Sulfonylureas what they are for, side effects, trade names

Sulfonylureas are a group of medications called oral hypoglycemic agents. That is, they reduce blood glucose values ​​and for this reason they are used in the treatment of diabetes mellitus in adults that is not dependent on insulin. They are given orally.

Diabetes mellitus is a disease in which failure occurs in the production of insulin or in the receptors for this hormone. Glucose needs insulin to enter many tissues, for example, skeletal muscles. When insulin fails, glucose cannot enter and accumulates in the bloodstream.

As a result, blood glucose values ​​increase, but the availability of glucose to tissues decreases. This causes a feeling of tiredness, hunger, thirst, increased urine output and, in many cases, weight loss..

There are two types of diabetes, type I and type II. Type I diabetes can only be treated with insulin (insulin-dependent) because the body no longer produces it. It is also called juvenile diabetes because it usually appears early in life.

Type II diabetes or adult diabetes is caused by a decrease in insulin secretion or by problems with insulin receptors. This type of diabetes is the one that can be treated with sulfonylureas.

Article index

• 1 What are they for
• 2 Mechanism of action
• 3 Side effects
• 4 Trade names
  • 4.1 First generation sulfonylureas
  • 4.2 Second generation sulfonylureas
• 5 References

What are they for

Sulfonylureas are used to lower blood glucose levels, that is, they are hypoglycemic drugs. This effect is achieved by increasing insulin levels. It is used in patients with type II diabetes or adult diabetes.

They are drugs that are well absorbed in the gastrointestinal tract, which is why they are administered orally. All sulfonylureas are metabolized in the liver and the end products of this metabolism are excreted in the urine..

The hypoglycemic effect of sulfonylureas was discovered accidentally in 1942 in experimental animals. Subsequently, their use as oral hypoglycemic agents was extended and the first drug of this group that was used for this purpose was carbutamide.

The carbutamide It was discontinued due to its harmful effects on the bone marrow, but it made it possible to develop a large group of so-called “first-generation” sulfonylureas. Since then, more than 20 drugs in this group have been developed and their use has spread throughout the world..

There are currently two major groups of sulfonylureas: 1) the first generation sulfonylureas and 2) the second generation sulfonylureas. In their hypoglycemic effects, the latter are approximately 100 times more powerful than the first generation.

Mechanism of action

The mechanism of action of these drugs consists in stimulating the secretion of insulin (hormone) from the β cells of the pancreas (endocrine portion of the pancreas). While this increases plasma insulin levels, these drugs also decrease liver metabolism of the hormone..

These effects are recorded as the short-term (acute) effect of the drug, however, with chronic use of these drugs, the stimulatory effect of the pancreatic cells decreases markedly, but the effect on the reduction of the levels of blood glucose.

The explanation for this phenomenon has not been fully elucidated. Insulin is believed to have a greater effect on your target organs, for one thing. On the other hand, chronic hyperglycemia reduces insulin secretion due to a toxic effect, and lowering blood glucose reduces this effect..

The acute effect of sulfonylureas on pancreatic β cells occurs because they bind to and block an ATP-sensitive potassium channel. This depolarizes the cell (excites) and increases the influx of calcium through voltage-gated channels and initiates insulin secretion..

The effect of chronic use of sulfonylureas appears to be accompanied by downregulation of these pancreatic β-cell surface receptors. If chronic administration is discontinued, the acute β-cell response to sulfonylureas is restored.

In patients with type II diabetes using sulfonylureas, an increase in the concentration of insulin receptors has been observed in monocytes (blood cells), adipocytes (fat cells) and erythrocytes (red blood cells). A decrease in hepatic gluconeogenesis has also been reported..

Hepatic gluconeogenesis is the synthesis of glucose that the liver makes from non-glycosidic substances.

Side effects

Currently, side effects from the administration of sulfonylureas are not very frequent. They have an approximate incidence of 4% in those patients who use first-generation sulfonylureas and slightly lower in those who use second-generation ones..

Sulfonylureas can cause hypoglycemia, including hypoglycemic coma. This can occur especially in elderly patients with poor liver and kidney function and with the use of long-acting sulfonylureas..

Sulfonylureas can be classified according to their half-life in order to reduce the risk of hypoglycemia. The shorter the half-life, the lower the risk of hypoglycemia and vice versa. Emergencies for this cause are treated with intravenous infusion of glucose solutions.

The concomitant use of sulfonylureas with sulfonamides, dicoumarol, salicylates, ethanol, phenylbutazone or clofibrate, potentiates the effect of sulfonylureas and increases the risk of hypoglycemia.

Other side effects that can accompany the use of sulfonylureas are:

- Nausea and vomiting

-Yellow tint of mucous membranes

-Agranulocytosis (significant decrease in white blood cell counts)

-Hemolytic or aplastic anemias (decrease in red blood cells due to destruction or lack of production, respectively)

-Hypersensitivity (allergic) reactions

-Dermatological reactions (skin problems)

Tradenames

Sulfonylureas are classified into two large groups: first and second generation. The most important and most used members of each group are listed below. Their trade names are listed in parentheses in the attached list for each component of each group..

Among the first generation sulfonylureas are the tolbutamide, the acetohexamide, the tolazamide and the chloropropamide. The second generation, which are more powerful, include the glyburide or glibenclamide, glipizide, gliclazide Y glimepiride.

First generation sulfonylureas

Some trade names are included. The generic name is included in bold and italic type.

Tolbutamide (ORINASE tablets of 250 and 500mg)

Acetohexamide (DYMELOR 500mg tablets)

Tolazamide (TOLINASE 100,250 AND 500mg tablets)

Chloropropamide (DIABENESE 100 and 250mg tablets)

Second generation sulfonylureas

Some trade names are included. The generic name is included in bold and italic type.

Gliburide or Glibenclamide (MICRONASE and DIABETA 1.25, 2.5 and 5 mg tablets, GLYNASE 1.5, 3 and 6mg tablets)

Glipizide (GLUCOTROL, SINGLOBEN 5 AND 10 mg tablets)

Gliclazide (DIAMICRON 60 mg)

Glimepiride (AMARYL 2 and 4 mg)

There are commercial presentations that combine some sulfonylurea with other oral antidiabetics that were not included in this list..

References

1. Ashcroft, F. M., & Gribble, F. M. (2000). Sulfonylurea stimulation of insulin secretion: lessons from studies of cloned channels. J Diabetes Complications.
2. Best and Taylor's Physiological Basis of Medical Practice, 12th ed, (1998) William and Wilkins.
3. Ganong, W. F., & Barrett, K. E. (2012). Ganong's review of medical physiology. McGraw-Hill Medical.
4. Goodman and Gilman, A. (2001). The pharmacological basis of therapeutics. Tenth edition. McGraw-Hill
5. Meyers, F. H., Jawetz, E., Goldfien, A., & Schaubert, L. V. (1978). Review of medical pharmacology. Lange Medical Publications.