anti diabetic drugs

• Sulfonylureas are second-generation oral hypoglycemic agents that stimulate insulin secretion by binding to ATP-dependent potassium channels on pancreatic beta cells, leading to depolarization and calcium influx.
• Insulin is a small protein with 51 amino acids arranged in two chains (A and B) linked by disulfide bridges; proinsulin is processed into insulin and C-peptide within beta cells
• Insulin is secreted in response to various stimuli, especially glucose, and other substances like amino acids, hormones, and drugs; the liver and kidney remove insulin from circulation
• Rapid-acting insulins like insulin lispro, aspart, and glulisine have a fast onset and short duration, mimicking normal prandial insulin secretion; they are preferred for use in continuous subcutaneous insulin infusion devices
• Short-acting insulin, like regular insulin, has a delayed onset and prolonged action due to its hexameric structure; it should be administered 30-45 minutes before meals to avoid postprandial hyperglycemia
• NPH insulin has an onset of approximately 2–5 hours and duration of 4–12 hours
• NPH insulin is usually mixed with regular, lispro, aspart, or glulisine insulin and given two to four times daily for insulin replacement
• The action of NPH insulin is highly unpredictable, with over 50% variability in absorption
• Insulin glargine is a long-acting insulin analog with a slow onset of action (1–1.5 hours) and a duration of action of 11–24 hours or longer
• Mixtures of insulins are often used in diabetic patients, with NPH insulins requiring supplements of rapid- or short-acting insulin before meals
• Intermediate insulins like NPL and NPA have been developed to provide stable premixed combinations with insulin lispro and insulin aspart
• Insulin glargine and detemir must be given as separate injections and are not miscible acutely or in a premixed preparation with any other insulin formulation
• Insulin delivery systems include standard subcutaneous injection, portable pen injectors, and continuous subcutaneous insulin infusion devices (insulin pumps)
• Complications of insulin therapy include hypoglycemia, insulin allergy, immune insulin resistance, lipodystrophy at injection sites, and an increased cancer risk
• Complications of insulin therapy include hypoglycemia, insulin allergy, immune insulin resistance, lipodystrophy at injection sites, and an increased cancer risk
• diabetes has 4 catergories

  1. type 1 [insulin dependent diabetes]
  2. type 2 [non-insulin dependent diabetes]
  3. type 3: others
  4. type 4 [gestational diabetes]
• Proinsulin, a long single-chain pro.is processed within the Golgi apparatus of beta cells and packaged into granules, where it is hydrolyzed into insulin

  proinsulin may have some mild hypoglycemic action, C-peptide has no known physiologic function.
• •Insulin is released from pancreatic beta cells at a low basal rate and at a much higher stimulated rate in response to a variety of stimuli, especially glucose[prandial insulin].
• Stimulatory drugs for insulin are sulfonylureas, meglitinide and nateglinide, isoproterenol, and acetylcholine.

  other stimulants for insulin are sugars,amino acids,CCK,glugagon
• •Inhibitory signals of insulin are hormones including insulin itself and leptin, α-adrenergic sympathetic activity, chronically elevated glucose, and low concentrations of fatty acids.


  •Inhibitory drugs include diazoxide, phenytoin, vinblastine, and colchicine [chemotherapy can cause hyperglycemia].
• The liver and kidney are the two main organs that remove insulin from the circulation. Liver removes 60% of insulin and kidney removes 40% of insulin
• •In insulin-treated diabetics receiving subcutaneous insulin injections, this ratio is reversed, with as much as 60% of exogenous insulin being cleared by the kidney and the liver removing no more than 30–40%.
• •The half-life of circulating insulin is 3–5 minutes.

  Basal insulin values of 5–15 μU/mL (30–90 pmol/L) are found in normal humans, 


  prandial rise to 60–90 μU/mL (360–540 pmol/L) during meals
• •Commercial insulin preparations differ in some ways, such as

  •differences in the recombinant DNA production techniques,

  •amino acid sequence,

  •concentration,

  •solubility,

  • the time of onset and duration of their biological action.
• There are 4 types of insulin: rapid-acting insulin, Short-acting insulin, intermediate-acting insulin, and long-acting insulin.
• Injected rapid-acting and short-acting insulins are dispensed as clear solutions at neutral pH and contain small amounts of zinc to improve their stability and shelf lifes
• •Injected intermediate-acting NPH insulins have been modified to provide prolonged action and are dispensed as a turbid suspension at neutral pH with protamine in phosphate buffer (neutral protamine Hagedorn [NPH] insulin).
• Insulin glargine and insulin detemir are clear, soluble long-acting insulins.
• short-acting insulin is the only type that should be administered intravenously because the dilution causes the hexameric insulin to immediately dissociate into monomers

  The others are subcutaneously administered

  most of them are stored at 2-8 degrees celsius
• •Rapid-acting insulin—insulin lispro, insulin aspart, and insulin glulisine— are commercially available.

  •Their duration of action is rarely more than 4–5 hours, which decreases the risk of late postmeal hypoglycemia.
• • The injected rapid-acting insulins have the lowest variability of absorption (approximately 5%) of all available commercial insulins (compared with 25% for regular insulin and 25% to over 50% for long-acting analog formulations and intermediate insulin, respectively).

  • They are the preferred insulins for use in continuous subcutaneous insulin infusion devices.
• Regular insulin[short acting] is a short-acting soluble crystalline zinc insulin that is now made by recombinant DNA techniques to produce a molecule identical to that of human insulin
• • •Short-acting insulin effect appears within 30 minutes, peaks between 2 and 3 hours after subcutaneous injection, and generally lasts 5–8 hours.
• short acting insulin has 3 rate of absorptions, with the the final monomeric phase having the fastest uptake out of the injection site.
• •The clinical consequence is that when regular insulin is administered at mealtime, the blood glucose rises faster than the insulin with resultant early postprandial hyperglycemia and an increased risk of late postprandial hypoglycemia

  .•Therefore, regular insulin should be injected 30–45 or more minutes before the meal to minimize the mismatching. its use is declining clinically.
• short acting insulin is particularly useful for intravenous therapy in the management of diabetic ketoacidosis and when the insulin requirement is changing rapidly, such as after surgery or during acute infections.
• • NPH insulin is an intermediate-acting insulin whose absorption and onset of action are delayed by combining appropriate amounts of insulin and protamine so that neither is present in an uncomplexed form (“isophane”).
• NPH means neutral protamine hagedorn or isophane
• •NPH insulin has an onset of approximately 2–5 hours and duration of 4–12 hours.

  •It is usually mixed with regular, lispro, aspart, or glulisine insulin and given two to four times daily for insulin replacement.
• •The action of NPH is highly unpredictable, and its variability of absorption is over 50%.