COURSE NAME: PHARMACOLOGY II

COURSE CODE:SHS.314
CREDIT HOURS: 2hrs
LECTURES: 20
INSTRUCTOR: Dr. Khurram
Antidiabetic Drugs
 Contents
 Introduction of Diabetes

 Types of Diabetes

 Mechanism of action of Anti diabetic drug

 Side effects of antidiabetic drugs

 Insulin and its types

 Diabetes Mellitus

 Chronic systemic disease characterized by metabolic and

vascular abnormalities

 Disorder of carbohydrate metabolism

 Results from inadequate production or underutilization of

insulin
 Diabetes Mellitus

 Characterized by glucosuria and hyperglycemia

 Two forms—Type 1 and Type 2

 Type 1—patient secretes no insulin. Cause is felt to be

autoimmune.

 Type 2- patient secretes insufficient amounts of insulin and

insulin receptors are resistant to existent circulating insulin
 Diabetes Mellitus

 Symptoms: hyperglycemia, glucosuria, polyuria, polydipsia,

polyphagia, and possibly itching.

 Fasting blood glucose is higher than 126

 Manifested by: weight loss, weakness, increased frequency of

infections
 Diabetes Mellitus

 Without intervention, significant complications will ensue.

 Retinopathies

 Glaucoma

 Neuropathies

 Cardiovascular disease

 Peripheral vascular disease(PVD)

 Increased incidence of toxemia of pregnancy

 Pathophysiology

 Insulin secreted by beta cells

 Insulin binds with and activates 80% of cells

 Liver, muscle, and fat cells are primary tissues for insulin
action

 With insulin receptor binding, cell membranes permeable to

glucose into the cells
 Pathophysiology cont.

 Increased cell permeability also allows for

 Amino acids

 Fatty acids

 Electrolytes to enter cells

 Changes cause anabolism and inhibit catabolism

 Pathophysiology cont.
Carbohydrate metabolism

 Insulin increases glucose transport into liver, skeletal muscle,

adipose tissue, the heart and uterus.

 Must be present for muscle and fat tissues to use glucose for
energy

 Insulin regulates glucose metabolism to produce energy for

cellular functions
 Pathophysiology cont.
Fat Metabolism

 Insulin promotes glucose into fat cells where it is broken down

 One of breakdown products is A-glycerophosphate, combines

with fatty acids which ultimately forms triglycerides

 This is the mechanism by which insulin promotes fat storage

 Fat Metabolism

 When insulin is lacking, fat is released into the bloodstream as

free fatty acids.

 Blood concentrations of triglycerides, cholesterol and

phospholipids are also increased
 Protein Metabolism

 Insulin increases the total amount of body protein by

increasing transport of amino acids into cells and synthesizing
protein within the cells

 Insulin potentiates the effects of growth hormone

 Lack of insulin causes protein breakdown into amino acids

 Endogenous Insulin

 Glucose is the major stimulus of insulin secretion

 Oral glucose is more effective than intravenous glucose

because glucose in digestive tract increases the release of
gastrin, secretin, cholecystokinin, and gastric inhibitory
peptide

 Also stimulates vagal activity

 Endogenous Insulin

Other hormones that raise blood glucose levels include:

 Cortisol

 Glucagon

 Growth hormone

 Epinephrine

 Estrogen

 Progesterone
 Endogenous Insulin

Factors that inhibit insulin secretion include:

 Hypoxia

 Hypothermia

 Stimulation of alpha adrenergic 2 receptors

 Classification of Two Types of Diabetes

 Type 1 diabetes results from an autoimmune disorder that

destroys pancreatic beta cells

 Usually has sudden onset

 Associated with high incidence of complications

 Requires exogenous insulin

 10% of those with diabetes are type I

 Diabetic Ketoacidosis (DKA)

 Life-threatening complication occurs with insulin deficiency

 Glucose cannot be used by body cells for energy so fat is

mobilized for this purpose

 Mobilized fat is then extracted by liver and broken down into

glycerol and fatty acids

 Fatty acids further broken down into ketones

 DKA

 Accumulation of ketones results in acidemia

 Attempts to buffer acidic H+occurs by ionic exchange,

intracellular potassium exits cells. H+ ions enter cells. Result is
excretion of potassium in urine.

 Kidneys attempt to buffer by excreting ketones

 Pulmonary attempt to buffer by Kussmaul breathing

 Clinical Signs and symptoms of DKA

 Kussmaul breathing

 Nausea and vomiting

 Thirst

 Polydipsia, polyphagia and polyuria

 Hypotension

 Tachycardia

 shock
 Type 2 Diabetes Mellitus

 Characterized by hyperglycemia and insulin resistance

 Results from increased production of glucose by liver and

decreased uptake of glucose in liver, muscle and fat cells

 Insulin resistance—higher than usual concentrations of insulin

are required
 Type 2 Diabetes Mellitus

 Occurs at any age

 Gradual onset

 Less severe symptoms initially

 Easier to control

 More MIs and strokes

 90% of those with diabetes are Type 2

 multifactorial
 Hyperosmolar hyperglycemia nonketotic coma
(HHNC)

 Occurs in Type 2 Diabetes

 Because patient has some endogenous insulin, no ketosis

develops

 Blood sugars can be >800-1000

 Can result in hypovolemic shock, renal problems, stroke, coma

and even death
 Metabolic Syndrome or Syndrome X

• Comprised of a set of risk factors which include:

1. Central abdominal adiposity (men waist size greater than 40

inches, women greater than 35 inches

2. Fasting triglycerides greater > or equal to 150 mg/dl

3. HDL cholesterol (less than 40 in men, less than 50 mg/dl in

women
 Metabolic Syndrome cont.

4. Blood pressure greater than or equal to 130/85

5. Fasting glucose greater than or equal to 110mg/dL

Also possess prothrombotic and proinflammatory tendencies

 Metabolic Syndrome cont.

All factors are interrelated

 Obesity and lack of exercise tend to lead to insulin resistance

 Insulin resistance has a negative effect on lipid production.

Increase VLDL, LDL, TG and decreasing the HDL.

 Insulin resistance leads to increased insulin and glucose levels

in blood.