Diabetes and Oral hypoglycemic drugs

Diabetes definition:
It is a chronic disease that occurs when the pancreas is no
longer able to make insulin, or when the body cannot make
good use of the insulin it produces.

Types of diabetes:

a) Type 1 diabetes:
It can develop at any age, but occurs most frequently in
children and adolescents. It is characterized by very little or no
insulin, which means that you need daily insulin injections to
maintain blood glucose levels under control.

b) Type 2 diabetes:
Type 2 diabetes is the major type ( 90% of diabetic patients). It
is more common in adults. When you have type 2 diabetes,
your body does not make good utilization of the insulin that it
produces. Type 2 diabetes treatment includes a healthy
lifestyle, increased physical activity and healthy diet. However,
patients may need taking oral hypoglycemic drugs to keep
their blood glucose levels under control.

c) Gestational diabetes (GDM):

It consists of high blood glucose during pregnancy and is
associated with complications to both mother and child, but it
usually disappears after pregnancy. However, it increases risk
of developing type 2 diabetes later in life.

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Drugs of treatment of diabetes:

1)Glimepiride (Amaryl):

Mechanism of action:
Glimepiride (sulfonylurea drug) enhances secretion of insulin. It
lowers blood sugar by stimulating the release of insulin by
pancreatic beta cells by inhibiting (KATP) which leads to
opening of calcium voltage channel. This leads to increase in
contraction of cells. Also, by inducing increased activity of
intracellular insulin receptors.

Uses:
Use is recommended together with diet and exercise for type 2
patients.

Adverse effects:
1)GIT disturbance.
2)Thrombocytopenia, leukopenia, and hemolytic anemia.
3)Hypoglycemia.

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 2)Metformin (Glucophage):

Mechanism of action:
The molecular mechanism of metformin is not completely
understood.
Multiple potential mechanisms of action have been proposed:
1) Inhibition of the mitochondrial respiratory chain (complex I).
2) Activation of AMP-activated protein kinase (AMPK).
3) Inhibition of glucagon-induced elevation of cyclic adenosine
monophosphate (cAMP) with reduced activation of protein
kinase A (PKA).
4) Inhibition of mitochondrial glycerophosphate dehydrogenase,
and an effect on gut microbiota.
5) It exerts an anorexiant effect in most people, decreasing
caloric intake.
6) It decreases gluconeogenesis (glucose production) in the
liver.
7) It also has an insulin-sensitizing effect with multiple actions
on tissues including the liver, skeletal muscle, endothelium,
adipose tissue, and the ovaries.

Uses:
1) It is used with type 2 diabetes.
2) It is also used as a second line agent for infertility in patients
with polycystic ovary syndrome.

Adverse effects:
1) GIT disturbance.
2) Increased flatulence.

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3) Lactic acidosis.

Contraindications:
1) Renal diseases.
2) Hepatic impairment.
3) Chronic or acute metabolic acidosis.
4) Alcoholism.
5) Heart failure.

3)Pioglitazone (Actos):

Mechanism of action:
Pioglitazone selectively stimulates the nuclear receptor
peroxisome proliferator-activated receptor gamma (PPAR-γ)
and to a lesser extent (PPAR-α). It modulates the transcription
of the genes involved in the control of glucose and lipid
metabolism in the muscle, adipose tissue, and the liver.
As a result, pioglitazone reduces insulin resistance in the liver
and peripheral tissues, decreases gluconeogenesis in the liver,
and reduces glucose and glycated hemoglobin in levels in the
circulation.

Uses:
Used in treatment of type 2 diabetes alone or in combination
with metformin or sulfonylurea or insulin.

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 ● Adverse effect:
1) Fluid retention and peripheral edema.
2) May cause anemia.
3) Mild weight gain.
4) Cholestatic hepatitis ( with long use).

Contraindications:
1) Acute liver diseases.
2) Type 1 diabetes.
3) Diabetic ketoacidosis.

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 ‫‪Diabetes and Oral hypoglycemic drugs‬‬

‫االسم‪ :‬محمد علي عبدالمنعم مرسي‪.‬‬

‫سكشن‪.6 :‬‬
‫رقم‪.74 :‬‬
‫الفرقة‪ :‬الثالثة‪.‬‬
‫قسم‪ :‬الكيمياء الدوائية‪.‬‬

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