1. Nursing 3703 Pharmacology By Linda Self
Antidiabetic Drugs
Nursing 3703
Pharmacology
By Linda Self

2. Diabetes Mellitus
Chronic systemic disease characterized by metabolic and vascular abnormalities
Disorder of carbohydrate metabolism
Results from inadequate production or underutilization of insulin

3. Diabetes Mellitus Characterized by glucosuria and hyperglycemia
Two forms—Type 1 and Type 2
Type 1—patient secretes no insulin. Cause is felt to be autoimmune.
Type 2- patient secretes insufficient amounts of insulin and insulin receptors are resistant to existent circulating insulin
Type 1 hereditary. Triggered by viral infection that inflames the beta cells of the pancreas. Exact mechanism is not known.

4. Diabetes Mellitus
Symptoms: hyperglycemia, glucosuria, polyuria, polydipsia, polyphagia, and possibly itching.
Fasting blood glucose is higher than 126
Manifested by: weight loss, weakness, increased frequency of infections, poly’s

5. Diabetes Mellitus
Without intervention, significant complications will ensue.
Include: retinopathies, glaucoma, neuropathies, cardiovascular disease.PVD. Increased incidence of toxemia of pregnancy.

6. Pathophysiology Insulin secreted by beta cells
Insulin binds with and activates 80% of cells
Liver, muscle, and fat cells are primary tissues for insulin action
With insulin receptor binding, cell membranes permeable to glucose into the cells

7. Pathophysiology cont.
Increased cell permeability also allows for amino acids, fatty acids and electrolytes to enter cells
Changes cause anabolism and inhibit catabolism
Anabolism includes use and storage of glucose, amino acids, and fatty acids.

8. Pathophysiology cont. Carbohydrate metabolism
Insulin increases glucose transport into liver, skeletal muscle, adipose tissue, the heart, and even uterus.
Must be present for muscle and fat tissues to use glucose for energy
Insulin regulates glucose metabolism to produce energy for cellular functions
If excess glucose is present after need is met, it is converted to glycogen and stored or converted to fat and stored.
The excess glucose transported to liver cells is converted to fat only after glycogen stores are saturated. Liver is especially important in restoring blood sugar levels by breaking down glycogen or by forming new glucose.

9. Pathophysiology cont. Fat Metabolism
Insulin promotes glucose into fat cells where it is broken down
One of breakdown products is A-glycerophosphate, combines with fatty acids which ultimately forms triglycerides
This is the mechanism by which insulin promotes fat storage
Actually, insulin transport of glucose into fat cells results first in alpha-glycerophosphate which combines with fatty acids and produces alpha-glycerophosphate, This then is converted to triglycerides.

10. Fat Metabolism
When insulin is lacking, fat is released into the bloodstream as free fatty acids.
Blood concentrations of triglycerides, cholesterol and phospholipids are also increased
Thus the high lipid concentration probably contributes to the accelerated atherogenesis seen in diabetics. Some of the free fatty acids may be converted to ketones, resulting in ketosis.

11. Protein Metabolism
Insulin increases the total amount of body protein by increasing transport of amino acids into cells and synthesizing protein within the cells
Insulin potentiates the effects of growth hormone
Lack of insulin causes protein breakdown into amino acids
These amino acids are not replaced by synthesis of new proteins; thus, protein wasting occurs resulting in weakness, weight loss and abnormal functioning of many body organs

12. Endogenous Insulin Glucose is the major stimulus of insulin secretion
Oral glucose is more effective than intravenous glucose because glucose in digestive tract increases the release of gastrin, secretin, chlecystokinin, and gastric inhibitory peptide
Also stimulates vagal activity

13. Endogenous Insulin
Other hormones that raise blood glucose levels include:
Cortisol
Glucagon
Growth hormone
Epinephrine
Estrogen
Progesterone

14. Endogenous Insulin Factors that inhibit insulin secretion include:
Hypoxia
Hypothermia
Stimulation of alpha adrenergic 2 receptors

15. Classification of Two Types of Diabetes
Type 1 diabetes results from an autoimmune disorder that destroys pancreatic beta cells
Usually has sudden onset
Associated with high incidence of complications
Requires exogenous insulin
10% of those with diabetes are type I

16. Diabetic Ketoacidosis (DKA)
Life-threatening complication occurs with insulin deficiency
Glucose cannot be used by body cells for energy so fat is mobilized for this purpose
Mobilized fat is then extracted by liver and broken down into glycerol and fatty acids
Fatty acids further broken down into ketones

17. DKA Accumulation of ketones results in acidemia
Attempts to buffer acidic H+occurs by ionic exchange, intracellular potassium exits cells. H+ ions enter cells. Result is excretion of potassium in urine.
Kidneys attempt to buffer by excreting ketones
Pulmonary attempt to buffer by Kussmaul breathing

18. Clinical S/S of DKA Kussmaul breathing Nausea and vomiting Thirst
Polydipsia, polyphagia and polyuria
Hypotension
Tachycardia
shock

19. Type 2 Diabetes Mellitus
Characterized by hyperglycemia and insulin resistance
Results from increased production of glucose by liver and decreased uptake of glucose in liver, muscle and fat cells
Insulin resistance—higher than usual concentrations of insulin are required

20. Type 2 Diabetes Mellitus
Occurs at any age
Gradual onset
Less severe symptoms initially
Easier to control
More MIs and strokes
90% of those with diabetes are Type 2
multifactorial

21. Hyperosmolar hyperglycemia nonketotic coma (HHNC)
Occurs in Type 2 Diabetes
Because patient has some endogenous insulin, no ketosis develops
Blood sugars can be >
Can result in hypovolemic shock, renal problems, stroke, coma and even death

22. Metabolic Syndrome or Syndrome X
Comprised of a set of risk factors which include:
Central abdominal adiposity (men waist size greater than 40 inches, women greater than 35 inches
Fasting triglycerides greater > or equal to 150 mg/dl
HDL cholesterol (less than 40 in men, less than 50 mg/dl in women

23. Metabolic Syndrome cont.
4. Blood pressure greater than or equal to 130/85
5. Fasting glucose greater than or equal to 110mg/dL
Also possess prothrombotic and proinflammatory tendencies
In US, 20% of adults (47 million) have metabolic syndrome with prevalence approaching 50% in elderly. Seen more often in those who are overweight. Root cause is poor eating habits and sedentary lifestyle.

24. Metabolic Syndrome cont.
All factors are interrelated
Obesity and lack of exercise tend to lead to insulin resistance
Insulin resistance has a negative effect on lipid production. Increase VLDL, LDL, TG and decreasing the HDL.
Insulin resistance leads to increased insulin and glucose levels in blood.
Increased glucose and insulin in blood affect kidneys by holding onto sodium which then increases BP and can lead to hypertension. Also chronically elevated glucose levels damage blood vessels and organs.

25. Hypoglycemic Drugs
Insulin lower glucose levels by increasing glucose uptake by cells
Indicated for Type 1 DM, often in Type 2 DM, in those with chronic pancreatitis, in those on TPN, to treat hyperkalemia (infusion with dextrose and insulin)
Available insulins are pork and human

26. Age-Related considerations
Type 1 DM in children
Consistent diet, blood glucose monitoring, insulin injections and exercise
Blood sugar control essential to maintain normal growth and development
Infections and illnesses can cause wide fluctuations

27. Type 1 DM in children cont.
Children highly susceptible to dehydration
Rotation of sites is very important
Avoiding hypoglycemia is a major goal in infants and young children d/t damaging effects on growth and development

28. Type 1 DM in children
s/s of hypoglycemia include: hunger, sweating, tachcardia, irritability and lethargy.

29. Age related considerations in older adults
Close monitoring of blood glucose levels
Visual impairment may affect their ability to self administer medication
May have renal insufficiency so caution w/certain antidiabetic meds a concern
Caution with metformin if renal impairment
Glitazones can predispose to fluid retention and heart failure

30. Insulin
Human insulin is chemically identical to endogenous insulin but it is not derived from the human pancreas
Cannot be given orally
Insulins differ in onset and duration of action. Ultra-short, short, intermediate and long acting.

31. Rapid acting insulin
Insulin lispro (Humalog) or insulin aspart (Novolog) are very shorting acting insulins
More effective in decreasing post-prandial hyperglycemia
Less likely to cause hypoglycemia before the next meal
Onset is 15’, peaks in 1-3 hours, duration is 3-5 hours

32. Insulin cont. Short acting Insulins
Regular Iletin II, Humulin R, Novolin R
May be given sub Q or IV
May be given as a continuous IV drip
The only insulin that may be given IV
Onset is ½-1 hour, peak is 2-3 hours and duration is 5-7 hours

33. Intermediate-acting Insulins
Isophane insulin suspension (NPH, NPH Iletin II, Humulin N, Novolin N)
Onset is hours, peaks in 8-12 hours and duration is 18-24

34. Long-acting Insulin Extended insulin zinc suspension
Onset is 4-8 hours, peaks in hours and duration is 36+ hours

35. Insulins cont. Insulin Mixtures NPH 70/30 (Humulin or Novolin 70/30)
Durations of actions same as individual components

36. Insulins cont. Insulin Analogs
Lispro and aspart as previously described
Insulin glargine (Lantus)-once daily at bedtime. Onset is 1.1 hours, peak is none, duration is 24 hours
Must not be diluted or mixed with any other insulin or solutions

37. Oral Hypoglycemic Drugs
Five types used to treat Type 2 DM
Sulfonylureas—oldest. Increase release of insulin. Also decrease production of glucose in the liver, increase the number of insulin receptors and increase peripheral use of glucose. Effective only if have functioning beta cells.
Primary side effect is hypoglycemia

38. Sulfonylureas cont. First generation are essentially obsolete
Use 2nd generation agents
Are glipizide (Glucotrol), glyburide (Diabeta)and glimepiride (Amaryl)
Can be used with metformin, glitazones, insulin or acarbones
Caution w/renal or hepatic impairment. Not used in pregnancy.

39. Alpha glucosidase Inhibitors
Acarbose (Precose) and miglitol (Glyset) inhibit alpha-glucosidase enzymes (maltase, amylase, sucrase) in GI tract. Delays absorption of complex CHO and simple sugars
Can be combined therapy w/insulin or w/sulfonylurea
Contraindicated in cirrhosis, malabsorption, severe renal impairment

40. Alpha-glucosidase Inhibitors
Take at beginning of each meal
Can cause bloating and diarrhea

41. Biguanides
Metformin (Glucophage) increases the use of glucose by muscle and fat cells, decreases hepatic glucose production, and decreases intestinal absorption of glucose
Does not cause hypoglycemia
May be used alone or in combination
Contraindicated in liver or renal impairment. Can result in lactic acidosis.

42. Biguanides cont.
Must check renal function before beginning this medication
Caution with parenteral radiographic contrast media containing iodine. May cause renal failure and has been associated with lactic acidosis.

43. Glitazones
Pioglitazone (Actos) and rosiglitazone (Avandia) are also called thiazolidinediones or TZDs
Are insulin sensitizers
Decrease insulin resistance. Stimulate receptors on muscle, fat, and liver cells. Results in increased uptake of glucose in periphery and decreased production by the liver.

44. Glitazones
Contraindicated in patients with liver disease or who have ALT levels > 2.5 of normal
May be used as monotherapy or in combination with insulin, metformin (Glucophage) or a sulfonylurea
Caution in patients with heart failure
Ensure baseline LFTs are performed

45. Meglitinides
Nateglinide and repaglinide are nonsulfonylureas that lower blood sugar by stimulating pancreatic secretion of insulin
Monotherapy or in combination with metformin
Should be taken before or up to 30 minutes before a meal. Dosage and frequency is flexible depending on food intake.

46. Herbals and Dietary Supplements that affect blood glucose levels
Bee pollen, gingko biloba and glucosamine are thought to increase blood sugars or may potentially affect beta-cell function and insulin secretions (see p. 378)
Basil and bay leaf may cause hypoglycemia
Chromium may increase production of insulin receptors and increase insulin effectiveness

47. DKA IV fluids to rehydrate No use of hypotonic solutions at this time
Potassium supplementation
IV insulin drip with gradual lowering of blood sugars
Judicious administration of sodium bicarbonate

48. HHNC
Treatment similar to that of DKA

49. Diabetic management “pearls”
When mixing insulins, draw up the regular insulin first
Tid glucose monitoring is highly recommended
Allow mild hyperglycemia for the patient undergoing surgery—treat with short acting insulins
For elective surgery, schedule patient early in day to avoid prolonged fasting

50. “Pearls” Use U-100 syringes for U-100 vials
In patients with insulin pumps, use regular insulin or insulin aspart. Generally will deliver one unit per hour w/bolus insulin before meals
Tight glycemic control can reduce the complications of diabetes.
Use ACE inhibitors to delay nephropathy
Limit dietary intake of protein

51. “Pearls” Glitazones must suspect r/t hepatotoxicity
Metformin cautiously with liver and renal impairment. Concern that with hepatotoxicity, because risks of lactic acidosis are increased.
Rotate sites of injection of insulin to avoid development of lipodystrophy

52. “Pearls”
Absorption of injected insulin in abdomen is not uniform with injections in arms or legs