المحاضرة الثانية اعداد د اسلام عبد العظيم

WE HAVE STARTED IN THE LAST LECTURE WITH
AGENT USED FOR TREATEMENT OF DM
Lets continue;

2-Meglitinides
Meglitinides help the pancreas produce insulin and are often called "short-acting secretagogues." By closing the potassium channels of the pancreatic beta cells, they open the calcium channels, hence enhancing insulin secretion.
They are taken with or shortly before meals to boost the insulin response to each meal. If a meal is skipped, the medication is also skipped.
• repaglinide (Prandin)
• nateglinide (Starlix)

3-Biguanides
Biguanides reduce hepatic glucose output and increase uptake of glucose by the periphery, including skeletal muscle. Although it must be used with caution in patients with impaired liver or kidney function, metformin, a biguanide, has become the most commonly used agent for type 2 diabetes in children and teenagers. Amongst common diabetic drugs, metformin is the only widely used oral drug that does not cause weight gain.
• metformin (Glucophage).
• phenformin (DBI): used from 1960s through 1980s, withdrawn due to lactic acidosis risk.
• buformin: also withdrawn due to lactic acidosis risk.
• Metformin is usually the first-line medication used for treatment of type-2 diabetes. It is generally prescribed at initial diagnosis in conjunction with exercise and weight loss as opposed to in the past, where Metformin was prescribed after diet and exercise had failed. Initial dosing is 500 mg once daily, then if need be increased to 500 mg twice daily up to 1000 mg twice daily. It is also available in combination with other oral diabetic medications.

4-Thiazolidinediones
Thiazolidinediones (TZDs), also known as "glitazones," bind to PPARγ, a type of nuclear regulatory protein involved in transcription of genes regulating glucose and fat metabolism. These PPARs act on Peroxysome Proliferator Responsive Elements (PPRE [1]). The PPREs influence insulin sensitive genes, which enhance production of mRNAs of insulin dependent enzymes. The final result is better use of glucose by the cells.
• rosiglitazone (Avandia)
• pioglitazone (Actos)
• troglitazone (Rezulin): used in 1990s, withdrawn due to hepatitis and liver damage risk.

5-Alpha-glucosidase inhibitors
Alpha-glucosidase inhibitors are "diabetes pills" but not technically hypoglycemic agents because they do not have a direct effect on insulin secretion or sensitivity. These agents slow the digestion of starch in the small intestine, so that glucose from the starch of a meal enters the bloodstream more slowly, and can be matched more effectively by an impaired insulin response or sensitivity. These agents are effective by themselves only in the earliest stages of impaired glucose tolerance, but can be helpful in combination with other agents in type 2 diabetes.
• acarbose (Precose/Glucobay)

DIABETES MELLITUS -Partt 1 اعداد د.اسلام عبد العظيم

Diabetes Mellitus

FACT

Insulin convert glucose to glycogen for internal storage in liver and muscle cells.

Lowered glucose levels result both in the reduced release of insulin from the beta cells and in the reverse conversion of glycogen to glucose by the hormone glucagon.

Higher insulin levels increase some anabolic ("building up") processes such as cell growth and duplication, protein synthesis, and fat storage. 

Insulin (or its lack) is the principal signal in converting many of the bidirectional processes of metabolism from a catabolic to an anabolic direction, and vice versa

If the amount of insulin available is insufficient glucose will not be absorbed properly by those body cells that require it nor will it be stored appropriately in the liver and muscles. The net effect is persistent high levels of blood glucose, poor protein synthesis, and other metabolic derangements, such as acidosis.

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Types:

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1. Type 1 diabetes: results from the body's failure to produce insulin, and presently requires the person to inject insulin.

2. Type 2 diabetes: results from insulin resistance, a condition in which cells fail to use insulin properly, sometimes combined with an absolute insulin deficiency.

3. Gestational diabetes: is when pregnant women, who have never had diabetes before, have a high blood glucose level during pregnancy. It may precede development of type 2 DM..

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Signs and symptoms

• polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger).[11] Symptoms may develop quite rapidly (weeks or months) in type 1 diabetes, particularly in children.

• However, in type 2 diabetes symptoms usually develop much more slowly and may be subtle or completely absent. Type 1 diabetes may also cause a rapid weight loss and mental fatigue. 

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Medications

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1-Sulfonylureas

• First-generation agents

o tolbutamide (Orinase)

o acetohexamide (Dymelor)

o tolazamide (Tolinase)

o chlorpropamide (Diabinese)

• Second-generation agents

o glipizide (Glucotrol)

o glyburide (Diabeta, Micronase, Glynase)

o glimepiride (Amaryl)

o gliclazide (Diamicron)

They are insulin secretagogues, The "second-generation" drugs are now more commonly used.

They are more effective than first-generation drugs and have fewer side effects. All may cause weight gain.

Sulfonylureas are only useful in Type II diabetes, as they work by stimulating endogenous release of insulin. They work best with patients over 40 years old, who have had diabetes mellitus for under ten years.

They can not be used with type I diabetes, or diabetes of pregnancy. They can be safely used with metformin or -glitazones. The primary side effect is hypoglycemia.