INSULIN.

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Insulin oral hypoglycaemic

• M.Prasad Naidu
• MSc Medical Biochemistry, Ph.D,.

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Diabetes mellitus - It is a group of
heterogenous disorder in which carbohydrate
metabolism is ?, while that of proteins lipids
are ?. Types - Type I - insulin dependent
DM Type II non insulin dependent DM Type III
DM occurs by other disorders Type IV
gestational DM
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Insulin - Chemistry , biosynthesis secretion
- Chemistry - Insulin is made up of 86
aminoacids , It contain A chain 21 AA, B chain
30 AA, Connecitng Peptide 35 AA. Biosynthesis
- Preproinsulin proinsulin Insulin
C peptide Secretion - Glucose transport to ß
cell by GLUT 2 glucose transporter, it undergoes
further metabolism, it generated ATP. Which
inhibit the activity of K CHANNELS. The
inhibition of K channel induces ß cell membrane
depolarisation, opening of voltage dependent Ca2
channel stimulates insulin secretion.
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• Pharmacological actions -
• Carbohydrate metabolism
• ?glycogenesis ? glycogenolysis
• Protein metabolism
• ? protein break down ?
• Fat metabolism
• ? lipogenesis ?fatty acid synthesis.

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Newer insulin preparations Insulin
syringes Portable pen injections Insulin
pumps Biodegradable microspheres Inhaled
insulins Therapeutic uses - Type 1 diabetes
NPH Regular Insulin Type 2 diabetes - Regular
Insulin Diabetic ketoacidosis Tr. IV fluids,
Kcl, sodium bicarbonate, phoshate Non
ketonic hyperglycemic Emergency treatment of
hyperkalaemia
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• Adverse effects -
• Hypoglycaemia
• Lipodystrophy
• Allergic manifestation
• Insulin resistance
• Edema

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Oral hypoglycaemic drugs - Classification
- Sulfonylureas 1st generation -
Tolbutamide Chlorpropamide 2nd generation
Glibenclamide Glipizide Gliclazide Glime
piride Meglitinide analogues - Repaglinide Nate
glinide
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Biguanides - Metformin Phenformin Alfa
glucosidase inhibitors - Acarbose Miglitol Thia
zolidinediones Rosiglitazone Pioglitazone
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Sulfonylureas - MOA - Sulfonylureas acts on
beta cells, stimulating insulin secretion and
thus reducing blood glucose levels. Drugs reuce
the permeability of K by competitively blocking
the sulfonylureas receptors present on ATP
sensitive K channels , causing depolarisation,
Ca2 entry and insulin secretion. Adverse
effects - Hypoglycaemia Weight gain, nausea,
vomiting, diarrhoea, constipation ,
agranulocytosis, hypersensitivity, cholestatic
jaundice.
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PK - Absorbed orally, high plasma protein
bindint(90-98) Metabolized in liver , excreted
in urine Duration of action 6-12 hr It croses
placental barrier it caused hypoglycaemia at
birth CI - Pregnancy Gestational diabetes
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Drug interactions - Drugs that potentiate the
effects of sulfonylureas Oral anticoagulants,
ketoconazole, chloramphenicol (-) metabolism
Salicylates, sulfonamides , clofibrate
displace protein binding sites Drugs that
decrease the effects of sulfonylurease
Phenobarbitone, phenytoin , rifampicin
decrease metabolism corticosteroids, thiadides,
estrogens - Biguanides - ? uptake and
utilization of glucose in skeletal muscle reduce
insulin resistant (-) renal hepatic
gluconeogenesis ? glucose absorption from GIT ?
Plasma glucagon levels
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Corticosteroids
Classification
- Glucocorticoids Short acting
Hydrocortisone Intermediate acting
Prednisolone Methyl
prednisolone
Triamcinolone Long acting - Betamethasone
Dexamethasone Meneralocorticoids
- Desoxycorticosterone acetate Fludrocortisone
aldosterone
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Mechanism of actions - Corticoids bind to
specific receptor in the cytoplasm , the drug
Receptor complex is transported into the
nucleous where it binds to specific Sites on DNA
and regulates the synthesis of new proteins that
bring about The hormone effects
. Pharmacological actions - Mineralocorticoids
highly effects on Na, k and fluid
balance Glucocorticoids highly effects on
carbohydrate, protein, fat and other. Metabolic
effects - Carbohydrate promote
gluconeogenesis Protein- enhance protein break
down Fat lipolysis, redistribution of fat
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Antiinflammatory and immunosuppressive effects
- Supress development of inflammatory response
to all types of stimuli inhibit bothLate and
early manifestations of inflammation. Supress
cell mediated immunity, prevent manifestations of
allergy Ca 2 metabolism (-) intestinal
absorption enhance renal excretion of ca2 CVS
- Skeletal muscle - hypocritism,
hypercritism CNS - euphoria Stomach - increase
gastric secretion Lymphoid tissue and blood cells
- increase destruction of lymphoid cells,
increase no. of RBC, neutrophils, platelets.

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• Therapeutic uses -
• Replacement therapy
• Acute adrenal insufficiency
• Chronic adrenal insufficiency
• Congenital adrenal hyperplasia
• Pharmacotherapy
• Arthritides NSAIDS glucocorticoids
• Rheumatoid arthritis
• Osteoarthritis
• Rheumatic fever
• Gout
• Collagen diseases SLE, nephrotic syndrome,
  glomerulonethritis
• Severe allergic reactions angioneuotic edema,
  urticaria and serum sickness

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• Autoimmune diseases haemolytic anaemia,
  thrombocytopenia,
• chronic hepatitis
• Bronchial asthma status asthmaticus, acute
  asthma excerbation
• Other lung diseases Pulmonary edema
  aspiration penumonia
• Infective diseases tuberculosis, severe
  lepra reaction
• Eye diseases keratitis, iridocyclitis,
  iritis, allergic conjuctivitis, prevent
  blindness
• Skin diseases exfoliative dermatitis,
  stevens hohnson syndrome
• Intestinal diseases ulcerative colitis,
  coeliac disease
• Cerebral edema
• Malignancies acute lymphatic leukemia,
  hodgkins breast carcinoma
• Organ transplantation and skin allograft
  liver, kidney, heart transplantation.
• Shock

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• Adverse effects -
• Mineralocorticoids hypokalemic alkalosis,
  edema, raise in BP
• Glucocorticoids -
• Cushings habitus
• Hyperglycaemia
• Muscular weakness
• Delayed healing
• Peptic ulceration
• Osteoporosis
• Galucoma
• Growth retardation
• Foetal abnormalities

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• Psychiatric disturbances
• Suppression of hypothalamo pituitary adrenal
  axis
• Fragile skin , purple striae
• Contraindications -
• Peptic ulcer
• DM
• HT
• Viral and fungal infections
• Tuberculosis other infections
• Osteoporosis
• Psychosis
• Epilepsy
• CHF
• Renal failure

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THANK U