Oral hypoglycemics

ORAL HYPOGLYCEMICS

Anti-diabetic drugs treat diabetes mellitus by lowering glucose levels in the blood. With the exceptions of insulin, exenatide, and pramlintide all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of anti-diabetic drugs, and their selection depends on the nature of the diabetes, age and situation of the person, as well as other factors.
Diabetes mellitus type 1 is a disease caused by the lack of insulin. Insulin must be used in Type I, which must be injected or inhaled.
Diabetes mellitus type 2 is a disease of insulin resistance by cells. Treatments include (1) agents which increase the amount of insulin secreted by the pancreas, (2) agents which increase the sensitivity of target organs to insulin, and (3) agents which decrease the rate at which glucose is absorbed from the gastrointestinal tract.
Several groups of drugs, mostly given by mouth, are effective in Type II, often in combination. The therapeutic combination in Type II may include insulin, not necessarily because oral agents have failed completely, but in search of a desired combination of effects. The great advantage of injected insulin in Type II is that a well-educated patient can adjust the dose, or even take additional doses, when blood glucose levels measured by the patient, usually with a simple meter, as needed by the measured amount of sugar in the blood.

INDICATIONS:

1. Treatment of NIDDM either alone, w/ metformin or w/ insulin whose hyperglycemia cannot be controlled by diet & exercise alone.

DRUGS:

GENERIC NAMES:
1. Metformin

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1.1 Glucophage

Side Effects: GI disturbances,metallic taste, lactic acidosis, mild erythema
Available Dosage Form: Tablet (XR and Forte)
Contraindications: 1.) May cause hypoglycemia with with sulfonylureas, insulin, beta blockers or ACE inhibitors.
2.) Alcohol and IV iodinated contrast media may cause lactic acidosis.
3.) Glucocorticoids and diuretics.
Pregnancy Category: B


1.2 Glucovance

Side Effects: Nausea, vomiting, diarrhea, metallic taste, loss of appetite
Available Dosage Form: Tablet (film-coated)
Contraindications: Hypersensitivity to Metformin HCl, or other sulfonylureas, diabetic precoma, renal failure
Pregnancy Category: B


1.3 I-max

Side Effects: Anorexia, weight loss, metallic taste, nausea, rarely, lactic acidosis
Available Dosage Form: Tablet
Contraindications: Renal impairment, liver or heart failure, dehydration,
Pregnancy Category: B

2. Glimepiride

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2.1 Getryl

Side Effects: Visual impairment, GI disturbances, thrombocytopenia, leukopenia, hyponatremia
Available Dosage Form: Tablet
Contraindications: Diabetic ketoacidosis w/ or w/o coma.
Pregnancy Category: C

2.2 Imerid

Side Effects: GI disturbances, allergic reactions, aplastic anemia, thrombocytopenia, exfoliative dermatitis
Available Dosage Form: Tablet
Contraindications: Type 1 DM, hypersensitivity to glimepiride or other sulfonylureas, diabeticketoacidosis, pregnancy and lactation
Pregnancy Category: C

2.3 Norizec

Side Effects: Dizziness, asthenia, nausea, diarrhea, allergic skin reactions
Available Dosage Form: Tablet
Contraindications: Diabetic ketoacidosis with or without coma
Pregnancy Category: C

3. Glibenclamide

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3.1 Amecladin

Side Effects: Increased appetite, wt gain; skin rash, pruritus, photosensitivity.
Available Dosage Form: Tablet
Contraindications: IDDM Ketoacidosis, Severe thyroid, renal & hepatic impairment
Pregnancy Category: C


3.2 Daonil

Side Effects: GI disturbances. Hypoglycemia & signs of adrenergic counter-regulation; temporary visual impairment; elevated liver enzymes, impairment of liver function (eg w/ cholestasis, jaundice)
Available Dosage Form: Tablet
Contraindications: IDDM, diabetic ketoacidosis, diabetic precoma or coma, severe renal or hepatic dysfunction. Pregnancy & lactation.
Pregnancy category: C

3.3 Euglotab

Side Effects: Weakness, allergy, GI discomfort, low WBC count.
Available Dosage Form: Tablet
Contraindication: IDDM, diabetic coma. Pregnancy & lactation.
Pregnancy Category: C

4. Rosiglitazone maleate

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Brand name: Avandia

Drug class and mechanism: Rosiglitazone is an oral drug that reduces the amount of sugar in the blood. It is used for treating patients with type 2 diabetes and is in a class of anti-diabetic drugs called thiazolidinediones. The other member of this class is pioglitazone(Actos). Insulin is a hormone produced by the pancreas that is important for controlling the levels of glucose in the blood. Insulin stimulates the cells of the body to remove glucose from the blood and thereby lowers the level of glucose in the blood. Patients with type II diabetes cannot make enough insulin. As a result, the cells in their bodies do not remove enough glucose from the blood, and the level of glucose rises. Rosiglitazone often is referred to as an "insulin sensitizer" because it attaches to the insulin receptors on cells throughout the body and causes the cells to become more sensitive (more responsive) to insulin and remove more glucose from the blood. At least some insulin must be produced by the pancreas in order for rosiglitazone to work). Rosiglitazone was approved by the FDA on May 28, 1999. .
Dosing: Rosiglitazone may be taken once or twice daily, with or without meals. Daily doses range from 4 to 8 mg either with or without other antidiabetic medications. Studies do not demonstrate additional effects when more than 8mg per day are taken.
Drug interactions: Rifampin decreases the blood concentration of rosiglitazone by increasing its breakdown in the liver. Therefore, use of rifampin may decrease the effect of rosiglitazone.
Gemfibrozil increases the concentration of rosiglitazone in the blood by reducing its breakdown. Therefore, rosiglitazone may increase the side effects of rosiglitazone.
Pregnancy: There are no adequate studies of rosiglitazone inpregnant women[[script/main/art.asp?articlekey=33915|.]]
Nursing mothers: It is unknown if rosiglitazone is secreted in breast milk. Therefore, the safety of rosiglitazone to nursing infants also is unknown.
Side effects and precaution: The most common side effects seen with rosiglitazone alone or in combination with metformin are upper respiratory tract infection, headache, back pain, hyperglycemia, fatigue, sinusitis, diarrhea, and hypoglycemia. Rosiglitazone has been shown to cause mild to moderate accumulation of fluid and can lead to heart failure. Patients who already have heart failure may develop worsening symptoms with rosiglitazone. In addition, anemia may occur with rosiglitazone alone or combined with metformin. Rosiglitazone also causes increasing amounts of weight gain with increasing doses.

5. Glyburide


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Brand names: Micronase, Diabeta, Glynase Prestab

Drug class and mechanism: Glyburide is an oral glucose lowering-drug in a class of diabetic drugs called sulfonylureas. Other sulfonylureas include glipizide(Glucotrol), glimepiride (Amaryl), tolbutamide (Orinase), tolazamide, and chlorpropamide (Diabinese). Insulin is a hormone that is made in the pancreas. When released into the blood, insulin reduces the formation of glucose by the liver and causes cells in the body to remove sugar (glucose) from the blood. Patients with type 2 diabetes have high glucose levels in their blood because the cells in their bodies are resistant to the effect of insulin. Their liver produces too much glucose. In addition, the pancreas cannot produce enough insulin to overcome the insulin resistance of the body's cells. Glyburide reduces blood glucose by stimulating the pancreas to produce more insulin. Glyburide is not a cure for diabetes. The FDA approved glyburide in May 1984.
Dosing: The recommended starting dose is 2.5 to 5 mg daily of regular tablets or 1.5-3 mg daily of micronized tablets. The maximum dose is 1.25 to 20 mg of regular tablets and 0.75 to 12 mg of micronized tablets. Glyburide usually is administered with the first main meal of the day.
Drug interactions: Bosentan (Tracleer) and glyburide should not be used together because blood levels of both drugs decrease, potentially reducing their effect, and there is an increase in liver toxicity. Bosentan may increase the breakdown of glyburide in the liver.
There have been reports of changes in blood sugar (increase or decrease) in patients treated with fluoroquinolone type antibiotics, for example, levofloxacin (Levaquin) and ciprofloxacin (Cipro) and antidiabetic agents such as glyburide.
Thiazide diuretics, for example, hydrochlorothiazide (Hydrodiuril) increase blood glucose levels, reducing the effect of glucose reducing medications such as glyburide.
Preganacy: There are no adequate studies of glyburide in pregnant women. Prolonged and severe hypoglycemia (low blood glucose) has occurred in infants whose mothers were receiving other sulfonylurea drugs.
Nursing mothers: It is not known whether glyburide is excreted in breastmilk. Since many sulfonylureas are excreted in breast milk and potentially may harm the infant, alternative diabetic therapies should be considered or breast feeding should be discontinued.
Side effects: Common side effects include nausea,heartburn,rashes, low blood sugar, blurred vision and weight gain. Rare but serious side effects include hepatitis, jaundice, and low blood sodium level.

6. Repaglinide


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BRAND NAME: Prandin

Drug class and mechanism: Repaglinide is an oral medication for lowering blood suga in individuals with diabetes. It is in a class of drugs for treating type 2 called meglitinides and is chemically unlike other anti-diabetic medication.
Approximately 90% of patients with diabetes have type 2 or non-insulin dependent diabetes mellitus. (Type 2 diabetes usually occurs in adulthood, and is associated with and a strong family history of diabetes.) Glucose intolerance in diabetes type II is caused by reduced insulin secretion from the pancreas after meals and resistance of the body's cells to insulin's effect which is to stimulate the cells to remove glucose from the blood. This leads to high levels of blood glucose.
Like Sulfonylureas, for example, (Glucotrol), (Amaryl), tolbutamide (Orinase), and (Tolinase), repaglinide stimulates cells in the pancreas to produce insulin. Glyburide may be more potent than repaglinide at increasing insulin release in persons with low or high blood glucose levels, whereas repaglinide may be more potent in persons with moderate blood glucose levels. Repaglinide is unusual in that it has a rapid onset of action and a short duration of action. When taken just prior to meals, it promotes the release of insulin that normally occurs with meals and is responsible for preventing blood glucose levels from becoming high. It has been shown to lower levels by 1.6% to 1.9%. (Hemoglobin A1c is a blood test which measures the effectiveness of a drug in controlling high blood glucose levels. The lower the hemoglobin A1c, the better the control.) Repaglinide was approved by the FDA in 1997.
Dosing: Repaglinide is taken immediately before a meal or 15 to 30 minutes before a meal. It should be taken with every meal up to 4 times a day. Doses are adjusted by the physician to achieve the best effect.
Drug interaction: Repaglinide is metabolized (eliminated) in the liver by an enzyme called CYP3A4. Drugs that affect this enzyme may affect the blood levels of repaglinide and thus alter its glucose lowering effect. The metabolism of repaglinide may be prevented by (Nizoral),(Sporanox), (Diflucan), and (Biaxin). As a result, blood levels of repaglinide rise and there is an enhanced glucose-lowering effect. Dangerous (very low blood glucose) reactions could occur. On the other hand, the elimination of repaglinide may be increased with drugs that increase levels of CYP3A4 in the liver, such as barbiturates, carbamazepine (Tegretol), and rifampin (Rifadin). This can result in lower blood levels of repaglinide and hyperglycemia (high blood glucose).
Anabolic steroids or androgens can increase the risk of developing hypoglycemia in diabetic patients taking glucose-lowering medications.
Some drugs increase blood sugar and therefore reverse the effects of repaglinide. Such drugs include amphetamines, glucorticoids such as prednisone, estrogens, isoniazid, phenothiazines such as chlorpromazine (Thorazine), phenytoin (Dilantin), decongestants, and thyroid drugs.
Beta blockers, for example, propranolol (Inderal), atenolol (Tenormin), can cause hypoglycemia or hyperglycemia. Also, beta-blockers can blunt some of the body's responses to hypoglycemia such as rapid heart rate, thus making it difficult for patients to recognize (and treat) hypoglycemic reactions. This not withstanding, beta-blockers have been used successfully in diabetic patients. (Treatment with beta-blockers is associated with improved survival in diabetics who are treated with the beta-blocker because ofhigh blood pressure.)
Gemfibrozil (Lopid) should not be combined with repaglinide because gemfibrozil may significantly increase blood levels of repaglinide leading to side effects.
Pregnancy: No adequate human studies on the effects of repaglinide on the fetus have been done; however, there have been no effects in animal studies in which the mother has received repaglinide during pregnancy. Nevertheless, animals given repaglinide during both lactation (nursing) and gestation have developed skeletal defects. Therefore, physicians must weight the potential benefits and risks of this medication when considering its use in pregnant women.
Nursing mothers: It is not known whether repaglinide accumulates in breast milk. However, animals given repaglinide during pregnancy and lactation have developed skeletal defects. Because of the possibility of hypoglycemia in nursing infants and the skeletal effects in nursing animals, it is recommended that repaglinide not be used in women who are breastfeeding.
Side effects: Hypoglycemia (low blood glucose) occurs somewhat less frequently with repaglinide (1 in 6 persons) than with sulfonylureas such as glyburide and glipizide (1 in 5 persons). Some symptoms of hypoglycemia include hunger, nausea, tiredness, perspiration, headache, heart palpitations, numbness around the mouth, tingling in the fingers, |tremors, muscle weakness, blurred vision, cold temperature, excessive yawning, irritability, confusion, or loss of consciousness. Headache is reported in 1 in 9 persons. Other possible side effects include nausea, vomiting, diarrhea, constipation, stomach pain, back pain, and chest pain.


7. Exenatide

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BRAND NAME: Byetta

Drug class and mechanism: Exenatide is an injectable drug that reduces the level of sugar in the blood. It is used for treating type 2 diabetes. Exenatide belongs in a class of drugs called incretin mimetics because these drugs mimic the effects of incretins. Incretins, such as human-glucagon-like peptide-1 (GLP-1), are hormones that are produced and released into the blood by the intestine in response to food. GLP-1 increases the secretion of insulin from the pancreas, slows absorption of glucose from the gut, and reduces the action of glucagon. (Glucagon is a hormone that increases glucose production by the liver.) All three of these actions reduce levels of glucose in the blood. In addition, GLP-1 reduces appetite. Exenatide is a synthetic (man-made) hormone that resembles and acts like GLP-1. In studies, exenatide-treated patients achieved lower blood glucose levels and experienced weight loss. Exenatide was approved by the FDA in May, 2005.
Dosing: The initial dose of exenatide is 5 mcg injected under the skin (subcutaneously) twice daily, 60 minutes before breakfast or dinner. Exenatide should not be administered after a meal. Each dose should be injected in the thigh, abdomen or upper arm. The dose can be increased to 10 mcg twice daily after 1 month of therapy.
Drug interactions: Exenatide slows down transit of food and drugs through the intestine and, therefore, can reduce the absorption of drugs that are taken orally. To avoid this interaction, administer oral medications one hour before exenatide is administered. Orally administered drugs that need to be administered with food should be given with a light meal or snack when exenatide is not administered.
​Pregnancy: There are no adequate studies of exenatide in pregnant women. Most experts agree that insulin is the drug of choice in pregnant women with diabetes.
Nursing mothers:There are no adequate studies of exenatide in nursing mothers, and it is not known whether exenatide is excreted in human breast milk.
Side effects: The most common side effect of exenatide is nausea. Nausea from exenatide is more common with the higher doses decreases over time. Other common side effects include hypoglycemia (excessively low blood glucose), vomiting, diarrhea, headache, nervousness and stomach discomfort. Patients may also experience decreased appetite, acid reflux and increased sweating. There have been reports of acute pancreatitis associated with the use of exenatide. Patients developing severe, persistent abdominal pain should seek prompt medical attention. If pancreatitis is suspected, exenatide should be discontinued and not started again until pancreatitis has been excluded.


Escudero, Regina Carmeli SL
Jung, Maria Liza S
Manangan, Racquel Ann
San Pedro, Criselda
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Posted Sep 19, 2009 6:23 pm

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