Antidiabetic Medications Pharm 585 February 15, 2011 Hy N Dang.
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Transcript of Antidiabetic Medications Pharm 585 February 15, 2011 Hy N Dang.
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Antidiabetic Medications
Pharm 585
February 15, 2011
Hy N Dang
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Goal
To understand the use and side effects of anti-diabetic medications and be able to educate patients.
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Nine to KnowThe minimum that every pharmacist must know about drugs!
Brand & Generic Name Mechanism of action Therapeutic effect Relevant pharmacokinetics and pharmacodynamics Dosing by route Adverse reactions and contraindications Monitoring parameters Drug-drug and drug food interactions Comparisons between agents w/in the same class of
drugs
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Contraindications/Cautions/Adverse Reactions
Adverse Reactions– Unwanted side effects: need to warn patient
Cautions– Warnings for clinicians to be aware when using
medication.
Contraindications– Conditions which will render the medication
absolutely unusable in that patient population
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High blood glucose
1. Defective beta cell function• Diminished phase 1 insulin release• Delayed phase 2 insulin release2. Overproduction of glucagon
Impaired GI motility
1. Tissues less sensitive to insulin2. Liver produces excess glucose
Type 2 Diabetes
Image Obtained From: Diabetes 101: Overview of Drug Therapy by Jennifer Danielson, RPh, CDE Type 2 Video from diabetes.com
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Biguanides
Metformin Glucophage 500, 850, 1000 mg tablets
(Glucophage XR) 500, 750 mg XR tablets
Indication Type II Diabetes Mellitus, Antipsychotic-induced weight gain
MOA Decrease hepatic glucose production, decrease intestinal absorption of glucose and increase insulin sensitivity therefore increasing peripheral glucose uptake
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Where does it work?
Image Obtained From: Diabetes 101: Overview of Drug Therapy by Jennifer Danielson, RPh, CDE
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Biguanides (cont)
Patient InfoN/V/DUpset stomach/dyspepsia – take with foodMetallic tasteMinimal Weight LossAlcohol may increase likelihood of lactic acidosisDoes not cause hypoglycemia
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Biguanides (cont)
Special Population Considerations:Geriatric: limited data suggests starting doses should be 33% lower for geriatric patients than that of an adult dose. Titration should also to a lower limit.
Cautions/Severe Adverse ReactionsBlack Box Lactic Acidosis: D/C immediately and notify practitioner if: myalgia, malaise, hyperventilation, unusual somnolence. Alcohol potentiates this reaction. Advise patients not to consume excessive amounts of alcohol.
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Biguanides (cont)
CONTRAINDICATIONSRenal disease or renal dysfunction (Scr > 1.5 mg/dL in males, >1.4 mg/dL in females)Abnormal Scr from any cause including: shock, acute MI, or septicemiaMetabolic acidosis (including diabetic ketoacidosis (DKA))Heart failure requiring pharmacologic therapy; active liver failure
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Dipeptidyl Peptidase-4 (DPP-4) Inhibitors
Sitagliptin (Januvia) 25, 50, 100 mg tablets
Sitagliptin/metformin (Janumet) 50/500, 50/1000 mg tablets
Saxagliptin (Onglyza) 2.5, 5 mg tablets
Saxagliptin/metformin (Kombiglyze XR)
2.5/1000, 5/500, 5/1000 mg
tablets
IndicationsDiabetes Mellitus Type II MOA Inhibits the breakdown of GLP-1 by DPP-4 therefore increasing GLP-1 levels resulting in increased glucose-dependent insulin release and decreased level of circulating glucagon and hepatic glucose production
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Where does it work?
Image Obtained From: Diabetes 101: Overview of Drug Therapy by Jennifer Danielson, RPh, CDE
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DPP-4 (cont)
Patient InfoN/VHypoglycemiaWeight neutralNasopharyngitis/URIHeadacheOnset: Reduction in postprandial serum glucose: 60 minutes
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DPP-4 (cont)
Special Population Considerations:Renal Impairment: avoid combo drugs w/ metformin
– For sitagliptin: CrCl 30-50 mL/min : 50 mg daily CrCl < 30 mL/min: 25 mg daily End Stage Renal Disease Requiring dialysis: 25 mg
dailyGeriatric: caution due to age related renal function decreases
Cautions/Severe Adverse ReactionsAcute pancreatitisRash (Stevens-Johnson syndrome)
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Sulfonylureas
Glimepiride (Amaryl) 1, 2, 4 mg tablets
Glipizide (Glucotrol, Glucotrol XL)
(2.5), 5, 10 mg (XL)
tablets
Glyburide (DiaBeta) 1.25, 2.5, 5 mg tablets
Indications Adjuncts to diet and exercise to lower blood glucose in patients w/ type II diabetes mellitus MOA
Stimulating insulin release from beta-cells of pancreatic islets
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Where does it work?
Image Obtained From: Diabetes 101: Overview of Drug Therapy by Jennifer Danielson, RPh, CDE
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Sulfonylureas (cont)
Patient InfoHypoglycemiaGI upset/abdominal painDizzinessWeight gainHeartburn/epigastric fullnessPossible disulfiram-like reaction with alcohol (mainly w/ glyburide)Onset: glucose lowering effect: 30 minutes with peak at 1.5-3 hours lasting 24 hours
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Sulfonylureas (cont)
Special Population Considerations:Pediatric: safety and efficacy not established for pts under age 16Hepatic/Renal Dysfunction: conservative dosing and titration recommended.
Caution/Severe Adverse ReactionsSyndrome of Inappropriate Anti-diuretic Hormone (SIADH)
CONTRAINDICATIONSDiabetes complicated by ketoacidosisType I DMDiabetes w/ pregnancy. Pregnancy Cat: C (except glyburide: B)
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Thiazolidinediones (TZD)
Pioglitazone (Actos) 15, 30, 45 mg tablets
Rosiglitazone (Avandia) 2, 4, 8 mg tablets
IndicationsAs adjunct to diet and exercise for type II diabetes MOAIncrease insulin sensitivity by affecting PPAR-γ (peroxisome proliferators-activated receptor) at adipose tissue, skeletal muscle and in the liver.
Special Alert February 2011: Addition of Risk Evaluation and Mitigation Strategy to rosiglitazone. The medication is restricted to those patients already on rosiglitazone for fails pioglitazone or cannot be managed by other oral antidiabetic medications.
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Where does it work?
Image Obtained From: Diabetes 101: Overview of Drug Therapy by Jennifer Danielson, RPh, CDE
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TZD (cont)
Patient InfoWeight gainEdemaHypoglycemia esp. when used with other antidiabetic medications and insulin (not w/ metformin)May cause or exacerbate heart failure with risk of fluid retentionURI, sinusitis, pharyngitisMyalgiaHeadache
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TZD (cont)
Cautions/Severe Adverse ReactionsBlack Box: Heart Failure (for all thiazolidinediones, mainly due to rosiglitazone)Hepatic failureAnemiaBone lossOvulation in premenopausal womenPregancy Cat: C
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TZD (cont)
Special Populations Considerations:Congestive Heart Failure: should be initiated at lowest approved dose with longer intervals between dose increases for NYHA class II. Use is not recommended in patients with NYHA Class III or IV CHF
CONTRAINDICATIONSNYHA Class III-IV heart failureActive liver disease (ALT > 2.5 upper limit of normal)
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Insulin
Indications
Type I diabetes mellitus, type II diabetes mellitus, hyperkalemia, DKA/diabetic coma
MOA
Stimulating peripheral glucose uptake and inhibiting hepatic glucose production
Patient Info Hypoglycemia (BG < 70 mg/dL) esp with higher doses
– Anxiety, blurred vision, palpitations, shakiness, slurred speech, sweating
Weight gain
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Where does it work?
Image Obtained From: Diabetes 101: Overview of Drug Therapy by Jennifer Danielson, RPh, CDE Insulin: the Movie from diabetes.org
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Insulin (cont)
Administration:Subcutaneous injectionRotate siteCheck blood sugars regularly
Storage:Refrigerate until useOnce vial is punctured, it is good for 28 days and can be left at room temperature (except for glargine which is 90 days)
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Insulin (cont)
Dosing:Starting daily dose: 0.5-1 unit/kg/day in divided dosesAdjust according to fasting (premeal) blood glucose of 80-130 mg/dL and peak postprandial blood glucose < 180 mg/dLProvide 50% as long acting insulin and 50% as prandial insulin1 unit of can account for 30 grams of carbohydrate (14-50)1 unit can lower 50 mg/dL blood glucose (10-100)
Special Population Consderations:Renal dysfunction
– CrCl 10-50 mL/min: 75% of normal dose– CrCl < 10 ml/min: 25-50% of normal dose; monitor closely
Exercise??? ---- Acute Stress???
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Insulin Action
Rapid/immediate
Fast
Intermediate
Slow
0 2 4 6 8 10 12 14 16 18 20 22 24
Blo
od c
once
ntra
tion
Time (hr)
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Insulin Dosing
Normal insulin secretion
Long-acting
Long-acting &Short-acting
70/30 pre-mixed
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Insulin Administration
Pharmacology for Technicians by Ballington, Lauglin. EMC Paradigm 2006, Fig. 14.9
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Insulin (cont)
Cautions/Severe Adverse ReactionsSevere hypoglycemia (seizure/coma) (BG < 40 mg/dL)EdemaLipoatrophy or lipohypertropy at injection site
CONTRAINDICATIONSSevere hypoglycemiaAllergy or sensitivity to any ingredient of the product
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Insulin Comparison Chart
courses.washington.edu/pharm504/Insulin%20Chart.pdf
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Adjunctive Therapy in Diabetes Mellitus Type II
Hypoglycemia– Complication of treatment!– Make sure patients inform the people around them of
these symptoms and what to do!– Symptoms: Anxiety, blurred vision, palpitations,
shakiness, slurred speech, sweating– Treatment: glucose/simple sugars: 3-4 glucose tablets,
½ can of soda (NOT diet!)– Treatment: glucagon injection
Dose: 1 mg IM, IV, SQ; may repeat in 20 minutes if needed
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Adjunctive Therapy (cont)
Energy balance, diet, exercise– Low-carb, low-fat, calorie-restricted diet is recommended
Cardiovascular disease/Hypertension– Systolic blood pressure goal < 130 mm Hg– Angiotensin Converting Enzyme II Inhibitor (ACE-I) is first
line Renal protective Angiotensin Receptor Blockers (ARB) can be used if
patient fails or is intolerant to ACE-I
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Adjunctive Therapies (cont)
Dislipidemia– Patients with type II diabetes have an LDL goal < 100
mg/dL– Weight loss– First line therapy: statins (i.e. atorvastatin, simvastatin,
rosuvastatin etc.)– Fiber, omega-3 fatty acids (fish oils) can be used as adjunct
therapy
Antiplatelet agents– Consider starting daily low dose aspirin (81 mg) to prevent
ischemic events
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Adjunctive Therapies (cont)
Smoking cessation Regular Screening for Cardiovascular Diseases and Coronary
Artery Disease Depression/Stress/Anxiety/Other psychosocial conditions need
to be screen for regularly Diabetic neuropathies especially in extremities need to be
screened for on a regular basis– Fastidious foot care– Regular foot exams (annually)
Eye exams Monitor kidney function