oral hypoglycemic drugs

1. {
ORAL
HYPOGLYCEMIC
AGENTS
ZAINUL KHAN
ASSISTANT PROFESSOR
AIPR, LUCKNOW

2. ORAL HYPOGLYCEMIC AGENTS
Agents that are given orally to reduce the blood glucose levels in diabetic
patients.
• Diabetes mellitus type 1 is a disease caused by lack of insulin. Insulin
must be used in type 1,which must be injected.
• Diabetes mellitus type 2 is a disease of insulin resistance by cells due to
several factors.
HYPOGLYCEMIC AGENTS WORKS BY:
Increasing the amount of insulin secreted by the pancreas.
Increasing the sensitivity of target organs to insulin
Decreasing the rate at which glucose is absorbed from the gastrointestinal
tract.
SELECTION OF ANTI DIABETIC DRUGS DEPENDS UP ON:
• Nature of the diabetes
• Age and situation of the person
• Other factors

3. SYMPTOMS OF HYPERGLYCEMIA
• Fatigue
• Blurred vision
• Weight loss
• Fast heart beat
• Poor wound heeling
• Dry mouth
• Dry or itchy skin
• Sweating
• Irritable
• headache

4. CLASSIFICATION

5. ORAL HYPOGLYCEMIC DRUGS

6. SULFONYLUREAS: The drugs of this class is divided into
two generations:
First Generation: Second Generation:
Tolbutamide Glyburide
Chlorpropamide Glipizide
Tolazamide Glimepiride
MECHANISM OF ACTION:
Stimulation of insulin from pancreas.
Reduce hepatic glucose production.
Increase peripheral insulin sensitivity.
ADVERSE EFFECTS:
Hypoglycemia
Weight gain
Skin reaction

7. TOLBUTAMIDE
Tolbutamide is a first-generation potassium channel blocker,sulfonylurea
oral hypoglycemic medication that acts by increasing the pancreatic
insulin secretion.
Mechanism of action: Binds to sulphonylureas
receptors on beta cells
Stimulates release of insulin from
beta cells of pancreatic islets
By inhibiting the ATP potassium channels on
the beta cells
which results in depolarization
Resulting in calcium influx, and this kinase gets
activated
and release of insulin containing granules by
exocytosis increases.

8. INDICATION
DOSE
INITIAL DOSE: 1 to 2 g orally once a day or in divided doses.
MAINTENANCE DOSE: 0.25 to 3 g orally once a day or in
divided doses.
MAXIMUM DOSE: 3 g per day.
Non-insulin dependent diabetes
if diet alone is not Effective.
Recommended when there is great danger
of hypoglycemia
Has a short duration of action due to its
rapid metabolism, so is safe for use in older
people.

9. PHARMACOKINETICS
ABSORPTION: Get absorbed in 30 to 60 minutes but can be altered
by increased pH.
ONSET OF ACTION: It is within one hour & lasts for 6-12 Hrs.
DURATION OF ACTION: Short
HALF LIFE: 7 Hrs.
POTENCY: Twice potent as the related second-generation agent
Glipizide
SIDE EFFECTS
Allergic reactions like itching; red, swollen, blistered, or peeling skin
with or without fever, wheezing, tightness in the chest or throat,
trouble breathing or talking, unusual hoarseness, or swelling of the
mouth, face, lips, tongue, or throat.
Dark urine
Dark urine
Hypoglycemia

10. GLIPIZIDE
Glipizide is an oral rapid- and short-acting anti-
diabetic medication from the sulfonylurea class. It
is classified as a second-generation sulfonylurea.
MECHANISM OF ACTION:
Insulin is a hormone secreted from the cells of
pancreas.
When released into the blood causes cells in the
body to remove sugar (glucose) from the blood.
It reduces the formation of glucose by the liver.
It causes inhibition of hepatic glucose
production and reduction in serum glucagon
levels.

11. PHARMACOKINETICS :
ABSORPTION: Readily absorbed from GI tract
ONSET: 15–30 min
DURATION: up to 24 h
METABOLISM: Metabolized extensively in liver.
ELIMINATION: Excreted mainly in urine with
some excretion via bile in faeces.
HALF LIFE: 3–5 h.
DRUGS OF GLINIDES
Repaglinide
MOA:
Stimulation of pancreatic insulin release.
By closing ATP dependent B-cells.
INDICATIONS:
Type II diabetes mellitus
Long term cardiovascular
Renal effects
CONTRAINDICATIONS:
Diabetic ketoacidosis
Co-administration with
gemfibrozil
Known hypersensitivity
SIDE EFFECTS:
Hypoglycemia
Rhinitis
Cardiac
Ischemia
Angina

12. Nateglinide
MECHANISM OF ACTION:
• Nateglinide has no impact on insulin discharge without glucose or
maybe, it potentiates the impact of extracellular glucose on ATP sensitive
potassium channel and also has little impact on insulin levels.
• Impacts of nateglinide are most elevated at intermediate glucose level
(3 to 10 mmo1/L) and it does not expand the insulin discharge
effectively stimulated by high glucose fixations.
• (It should be greater than 15 mmo1/L)
• Nateglinide seems to be specific for pancreatic B-cells and does not seems
to be influence skeletal or cardiovascular muscle or thyroid tissue.
PHARMACOKINETICS
• ABSORPTION: Nateglinide is rapidly absorbed in the intestine.
• ONSET: After 30 min of administration.
• DURATION: 1 hour
• METABOLISM: Nateglinide is extensively metabolised, primarily
by cytochrome P450 2C9.
• ELIMINATION: eliminated By Urine (83%) and feces (10%).
• HALF LIFE: 1.5 hours

13. CONTRAINDICATIONS
Nateglinide is contraindicated in patients who:
Hypersensitivity.
Type 1 (namely insulin-dependent) diabetes mellitus.
SIDE EFFECT:
SERIOUS SIDE EFFECTS:
• Seizure (convulsions)
• Jaundice (yellowing of the skin or eyes)
LESS SERIOUS SIDE EFFECTS:
• Runny or stuffy nose, sneezing, cough,cold or
• flu symptoms
• Diarrheal, nausea
• Back pain
• Dizziness or
• Joint pain or stiffness

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