antidiabetic medications gizi

8/12/2019 Antidiabetic Medications Gizi

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Normal Glucose


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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 insulin

2. 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
http://professional.diabetes.org/UserFiles/What%20happens%20in%20Type%202%20Diabetes.wmvhttp://professional.diabetes.org/UserFiles/What%20happens%20in%20Type%202%20Diabetes.wmv


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ORAL ANTI DIABETICS

Metformin Glucophage 500, 850, 1000 mg tablets

(Glucophage XR) 500, 750 mg XR tablets

Pharmacokinetics

Given orally, Not bind to plasma proteins, Not metabolized, Excreted

unchanged in urine, t 1/2 2 hr

Indication

Type II Diabetes Mellitus,

MOA

Decreasehepatic glucose production, decrease intestinal absorptionof

glucose and increase insulin sensitivity therefore increasing peripheral

glucose uptake

Biguanides


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Biguanides (cont)

SIDE EFFECT

N/V/D Upset stomach/dyspepsiatake with food

Metallic taste

Minimal Weight Loss Alcohol may increase likelihood of lactic

acidosis

Does not cause hypoglycemia


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Biguanides (cont)

Special Population Considerations:

Geriatric:limited data suggests starting doses should be33% lower for geriatric patients than that of an adult dose.

Titration should also to a lower limit.

Cautions/Severe Adverse Reactions

Black Box Lactic Acidosis: D/C immediately and notifypractitioner 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)

CONTRAINDICATIONS

Renal disease or renal dysfunction (Scr > 1.5 mg/dL

in males, >1.4 mg/dL in females)

Abnormal Scr (serum creatinin) from any cause

including: shock, acute MI, or septicemia

Metabolic acidosis (including diabetic ketoacidosis

(DKA)

Heart failure requiring pharmacologic therapy;

active liver failure


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Sulfonylureas

Glimepiride (Amaryl) 1, 2, 4 mg tablets

Glipizide (Glucotrol,

Glucotrol XL)

(2.5), 5, 10 mg

(XL)

tablets

Glyburide

(Glibeclamide)

(DiaBeta) 1.25, 2.5, 5 mg tablets

Pharmacokinetics

Well absorp from GIT, metab.by hepar,, excr urine

glucose lowering effect: 30 minutes with peak at 1.5-3 hours lasting 24 hours,

duration 10-24h

MOA

Stimulating insulin release from beta-cells of pancreatic islets

Indications

Adjuncts to diet and exercise to lower blood glucose in patients w/ type IIdiabetes mellitus


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Sulfonylureas (Oral Hypoglycemic drugs)

Tolbutamide Acetohexamide

Tolazamide

Chlorpropamide GlipizideGlyburide

(Glibenclamid

Glimepiride

Short

acting

First generation

Intermediate

acting

Long

acting

Long

acting

Short

acting

Second generation


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Sulfonylureas (cont)

Side Effects Hypoglycemia

GI upset/abdominal pain

Dizziness

Weight gain

Heartburn/epigastric fullness

Possible disulfiram-like reaction with alcohol (mainly w/glyburide)


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Sulfonylureas (cont)

Special Population Considerations:

Pediatric:safety and efficacy not established for px under age 16

Hepatic/Renal Dysfunction:conservative dosing and titrationrecommended.

Caution/Severe Adverse Reactions

Syndrome of Inappropriate Anti-diuretic Hormone (SIADH)

CONTRAINDICATIONS

Diabetes complicated by ketoacidosis

Type I DM

Diabetes w/ pregnancy. Pregnancy Cat: C (except glyburide: B)


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Meglitinides

e.g. Repaglinide, NateglinidePHARMACOKINETICS

Taken orally, Rapidly absorbed ( Peak approx. 1hr )

Metabolized by liver, t1/2= 1 hr, Duration of action 4-5 hr

MECHANISM of ACTION

as do Sulfonylureas, to cause insulin release from -cells.

CLINICAL USE

Approved as monotherapy and in combination with metformin in type 2 DM

SIDE EFFECTS:

Hypoglycemia

Wt gain ( less than SUs )

Caution in px with renal & hepatic impairement.


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-Glucosidase Inhibitors

e.g. Acarbose

Pharmacokinetics

Given orallyNot absorbed from intestine except small amount

t1/2 3 - 7 hr

Excreted with stool

Mechanism of ActionInhibits intestinal alpha-glucosidases and

delays carbohydrate absorption,

reducing postprandial increase in blood glucose


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Side Effects

Flatulence, Loose stool or diarrhea, Abdominal painAlone does not cause hypoglycemia

-Glucosidase Inhibitors(Contd.)

Indications

Patients with Type II inadequately controlled bydiet with or without other agents( SU, Metformin)

Can be combined with insulin

may be helpful in obese Type II patients

(similar to metformin)


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Thiazolidinediones (TZD)

Pioglitazone (Actos) 15, 30, 45 mg tablets

Rosiglitazone (Avandia) 2, 4, 8 mg tablets

Indications

As adjunct to diet and exercise for type II diabetes

MOA

Increase insulin sensitivity by affecting PPAR- (peroxisome

proliferators-activated receptor) at adipose tissue, skeletal muscle and inthe liver.

Glucose uptake , gluconeogenesis


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TZD (cont)

Side Effects

Weight gain

Edema

Hypoglycemia esp. when used with other antidiabetic

medications and insulin (not w/ metformin)

May cause or exacerbate heart failure with risk of fluid

retention URI, sinusitis, pharyngitis

Myalgia

Headache


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TZD (cont)


Black Box: Heart Failure (for all thiazolidinediones,

mainly due to rosiglitazone)

Hepatic failure

Anemia

Bone loss Ovulation in premenopausal women

Pregancy 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 class II. Use is not recommended

in patients with Class III or IV CHF

CONTRAINDICATIONS

Class III-IV heart failure

Active liver disease (ALT > 2.5 upper limit of

normal)

I li


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Insulin

Indications

Type I diabetes mellitus, type II diabetes mellitus

(+pregnant), hyperkalemia, DKA/diabetic coma

MOA

Stimulating peripheral glucose uptake and

inhibitinghepatic glucose production

Side Effects

Hypoglycemia (BG < 70 mg/dL) esp with higherdoses

Anxiety, blurred vision, palpitations, shakiness,

slurred speech, sweating

Weight gain


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Insulin (cont)

Administration:

Subcutaneous injection

Rotate site

Check blood sugars regularly

Storage:

Refrigerate until use

Once 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 Action

Rapid/immediate

Fast

Intermediate

Slow

0 2 4 6 8 10 12 14 16 18 20 22 24

Bloodco

ncentration

Time (hr)


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Insulin (cont)


Severe hypoglycemia (seizure/coma) (BG

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