Antidiabetic Drugs

Nursing 3703PharmacologyBy Linda Self

Diabetes Mellitus Chronic systemic disease

characterized by metabolic and vascular abnormalities

Disorder of carbohydrate metabolism Results from inadequate production

or underutilization of insulin

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

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

Diabetes Mellitus Without intervention, significant

complications will ensue. Include: retinopathies, glaucoma,

neuropathies, cardiovascular disease.PVD. Increased incidence of toxemia of pregnancy.

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

Pathophysiology cont. Increased cell permeability also

allows for amino acids, fatty acids and electrolytes to enter cells

Changes cause anabolism and inhibit catabolism

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

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

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

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

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

Endogenous InsulinOther hormones that raise blood glucose

levels include: Cortisol Glucagon Growth hormone Epinephrine Estrogen Progesterone

Endogenous InsulinFactors that inhibit insulin secretion

include: Hypoxia Hypothermia Stimulation of alpha adrenergic 2

receptors

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

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

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

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

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

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

Hyperosmolar hyperglycemia nonketotic coma (HHNC)

Occurs in Type 2 Diabetes Because patient has some

endogenous insulin, no ketosis develops

Blood sugars can be >800-1000 Can result in hypovolemic shock,

renal problems, stroke, coma and even death

Metabolic Syndrome or Syndrome X Comprised of a set of risk factors

which include:1. Central abdominal adiposity (men

waist size greater than 40 inches, women greater than 35 inches

2. Fasting triglycerides greater > or equal to 150 mg/dl

3. HDL cholesterol (less than 40 in men, less than 50 mg/dl in women

Metabolic Syndrome cont.4. Blood pressure greater than or equal

to 130/855. Fasting glucose greater than or equal

to 110mg/dLAlso possess prothrombotic and

proinflammatory tendencies

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.

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

Age-Related considerationsType 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

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

Type 1 DM in children s/s of hypoglycemia include: hunger,

sweating, tachcardia, irritability and lethargy.

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

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.

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

Insulin cont. Short acting Insulins1. Regular Iletin II, Humulin R, Novolin R2. May be given sub Q or IV3. May be given as a continuous IV drip4. The only insulin that may be given IV5. Onset is ½-1 hour, peak is 2-3 hours

and duration is 5-7 hours

Intermediate-acting Insulins Isophane insulin suspension (NPH,

NPH Iletin II, Humulin N, Novolin N) Onset is 1-1.5 hours, peaks in 8-12

hours and duration is 18-24

Long-acting Insulin Extended insulin zinc suspension Onset is 4-8 hours, peaks in 10-30

hours and duration is 36+ hours

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

individual components

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

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

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.

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

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

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.

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.

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.

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

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.

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

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

HHNC Treatment similar to that of DKA

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

“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

“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

“Pearls” Absorption of injected insulin in

abdomen is not uniform with injections in arms or legs