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
KATP
Channel
Glucose ATP

+ - -
Metabolism Binding

Sulfonylurea
- Voltage

Insulin Ca trigger
Ca i Passive flux
Secretion Ca
Channel

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

Depolarization

Resting celll Stimulated cell

3 Pancreas : Insulin secretion
Sulfonylureas  Insulin secretion
 SULFONILUREA
1. Generasi I :
Carbutamide
Tolbutamide
Chlorpropamide
2. Generasi II :
Glyburide = glyclaside
Glipizide
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 the 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 flatulance, 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

Thiazolidinedione PPAR Υ RXR

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
 GLIPTINE
• DPP-4 inhibitors (Dipeptidyl peptidase-4)
• Linagliptin, sitagliptin, vilda and saxagliptin

Mechanism of action: enhance and prolong the

action of incretin hormones by competitively
antagonizing the enzyme DPP-4
 gliptin
Pharmakokinetics
• Rapidly absorbed after oral administration,
with peak plasma concentration occuring in 1-
4 hours
• Bioavaibility is more than 87%
• 79% is excreted unchanged in the urine,
primarily via renal excretion
• Only slightly is metabolized by using CYP3A4
and CYP2C6 in liver
 gliptin
CONTRINDICATION
• DM type 1
• Hipersensitivity
• Pregnancy

• SIDE EFFECTS
• Upper respiratory tract infection
• Headache, nausea
• Hypersensitivity reaction
 gliptin
DRUG INTERACTION:
• Alpha adrenergic agonist, isoniazid,
antipsychotic first generation reduced it’s
effect
• Etanol and quinolone enhanced it’s effect