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 -cells are functional
Block ATP-sensitive K + channels in cells

Mechanism of Insulin Secretion

K

ATP

Channel

Glucose

ATP

Metabolism

Binding

Sulfonylurea

Insulin
Secretion

Ca trigger

Ca

Passive flux

Voltage

Ca
Channel

Sulfonylurea
K

VDCC

ATP

or

VDCC

ATP

Ca2+

ATP
K+
Depolarization

Resting celll

Stimulated cell

3 Pancreas : Insulin secretion

Sulfonylureas Insulin secretion

SULFONILUREA
1.

2.

3.

Generasi I :
Carbutamide
Tolbutamide
Chlorpropamide
Generasi II :
Glyburide = glyclaside
Glipizide
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-tomoderate 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- (Peroxisome Proliferator
Activated Receptor) in adipose tissue, skeletal
muscle and liver

Liver : Hepatic Glucose

Output
Thiazolidinediones HGO

Improve
cell function

Proteins involve in glucose

lipid metabolism

Thiazolidinedione

PPAR

RXR

mRNA
Response
elements

Promoter

Gene transcription

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 its
effect
Etanol and quinolone enhanced its effect