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
Glucose

Insulin
Secretion


Ca
i



ATP

K
ATP
Channel
+
-
-
-
+
+
Ca
Channel
Metabolism Voltage Binding
Sulfonylurea
Passive flux
Ca trigger
Resting celll
Stimulated cell
Sulfonylurea
or
ATP
Depolarization
VDCC
K
ATP

K
+
VDCC
Ca
2+
K
ATP
Mechanism of Insulin Secretion

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- (Peroxisome Proliferator
Activated Receptor) in adipose tissue, skeletal
muscle and liver
Liver : Hepatic Glucose
Output
Thiazolidinediones HGO
Improve
cell

function
Promoter Coding Region
Nucleus
Gene transcription
PPAR
RXR
Response
elements
mRNA
Thiazolidinedione
Proteins involve in glucose
lipid metabolism
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