Antidiabetic Drugs
Nursing 3703
Pharmacology
By 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 Aglycerophosphate, 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 Insulin
Other hormones that raise blood
glucose levels include:
 Cortisol
 Glucagon
 Growth hormone
 Epinephrine
 Estrogen
 Progesterone
Endogenous Insulin
Factors 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
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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
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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 130/85
5. Fasting glucose greater than or equal
to 110mg/dL
Also 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 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
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 postprandial 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 Insulins
1. Regular Iletin II, Humulin R, Novolin
R
2. May be given sub Q or IV
3. May be given as a continuous IV drip
4. The only insulin that may be given IV
5. 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