. Generasi III :
Glimepiride
Mechanism of action ≈ Thiazolidinediones
 SULFONILUREA
• SIDE EFFECTS
• Hypoglicemic reactions including coma
• Particularly, elderly patients with impaired hepatic or
renal function
• Glyburide=chlorpropamide > glipizide > tolbutamide
• Nausea and Vomiting
• Aplastic and hemolytic anemia
• Hypersensitivity and dermatological reactions
 SULFONIL UREA
• CONTRAINDICATIONS
• Hypersensitivity
• Diabetic keto acidosis

• DRUG INTERACTION
• Clofibrate, dicumarol, salysilates displace the
sulfonyl ureas from binding site
 SECRETAGOGUE LAIN
MEGLITINIDES :
1. Repaglinide
2. Meglitinide
3. Nateglinide
 BIGUANIDE (METFORMIN)

• Increase glucose uptake in striated muscle

• Inhibit hepatic glucose output & intestinal glucose
absorbtion
• Cause anorexia  assist in weight loss
• Are used with sulphonylurea when these have
ceased to work adequately
• Reduction of total cholesterol, LDL cholesterol &
trigliceride
• Increase HDL cholesterol concentration
 2. Muscle and adipose tissue :
Glucose uptake
Metformin  glucose utilization

4. Liver : Hepatic
Glucose Output
Metformin  HGO
 METFORMIN
• DRUG INTERACTION
• Cimetidine and furosemide increased yhe metformin plasma
• Alcohol potentiate the effect of metformin
1. Intestine : glucose absorption

Acarbose  glucose absorbtion secondary

to  digestion of carbohydrate

2. Muscle and adipose

Tissue : glucose uptake

 ACARBOSE
• SIDE EFFECTS: usually during the first week of
therapy; most commonly mild-to-moderate GI
tracts such as flatulantce, diarrhea, and
abdominal discomport
• CONTRAINDICATION:
- Hypersensitifity
- Diabetic ketoacidosis
- Cirrhosis
 THIAZOLIDINEDIONES
• Antidiabetic agents that increase insuline sensitivity
through the modulation of several processes
• These agents affect:
- insulin receptor kinase activity
- insulin receptor phosphorylation
- insulin receptor numbers
- hepatic glucose metabolism
• May activate PPAR-γ (Peroxisome Proliferator –
Activated Receptor) in adipose tissue, skeletal muscle
and liver
Liver : Hepatic Glucose
Output
Thiazolidinediones  HGO

Improve β –

cell function
 Proteins involve in glucose
lipid metabolism

Thiazolidinedio PPAR Υ RXR

ne

mRNA
Response
elements Gene transcription

Promoter Coding Region

Nucleus

Thiazolidinediones activate nuclear receptors, resulting in expression

of proteins involved inglucose and lipid metabolism
 TZD
• CONTRAINDICATION
- Hypersensitivity
- Liver disease
- Pregnancy category C
- Nursing woman
• DRUG INTERACTION
- May induce drug metabolism by CYP3A4: Consider
this when prescribing with others CYP3A4 substrate
such as CCB, cisapride, steroid and HMG-CoA
reductase inhibitors