Anti diabetic drugs

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Diabetes mellitus DM is characterized by elevated blood sugar levels due to absolute or relative lack of insulin. Type 1 diabetes - -cell failure at outset Insulin dependent Type 2 diabetes - Gradual -cell deterioration Early stages: Diet and Oral agents Late-stage: Insulin therapy

Transcript of Anti diabetic drugs

Page 1: Anti diabetic drugs

Diabetes mellitus

• DM is characterized by elevated blood sugar levels due to absolute or relative lack of insulin.

• Type 1 diabetes - -cell failure at outset– Insulin dependent

• Type 2 diabetes - Gradual -cell deterioration– Early stages: Diet and Oral agents – Late-stage: Insulin therapy

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Diabetes mellitus

• Glycosylated hemoglobin Hb-A1c : It is used to monitor the plasma glucose concentration over prolonged periods of time (4-6 weeks).

• Insulin secretion is promoted by ↑ blood glucose levels, amino acids, GI hormones and by β-2 agonist.

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Insulin• Proinsulin is converted to insulin and C

peptide.• Insulin is referred as the storage

hormone as it promotes anabolism and inhibits catabolism of carbohydrates, fatty acids and protein.

• In the absence of insulin, most tissues cannot use glucose and fats/proteins are broken down to provide energy.

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Insulin

Mechanism of action :• Insulin binds to insulin receptors on

the plasma membrane and activates tyrosine kinase – primarily in adipose tissue, liver and skeletal muscle.

• The Nerves, RBC’s, Kidney, and Lens of the eye do not require insulin for glucose transport.

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Insulin

Liver : • Insulin increase the storage of glucose

as glycogen in the liver. • It inserts the GLUT-2 glucose transport

molecule in the cell membrane. • It inhibits gluconeogenesis – thus

significantly ↓ glucose output by the liver.

• It decrease the protein catabolism.

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Insulin

Muscle : • Insulin stimulates the glycogen

synthesis and protein synthesis.• Glucose transport into the cells is

facilitated by GLUT-4 into the cell membrane.

• It inhibits the protein catabolism.

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Insulin

Adipose tissue :• Insulin facilitates the storage of

triglyceride by activating plasma lipoprotein lipase and inhibiting intracellular lipolysis.

• It increase the glucose uptake by GLUT-4 insertion into the cell membrane.

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Insulin

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Insulin

• Insulin is a 51 AA peptide• Not active orally.• Insulin is inactivated by insulinase

found mainly in liver and kidney.• Dose reduced in renal insufficiency• Sources of Insulin :

– Beef pancreas / Pork pancreas – Human insulin: recombinant DNA origin

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Insulin

Human Insulin : • Do not contain measurable

amounts of proinsulin or contaminants.

• Diminished antibody• Less allergic reactions• Less lipodystrophy• Preferred in gestational diabetes

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InsulinInsulin preparations :• Rapid acting insulin :

Lispro, Aspart and Glulisine• Short acting insulin:

Regular (crystalline)• Intermediate acting insulin:

NPH (isophane) and Lente (insulin zinc)

• Long acting insulin: Ultralente, Detimir and Glargine

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Insulin Duration Route Features

Lispro 3 – 5 hrs I.V or S.C

Onset within 15 minutes

Regular (crystalline)

7 – 10 hrs I.V or S.C

common

NPH (Neutral protamine hagedorn)

16 – 20 hrs

S.C NPH can mix with regular

Ultralente 24 – 30 hrs S.C Basal level

Insulin

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Insulin

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Insulin

Adverse effects of Insulin :• Hypoglycemia • Allergic reactions• Lipodystrophy• Others includes

– Seizures– Coma

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Oral Anti-diabetic drugsMechanisms to reduce blood sugar :• Stimulation of pancreatic insulin

release – Sulfonylureas, Meglitinide• Reduce the bio-synthesis of glucose

in liver – Biguanides (Metformin)• Increase the sensitivity of target

cells to insulin -- Thiazolidinediones• Retard the absorption of sugars

from the GI tract – Acarbose, Miglitol

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Oral Anti-diabetic drugs

Sulfonylureas :• First generation : Acetohexamide,

Chlorpropamide, Tolbutamide, Tolazamide

• Second generation : Glipizide, Glyburide – more potent, more efficacious and fewer adverse effects.

• Third generation : Glimiperide

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Sulfonylureas

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Sulfonylureas Dose(mg)

Duration(h)

First Generation

Tolbutamide (Orinase) 1000-1500 6-8

Chlorpropamide (Diabinese) 250-375 24-60

Tolazamide (Tolinase) 250-375 12-24

Second generation

Glipizide (Glucotrol) 10 10-24

Glyburide (Micronase) (Glibenclamide)

Third generation

5 16-24

Glimepiride (Amaryl) 1-2 24

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Oral Anti-diabetic drugsSulfonylureas : Adverse effects :• Hypoglycemia• Cholestatic jaundice• Weight gain• Cross placenta – fetal hypoglycemia.• Chlorpropamide : It can cause water

retention by ↑ release of ADH (SIADH)• Disulfiram-like reaction with alcohol.

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Oral Anti-diabetic drugs

Repaglinide, Nateglinide : • More rapidly acting insulin

enhancers and shorter duration than

sulfonylurea.• Hypoglycemia is the common

adverse effect.• Less weight gain

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Oral Anti-diabetic drugs

Repaglinide, Nateglinide• The drug has minimal renal

excretion thus useful in patients with DM and impaired renal function. 

• It is designed to be taken with each meal to stimulate insulin release with meal. If a meal is skipped, so is the repaglinide.

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Oral Anti-diabetic drugs

Biguanides (Metformin): • Inhibits gluconeogenesis.• Does not promote insulin secretion. • It increase the sensitivity of liver

and muscle to insulin. • It causes modest weight loss.

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Oral Anti-diabetic drugs

Metformin (Glucophage) :• It does not cause hypoglycemia.

• It produces a significant ↓ TG and

LDL, and ↑HDL.• There is a serious concern about

lactic acidosis especially in patients with kidney disease.

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Oral Anti-diabetic drugs

Thiazolidinediones• Enhance glucose and lipid

metabolism through action on Peroxisome Proliferator Activated Receptor (PPAR–γ)

• Enhance sensitivity to insulin in muscle and fat by increasing the GLUT 4 glucose transporters.

• E.g. ; Pioglitazone Actos, Rosiglitazone Avandia

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Anti-diabetic drugs

Thiazolidinediones : • Beneficial effects on serum lipid;

↓TG and ↑HDL.• Troglitazone is associated with

hepatitis.• Edema.

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Anti-diabetic drugs

Alpha-Glucosidase Inhibitors: • It inhibits -glucosidase which

converts dietary starch and complex carbohydrates into simple sugars

• It reduces absorption of glucose after meals.

• The main side effects includes flatulence and diarrhea.

• Acarbose Acarbose (Glucobay)(Glucobay) , Miglitol , Miglitol (Glyset)(Glyset)

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Anti-diabetic drugs

Glucagon like Peptide : GLP-1 analog : Xenatide : (Byetta) :

• GLP is an incretin released from the small intestine which increase the glucose dependent insulin secretion.

• Xenatide suppress glucagon release and reduce appetite

• It is administered by SC injection.

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Anti-diabetic drugsGlucagon like Peptide : GLP-1 analog : Xenatide : (Byetta) :

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Anti-diabetic drugs

Dipeptidyl peptidase 4 (DPP-4) inhibitors: SITAGLIPTIN (januvia)

Xenatide (Byetta) inj

Sitagliptin(januvia)

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Anti-diabetic drugs• Sitagliptin (Januvia) is an oral anti-

diabetic drug.• It inhibit the dipeptidyl peptidase 4

(DPP-4), an enzyme which inactivates the incretins GLP-1 and GIP, that are released in response to a meal.

• It potentiates the secretion of insulin and suppress the release of glucagon by the pancreas.

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Endocrine pancreasGlucagon :• It has positive inotropic action and

chronotropic action on the heart.• It acts by stimulation of glucagon

receptors and not through beta 1 receptors.

• This is the basis for using glucagon in beta blocker overdose.