Antidiabetogenic drugs

I. INSULIN
Sources include pork or beef, combination of pork and beef and also human insulin
(Recombinant DNA technique)
Actions:

• Insulin lower blood glucose level through increasing utilization of glucose by peripheral
  tissue and promoting synthesis and storage of glycogen
• The main actions of the hormone are exerted on metabolism of carbohydrate (CHO), fat and
  protein in liver, muscle & adipose tissue.
  Effects of insulin
  Carbohydrate metabolism
  Liver: it increases glycogen synthesis from glucose and glucose utilization while
  decreases gluconeogenesis and glycogenolysis
  Muscle: it increases glucose uptake, glucose utilization and glycogen synthesis.
  Adipose tissue: it increases glucose uptake and glycerol synthesis (esterifies fatty acid)
  Fat metabolism
  Liver: it increases lipogenesis
  Adipose tissue: it increases synthesis of triglycerides and synthesis of fatty acid
  
  Protein metabolism
  Liver: it increases protein catabolism
  Muscle: it increases aminoacid uptake and protein synthesis
  Other metabolic effect:
  It increases uptake of K+
  and Ca++ into cells and synthesis of nucleic acids
  There are some factors that increase insulin demand: like Infection, surgery, pregnancy and
  drugs (those that antagonize actions of insulin glucocorticoids, thyroid hormone, adrenaline)
  Type of insulin preparation:
  A. Short acting (rapid onset): Eg Regular Insuline
  B. Intermediate acting Eg Lente insuline,NPH insuline
  C. Long acting E.g Protamine Zn insuline
  Types Route Onset (hrs) Duration (hrs)
  Regular insulin IV, SC, IM ¼ – 1 5 – 7
  Lente insulin SC, IM 1 – 1½ 18 – 24
  Protamine Zn insulin SC, IM 4 – 8 36
  N.B. It is only regular insulin that can be given by intravenous route.
  Therapeutic use -IDDM, NIDDM (not controlled by diet and oral hypoglycemic agents), diabetic
  ketoacidosis, Control of diabetes in pregnancy, during surgery and in infections.
  They are also used in the treatment of hyper kalmia due to renal failure
  Adverse Reaction: can be categorized as
  Local: Atrophy or hypertrophy at site of injection, local hypersensitivity and secondary
  infections.
  Systemic: Hypoglycemic coma and Immunologic reaction like hypersensitive and insulin
  resistance
  II. ORAL HYPOGLYCEMICS
  These are drugs administered orally to lower blood glucose level used in mild diabetes.
  They are grouped as Sulphonylureas and Biguinides.
  
  Sulphonyl ureas
  These compounds are chemically related to sulphonamides.
  First generation: Tolbutamide, Chlorpropamide
  Second generation: Glibenclamide, Glipizide
  Mechanism: hypoglycemic action is due to Stimulation of insulin release from β cell, Depression
  of glucagon secretion, Increase number of insulin receptor, Reduce insulin output from liver
  (Decrease hepatic gluconeogenesis and glycogenolysis)
  Pharmacokinetics: They are rapidly absorbed from the gastrointestinal tract. They are also
  extensively plasma protein bound and are mainly metabolized in the liver.
  Use: Mild diabetes mellitus in old patients (type II)
  Adverse reaction: The toxicity of these compounds is remarkably low. The important toxic
  effects include: hypoglycemia, allergic skin rash and bone marrow depression, cholestatic
  jaundice (esp. chlorpropamide)
  Side effects: Gastric irritation, prolonged hypoglycemia (esp. chlorpropamide), large doses
  confusion, vertigo, ataxia, leucopenia, aggranulocytosis, thrombocytopenia, and teratogenecity
  Drug interaction:

1. Hypoglycemia is enhanced by sulphonamides, phenylbutazone
2. Alcohol produces “Disulfirum” like action (flushing of the face, severe headache,
   vomiting etc.)
3. Sulphonyl ureas increase anticoagulant effect of oral anticoagulant
4. Thiazides oppose the action of sulphonylureas.
   Biguinides
   They potentiate the hypoglycemic action of insulin and sulphonyl ureas but they don’t produce
   clinical hypoglycemia in diabetics.
   Biguanides include drugs like metformin and phenformin
   Mechanism: They do not stimulate the release of insulin. They increase glucose uptake in
   skeletal muscle, and have effects on glucose absorption and hepatic glucose production.
   They also enhance anaerobic glycolysis.
   
   Pharmacokinetics: Phenformin and metformin are rapidly absorbed from the gastrointestinal
   tract. Metformin is largely excreted unchanged in the urine and has a longer duration of
   action.
   Side effects: Nausea, vomiting, anorexia, diarrhea, abdominal cramp, lactic acidosis (esp.
   phenformin)
   Use: Obese diabetics (uncontrolled by diet alone), Supplement to sulphonyl urea
   Contraindication: Diabetes with hepatic, renal insufficiency, In IDDM, NIDDM (with
   infection, fever, surgery) and during pregnancy
   They have no value in diabetes complicated by acidosis or coma