It is a metabolic disorder characterized by hyperglycaemia , ( fasting plasma glucose more than or equal to 126 mg/dL and /or more than or equal to 200 mg/dL 2 hours after 75 g of oral glucose ) .
- Type I DM : its also known as insulin-dependent diabetes mellitus (IDDM) , In this condition the is beta cell destruction in pancreatic islets ; majority of cases are autoimmune (type 1A) antibodies that destroy beta cells are detectable in blood , but some are idiopathic (type 1B) - no beta cell antibody is found.
- Type II : Noninsulin-dependent diabetes mellitus (NIDDM). Over 90% cases of diabetes are type 2 DM , causes may be abnormality in gluco-receptor of beta cells so they respond at higher concentration or relative beta cell deficiency . Reduced sensitivity of receptors or "down regulation" reduced in number of insulin receptors .
- Types of insulin and insulin analogues :
- short acting : (6-8 hrs)
- It is a buffered neutral pH solution unmodified insulin stabilized by a small amount of zinc.
- Forms hexamers ; after s.c injection insulin monomers are released slowly by dilution.
- Can be administered by s.c and i.v in Diabetic keto acidosis (DKA).
- Onset of action 0.5-1 hour .
- Rapid acting (Insulin analogues) : (3-5 hrs)
- Produced by reversing proline and lysine aminoacids B28 and B29 positions.
- It forms very weak hexamers that dissociate rapidly after s.c injection.
- Onset of action 12-18 min.
Insulin aspart :
- The proline at B 28 of human insulin is replaced by aspartic acid .
- This change reduces the tendency for self-aggregation.
- Onset of action 12-18 min.
Insulin glulisin :
- It is produced by replacing lysine B29 by glutamic acid.
- Properties and advantages are similar to insulin lispro.
- It has been particularly used for continuous s.c insulin infusion by a pump.
- Onset of action 12-24 min .
- Intermediate acting: (12-20 hrs )
- Protamine is added in a quantity just sufficient to complex all insulin molecules .
- Neither insulin nor protamine is present in free form and pH is neutral .
- On s.c inj. the complex dissociates slowly to give an intermediate duration of action.
- Onset of action 1-2 hours .
- It is mostly combined with regular insulin (70:30 or 50:50) injected s.c twice daily.
Insulin zinc suspension or Lente :
- Two types of insulin-zinc suspensions have been produced.
- The one with large particles is crystalline and practically insoluble in water (ultralente),it is long-acting.
- The other has has smaller particles and is amorphous (semilente),is short acting.
- Their 7:3 ratio mixture is called" lente insulin", intermediate acting.
- Onset of action 1-2 hours .
- Long acting: ( 20-24 hrs )
- This produced by addition of two arginine residues at B chain and glycine replaces asparagine at A 21
- On s.c slowly absorbed with "peakless" plasma concentration.
- Cannot be mixed with other insulin preparations because of its acidic pH.
- Onset of action 2-4 hours .
- Should be avoided in pregnant diabetics.
Insulin detemir :
- Myristoyl ( a fatty acid ) radical is attached to the amino group of lysine at B29 of insulin chain.
- As a result, it binds to albumin after s.c injection , prolonged the duration of action.
- Usually given twice daily
- Onset of action 1-4 hours.
- Indications / uses of insulin:
- Type I diabetes mellitus
- Diabetic ketoacidosis (DKA)
- Nno-ketotic hyperglycaemic coma /Hyperosmolar Hyperglycaemia State (HHS).
- Diabetes during pregnancy
- Stress of surgery, infections and trauma ( temporarily to tide over trauma,infection etc,) in diabetes.
- Primary or secondary failure of oral antidiabetics .
- Under weight patients.
- Type two DM in addition to oral antidiabetics drugs.
- Drug Interactions:
- Concurrent use of fluoroquinolones and antidiabetics agents may result in changes in blood glucose and increased risk of hypoglycaemia or hyperglycaemia. probable mechanism is UNKNOWN
Clinical Management:
2. Chloroquine
-Concurrent use of CHLOROQUINE and ANTIDIABETIC AGENTS may result in hypoglycemia. because of the additive hypochycemic effect.
Clinical Management:
Chloroquine may enhance the effects of hypoglycemic treatment, a decrease in doses of insulin or other antidiabetic drugs may be required.
3. Somatostatin Analogues
- Concurrent use of ANTIDIABETIC AGENTS and SOMATOSTATIN ANALOGUES may result in impaired glucose regulation, by altering glucose metabolism .
Clinical Management:
Somatostatin analogs inhibit the secretion of insulin and glucagon . Severe increases in blood glucose levels may occur. Optimize antidiabetic treatment in patients with poorly-controlled diabetes prior to starting the somatostatin analog . Dose adjustment of the antidiabetic agent and increased frequency of glucose monitoring may be necessary .
4. Angiotensin receptors blockers
- Concurrent use of ANGIOTENSIN RECEPTOR BLOCKERS and INSULIN may result in increased risk of hypoglycemia. probable mechanism is UNKNOWN .
Clinical Management:
Coadministration of insulin and angiotensin II receptor blockers may increase the risk of hypoglycemia. If concomitant use is required, consider insulin dose adjustments and increasing the frequency of glucose monitoring .
5. ACE Inhibitors
- Concurrent use of ACE INHIBITORS and ANTIDIABETIC AGENTS may result in increased risk of hypoglycemia. probable mechanism is UNKNOWN .
Clinical Management:
Coadministration of ACE inhibitors with antidiabetic agents may increase the risk of hypoglycemia . If concomitant use is required, conduct more frequent glucose monitoring, both during treatment and after withdrawal of an ACE inhibitor . Insulin dose adjustments may also be needed .
6. Fibrates
- Concurrent use of FIBRATES and INSULINS OR PRAMLINTIDE may result in increased risk of hypoglycemia. probable mechanism is UNKNOWN.
Clinical Management:
Use caution when coadministering insulins or pramlintide and fibrates, as this may increase the risk of hypoglycemia. Monitor glucose levels more frequently and adjust the dose of insulin or pramlintide if necessary .
7. Lithum
- Concurrent use of INSULIN and LITHIUM may result in hypoglycemia or hyperglycemia. probable mechanism ; variable effects of lithum on glucose metabolism.
Clinical Management:
Lithium salts may either increase or decrease the blood glucose-lowering effect of insulin. Monitor blood glucose levels more frequently when lithium is added or discontinued in a patient receiving insulin. Changes in the dose of insulin may also be required with concomitant therapy.
8. SULFONAMIDES
- Concurrent use of ANTIDIABETIC AGENTS and SULFONAMIDES may result in increased risk of hypoglycemia. probable mechanism ; displacement of antidiabetic agent from protein-binding sites; inhibition of CYP2C9-mediated metabolism of some antidiabetic agents.
Clinical Management:
Due to interference with protein-binding and/or inhibition of the CYP2C9-mediated metabolism of some antidiabetic agents, the hypoglycemic action of some drugs, including sulfonylureas, insulins, meglitinides, and pramlintide may be potentiated during concomitant use with sulfonamide drugs. Monitor patient for hypoglycemia during concomitant use, or worsening glycemic control when withdrawing the sulfonamide. More frequent monitoring of glucose levels and dose adjustment of insulin may be required.
9. Beta blockers
- Concurrent use of ANTIDIABETIC AGENTS and BETA-ADRENERGIC BLOCKERS may result in hypoglycemia or hyperglycemia; decreased symptoms of hypoglycemia, probable mechanism ;beta blockers altered glucose metabolism and beta blockade.
Clinical Management:
Concurrent use of antidiabetic agents with beta-blockers may increase or decrease the blood glucose lowering effect of the antidiabetic agent, and may decrease or obscure signs and symptoms of hypoglycemia. Increased frequency of glucose monitoring or dose adjustment of the antidiabetic agent may be required. Closely monitor for hypoglycemia with concurrent use, and if the beta-blocker is withdrawn, observe for signs of loss of glycemic control.
10. Diuretics
- Concurrent use of ANTIDIABETIC AGENTS and SELECTED DIURETICS may result in increased hyperglycemia risk; increased insulin requirement. probable mechanism ; altered glucose metabolism.
Clinical Management:
Certain diuretic agents may alter glucose tolerance or blood glucose levels, possibly predisposing the patient to hyperglycemia or loss of glycemic control. Insulin requirements may be increased, decreased, or unchanged. If concomitant use of a diuretic and an antidiabetic agent is required, monitor glucose levels more frequently, including upon withdrawal of the diuretic. Dose adjustment of oral antidiabetic agents or insulin may be required.
11. Salicylates
- Concurrent use of INSULIN OR PRAMLINTIDE and SALICYLATES may result in increased risk of hypoglycemia. probable mechanism; UNKNOWN.
Clinical Management:
Use caution when coadministering insulin or pramlintide and salicylates, as it may increase the risk of hypoglycemia. Monitor glucose levels more frequently and adjust the dose of insulin if necessary.
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