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Common examples of drug therapy

Diabetes Mellitus: Oral Blood Glucose Lowering Agents-contd

Use in Diabetes





The patients how to Hypoglycemia may

(glimepiride/rosiglitazone) added to regimen prevent and treat occur

Usual doses:


1mg/4 mg






blood hypoglycemia






glimepiride therapy

Met Pioglitazone added Instruct patients in Hypoglycemia may


to regimen when measures

Usual doses:

blood glucose is prevent and treat metformin is given

15 mg/500 mg


15 mg/860 mg



metformin therapy

to occur


in combination with

Because of its long duration of action. Underweight older patients with cardiovascular, liver,
or kidney impairment are more susceptible to hypoglycemia. Many drugs can potentiate ir
interfere with sulfonylureas.
First generation sulfonylurea agents are seldom used but are still available in
pharmacies. The joint commission 2007 National Patient Safety Goals include improving
safety of look-alike/sound alike drugs. Take care to avoid confusing the dosage of
acetohexamide (Dymelor) with that oh acetazolamide (Diamox), a diuretic used in the
treatment of glaucoma, and teach the patient how to avoid this drug error.
Meglitinide analogues are classified as insulin secretagogues and have actions and
adverse effect similar to those of sulfonylureas. Repaglinide (Prandin) and Nateglinide
(Starlix) lower blood glucose by triggering insulin secretion from pancreatic beta cells. These
drug were designed to increase meal-related insulin secretion. They are rapidly absorbed and
have a short duration of action.

Repaglinide (Prandin) is taken before meals, has a rapid onset with limited duration of
action, and is used to treat both fasting and postprandial hyperglycemia. Adverse effects
include hypoglycemia, GI disturbances, upper respiratory tract infection, arthralgia or back
pain, and headache.
Nateglinide (Starlix) is rapidly absorbed and stimulates insulin secretion within 20
minutes of ingestion. It is taken just before meals to control mealtime hyperglycemia and
improves overall glycemic in patients with type 2 diabetes. The major adverse effect is
hypoglycemia. Patients who skip meals should also skip their scheduled dose of Starlix to
reduce the risk for hypoglycemia.
Biguanides are anti hyperglycemic agents and insulin sensitizers. Metformin
(Glucophage) is the major drug in this class. It does not increase insulin secretion. Instead, it
decreases liver glucose production, thereby reducing fasting plasma glucose release, and
improves insulin receptor sensitivity. The ADA recommends metformin as initial therapy for
type 2 diabetes because the drug does not induce weight gain or hypoglycemia, has a
relatively low cost, and has few adverse effects. It should not be given to anyone with kidney
disease and elevated blood creatinine levels. The drug should be withheld for 48 hours before
and after using contrast material and surgical procedures requiring anesthesia.
Drug interactions with Sulfonylurea agents (table 67-8)
Causes or Worsens Hyperglycemia

Causes or Worsens Hypoglycemia

Angiotensin-converting agents (Captopril

Calcium channel blocking gents (Diltiazem

[Cardizem], Niedipine [Procardia])


Corticosteroid (Prednison)


Allopurinol (Zyloprim)



Antifungal azoles (Fluconazole [Diflucan],


contraceptive (Brevicon, Depo-Provera,

Furosemide (Lasix)



Estrogen (Estrace, Premarin)


[Capoten], Enalapril [Vasotec])




Beta-adrenergic blocking agents (Atenolol
[Tenormin], Propranolol [Inderal])

Isoniazid (INH)

Chloramphenicol (Chloromycetin)

Nicotinic Acid (Nicolar)

Clofibrate (Atromid-S)

Phenothiazines (Chlorpromazine [Thorazine], Coumarin Anticoagulants (Warfarin)


[Compazine], Floroquiolones

Trifluoperazine [Stelazine])
Phenytoin (Dilantin)









Rifampin (Rifadin)



[HydroDIURIL], Chlorothiazide [Diuril])




[Tagamet], Ranitidine [Zantac])





(Phenelzine [Nardil])
Nsaids (Indomethacin [Indocin], Ibuprofen
Octreotide (Sandostatin)
Probenecid (Benemid, Probalan)
Sulfinpyrazone (Anturane)
[Bactrim], Sulfosixazole [Gantrisin])






Hydrochloride [Sinequan])

The most common side effects are abdominal discomfort and diarrhea. Metformin can
cause lactic acidosis in diabetic patients with renal insufficiency and should not be used in
conditions that decrease drug clearance, such as renal insufficiency, liver disease, alcoholism,
or severe congestive heart failure or in patient older than 80 years. Hypoxemia, dehydration,
and sepsis also increase the risk for lactic acidosis. Symptoms of lactic acidosis can be subtle.
Teach the patient to report symptoms of fatigue, unusual muscle pain, difficulty breathing,
unusual or unexpected stomach discomfort, dizziness, lightheadedness, or irregular heartbeats
to the primary care provider. Instruct patients to take metformin with meals to reduce GI
effects. Caution against excessive alcohol intake because alcohol increases the risk for lactic
Alpha-glycosidase inhibitors are agents that prevent hyperglycemia by delaying
absorption or carbohydrate from the small intestine. These drugs inhibit enzymes in the

intestinal tract, reducing the rate of digestion of starches and the absorption of glucose.
Acarbose delays rather than prevent glucose absorption and does not cause weight loss.
The most common side effects are flatulence, diarrhea, and abdominal discomfort.
There are two drugs in this class. Acarbose (Precose) is well tolerated when started at a low
dose (25 mg once daily to three times daily with meals) and increase slowly. At higher doses,
poor carbohydrate absorption occurs. Miglitol (Glyset) should be taken three times daily with
the first bite of each main meal.
These drugs do not cause hypoglycemia unless given with sulfonylureas or insulin.
Because alpha-glycosidase inhibitors delay carbohydrate absorption and interfere with the
conversion of complex sugars to glucose, many of standard glucose-based products used to
treat hypoglycemia have a slower onset of action. These drugs do not inhibit absorption of
glucose or lactose. Teach patients to use oral glucose tablets, glucose gel, or low-fat milk to
treat hypoglycemia. Severe hypoglycemia may require glucose infusion or glucagon
Thiazolidinediones (TZDs) are anti-hyperglycemic agents and insulin sensitizers. They
improve insulin sensitivity and reduce liver glucose production. TZDs also improve insulin
action in muscle, fat, and liver tissue by stimulating an enzyme receptor that regulates
glucose and lipid metabolism (peroxisome proliferator activated receptor). The two drugs in
this class are rosiglitazone (Avandia) and pioglitazone (Actos). Although rosiglitazone is
available, its use has been associated with an increased risk for heart-related deaths, bone
fractures, and macular edema (Ledbetter & Lausttseen, 2008). It should be used cautiously in
patients who have pre-existing cardiac problems.
All drugs in this class reduce blood lipid levels. Major side effects of TZD treatment are
an increase in adipose tissue and fluid retention. Some patients taking these drugs gain
weight. Edema, with development of congestive heart failure, is possible but not common.
Other side effects of these drugs include infection, headache, peripheral edema, and pain.
Patients taking these drugs should have periodic liver function studies because of the
potential for liver damage.
Combination abents combine drugs with different mechanisms of action. Glucovance,
for example, combines glyburide with metformin. Combining drugs with different
mechanisms of action may be highly effective in maintaining desired blood glucose control.
Some patients may need a combination of oral agents and insulin to control blood glucose

Drug administration. Drug s are started at the lowest effective dose and increased
every 1 to 2 weeks until the patient reaches desired blood glucose control or the maximum
dosage. If the maximum dosage does not control blood glucose levels, a second oral agent
with a different mechanism of action may be added. Insulin therapy is indicted when blood
glucose cannot be controlled after the use of two or three different oral agents.
Anti-diabetic drugs are not a substitute for dietary modification and exercise. Teach the
patient about the need for continuing dietary restrictions and regular exercise while taking
anti diabetic drugs. To avoid adverse drug interactions, teach the patient to consult with the
primary care provider or pharmacist before using any over-the-counter drugs.
Drug selection. The choice of oral anti diabetic drug is based on cost, the patients
ability to manage multiple drug doses, age, and response to the drugs. Shorter-acting agents
(e.g., glipzide) re preferable in older patients, those with irregular eating schedules, or those
with liver, kidney, or cardiac dysfunction, whereas longer-acting agents (e.g., glyburide,
glimepiride) with once-a-day dosing are better for adherence. Beta-cell function in type 2
diabetes often declines over time, reducing the effectiveness of some oral agents. The
treatment regimen for the patient with type 2 diabetes may eventually require insulin therapy
either alone or with oral agents.
Insulin therapy. Insulin therapy is needed for type 1 diabetes. The safety of insulin
therapy in older patients may be affected by reduced vision, mobility and coordination
problems, and decreased memory. There are many types of insulin and regimens, all aimed at
achieving normal blood glucose levels
Types of insulin. Insulin is manufactured using DNA technology to synthesize pure
human insulin. Insulin analogues are genetically engineered human insulins in which the
structure of the insulin molecule is altered to change the rate of absorption and duration of
action within the body. One example is Lispro insulin, a rapid-acting insulin analogue that is
created by switching the positions of lysine and proline in one area of the insulin molecule.
Rapid-, short-, intermediate-, and long-acting forms of insulin can be injected
separately, and some can be mixed same syringe. Insulin is available in 100 units/mL (U-100)
and 500 units/mL (U-500). U-500 is used only in rare cases of insulin resistance.
Teach the patient that the insulin types, the injection technique, the site of the injection,
and the patient response can all affect the absorption, onset, degree, and duration of insulin
activity. Reinforce that changing insulins may affect blood glucose control and should be
done only under supervision of the health care provide. Table 67-9 outlines the time activity
of human insulin.

Insulin regimens. Insulin regimens try to duplicate the normal insulin release pattern
from the pancreas. The pancreas produces a constant (basal) amount of insulin that balances
liver glucose production with glucose use and maintains normal blood glucose levels between
meals. The pancreas also produces additional (prandial) insulin to prevent blood glucose
elevation after meals. The insulin dose required for blood glucose control varies among
patients. A usual sarting dose is between 0,5 and 1 unit/kg of body weight per day. For
multiple-dose regimens or continuous subcutaneous insulin infusion (CSII), basal insulin
makes up about 40% to 50% of the........