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Pp insulin
1. INSULIN AND DIABETES MELLITUS
1921Banting and Best
1923 Nobel Prize (sharing)
1926 crystalline form obtained by Abel
1956-69 chemical and molecular structure
was worked out by Sanger and Hodgkin.
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2. Dog, Margorie was
injected with the
first insulin in
1921
CHARLES H. BEST & FREDERICK G. BANTING
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8. TYPES OF DIABETES
Type-I : deficiency of insulin (IDDM, Juvenile
onset DM). Type-IA: autoimmune disease of the
pancreatic cell. Type-IB is idiopathic
Type-II: inadequate insulin (Type II, NIDDM,
Maturity onset DM)
Gestational Diabetes Mellitus (GDM):
pregnancy and usually resolved during the
postpartum period.
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11. Diabetic control
Blood from vein determines blood glucose
Value is on day to day basis
Glycosylated haemoglobin (HbAIC) in RBC is
directly proportional to glucose concentration
over a period of time
Life span of RBC is 120 days
6% = 110 mg/dL of blood glucose. Value more
than 8% shows poor control of diabetes.
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20. Determination of diabetic type
C-peptide
Insulin & C-peptide released in equal amounts
Type-1 diabetes little or no C-peptide
Type-2 diabetes typically normal or high.
C-peptide as biological marker
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21. Insulin administration
Being a protein, it is degraded in GIT, if
taken orally.
Generally administered by SC route
Onset and duration of activity vary among
different preparations
This is due to the size and composition of
insulin crystals
The less soluble an insulin is long acting
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22. TYPES OF INSULIN PREPARATIONS
Short Acting Insulin
Regular Insulin: Soluble clear solution for
I.V. equal to endogenous insulin
Severe hyperglycemia
Addition of zinc : Increased solubility,
stability and shelf life
Addition of protamine : Increased duration
of action
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23. Ultra short acting:
• Lispro, aspart,
• short acting
Plain insulin,
Semi lente
Intermediate acting
NPH(isophane),
Lente
Long acting:
PZI
Ultra lente
glargine, detemer
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24. Long acting insulin
Intermediate long acting
(Lente Insulin, NPH) (Ultralente)
twice daily once daily
NPH: Neutral Protamine Hagedorn
After addition of zinc and protamine
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25. Onset: within 30 minutes
Maximum effect: 1-3 hours
Duration: 8 hours
Short acting
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29. Reactions to insulin
Hypoglycemia: Overdose or failure to eat
or extensive exercise. sympathomimetic
signs are warning. Advise the patients to
carry sugar candy.
Lipodystrophy: Change the place of
injection or Newer insulins
Allergy: Use purified insulins
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31. Newer Insulin
Older insulin: porcine/bovine - contaminants
1. purified by gel filtration
2. After gel filtration further purified by ion
exchange chromatography.
3. Human Insulins: Decombinant DNA
technology (E.coli).
4. Insulin lispro, Insulin aspart, Insulin
Glulisine – short acting
5. Insulin glargine – long acting
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32. Advantages of newer insulins
Less allergic
More stable
Less insulin resistance
Less lipodystrophy
Blood glucose level easily controlled
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36. LISPRO INSULIN
28th and 29th amino acids on the insulin B
chain, lysine and proline = Lispro
Type of insulin Onset Peak
effect
Duration
Lispro Insulin
(rapid acting)
0-15
min
30 – 90
min
< 5 hr
Regular Insulin
(short acting)
30 – 45
min
2 – 4 hr 6 – 8 hr
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37. Insulin aspart
Apartic acid at B28
Insulin Glulisine
Lysine at B23 and Glutamic acid at B29
Advantages and actions are similar to
Insulin lispro
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40. INSULIN GLARGINE
Onset of action: 1-1½ hours
Maximum effect: 4-6 hours (peakless)
Duration of action: 24 Hours (ultra long
acting)
Don’t mix with other insulin preparations in
the same syringe – it is acidic (pH 4)
Absorption pattern: independent of
anatomic site of injection
Less immunogenicity
6-7 fold greater binding than native insulin04/23/19 PATKI 40
42. NEWER INSULIN DELIVERY DEVICES
Jet injectors: Insulin pumps:
Painless rapid Insulin is infused
delivery through at a calculated rate
needless device
Nasal insulin delivery
Rectal and subcutaneous pellets:
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43. DRUG INTERACTIONS
Beta adrenergic blockers suppress warning
signs
Thiazides, frusemide, corticosteroids, oral
contraceptives, salbutamol, calcium channel
blockers raise the blood sugar by inhibiting the
insulin secretion.
Alcohol precipitates hypoglycemia (depleting
breaking the glycogen)
Salicylates, lithium and theophylline enhance
insulin secretion and peripheral glucose
utilization resulting the hypoglycemia.
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44. USES OF INSULIN
Infection and ketoacidosis: Short term
use
Long term use is advised in CVS, retinal,
renal, neurological conditions etc.
IDDM: compulsory use
NIDDM: it is advised
a. Failure of oral hypoglycaemic agents.
b. Temporary use in infection, trauma,
surgery, pregnancy.
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45. INSULIN RESISTANCE
Requirement of insulin: more than 200
U/day
May be due to antibodies production
Resistance should be in the absence of
ketoacidosis, Infection or stress.
Select more purified newer insulin
Oral hypoglycemic agents may be added
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46. Symptoms of Ketoacidosis
high blood sugar levels
frequent urination (polyuria) and thirst
fatigue and lethargy
nausea
vomiting
abdominal pain
fruity odor to breath
rapid, deep breathing
muscle stiffness or aching
coma
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47. Treatment of Ketoacidosis
Regular insulin by i.v.
i.v. fluids
KCl
Bicarbonate to correct acidosis
Phosphate (when required)
Antibiotics
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48. GLUCAGON
Alpha cells of islets of Langerhans
Hyperglycemic hormone
It is inactive orally
It is used in severe hypoglycemia
where glucose administration is
impossible.
It is also used as a diagnostic agent.
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