Insulin and Hypoglycemic Agents-1
Insulin and Hypoglycemic Agents-1
Insulin and Hypoglycemic Agents-1
HYPOGLYCEMIC
AGENTS
Syed Tajamul
BHCNMT
INTRODUCTION
• The endocrine pancreas consists of aaproximately about one million
islets of Langerhans which secrete at least five hormones:
• 1. Insulin: storage and anabolic hormone of the body
• 2. Amylin: modulates appetite,gastric emptying, glucagon and and
Insulin secretion
• Glucagon: Hyperglycemic factor that mobilizes glycogen stores
• 4. Somatostatin: universal inhibitory of secretory cells
• 5. Gherlin: a peptide to increase pituitary growth hormone release
DIABETES MELLITUS
• Diabetes mellitus is
defined as an elevated
blood glucose associated
with absent or inadequate
pancreatic insulin
secretion, with or without
concurrent impairment of
insulin action. The disease
states underlying the
diagnosis of diabetes
mellitus are now classified
into four categories: type
1, type 2, other, and
gestational diabetes
mellitus.
INSULIN
• Insulin is a small protein with molecular weight of 5808, contains 51
amino acids arranged in two chains A&B linked to disulphide bridges.
• Proinsulin a long chain protein molecule is hydrolysed into insulin in
Golgi apparatus of beta cels.
• 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.
• After insulin has entered the circulation, it diffuses into tissues,
where it is bound by specialized receptors that are found on the
membranes of most tissues.
Mechanism of action of Insulin
• The insulin receptors is composed of two alpha and two Beta subunits linked by
disulfide bonds to constitute Beta-alpha Alpha beta heterotetramer.
• When insulin binds to receptors this results in cascade of phosphorylation and
dephosphorylation reactions of Alpha and Beta subunits called Insulin Receptor
Substrate (IRS).
• This result in activation of specific phospholipase-C, believed to mediate the rapid
action of insulin on different metabolising enzymes
• Also stimulates the glucose transport across cell membrane by ATP-dependent
translocation of glucose transporter-4(GLUT-4) to plasma membrane present on
skeletal and and adipose tissue.
• IRS also result in transcription of DNA synthesis and proliferation and
differentiation of several cell types— long term effects of insulin
• Finally, the insulin receptor complex is internalised by endocytosis followed by
degradation of insulin and recycling of the receptor to the cell surface.
Pharmacokinetics
• Insulin is rapidly inactivated after oral administration; I/M insulin
injections have rapid absorption; I/V insulin injections can be give in
emergencies. Hence insulin is usually given Subcutaneously.
• Metabolized in liver and kidneys. 60% is destroyed in liver by Hepatic
Insulinase. Plasma half life is 10 mins.
Insulin Preparations
1. Ultrashort acting( Rapid/ Fast acting ) Insulin
• Insulin Lispro S/C
• Insulin Aspart S/C; IV
• Insulin Glulisine S/C
• Absorption: Rapidly absorbed as monomers from subcutaneous
tissue, action starts within 10-30 mins and lasts for 3-4 hrs.
• Useful in hyperglycemia that occurs after meals, used in combination
with long acting insulins to maintain baseline levels of insulin
between meals.
2. Short Acting Insulin( Regualr Insulin)
• Regular insulin –Homulin-R, Novolin-R) U100-U500
• Regular insulin inhaled
• Soluble human crystalline insulin made by recombinant DNA tech.
Added with zinc ions for stability
• Exists as hexamer absorbed as monomer; Onset of action 30-60mins
lasts upto 6-8hrs.
• Indications: post meal hyperglycemia and management of Diabetic
Ketoacidosis(I/V)
3. Intermediate acting Insulin
• Isophane Insulin ( Neutral protamine Hagedorn- NPH) U100 S/C and
no other route
• NPH is a cloudy complex of insulin and a protein –protamine Derived
from fish sperm, contains 6 molecules of insulin per molecule of
protamine.
• Onset of action 2hrs lasts about 16-20hrs
• Indications: diabetic control except DKA
Long acting Insulin
• Insulin Glargine U100
• Insulin DetemirU100-U300
• Insulin Degludec U100, U200
• These human insulins are embedded with extra amino acids and fatty
acid chains. Soluble at PH 4 but less soluble at pH in cutaneous tissue
as a result steady and sustained release of insulin of insulin from site
of injection
• Onset of action more than 4 hrs lasts more than 24 hrs.
Premixed Insulins
• 70 NPH/30 regular U100
• 75/25 NPL, Lispro U100
• 50/50 npl, Lispro u100
• 70/30Degludec u100
• INHALED INSULINS : due accumulation of insulin deposits in pharynx
causing pharyngitis and pulmonary fibrosis, and formation of
antibodies two inhaled recombinant human regualar insulins have.
Been developed:
• 1. EXUBERA 2. AFREZZA
• NPH=Neutral protamine Hagedorn
Clinical Uses of Insulin
• Type 1 DM—NPH and short acting before meals
• Type 2 DM
• Gestational Diabetes
• Emergency treatment of DKA( diabetic Coma) — complication of type1 DM
• Bolus dose of 0.1U/kg IV of short acting regular insulin f/b 0.1U/kg/hr IV till glucose falls to
300mg/dL f/b 2-3 U/hr(not per kg) untill patient gains consciousness
• Normal salin to correct dehydration and 5% glucose if patient is hypoglycaemic
• Inj KCL 20mEq/hr to correct hypokalemia
• Inj sodium bicarbonate 50mEq iv drip to prevent respiratory acidosis due to
hyperventilation
• Non ketones hyperglycemia( hyperosmolar coma)—Type2 Complication
• For emergency treatment of hyperkalemia
Adverse effects
• Hypoglycemia
• Lipodystrophy— due to sc injections
• Allergic reactions— urticaria. And angioedema
• Insulin resistance
1. ORAL HYPOGLYCAEMIC AGENTS