dm drugs
DESCRIPTION
made simpleTRANSCRIPT
Drugs forDiabetesMellitus
Internal Medicine2010
Islets of Langerhansa cells – glucagon
b cells – insulind cells – Somatostatin
PP cells – pancreatic polypeptide
Drugs used in Diabetes Mellitus
Insulin per orem
Rapid Short-Acting
Intermediate Acting
Slow, long acting
Insulin Secretagogue
Biguanides
Insulin Synthesizer
Glucosidase inhibitor
Insulin• duplicate normal physiologic secretion of
insulin• type 2 DM
• use during times of illness or stress to maintain glycemic control
• patients who are unable to maintain adequate control
• exact time course of each insulin will depend on each particular preparation and site of injection
Effects of Insulin• Liver
• Increases storage of glucose as glycogen in liver• Decrease protein catabolism
• Muscle• Stimulates glycogen synthesis and protein
synthesis• Adipose Tissue
• Facilitates triglyceride storage by: 1. activating plasma lipoprotein lipase2. Increasing glucose transport into cells via GLUT 4
transporters3. Reducing intracellular lipolysis
Normal Plasma Glucose and Insulin Profile
Human Insulin• 1982: "recombinant DNA" into lab-cultivated
bacteria or yeast• very short half life • insulin preparations are formulated to release
insulin slowly into circulation• recombinant human insulin has replaced animal-
derived insulin, such as pork and beef insulin• insulin analogs
• structure differs slightly from human insulin to change onset and peak of action
Insulin and Insulin Analogs
Insulin Onset of action(minutes)
Time to peak concentration(minutes)
Maximum duration of action (hours)
Regular insulin 30-60 90-120 5-12
Insulin lispro(Humalog)
10-15 30-60 3-4
Insulin aspart 10-15 40-50 3-5
Insulin glulisine 10-15 55 3-5
NPH insulin 60-120 240-480 10-20
Insulin glargine 60-120 None 24
Insulin detemir 60-120 None 20
Short and Rapid-Acting Insulin• act as mealtime insulin• administer before meals to mimic
physiologic increases of insulin which occurs after meals
ASPART, GLULISINE, LISPRO• more rapid onset of action and shorter
duration of action than regular insulin• premeal control before the next meal may
be difficult due to short duration of action if used alone
Crystalline zinc (Regular) Insulin• as a mealtime insulin, its use may be limited
because onset is not so rapid to meet the quick, unpredictable increase in postprandial blood glucose
• considered basal insulin• can be given IV or SQ• given 30 to 45 minutes ac
Intermediate and Long-Acting Insulins• given SQ only• intend to mimic normal physiologic basal
insulin secretion• usually given 1-2 times/day
LENTE• Intermediate-Acting Insuline
ULTRALENTE, DETEMIR, GLARGINE• Basal/ Long-Acting Insulins
Combinations• short- and long-acting combinations are
available commercially or may be combined in a single syringe by the patient
• 30% R/ 70% NPH• 50/50• 20/80
Different Insulin Regimen• 2 daily injections• Multiple Daily Insulin Injection• Continuous Subcutaneous Insulin Infusion
Adverse Reactions• Hypersensitivity reactions• Hypoglycemia• Lipoatrophy or lipohyperthrophy
Oral Antidiabetic Agents• sensitizers
• Biguanides: Metformin• TZDs (PPAR): Pioglitazone, Rivoglitazone,
Rosiglitazone• Dual PPAR agonist: Muraglitazar
Oral Antidiabetic Agents• secretagogues
• K+ ATP• sulfonylureas
• 1st gen: Gliclazide• 2nd gen: Glibenclamide, Glipizide• 3rd gen: Glimepiride
• meglitinides: nateglinide, repaglinide• GLP-1 analogs: exenatide• DPP-4 inhibitors: saxagliptin, sitaglipitin
Oral Antidiabetic Agents• α –glucosidase inhibitors
• acarbose, voglibose, miglitol• amylin
• pramlintide• SLGT2 inhibitors
• dapaglifozine• others
• benfluorex, tolrestat
SulfonylureasMechanism of Action• Stimulate insulin release from pancreatic β cells• Decrease hepatic clearance of insulin• Primarily act by binding to the SUR subunit of the
ATP-sensitive potassium (KATP) channel and inducing channel closure
SulfonylureasAbsorption, Fate, and Excretion• absorbed from git• decreased absorption with food and hyperglycemia• 90 to 99% protein bound in plasma• metabolize in liver• metabolites excreted in kidney• 2nd gen half life
• short (3 to 5h)• long duration of action (12 to 24h)
Sulfonylureas1st GENERATION• Chlorpropamide/ Tolazamide/ Tolbutamide: once
daily dosing, administer with breakfast
2nd GENERATION• Glibenclamide/ Gliclazide/ Glimepiride: once daily,
administer with breakfast• Glipizide: 15-30 min before breakfast
Sulfonylureas• Adverse Reactions: hypoglycemia, allergic
reactions. GI upset• use with caution in patients with hepatic or renal
failure• should not be used in DKA, major surgery, severe
infections. stress or trauma, sulfa allergy• disulfiram reaction may occur with chlorpropamide
and alcohol
Generic Name
Daily Dose
Duration of Action
Clearance
Glimepiride
1 – 8 mg 24H H, R
Glipizide 2.5 – 40 mg
12-18H H
Glipizide (ER)
5 – 10 mg 24H H
Glyburide 1.25 – 20 mg
12-24H H, R
Glyburide (Micronized)
0.75 – 12 mg
12-24H H, R
Repaglinide
0.5 – 16 mg
2-6H H
MeglitinidesREPAGLINIDE• initial dose: 0.5 mg PO prior to meals; max:
16mg/day• MOA: derivative of benzoic acid; stimulate insulin
release by closing ATP-dependent K channels in pancreatic β cells
• absorbed rapidly from GIT; peak blood levels within 1 hour
• Metabolize• 90% in liver• 10% in kidney
MeglitinidesNATEGLINIDE• 120mg PO 1-30min prior to main meals• MOA: from D-phenylalanine; stimulate insulin
release by closing ATP-dependent K channels in pancreatic β cells
• Reduce postprandial hypoglycemia• Metabolize:
• 84% IN LIVER• 16% IN KIDNEY
BiguanidesMETFORMIN• absorbed mainly in small intestine• stable but does not bind with protein• excreted unchanged in urine• half life – 2 hours
MOA:• decrease hepatic glucose production -
gluconeogenesis• increase insulin action in muscle and fat
BiguanidesMETFORMIN
CONTRAINDICATIONS: renal impairment, hepatic disease, past history of lactic acidosis, cardiac failure, chronic hypoxic lung disease
• Withheld for 48 hours after giving contrast media – to insure N kidney
ADVERSE REACTIONS: lactic acidosis, diarrhea, GI discomfort, nausea, metallic taste, anorexia
• uptitrate slowly
Thiazolidinediones (TZDs)• selective agonist for nuclear peroxisome
proliferator-activated receptor-gamma (PPAR)• requires insulin• insulin resistance in peripheral tissue
Thiazolidinediones (TZDs)ROSIGLITAZONE AND PIOGLITAZONE• OD dose• Absorbed within 2 hours• Max effect observed in 6 to 12 weeks• Metabolized in Liver
• Cytochrome P450 enzymes• Monitor liver enzymes regularly
• May be given to patients with renal insufficiency• AE: anemia, weight gain, edema• C/I: Heart Failure
Glucosidase Inhibitor• GI absorption of starch, dextrin, disaccharide by
inhibiting the action of intestinal brush border ( glucosidase)
• slow carbohydrate absorption
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