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ANTIDIABETIC
DRUGS
PRESENTED BY,
SHARON SEQUEIRA
1ST M.PHARM
DEPARTMENT OF
PHARMACOLOGY
INTRODUCTION
Diabetes mellitus is a disease characterized by
persistent hyperglycemia , resulting either from
inadequate secretion of the hormone insulin, an
inadequate response of target cells to insulin
combination of these factors.
Type 1 diabetes mellitus is characterized by loss of
the insulin-producing beta cells islets of Langerhans
of the pancreas.
Type 2 diabetes mellitus is a metabolic disorder that
is primarily characterized by insulin resistance,
relative insulin deficiency, and hyperglycemia.
Gestational diabetes, Type 3 ,also involve a
combination of inadequate insulin secretion
responsiveness , resembling type 2 diabetes in
several respects .
It develops during pregnancy and improve or
disappear after delivery.
Normal blood glucose level-120mg/dl.
Fasting blood glucose level-100mg/dl.
PATHOLOGICAL CHANGES
Increase in vessel wall matrix.
Thickening of capillary basement membrane.
Cellular proliferation resulting in vascular
complication:
Lumen narrowing
Early atherosclerosis
Retinopathy
Neuropathy
SYMPTOMS OF DIABETES
Polyuria [increase urination]
Polydipsia [increase thirst]
Polyphagia [increase hunger]
TREATMENT
Conventional preparations of insulin
o Short acting:
Regular insulin
Prompt insulin Zinc suspension (semi lente)
Intermediate Acting
Insulin Zinc suspension(Lente)
Neutral protamine hagedron or Isophane insulin
Long Acting
Extended insulin Zinc suspension (Ultra lente)
Protamine Zinc insulin.
Purified Insulin Preparations
Single Peak Insulins :Actrapid, Lentard,
Actraphane
Monocomponent Insulins :Monotard
Human Insulin :Human Actrapid.
Oral Hypoglycemics
1.Sulponyl Ureas
a.First Generation
Tolbutamide
Chlorpropamide
Acetohexamide
b.Second Generation
Gilbenclamide
Glipizide
Gliclazid
2.Biguanides
Phenformin
Metformin
3.Miscellaneous
Acarbose
Guargum
VARIOUS SCREENING MODELS
IN VIVO METHODS
1.Alloxan induced diabetes.
2.Streptozotocin induced diabetes.
3.Hormone induced diabetes
a.Growth hormone induced diabetes
b.corticosteroid induced diabetes [DEXAMETHASONE]
4.Insulin deficiency due to insulin antibodies
5.Surgically induced diabetes
1.ALLOXAN INDUCED DIABETES
Purpose
Induction of diabetes using chemical alloxan.
Alloxan is toxic glucose analouge which selectively
destroys insulin producing beta cells when
administered to species
IN most species , triphasic time course is observed
.[Initial rise of glucose is followed by sustain
increase of blood glucose].
Animal used
Baboons 65-200mg/kg
Beagle dogs 60mg/kg
Wistar rat 100-
175mg/kg
Rabbits 150mg/kg
PROCEDURE
Limitations:
Long standing procedure.
3.INSULIN DEFICIENCY DUE TO INSULIN
ANTIBODIES
PRINCIPLE
A transient diabetic syndrome can be induced by
injecting guinea pigs anti insulin serum.
Diabetes persists as long as antibodies are capable of
reacting with insulin remaining in the circulation.
Preparation of antibody:
DISADVANTAGES
PRINCIPLE
ANIMAL USED:
Male Wistar Rats(200-250g).
PROCEDURE
After anaesthesia , pancreas are
removed.