Medication Presentation

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Medication Presentation

• Torry A. Hansen

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Glyburide

• Generic name Glyburide
• Brand name Micronase
• Other brand names DiaBeta, Glynase
• Classifications
• Therapeutic Antidiabetics
• Pharmacologic Sulfonylureas
• Pregnancy Category B

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Description

• Glyburide is an oral blood-glucose-lowering drug
  of the sulfonylurea class. Glyburide is a white,
  crystalline compound. , The chemical name for
  glyburide is1- p-2-(5-chloro-o-anisamido)-eth
  ylphenyl-sulfonyl-3-cyclohexylurea and the
  molecular weight is 493.99. The structural
  formula is represented below.

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Glyburide

• Indications (Pharmacia Upjohn, 2005)
• Glyburide tablets are indicated as an adjunct
  to diet to lower the blood glucose in patients
  with non-insulin-dependent diabetes mellitus
  (Type II) whose hyperglycemia cannot be
  satisfactorily controlled by diet alone.
• Glyburide may be used concomitantly with
  metformin when diet and glyburide or diet and
  metformin alone do not result in adequate
  glycemic control.

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Actions/Uses

• Glyburide appears to lower the blood glucose
  acutely by stimulating the release of insulin
  from the pancreas, an effect dependent upon
  functioning beta cells in the pancreatic islets.
  The mechanism by which glyburide lowers blood
  glucose during long-term administration has not
  been clearly established.Extrapancreatic effects
  may be involved in the mechanism of action of
  oral sulfonylurea hypoglycemic drugs.

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Glyburide

• Pharmacokinetics/Pharmacodynamics (Pharmacia
  Upjohn, 2005)
• Single dose studies with glyburide in normal
  subjects demonstrate significant absorption of
  glyburide within one hour, peak drug levels at
  about four hours, and low but detectable levels
  at twenty-four hours.
• The major metabolite of glyburide is the
  4-trans-hydroxy derivative. A second metabolite,
  the 3-cis-hydroxy derivative, also occurs. These
  metabolites probably contribute no significant
  hypoglycemic action in humans since they are only
  weakly active (1/400th and 1/40th as active,
  respectively, as glyburide) in rabbits.
• Glyburide is excreted as metabolites in the
  bile and urine, approximately 50 by each route.
  This dual excretory pathway is qualitatively
  different from that of other sulfonylureas, which
  are excreted primarily in the urine.

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Glyburide

• Sulfonylurea drugs are extensively bound to
• serum proteins. Displacement from protein
• binding sites by other drugs may lead to
• enhanced hypoglycemic action. In vitro, the
• protein binding exhibited by glyburide is
• predominantly non-ionic, whereas that
• of other sulfonylureas (chlorpropamide,
• tolbutamide, tolazamide) is predominantly
• ionic.
• Acidic drugs such as phenylbutazone,
• warfarin, and salicylates displace the ionic-
• binding sulfonylureas from serum proteins to
• a far greater extent than the non-ionic
• binding glyburide.
• It has not been shown that this difference in
• protein binding will result in fewer drug-
• drug interactions with glyburide.

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Contraindications

• Glyburide is contraindicated in patients with
• 1. Known hypersensitivity or allergy to the
  drug.
• 2. Diabetic ketoacidosis, with or without coma.
  This condition should be treated with insulin.
• 3. Type I diabetes mellitus, as sole therapy.
• The administration of oral hypoglycemic drugs
• has been reported to be associated with increased
  
• cardiovascular mortality as compared to treatment
  with diet
• alone or diet plus insulin (Herfindal Gorley,
  2003).

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Interactions
Glyburide may interact with the following (Deglin
Vallerand, 2005)
Nonsteroidal anti-inflammatory agents Salicylates Sulfonamides and Ciprofloxacin Chloramphenicol, clofibrate, guanethidine Probenecid
Coumarins Monoamine and Oral miconazole Oxidase inhibitors Beta adrenergic blocking agents Thiazides and other diuretics
Corticosteroids Phenothiazines Thyroid products Estrogens, Oral contraceptives, and androgens Alcohol, glucosamine, fenugreek, chromium, coenzyme Q-10
Phenytoin Nictotinic acid Sympathomimetics Calcium channel blocking drugs Isoniazid
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Common Side Effects

• Hypoglycemia
• Gastrointestinal Reactions Cholestatic
• jaundice, hepatitis, liver function
  abnormalities.
• Gastrointestinal disturbances, (eg, nausea,
• epigastric fullness, and heartburn are the most
• common).
• Dermatologic Reactions Allergic skin
• reactions, (eg, pruritus, erythema, urticaria,
• and morbilliform or maculopapular eruptions),
• Porphyria cutanea tarda and photosensitivity
• reactions have been reported with
• sulfonylureas.
• Hematologic Reactions Leukopenia,
• agranulocytosis, thrombocytopenia,
• hemolytic anemia, aplastic anemia, and
• pancytopenia have been reported with

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Common Side Effects

• Metabolic Reactions (Pharmacia Upjohn, 2005)
• Cases of hyponatremia have been reported with
• glyburide and all other sulfonylureas, most often
  in
• patients who are on other medications or have
  medical
• conditions known to cause hyponatremia or
  increase
• release of antidiuretic hormone. The syndrome of
• inappropriate antidiuretic hormone (SIADH)
• secretion has been reported with certain other
• sulfonylureas, and it has been suggested that
  these
• sulfonylureas may augment the peripheral
• (antidiuretic) action of ADH and/or increase
  release
• of ADH.
• Other Reactions (Pharmacia Upjohn, 2005)
• Changes in accommodation and/or blurred vision
• have been reported with glyburide. These are
  thought
• to be related to fluctuation in glucose levels.
  In
• addition to dermatologic reactions, allergic
  reactions
• such as angioedema, arthralgia, myalgia and
  vasculitis

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Common dosages frequency

• There is no fixed dosage regimen for the
• management of diabetes mellitus with glyburide or
  
• any other hypoglycemic agent.
• The usual starting dose of glyburide is 2.5 to 5
• mg daily, administered with breakfast or the
  first
• main meal.
• Those patients who may be more sensitive to
• hypoglycemic drugs should be started at 1.25 mg
• daily. Failure to follow an appropriate dosage
• regimen may precipitate hypoglycemia.
• Transfer of patients from other oral antidiabetic
  
• regimens to glyburide should be done
  conservatively
• and the initial daily dose should be 2.5 to 5 mg
• (Pharmacia Upjohn, 2005).

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Common dosages frequency

• Maximum Dose
• Daily doses of more than 20 mg are not
• recommended.
• Dosage Interval
• Once-a-day therapy is usually
• satisfactory.
• Some patients, particularly those
• receiving more than 10 mg daily, may
• have a more satisfactory response with
• twice-a-day dosage.
• HOW SUPPLIED
• 1.25 mg Tablets
• 2.5 mg Tablets
• 5 mg Tablets

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Specifics of taking/administration of medication

• In diabetic subjects, there is no fixed dosage
  regimen for management of blood
• glucose levels. Individual determination of the
  minimum dose that will lower the
• blood glucose adequately should be made. If the
  maximal recommended dose
• fails to lower blood glucose adequately in
  patients on initial trial, glyburide should
• be discontinued. During the course of therapy a
  loss of effectiveness may
• occur. It is advisable to ascertain the
  contribution of the drug in the control of
• blood glucose by discontinuing the medication
  semi-annually or at least annually
• with careful monitoring of the patient (Pharmacia
  Upjohn, 2005).
• Glyburide is usually administered with breakfast
  or the first main meal. Do not
• administer after the last meal of the day.
• Patients who do not adhere to their prescribed
  dietary and drug regimen are
• more prone to exhibit an unsatisfactory response
  to therapy.

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Monitoring

• In addition to the usual monitoring of urinary
  glucose, the patients blood glucose must also be
  monitored periodically to determine the minimum
  effective dose for the patient to detect primary
  failure, ie, inadequate lowering of blood glucose
  at the maximum recommended dose of medication
  and to detect secondary failure, ie, loss of
  adequate blood glucose lowering response after an
  initial period of effectiveness.
• Glycosylated hemoglobin levels may be of value in
  monitoring the patients response to therapy.
• The CBC should also be monitored periodically
  throughout therapy.

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Prescribing Implications

• Glyburide is not recommended for use in pregnancy
  or for use in pediatric patients.
• In elderly patients, debilitated or malnourished
  patients, and patients with impaired renal or
  hepatic function, the initial and maintenance
  dosing should be conservative to avoid
  hypoglycemic reactions.
• Adjustment of glyburide dosage should be
  considered whenever factors predisposing the
  patient to the development of hypo- or
  hyperglycemia, such as weight, life-style
  changes, stress, or infection are present.
• Half-life10 hr.

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Glyburide

• Dietary/drug restrictions (Deglin Vallerand,
  2005)
• Restrict all drugs previously mentioned that are
  known to interact with glyburide.
• Ingestion of alcohol may result in a
  disulfiram-like reaction.
• Glucosamine may worsen blood glucose control.
• Fenugreek, chromium, and coenzyme Q-10 may
  produce additive hypoglycemic effects.
• Suggest a daily intake of no more than 10-20
  protein, 10-20 from fat (less than 10
  saturated), and 60-70 from carbohydrates.

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Glyburide

• Storage
• Store at controlled room temperature 20 degrees
  to 25 degrees C
• (68 degrees to 77 degrees F). Dispense in well
  closed containers
• with safety closures. Keep container tightly
  closed.

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Glyburide

• Other items specific to this medication
• This drug may cause an increase in AST, LDH, BUN,
  and serum creatinine levels.
• Overdose of sulfonylureas can produce
  hypoglycemia. Mild hypoglycemic symptoms,
• without loss of consciousness or neurological
  findings, should be treated aggressively with
• oral glucose and adjustments in drug dosage
  and/or meal patterns. Close monitoring
• should continue until the nurse practitioner is
  assured that the patient is out of danger.
• Severe hypoglycemic reactions with coma, seizure,
  or other neurological impairment occur
• infrequently, but constitute medical emergencies
  requiring immediate hospitalization. If
• hypoglycemic coma is diagnosed or suspected, the
  patient should be given a rapid
• intravenous injection of concentrated (50)
  glucose solution. This should be followed by a
• continuous infusion of a more dilute (10)
  glucose solution at a rate which will maintain
• the blood glucose at a level above 100 mg/dL.
  Patients should be closely monitored for a
• minimum of 24 to 48 hours, since hypoglycemia may
  recur after apparent clinical recovery
• (Pharmacia Upjohn, 2005).

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GlyburideClinical Research

• Describe and discuss the type of clinical
  research conducted using this drug (Pharmacia
  Upjohn, 2005)
• In a single dose interaction study with
  metformin, NIDDM subjects had decreases in
  glyburide AUC and Cmax. Results also demonstrated
  that coadministration of glyburide and metformin
  did not result in any changes in either metformin
  pharmacokinetics or pharmacodynamics.
• An animal study was undertaken utilizing rats.
  These rats were given doses of up to 300
  mg/kg/day of glyburide for 18 months. Results
  showed that glyburide was nonmutagenic when
  studied in the Salmonella microsome test (Ames
  test) and in the DNA damage/alkaline elution
  assay. Researchers concluded that there were no
  drug related carcinogenic effects in any of the
  criteria evaluated in this oncogenicity study.

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GlyburideClinical Research

• Reproduction studies have been performed in
  rabbits and rats at doses up to 500 times the
  human dose and have revealed no evidence of
  impaired fertility or harm to the fetus due to
  glyburide. There are, however, no adequate and
  well controlled studies in pregnant women.
  Because animal reproduction studies are not
  always predictive of human response, glyburide
  should be used during pregnancy only if clearly
  needed.
• The University Group Diabetes Program (UGDP)
  conducted a randomized, long-term prospective
  study. The study was designed to evaluate the
  effectiveness of glucose lowering drugs in
  preventing or delaying vascular complications in
  patients with non-insulin-dependent diabetes.
  UGDP reported that patients treated for 5 to 8
  years with diet plus a fixed dose of tolbutamide
  (1.5 grams per day) had a rate of cardiovascular
  mortality approximately 2 ½ times that of
  patients treated with diet alone. It is important
  to note that only one drug in the sulfonylurea
  class (tolbutamide) was included in this study.
  However, it is prudent from a safety standpoint
  to consider that this warning may also apply to
  other oral hypoglycemic drugs in this class (such
  as glyburide), in view of their close
  similarities in mode of action and chemical
  structure.

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GlyburideAdditional Research

• A double-blind, randomized crossover study was
  conducted using 16 healthy volunteers. The
  objective of this study was to investigate the
  impact of glyburide on glucose counterregulatory
  hormones during stepwise hypoglycemic clamp
  studies. Researchers concluded that glyburide
  induces multiple defects in glucose
  counterregulatory hormonal responses, notably
  decreases in both glucagon and GH release (Van
  Haeften, 2002).
• Langer, et. al. (2000) conducted a randomized,
  non-blinded, active-controlled study involving
  404 gestational diabetic women with single fetus
  pregnancies. These women were randomly assigned
  to receive either glyburide or human insulin
  between 11 and 33 weeks of gestation. Achievement
  of desired glucose control was the primary
  endpoint. Maternal and neonatal complications
  were secondary endpoints. From their findings
  researchers concluded that glyburide is a safe
  and effective alternative to insulin in women
  with gestational diabetes.
• A randomized, double-blind, placebo-controlled
  multicenter study was conducted in 152 patients
  who received either nateglinide (120 mg before
  three meals daily, n 51), glyburide (5 mg q.d.
  titrated to 10 mg q.d. after 2 weeks, n 50), or
  placebo (n 51) for 8 weeks. The researchers
  concluded that nateglinide selectively enhanced
  early insulin release and provided better
  mealtime glucose control with less total insulin
  exposure than glyburide (Hollander, et. al.,
  2001).

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Objective data about the patient that the
prescriber needs

• Confirmation that the patient is diabetic (i.e.
  blood glucose levels).
• Knowledge concerning whether the patient has (or
  has ever had) kidney or liver disease.
• Assessment data that excludes adrenal or
  pituitary insufficiency.
• For females, confirmation that patient is not
  pregnant, planning to become pregnant, or
  breastfeeding.

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Patient Teaching

• Educate the patient on glyburide, potential side
  effects and drug interactions.
• Educate on the pathophysiology of Type II
  diabetes.
• Educate on the importance of monitoring blood
  sugar levels.
• If the patient is having surgery, including
  dental surgery, instruct him/her to tell the
  doctor or dentist that they are taking glyburide.
  
• Tell the patient that this drug may make them
  drowsy. Advise him/her to not drive a car or
  operate machinery until they know how the drug
  affects them.
• Inform the patient that alcohol can add to the
  drowsiness caused by this drug.

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Patient Teaching Points

• Cigarette smoking may decrease the effectiveness
  of glyburide.
• Glyburide may make skin sensitive to sunlight.
  Plan to avoid unnecessary or prolonged exposure
  to sunlight and to wear protective clothing,
  sunglasses, and sunscreen.
• Diet should be emphasized as the primary form of
  treatment. Caloric restriction and weight loss
  are essential in the obese diabetic patient.
• The importance of regular physical activity
  should be emphasized.
• Emphasize the importance of yearly podiatric and
  opthalmologic exams.
• Educate on the need for regularly scheduled lab
  studies and the importance of keeping all
  regularly scheduled follow-up appointments
  (American Society of Health-System Pharmacists,
  2004).

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Monitoring that should be implemented with this
drug

• Patients need to be monitored closely for adverse
  reactions.
• Periodic assessment of cardiovascular,
  ophthalmic, hematologic, renal and hepatic status
  is advisable.
• Routine laboratory tests that should be performed
  include
• CBC
• Urinary glucose
• Blood glucose
• Glycosylated hemoglobin levels
• The effectiveness of any hypoglycemic drug
  including
• glyburide, in lowering blood glucose to a desired
  level
• decreases in many patients over a period of time
  which may
• be due to progression of the severity of diabetes
  or to
• diminished responsiveness to the drug. This
  phenomenon is
• known as secondary failure, (to distinguish it
  from primary
• failure in which the drug is ineffective when
  first given).
• Adequate adjustment of dose and adherence to diet
  should
• be assessed before classifying a patient as a
  secondary
• failure (Pharmacia Upjohn, 2005).

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Sample prescription

• Quality Health Care
• Torry Ann Hansen FNP
• 1234 Main Street
• Hermitage, TN 37076
• Patient Name Jane Jacobs
• Date 11-05-05
• Allergies None
• Indication Type II Diabetes
• Rx
• Glyburide 2.5 mg PO qd (every day)
• Quantity 32 (thirty-two)
• Refill 0 (zero) times
• Torry Ann Hansen FNP

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References

• American Society of Health-System Pharmacists.
  (2004). Glyburide. Retrieved October 29, 2005
  from,
• http//www.nlm.nih.gov/medlineplus/druginfo/medmas
  ter/storage-conditions
• Deglin, J.H., Vallerand, A.H. (2005). Daviss
  Drug Guide For Nurses. 9th Ed. Philadelphia. F.A.
  Davis.
• Herfindal, E. T., Gorley, D. R.
  (2003). Textbook of therapeutics Drug and
  disease management (7th
• Ed.). Philadelphia Lippincott Williams
  Wilkins.
• Hollander, P.A, Schwartz, S.L., Gatlin, M.R.,
  Haas, S.J.,, Zheng, H., Foley, J.E., Dunning,
  B.E. (2001).
• Comparison of nateglinide and glyburide in
  previously diet-treated patients with type 2
  diabetes. Diabetes
• Care 24983-988.
• Langer, O.D, Conway D.L., Berkus, M.D., Xenakis,
  E.M.J, Gonzales, O. (2000). A comparison of
  glyburide and
• insulin in women with gestational diabetes. New
  England Journal of Medicine, 3431134-38.
• Pharmacia Upjohn. (2005). Micronase. Retrieved
  October 28, 2005 from,
• http//66.218.69.11/search/cache?pmicronasesmYa
  hoo21Searchtoggle1eiUTF-
• 8uwww.pfizer.com/download/uspi_micronase.pdfwm
  icronasedTXydx2FULdKbicp1.intlus