INTRO

Hehehehehehehe ……………..The one thing which has made a substitute for INSULIN…………….the only drug of choice for a early diagnosed and well diet controlled patient with Non insulin diabetes mellitus  ……….

Oral hypoglycemic agents commonly are referred to as sulfonylureas, a class of compounds. Sulfonylurea compounds are among the most widely prescribed medications in the world. The drugs are frequently used to treat patients with type II diabetes. Wide availability of these medications increases potential for either intentional or unintentional overdose in pediatric and adult populations.

First-generation sulfonylurea compounds became widely available in 1955. They are acetohexamide, chlorpropamide, tolazamide, and tolbutamide. First-generation agents have longer half-lives (eg, 49 hours for chlorpropamide). Second-generation sulfonylureas were introduced in 1984. Known as glipizide, glyburide, and glimepiride, second-generation sulfonylureas are more potent and have shorter half-lives than the first-generation sulfonylureas.

Other agents besides sulfonylureas are used to treat type II diabetes, including biguanides, alpha-glucosidase inhibitors, and troglitazone. Metformin (Glucophage in the United States) is one such agent. Even in excessive dosage, these agents do not decrease serum glucose below euglycemia; consequently, they are referred to appropriately as antihyperglycemic agents rather than hypoglycemic agents.

The Joslin Diabetes Center released a clinical guideline for the pharmacological management of type II diabetes in 2007.

CLASSIFICATION OF DRUGS

1. SULFONYL UREA’S
2. BIGUANIDES
3. ALPHA GLUCOSIDASE INHIBHITORS
4. MEGLITINIDES
5. THIAZOLINEDIONES

SULFONYLUREA’S

Sulfonylureas work primarily by stimulating pancreatic insulin secretion, which in turn reduces hepatic glucose output and increases peripheral glucose disposal.

The sulfonylureas are often classified as belonging to the first or second generation.

The First generation sulfonylureas:

• Acetohexamide
• Chlorpropamide
• Tolazamide
• Tolbutamide.

The Second generation sulfonylureas :

• Glibenclamide
• Glyburide
• Glipizide
• Glicazide
• Glimepiride

The first generation sulfonylureas are rarely used now.

NEWER DRUGS ARE Glimipiride (Amaryl) and Glicazide MR and XR ………Nowadays new medicine is used vastly in the practice of longterm NIDDM cases (Non insulin dependant Diabetes Mellitus)……..

The SU class of oral hypoglycemic agents (insulin secretagogues) has been in existence since tolbutamide was introduced in 1956.

The sulfonylurea drugs have effects which are still not completely understood. Initially, they work primarily by stimulating pancreatic insulin secretion, which in turn reduces hepatic glucose output and increases peripheral glucose disposal. They are potassium channel blockers whose effect on the pancreatic beta-islet cells is to allow an influx of calcium into the cell, which causes an increase in the release of insulin.

However, after several months, blood levels of insulin return to pre-medication levels, yet blood glucose levels remain reduced. Clearly, the sulfonylurea drugs must have other effects. Several have been identified, among them: sulfonylurea medications slow the rate at which the liver releases glucose into the bloodstream, and they increase the number of insulin receptors on cell membranes, thus increasing insulin efficiency.

The efficacy of the first- and second-generation sulfonylureas is similar, although second-generation agents are better formulated and, although costlier than the older sulfonylureas, have some advantages. Second-generation sulfonylureas:

Are more potent on a per milligram basis
Tend to produce fewer side effects
In addition, the pharmacokinetics of these second-generation agents allows for more effective once-a-day dosing, which enhances compliance.

Although some consider SUs to be dated compared with the newer oral hypoglycemic drugs, there remains a large number of patients that will continue to benefit from them.

BIGUANIDES

Two drugs in this category are phenformin and metformin.

Biguanides work mainly by

• Suppressing excessive hepatic glucose production
• Increasing glucose utilization in peripheral tissues to a lesser degree.
• Possibly reduce food intake and thus reduce intestinal glucose absorption

As the biguanides do not stimulate endogenous insulin secretion, hypoglycemia does not occur when they are used alone and therefore they are sometimes called anti-hyperglycemic agents rather hypoglycemic agents.

The use of phenformin has decreased considerably and it is usually metformin that is now used when a biguanide is prescribed.

The biguanides were introduced in 1957. Both phenformin and metformin have been widely used here, although in recent times, the use of phenformin has decreased significantly and most people now use metformin when a biguanide is to be used.

Metformin works mainly by suppressing excessive hepatic glucose production, although it may increase glucose utilization in peripheral tissues to a lesser degree, by decreasing insulin resistance in muscle cells. Metformin may also improve glucose levels by reducing intestinal glucose absorption.

Metformin is not metabolized and is excreted unchanged by the kidneys.

Metformin has many characteristics that are ideal for treating type 2 diabetes, including weight loss, insulin sensitization, positive lipid effect, mild hypotensive effect, and low or no incidence of hypoglycemia.

Because metformin does not stimulate endogenous insulin secretion, hypoglycemia does not occur when this dose is used alone, although hypoglycemia may occur if metformin is taken with insulin, a sulfonylurea, or an excessive amount of alcohol.

Treatment with metformin has beneficial effects on plasma lipids (it lowers triglyceride and low-density lipoprotein [LDL] cholesterol levels while increasing high-density lipoprotein [HDL] cholesterol) that are greater than expected from improved glucose control alone.

In addition, metformin therapy has been associated with weight loss or no weight gain. This may be particularly helpful in obese patients with type II diabetes.

Metformin is effective as monotherapy or in combination with sulfonylureas, alpha-glucosidase inhibitors, and insulin. The combination of metformin and troglitazone has also been shown to be safe and effective, although this combination is not an USA FDA- approved indication and extensive published data on this combination is lacking.

ALFA GLUCOSIDASE INHIBHITORS

There are Acarbose and Miglitol. Acarbose (Precose) is an alpha-glucosidase inhibitor that slows down the breakdown of disaccharides and polysaccharides and other complex carbohydrates into monosaccharides. The enzymatic generation and subsequent absorption of glucose is delayed and the postprandial blood glucose values, which are characteristically high in patients with type II diabetes, are reduced with acarbose. AGIs do not prevent the absorption of carbohydrates and complex sugars, but they do delay their absorption.

Delaying the absorption of carbohydrates is a unique mechanism among oral diabetic medications for lowering HgbA1c levels. The effectiveness of this mechanism is one of the physiologic characteristics of type 2 diabetes. Patients with type 2 diabetes demonstrate a delayed or sluggish insulin response from the pancreas to a glucose (a meal) load. By delaying the absorption of glucose, the insulin response is more matched to the serum glucose, resulting in less postprandial hyperglycemia and a lowering of the HbA1c. The AGIs also demonstrate a lowering of total insulin output of the pancreas, increased insulin sensitivity, a variable but mild decrease in triglycerides, with no effect on patient weight.

One disadvantage with the use of acarbose is that it is to be taken along with the first bite of a meal. Moreover, it has to be taken three times daily with meals. These factors often lead to non compliance and a decrease in the efficacy of the drug.

MEGLITINIDES +AMINOACID DERIVATIVES

A very recent addition to the OHA group. It is a ultra short acting drug which acts directly on the the beta cells of the pancreas and increases the secretion of insulin. It also corrects the problems with the pulsatile release of insulin which is seen in Type II diabetes.

Repaglinide from the meglitinide drug class, acts like an extremely short-acting SU (an insulin secretagogue) and is potentially useful as a SU replacement. The effect of repaglinide on the pancreas is very similar to that of the SUs. Repaglinide, like the SUs, blocks the potassium channels on the pancreatic islet beta-cells, which causes an influx of calcium into the cell and increasing the secretion of insulin. There appears to be 2 similar potassium channels on islet beta-cells, one of which is predominantly affected by repaglinide and the other is predominantly affected by SUs.

The repaglinide-affected potassium channel appears to be glucose dependent, which may partially explain why repaglinide is associated with a much lower incidence of hypoglycemia.

What makes repaglinide clinically different from the SUs is its ultra-short half-life (1 hour). Repaglinide is taken just before or with meals, and the stimulation of the pancreas is limited only to a brief time around meals. Because of the short duration, the patient does not have continuous high levels of insulin and the resulting adverse effects.

Its biggest advantage over the other oral hypoglycemic medications is that it allows for flexible timing and missed meals.

Repaglinide has been approved for use with metformin, and the combination appears to be a very effective. There are no clinical trials of repaglinide with the alpha-glucosidase inhibitors, and of the TZD class, only 1 clinical trial with troglitazone has been reported. There are theoretical interactions between repaglinide and the TZDs through their common metabolism in the P450 pathway, so more clinical trials are clearly needed.

THIAZOLIDINEDIONES

Thiazolidinediones are a new class of oral antidiabetic agents (commercially known as glitazones) that enhance insulin sensitivity in peripheral tissues. Troglitazone was the first glitazone introduced to the market, and though widely used, it has now been withdrawn from the market as its use has been linked with hepatocellular injury and death secondary to liver failure.

Rosiglitazone and Pioglitazone are now available for clinical use and are extremely potent in reducing peripheral insulin resistance.

The thiazolidinedione (TZD) class of oral hypoglycemics ( popularly known as glitazones) was developed in 1997 and offers a new mechanism for treatment of type 2 diabetes. The first, troglitazone was taken off the market in 1999 because of its association with hepatic toxicity. Rosiglitazone and pioglitazone have been available since 1999, and have recently been introduced in the Indian market.

The primary effect of TZDs is peripheral, with increasing insulin sensitivity and increased glucose uptake. The TZDs have some effect on hepatic glucose uptake and sensitivity to a lesser degree. They do not stimulate the pancreas to produce more insulin.

TZDs are hepatically metabolized and thus can be used safely in patients with renal dysfunction. They can be dosed once daily, although rosiglitazone works better with twice-daily dosing. Reports have suggested that rosiglitazone works better in women, but the reason for this is not known.

Both pioglitazone and rosiglitazone are approved for monotherapy and in combination with metformin, SUs, and insulin.

Besides their effect in lowering the blood glucose levels, both drugs also have notable effects on lipids. The current data show that pioglitazone has a minimal effect on low-density lipoprotein (LDL) cholesterol levels and a favorable effect on high-density lipoprotein (HDL) cholesterol and triglyceride levels. Rosiglitazone has a favorable effect on HDL cholesterol levels but a negative effect on LDL cholesterol levels.

With use of glitazones, patience is required. Blood sugar levels may show a significant reduction statistically in as little as two to four weeks, but the maximum effects are not seen until two or three months have passed.

CONCLUSION

So i dont have a conclusin yet……………………Postin it soon !!!!!!!!!!!!!!!!!!!!!!!!

INTRODUCTION

In each menstrual cycle, follicles grow on the ovaries. Eggs develop within those follicles, one of which will reach maturity faster than the others and be released into the fallopian tubes. This is “ovulation”. The remaining follicles will degenerate.

In the case of polycystic ovaries, however, the ovaries are larger than normal, and there are a series of undeveloped follicles that appear in clumps, somewhat like a bunch of grapes. Polycystic ovaries are not especially troublesome and may not even affect your fertility.

However, when the cysts cause a hormonal imbalance, a pattern of symptoms may develop. This pattern of symptoms is called a syndrome. These symptoms are the difference between suffering from polycystic ovary syndrome and from polycystic ovaries.

How common in PCOS???

Polycystic ovary syndrome is the most common hormonal disorder occurring in women during their reproductive years. It’s thought that 4% to 10% of all women have the disorder. However, since many women don’t know they have polycystic ovarian syndrome or some aspect of it, the actual number probably exceeds 10%. Polycystic ovarian syndrome is one of the leading causes of infertility. Symptoms frequently start to show up soon after puberty.

Causes????

There is disagreement and uncertainty as to what causes polycystic ovarian disease. Polycystic ovaries and polycystic ovary syndrome have been associated with one or more of these factors:

• Genetic predisposition.
• Insulin resistance or hyperinsulinism (high blood levels of insulin).
• Obesity.
• Hyperandrogenism (excessive production of male hormones).
• Abnormality of the hypothalamic-pituitary-gonadal axis (organ/hormonal disorder).
• Environmental chemical pollution (hormonal disruptors)
• Food adulterantion (excitatory amino acids, for example)
• Chronic inflammation.

Some of these causal factors may also be consequences of polycystic ovary disease. In other words, we have an amazingly complex network of interacting variables, each of which influences the other. Polycystic ovarian syndrome is not a simple disease with a single cause.

The Natural Diet Solution for PCOS and Infertility describes the possible causes of polycystic ovary syndrome in great detail.

Symptoms???

Polycystic ovarian syndrome presents a complex and baffling array of symptoms, consisting of some combination of the following symptoms that vary with each individual:

• Multiple ovarian cysts
• Irregular or absent menses
• Infertility
• Acne
• Obesity or inability to lose weight
• Excessive body or facial hair (hirsutism)
• Insulin resistance and possibly diabetes
• Thinning of scalp hair
• Velvety, hyperpigmented skin folds (acanthosis nigricans)
• High blood pressure
• Polycystic ovaries that are 2-5 times larger than healthy ovaries.
• Multiple hormone imbalances, commonly including:
  • Androgens (testosterone)
  • Cortisol
  • Estrogens
  • FSH (follicle stimulating hormone)
  • Insulin.
  • LH (luteinizing hormone)
  • progesterone
  • Prolactin.
  • Thyroid hormones.
• Impaired lung function.
• Sleep apnea.
• Fatty liver degeneration (NAFLD).
• Depression

Treatment ????

The first PCOS treatment for Infertility is usually the administration of medications to stimulate ovulation.

Clomiphene citrate (Clomid or Serophene)

An oral fertility drug used to stimulate ovulation, correct ovulation process, to improve egg production and to fix luteal phase deficiency. The drug is taken for five days early in the menstrual cycle. Clomid may become futile with a long use, for more than six cycles.

With some evidence, it has been stated that continual use of the drug, for twelve or more cycles, may increase the risk of ovarian cancer.

Metformin (Glucophage)

It is an insulin-sensitizing agent used to induce ovulation. Common Metformin medications include, Generic Metformin Hcl, Glucophage, and Glucophage XR. If Clomid fails to ovulate, a combination of “Metformin” and “Clomid” is taken as a PCOS treatment drugs for infertility.

The medication ‘Metformin’ increases the fertility by improving the effectiveness of the insulin while decreasing the insulin levels and in turn androgen levels. Normalizing the androgen levels enhances the natural ovulation.

hCG (human chorionic gonadotrophin) (Profasi)

An intramuscular injection used in conjunction with Clomid. The effect of hCG on follicle is same as LH (luteinizing hormone). HCG stimulates the follicle to release its egg (ovulate) approximately 36 hours later.Ovulation may be blocked, when hCG is taken too early. Ovarian hyper stimulation and cyst formation can result with too much hCG usage.The other commonly used PCOS treatment drugs for infertility include hMG (human menopausal gonadotrophin), FSH (follicle stimulating hormone), GnRH (gonadotrophin releasing hormone), GnRHa (GnRH analogs) and Prolactin inhibition drugs.

PCOS Treatment For Infertility – Medical Procedures

IUI (intrauterine insemination)

A basic PCOS treatment for women with infertility problem is intrauterine insemination, also known as Artificial Insemination. It is a fast and painless medical procedure where the male partner’s sperm is introduced directly into the female’s uterus (intrauterine) for the purpose of conception.

The procedure is usually done in conjunction with the ovarian stimulation drugs because regular menstrual cycle and healthy ovulation makes conception very successful.

IVF (in-vitro fertilization)

A simpler, safer and more successful PCOS treatment option to induce ovulation in infertile women is in vitro fertilization. The procedure involves the removal of eggs from female partner’s body and fertilizing them with the sperm of male partner.

The embryo (fertilized egg) is then introduced into the uterus (womb). Ovarian stimulation drugs (hCG, hMG, FSH or progesterone) are used to stimulate the ovaries to produce fertilizable oocytes (eggs).GIFT (Gamete Intra Fallopian Transfer), ICSI (Intracytoplasmic Sperm Injection) are the medical procedures of PCOS treatment for infertile women.The success rate of PCOS treatment options to induce ovulation depends on the age of the woman, the type of ovarian stimulation medication, and other factors that contribute to infertility in the woman.

Yoga asans that help PCOS???

Down the years, it has been found that Yoga is the only recourse left to PCOD / PCOS sufferers. Yoga is a holistic science and art of living. This is because routines Yoga consisting of asanas (poses), pranayamas (breathing techniques) and kriyas (cleansing exercises) prescribed in Yoga help tone up the whole system. There are certain fixed Yoga asanas (poses) like the sitting, standing and supine poses that haven proven to greatly help PCOD / PCOS patients. In general, the Yoga program for PCOD / PCOS is as follows:

• A series of Yoga asanas (poses). While there is no exact pose or exercise that is known to help heal PCOD / PCOS, experience tells us that some of the poses – if done regularly – sitting, standing and lying on the back, over time yield the desired results. But, you should make sure to avoid all the inverted poses.
• Practice lots of Pranayamas (Breathing Exercises) in a slow, unhurried, relaxed rhythm. You may breathe at your own slow pace, or inhale and exhale to the count of 3 or 4. But do this very slowly and avoid straining or putting pressure on your lungs. The recommended pranayamas (breathing exercises) for PCOD / PCOS women are Mild Kapalabhatti (Skull Cleansing), Anuloma-Viloma (Alternate Nostril Breathing) and Ujjayi (Ocean Breath).
• You should also practise Nispanda Bhava (Unmoving Observation) and Shavasana (Corpse pose) 2 – 3 times every day. These will definitely help since PCOD / PCOS victims are, by and large, tense and stressed out. Subsequently, they need plenty of relaxation.
• Finally, let your diet be Yogic and Sattvic. This essentially means pure and predominantly vegetarian, with lots of seasonal fruits, sprouts, fresh salads and dried fruits. Steer clear of milk and milk products, particularly cheeses and butter, all confectionery products, fatty, fried and spicy foods, cigarettes and alcohol
• Likewise, avoid stress and tension, so try and avoid all stressful situations. Even if difficult, you will find that taking the trouble and making a few short term sacrifices will benefit you enormously in the long run.