ANTI DIABETIC AGENT

(INSULIN & ORAL

HYPOGLYCEMIC DRUGS)

Wiwik Rahayu,
Rahayu, dr.,
dr., M.Kes
M.Kes
Wiwik
Depart. of
of Pharmacology
Pharmacology &
&Therapy
Therapy
Depart.
Medical Faculty
Faculty Riau
Riau University
University
Medical

It is a heterogeneous group of
syndromes
all characterized by an elevation of
blood
glucose caused by a relative or
absolute
deficiency of insulin.
Symptom:

DM
DM

A. TYPE I (INSULIN DEPENDENT

DIABETES MELLITUS, IDDM)

Absolute deficiency of insulin

Caused by massive -cell lesions or
necrosis
Treatment: exogenous insulin

B. TYPE II (NON INSULIN DEPENDENT

DIABETES MELLITUS, NIDDM)

Inability of -cell to produce appropriate

quantities of insulin
Insulin resistance
Other unknown defects
Treatment: Hypoglycemic oral drugs
insulin

INSULIN
Insulin exogen
Beef
Pork
Human (by. E.colli, OOA <<, DOA <<)

Effect
Hyperglycemia

Normal

PHARMACOKINETICS
PHARMACOKINETICS
Insulin

p.o degradation
subcutaneous
IV: in hyperglycemic
emergency

ADVERSE EFFECT
EFFECT &&
ADVERSE
OVERDOSE TOXICITY
TOXICITY
OVERDOSE
Hypoglycemia

Hypoglycemia
brain
damage !
Symptom of hypoglycemia

Tachycardia
Confusion
Vertigo
Diaphoresis

Lipodystrophy
Hypersensitivity

INDICATION
INDICATION
1. All patients with type I DM regardless of age
2. Patient who have ketoacidosis or

hyperosmolar coma
3. Patient with type II DM when diet
restriction, exercise and oral hypoglycemic
agent have failed to maintain satisfactory
blood glucose concentration
4. Patient with type II DM in presence of
surgery fever, infections, serious renal or
hepatic dysfunction, and other metabolic
disturbances
5. Pregnant diabetic women

CONTRAINDICATION
CONTRAINDICATION
There are no contraindications if the
proper
indication exists.
Patients must be well educated
regarding the
role of diet, exercise and illness in
modifying
their insulin requirements.

INSULIN PREPARATIONS
A. RAPID ACTION INSULIN

PREPARATION
Zinc insulin: sc
iv (in emergencies)

B. INTERMEDIATE ACTION INSULIN

PREPARATION
1.
2.
3.
4.

Semilente insulin suspension

Isophane insulin suspension
Lente insulin
Insulin incombination

C. PROLONGED ACTION INSULIN

PREPARATION

ORAL HYPOGLYCEMIC AGENTS

SULFONILUREAS

I.

II.

First generation
Tolbutamide, Chlorpropamide, Tolazamide
Second generation
Glipizide, Glyburide

BIGUANIDES
Metformin

GLUCOSIDASE INHIBITORS
Acarbose

IV.

REPAGLINIDE (?)
Repaglinide

V.

THIAZOLIDINEDIONES
Troglitazone

SULFONILUREAS

Mechanism of action
1. Stimulation of insulin release from the

cells
2. Reduction of serum glucagon levels
3. Increased binding of insulin to target
tissues

Pharmacokinetics
Oral, bind to serum proteins
Metabolized by liver

1st G : inactive, less active, active

2nd G: inert

Excreted by kidney or liver

 Side effect
Hypoglycemia (especially:
chlorpropamide, Glyburide)
Contraindication:
Renal or hepatic insufficiency
Pregnancy
Elderly

INTERACTION
INTERACTION
Klofibrat,
fenilbutazon,
salisilat,
sulfonamid
Mengganti sulfonil
urea dari protein
plasma

Alopurinol,
Probenesid,
fenilbutazon, Salisilat,
sulfonamid
Berkurangnya
ekskresi sulfonilurea

Meningkatnya kerja obat-obat

sulfonilurea
Berkurangnya metabolisme hepatik
sulfonilurea
Dikumarol, kloramfenikol,
inhibitor mono amin oksidase,

METFORMIN
Used alone or in combination with

sulfonilurea, others
Drugs of choice in newly diagnosed type II
DM
Decreasing hepatic glucose output
Reduced hyperlipidemia (LDL, VDL,
cholesterol, HDL)
Oral, unbound to serum protein
Not metabolized
Excreted by kidney
Side effect: GI disturbance, hypoglycemic <<

BIGUANIDES
METFORMIN
Inhibiting gluconeogenesis
Reduce hyperlipidemia (LDL, VDL,
cholesterol, HDL)
Not bound to serum protein
Is not metabolized
SE: hypoglycemic <<

ACARBOSE
Inhibits glucosidase in intestinal

decreased the absorption of

disaccharides
Taken with meals
Not cause hypoglycemia
Side effects: flatulence
diarrhea
abdominal cramping

REPAGLINIDE
Binds to the ATP- sensitive potassium

channels of cells
insulin
Metabolized

release of
inactive

TROGLITAZONE
Decreases insulin resistance