DIABETES

1. • A
SEMINAR ON
ANTI-DIABETIC DRUGS
PRESENTED
BY.
SADIA UNNISA
Reg. No. 16S61S0101
MASTER OF PHARMACY I -Yr. I Sem.
(PHARMACOLOGY)
SUBMITTED TO
MR.SYEDSAFIULLAHGHORI
M.PHARM,PH.D
DEPT. OF PHARMACOLOGY
ANWARUL ULOOM COLLEGE OF PHARMACY
New Mallepally, HYD.
2O16-2017
1

2. CONTENTS
 INTRODUCTION TO DIABETES MELLITUS
 ANTI-DIABETIC DRUGS
 INSULIN
 ORAL HYPOGLYCEMIC AGENTS
1. SULPHONYLUREAS
2. BIGUANIDES
3. THIAZOLIDINEDIONE
4. MEGLITINIDE
5. ALPHA-GLUCOSIDASE INHIBITOR
6. DIPEPTIDYL PEPTIDASE INHIBITOR
 MANAGEMENT
 PREVENTION
 AWARENESS
 CONCLUSION
 REFERENCES
2

3. What is Diabetes Mellitus ?
• .
3

4. DIABETES MELLITUS
DIABETES Greek
• To pass water like a
siphon
MELLITUS Latin
• Sweet as honey
4

5. DIABETES MELLITUS:
• DIABETES MELLITUS is a metabolic disorder by
high levels of sugar in the blood.
• It can be CAUSED by:
• Too little insulin
• Resistance to insulin or both.
5

6. TYPES OF DIABETES MELLITUS:
• TYPE I(IDDM or Juvenile)
• TYPE II(NIIDM or adult)
• Gestational diabetes.
6

7. TYPE I (IDDM or Juvenile):
• It is usually diagnosed in childhood.
• The beta-cells of the pancreas makes little or
no insulin.
7

8. TYPE II (NIIDM or Adult):
• It usually occurs in adulthood.
• Pancreas does not make enough insulin to
keep blood glucose levels normal, often
because the body does not respond well to
the insulin.
8

9. GESTATIONAL DIABETES:
• It is usually diagnosed during pregnancy.
• It is caused by not enough insulin in the
setting of insulin resistance is when develop
without diabetes develops high blood sugar
levels during pregnancy.
9

10. SYMPTOMS OF DIABETES INCLUDE:
• Hyperglycemia
• Glycosuria
• Hyperlipaemia
• Negative nitrogen balance
• Ketouria
• Increased thirst and hunger
• Fatigue
• Blurred vision
• Numbness and tingling in the feet or hands
• Sores that do not heal
10

11. POLYPHAGIA POLYURIA
EXCESSCIVE THIRST
BLURRED
VISION
POOR WOUND
HEALING
WEAKNESS
FATIGUE
11

12. COMPLICATIONS:
• Heart diseases
• Stroke
• Kidney disease
• Eye problems
• Dental diseases
• Nerve Damage
• Foot Problems
12

13. ANTI-DIABETIC DRUGS
13

14. ANTI DIABETIC DRUGS
• Anti Diabetic drugs are the medicines that help to
control blood sugar level in people with diabetes
mellitus.
• Anti Diabetic patients aims to achieve
normoglycemia and relief diabetic symptoms
such as thirst, polyuria, weight loss, ketoacidosis.
• The longer term goals are to prevent the
development of slow progression of long term
complications of the diseases.
14

15. TYPES OF ANTIDIABETIC DRUG
INSULIN
• .
ORAL HYPOGLYCEMIC DRUGS
• .
I
INSULIN
ORAL HYPOGLYCEMIC
DRUGS
15

16. CHOICE OF ANTI DIABETIC AGENTS
• It depends on the type of diabetes
• Type 1 diabetes is where the body does not produce
any insulin. So insulin is the only treat choice.
• Injected insulin acts similar to endogenous insulin to
lower blood glucose levels.
• Type 2 diabetes is first treated with oral anti diabetic
medicines. This medicine either makes the pancreas
more insulin or help decrease insulin requirements by
the body or reduces gluconeogenesis by the liver. If
the normoglycemia is not achieved with oral medicine
than insulin can be added to the therapy.
16

17. INSULIN:
• Insulin is a hormone that is important for metabolism and
utilization of energy from the ingested nutrients - especially glucose
• Insulin is commonly used as either adjuvant therapy to oral anti
diabetic drug or either as a monotherapy as the disease process.
• The hormone insulin is prepared is endogenously stored released
from the beta cells of the pancreas .
• Patients with type I diabetes have an absolute deficiency of insulin
and patients with type II diabetes may also have a decrease
production of endogenous insulin.
• Insulin is required in type I diabetes patients as long as treatment
17

18. History Of Insulin:
• The hypoglycemic effect of pancreatic extract
were first published by kleinier in 1919.
• The isolation of insulin in 1921 by Frederick
Grant Banting and Charles H.Best led to
revolution in the management of diabetes
18

19. CHEMISTRY OF INSULIN
• Polypeptide hormone MW 5808.
• It contains 51 amino acids arranged in 2
chains A(21) and B (30) linked by two
disulphide bonds.
• Insulin is produced in the islets of
Langerhans in the pancreas. The name
insulin comes from the Latin ''insula'' for
"island" from the cells that produce the
hormone in the pancreas.
• Beta cells of pancreatic islets synthesis
insulin from a precursor insulin called
proinsulin.
• Proinsulin is hydrolyzed into insulin and C
peptide.
• Insulin and C-peptide are secreted in
equimolar amounts in response to all insulin
secreatagogeous.
• Proinsulin might have mild hypoglycemic
action but C-peptide is inactive
STRUCTURE OF INSULIN
19

20. SECRETION OF INSULIN
• Insulin is synthesized in significant quantities only
in beta cells in the pancreas.
• It is secreted primarily in response to elevated
blood concentrations of glucose.
• Insulin thus can regulate blood glucose and the
body senses and responds to rise in blood
glucose by secreting insulin.
• Other stimuli like sight and taste of food, nerve
stimulation and increased blood concentrations
of other fuel molecules, including amino acids
and fatty acids, also promote insulin secretion
20

21. .
• .
Insulin
Glucose
Glucose
GLUT-2
Glucose-6-Phosphate
GlucokinaseATP
K+
Ca2+
Ca2+
Depolarization
Regulation of Insulin Secretion from the Pancreas
21

22. MODE OF ACTION OF INSULIN
• Insulin initiates its action by binding to a glycoprotein
receptor on the surface of the cell. This receptor
consists of an alpha-subunit, which binds the hormone,
and a beta-subunit, which is an insulin-stimulated,
tyrosine-specific protein kinase.
• Activation of this kinase is believed to generate a
signal that eventually results in insulin's action on
glucose, lipid, and protein metabolism. The growth-
promoting effects of insulin appear to occur through
activation of receptors for the family of related insulin-
like growth factors.
22

23. MODE OF ACTION OF INSULIN
23

24. PHARMACOLOGICAL ACTION:
• Insulin facilitates glucose transport across cell
membranes , skeleton , muscle and fat tissue.
• Insulin influences glucose metabolism in most
tissues especially in liver where it inhibits
glucogenolysis and gluconeogenesis while
stimulating glucose synthesis.
• Insulin inhibits lipolysis in adipose tissue as well
as skeleton muscles.
• Insulin enhances transcription in vascular
endothelial lipoprotein lipase and thus increases
clearance of VLDL and chylomicrons
24

25. INSULIN ACTION
25

26. PHARMACOKINETICS
• Oral insulin is ineffective .it must be given
parentally
• Presence of zincproteins slows down its
absorption
• Therapeutically used insulin are minimally
diffusible.
• Exercising the limb into which soluble insulin is
injected speed up its absorption.
26

27. .
Usage:
• Diabetes mellitus
Adverse reactions:
• Hypoglycemia
• Insulin allergy
• Insulin lipodystrophy.
• Obesity
• Edema
• Hepatomegaly
27

28. .
Interactions:
• Diuretics
• Oral contraceptives
• Epinephrine
• Phenothiazine
Contraindications:
• Allergy or sensitivity to any ingredient of the
product.
28

29. STORAGE AND SAFETY OF INSULIN
• There are some general rules you should follow when it comes to the storage and
usage of insulin.
• Using cold insulin can make your shot more painful.
• You can warm an insulin bottle by gently rolling it between your hands before you
fill your syringe.
• If you buy more than one bottle of insulin at a time, store the extra bottles in the
refrigerator until you start to use them.
• Never store insulin at very cold or very hot temperatures as extreme temperatures
destroy insulin.
• Do not put your insulin in the freezer or in direct sunlight.
• Insulin may lose some potency if the bottle has been opened for more than 30
days.
• Look at the bottle closely to make sure the insulin looks 'normal'. For example, if
you use regular insulin, it should be perfectly clear - no floating pieces or color.
• Do not use insulin past the expiration date.
29

30. Types Of Insulin
• The types of insulin include:
•
• I. RAPID ACTING:
• Aspart (Novolog)
• Glulisine (Apidra)
• Lispro (Humalog)
•
• II. Short Acting :
• Regular insulin( Humulin R, Novolin R )
•
• III.Intermediate Acting
• NPH Insulin (Humilin N, Novolin N)
• Lente Insulin (Humilin L, Novolin L)
•
• IV. Long Acting Insulin
• Determier (Levemir),
• Glargine (Lantus)
V.Pre-mixed
30

31. Rapid-Acting
– It has onset of action of 5 to 15 minutes, peak
effect in 1 to 2 hours and duration of action that
lasts 4-6 hours
– It is absorbed quickly from your fat tissue
(subcutaneous) into the bloodstream.
– It is used to control the blood sugar during meals
and snacks and to correct high blood sugars .
Aspart (Novolog)
Glulisine (Apidra)
Lispro (Humalog)
31

32. Short-Acting
Short-acting insulin covers insulin needs for meals
eaten within 30-60 minutes .which has an onset of
action of 1/2 hour to 1 hour, peak effect in 2 to 4
hours, and duration of action of 6 to 8 hours
• Regular (R) or novolin
• Velosulin (for use in the insulin pump)
32

33. INTERMEDIATE ACTING INSULIN
• Intermediate-acting insulin covers insulin needs for about half
the day or overnight.
• This type of insulin is often combined with a rapid- or short-
acting type.
• It has an onset of insulin effect of 1 to 2 hours, a peak effect
of 4 to 6 hours, and duration of action of more than 12 hours.
• NPH Insulin (Humilin N, Novolin N)
• Lente Insulin (Humilin L, Novolin L)
33

34. Long acting insulin
• (Insulin Glargine, Insulin Detemir) which have an
onset of insulin effect in 1-2 hours. The insulin
effect plateaus over the next few hours and is
followed by a relatively flat duration of action
that lasts 12-24 hours for insulin detemir and 24
hours for insulin glargine.
• Long-acting insulin covers insulin needs for about
one full day. This type is often combined, when
needed, with rapid- or short-acting insulin
34

35. PRE MIXED INSULIN
• Premixed insulins combine specific amounts
of intermediate-acting and short-acting insulin
in one bottle or insulin pen.
• These products are generally taken two or
three times a day before mealtime.
• Humulin 70/30
• . Novolin 70/30
35

36. …
36

37. .
37

38. Insulin Delivery Systems
ExuberaInhaled

39. INSULIN DELIVERY SYSTEM
ISULIN PUMP INSULIN PEN
.
39

40. Major Adverse Effect of Insulin Therapy:
Insulin in the Absence of Carbohydrate can Lead to Severe Hypoglycemia
• . First discerned at a plasma glucose level of 60 to 80 mg/dl (3.3 to 4.4
mM).
• - Sweating, hunger, paresthesia (numbness) , palpitations, tremor,
and anxiety,
• -principally of autonomic origin
• 2. At < 60 mg/dl
• - Difficulty in concentrating, confusion, weakness, drowsiness, a feeling of
warmth, dizziness, blurred vision, and loss of consciousness
•
• - Neuroglycopenic symptom: occur at lower plasma glucose levels than do
autonomic symptoms.
40

41. ORAL HYPOGLYCEMIC AGENTS:
• Oral hypoglycemic agents are the drugs which
lower the blood glucose levels and ideal anti-
diabetic drug should be effective by orally,
should be non toxic, should correct the
metabolic defects in a diabetic, in addition to
lowering the blood sugar.
41

42. Type 2 Diabetes Mellitus
42

43. CLASSIFICATION OF ORAL ANTI DIABETIC
AGENTS
• Sulfonylurea’s:
• Generation I: Tolbutamide, Chlorpropamide, Tolazamide.
• Generation II: Glibenclamide, Glipizide, Gliclazide,
Gliquidone.
• Generation III: Glimepiride.
• Biguanides: Metformin, Buformin.
• Thiazolidinediones: Pioglitazone, Rosiglitazone.
• Meglitinides: Repaglinide, Nateglinide.
• Alpha glucosidase inhibitors: Acarbose, Miglitol, Voglibose.
• Dipeptidase peptide inhibitor:Sitagliptin,Vildagliptin
43

44. 44

45. SULFONYLUREAS
• The sulfonylureas are used as adjuncts to diet and exercise patients
with type 2 diabetes.
• Mode Of Action:
• It lowers the blood glucose by stimulating insulin release from beta
cells of the pancreatic islets.
• . Sulphonylureas are fixing on specific receptors and acts through
the potassium channel from the pancreatic and the extra-
pancreatic level. At pancreatic level, increase insulin secretion and
at the level of pancreatic beta cells, they increase the number of
insulin receptors. At extra-pancreatic sulphonylurea drugs decrease
hepatic gluconeogenesis (glucose synthesis from non-carbohydrate
sources), increased glycolysis and enhances insulin action in skeletal
muscle and in adipose tissue.
45

46. Na+
Na+
K+
K+
K+
K+
GLUT2
Ca2+
Voltage-gated
Ca2+ channel
KIR
Pancreatic
ß cell
Insulin granules
↑Ca2+
-
Sulfonylureas
-
Vm
Sulfonylureas: Mechanism of Action
46

47. Sulfonylureas: Mechanism of Action
47

48. .
• Pharmacological actions:
• It lowers the blood glucose level in non-diabetic and selected diabetic
patients.
• They are effective only in the presence of functioning pancreas.
• When effective they also normalize the metabolic status of diabetic patient.
•
• Pharmacokinetics:
• The sulfonylureas are rapidly absorbed from GIT
• About 90% or more drugs bounds to the plasma proteins.
• They are poorly distributed in the body.
• They are metabolized in the liver and excreted unchanged in the urine.
•
48

49. • Usage:
• Diabetes insipidus
• Bronchial asthama
• Intestinal diseases
• Cerebral edema
•
• Interactions:
• Drugs that enhances the action
• Phenylbutazone
• Sulfinpyrazine
• Sulfonamides
• Drugs that decreases the action
• Phenobarbitone
• Phenytoin
• Rifampicin
49

50. .• Adverse reactions:
• Hypoglycemia
• Weight gain
• Hypersensitivity reactions.
• CONTRAINDICATIONS:
• Diabetes is complicated by ketoacidosis with or
without coma.
• Type 1 diabetes
• Diabetes is complicated by pregnancy
50

51. BIGUANIDES
• The biguanides metformin is the drug of
choice as initial therapy for a newly diagnosed
patients with type 2 diabetes as an adjunct to
diet and exercise.
51

52. MODE OF ACTION
• Major mechanism of action:  AMP-
dependent kinase
• - Inhibits conversion of acetyl CoA to malonyl CoA, by acetyl-
CoA carboxylase, the rate-limiting step in lipogenesis. Net result
is a faster rate of fatty acetyl-CoA influx into the mitochondria
where it undergoes oxidation to ketone bodies
- Increases expression or activity of glycolytic enzymes and GLUT-4,
decreases activity of gluconeogenic enzymes
- Net: hepatic glucose production and  glucose uptake in muscle
and adipose.
52

53. MOA
53

54. .PHARMACOLOGICAL ACTION:
• It improves the glucose tolerance by lowering
both basal and post prandial plasma glucose.
• It decreases the hepatic glucose production
• It decreases intestinal absorption of glucose.
• It improves insulin sensitivity by increasing
peripheral glucose uptake and utilization.
• Reduces plasma glucose level.(LDL,VLDL)
54

55. Metformin: Mechanism of Action
2nd Generation Biguanide
55

56. • Pharmacokinetics:
• It is taken orally
• It does not bound to serum proteins.
• It is not metabolized and excreted remain unchanged in
urine.
• Usage:
• Insulin sensitizer
• It is use with obsese patients with type 2 diabetes
• It is used as monotherapy or in combination.
•
56

57. • Interactions:
• Alcohol potentiates the effect on lactate metabolism.
• Iodinate constrast media can lead to acute renal failure and metformin
toxicity.
• Adverse reactions:
• GIT disturbances
• Lactic acidosis
• Long term use interference with B12 absorption.
•
• Contraindications:
• Pregnancy
• Renal diseases
• Liver diseases
• Alcoholism
57

58. THIAZOLIDINEDIONES
• The thiazolidinediones ; pioglitazone and
rosiglitazone decrease insulin resistance by
enhancing insulin receptor sensitivity.
58

59. Mode Of Action:
• It activate nuclear receptors (peroxisomes
proliferator activated receptor-ᵞgamma)PPAR-ᵞ
• it increases the sensitivity of the target tissue
to insulin.
• It increase the glucose uptake and utilization
in muscle and adipose tissue.
• It decrease the level of triglycerides and HDL
59

60. MOA OF THIAZOLIDINEDIONE
60

61. • Pharmacokinetics:
• It is taken orally once daily dose.
• It is highly bound to plasma albumins 99%
• Slow onset of activity
• Half life is about 3-4 hours.
• Metabolized by CYP450.
• It gives the active metabolities.
• It is excreted in urine 64% and bile.
• Usage:
• Type 2 diabetes with insulin resistance.
• It is used either alone or in combination with
sulfonylurea,biguanides or insulin.
• Polycystic ovarian syndrome.
• No risk of hypoglycemia when used alone.
61

62. • Interactions:
• Increased efficacy
• Gemfibrozil
• Rifampicin
– Decreased efficacy
• Oral contraceptive
• Adverse reactions:
• Edema
• Weight gain
• Failure of estrogen-containing oral contraceptives.
•
• Contraindications:
• Heart failure
• Pregnancy
• Significant liver diseases.
62

63. MEGLITINIDES
• They are rapidly acting insulin secretagenous.
• Mode Of Action:
• It stimulate insulin release from functioning ᵝ
beta cells by modulating K efflux via blocking
ATP sensitive K channels resulting in
depolarization and calcium influx.
63

64. Pharmacokinetics:
•It is well absorbed orally.
•It has very fast onset of action
•It metabolized into inactive products in liver(CYP3A4) and excreted mainly in
the bile.
•It is effective in early release of insulin after meal.
Usage:
•Type 2 diabetes
•It is use as monotherapy or combined therapy with metformin.
•It is use in patients allergic to sulfur or sulfonylurea.
Interactions:
•Enzyme inhibitors-cimetidine,flucanazone,erythromycin
•Enzyme inducers-barbiturates,rifampicin,phenytoin.
64

65. ALPHA-GLUCOSIDASE INHIBITORS
It is used to treat type 2 diabetes which is
inadequately controlled by diet.
• Mode Of Action:
• Reversible inhibitors of intestinal alpha-
glucosidase in intestinal brush border responsible
for degradation of oligosaccharide to
monosaccharide.
• Thus preventing the digestion and absorption of
carbohydrates along the small intestine.
•
65

66. 66

67. .
Pharmacokinetic:
• It is metabolized by intestinal bacteria found
in colon into short chain fatty acids.
• Then excreted in stool and urine.
• Usage:
• Type 2 diabetes inadequately controlled by
diet with or without any agents.
• It is used alone or combined with insulin or
sulfonylurea.
67

68. .
• Adverse reactions:
• Weight gain
• Abdominal bloating
• Flatulence
• Abdominal discomfort
• Diarrhea
•
• Contraindications:
• Inflammatory bowel disease
• Renal disease
• Hepatic disease
• Intestinal obstruction
68

69. Dipeptidyl peptidase -4 inhibitor
(DPP4-INHIBITOR)
• Sitagliptin is the first DPP-4 inhibitor available.
• It is used as monotherapy or as an adjunct to diet
and exercise or in combination of other anti-
diabetic drugs.
• Mode Of Action:
• It inhibit DPP-4 enzyme(GLP-1 glucagon like
peptide)and leads to an increase in incretin
harmone levels(GI harmone secreted in response
to food).
• This result in an increase secretion and decrease
in glucagon secretion
69

70. .
.
• Pharmacokinetics:
• It is taken orally
• It is given once daily.
• The half life is 8-14 hours.
• Usage:
• Type 2 diabetes as an adjunct to diet and exercise as an monotherapy or in
combination with other anti-diabetic drug.
• Interactions:
• Digoxin increased efficacy.
• Adverse effects:
• Nausea
• Abdominal pain
• Diarrhea
• Nasopharyngitis
• Contraindications:
• Dose is reduced in patients with renal impairment
70

71. DIET
EXERCISE
MEDICATION
EDUCATION
MANAGEMENT
71

72. DIET
AVOID THE FOLLOWING
FOODS THAT BRING UP THE
BLOOD SUGAR LEVELS
72

73. PARTICIPATE IN ACTIVE SPORTS AND
REGULAR EXERCISES
EXERCISE
73

74. TAKE YOUR MEDICINES EVERY
DAY AS INSTRUCTED BY YOUR
DOCTORS
ORAL HYPOGLYCEMIC DRUGS
INSULIN
74

75. LEARN MORE ABOUT THE DISEASE. PARTICIPATE IN
THE FREE LECTURES
EDUCATION
75

76. PREVENTION
• Checking blood glucose levels: Keep a regular
check on blood sugar levels and identify the
onset of symptoms.
• Eat regularly: Keep to your eating routine.
• Exercise: Make sure you have eaten some
carbohydrate rich food before you do any
exercise.
• Be ready: Children with diabetes type1
should always carry a container of sugary fruit
or a candy bar so that they are ready if
symptoms are felt.
• Let people know: If you are susceptible to
attacks of hypoglycemia ,let your friends
,colleagues and family members know.
explain what signs and what should be done.
76

77. REASEARCH:
• Artificial beta cells from the human kidney:
• Researchers have used the simplest approach yet to produce
artificial beta cells from the kidney cells. Like their natural
model, the artificial cells act as both sugar sensor and insulin
producers.
• Chemically modified insulin is available more
quickly:
• Replacing a hydrogen atom by an iodine atom in insulin the
hormone retains its efficacy but is available more rapidly to the
organism. Researchers were able to predict this effect based on
computer simulations and then confirm with experiments.
77

78. AWARENESS:
• WORLD DIABETIC DAY is celebrated every year on November 14. The
campaign is led by International Diabetes Federation (IDF) and its member.
• National diabetic month is observed every November so individuals,
organizations and communities across the country can bring the attention
to diabetes and its impact on millions of people.
• This year ,the national diabetes education program theme is “Managing
Diabetes –Its Not Easy ,But Its Worth It.
• This theme highlights the importance of managing diabetes to prevent
diabetes related health problems such as heart attack, stroke, kidney loss,
vision loss etc.
• Wear blue: throughout the November and ask your friends, family and
colleagues to join you.
• Organize a physical activity: walk, cycle , ride, aerobic workout, flash mob
or dance.
• The theme also serves as reminder to people who may be struggling with
the demands of managing diabetes that they are not alone.
78

79. CONCLUSION:
• Diabetes mellitus results from a failure of the pancreas to
produce a sufficient amount of insulin.
• There are several symptoms and complications of the
disease.
• Although the disease has many complications there are
also treatments to follow to avoid serious problems.
• Diabetes is a slow killer with no curable treatments.
However, its complications can be reduced through proper
awareness and timely treatment.
• Researchers now look for alternative methods for diabetes
treatment. They believes that diabetes is one of the highly
demanding research topics of new century and wants to
encourage new researchers to take up the challenge.
79

80. REFERENCES:
• Tripathi , K.D. Essentials of medical pharmacology,4th edition ,1999,publisher
Jaypee, Delhi.
• Satoskar, R.S. and Bhadarkar , S.D. Pharmacology and pharmacotherapeutics
,16th edition ,1999,publisher,Popular Dubai.
• www.webmed.com
• www.news_medical.net.
• mct.aacrjournals.org
• www.researchgate.net
• www.mediographia.com
• www.ncbi.nlm.gov.in
• www.medbio.info
• www.drugbank.com
• www.diabetes.co.uk
• www.diabetesresearch.org
• www.healthline.com
•
80

81. 81

82. .
82