Lecture 14

Chapter 46
Antidiabetic Drugs
 Antidiabetic Drugs

• Drugs used to control diabetes mellitus - a chronic disease

that affects carbohydrate metabolism
• 2 groups of antidiabetic agents: Insulin & oral
hypoglycemic agents
- Oral hypoglycemic agents = synthetic preparations that
stimulate insulin release or alter metabolic response to
hyperglycemia
- Insulin = a protein secreted from the beta cells of the
pancreas - necessary for carbo metabolism & an important
role in protein & fat metabolism
 Antidiabetic Agents

• Diabetes Mellitus - A chronic disease resulting from

deficient glucose metabolism, caused by insufficient
insulin secretion from the beta cells high blood sugar
(hyperglycemia). 3 P’s
1. Polyuria - inc. urine output
2. Polydipsia - inc. thirst
3. Polyphagia - inc. hunger
• 2 forms of diabetes
1. Insulin-dependent diabetes mellitus (IDDM) or type I -
was refereed to as juvenile-onset w/ no insulin secretion
 Antidiabetic Agents

2. Non-insulin-dependent diabetes mellitus (NIDDM) or

type II - was referred to as maturity-onset or adult-onset
diabetes w/ some insulin secretion
• Unknown how lack of insulin causes diabetes - poss. =
infection, heredity
• Insulin - Released from the beta cells of the islets of
Langerhans in the pancreas in response to an increase in
bld. glucose
- Promotes the uptake of glucose, amino acids, & fatty
acids & converts them to substances stored in body cells
 Antidiabetic Agents

- Glucose is converted to glycogen for future glucose needs

in the liver & muscle = lowers bld. glucose level (range
for bld. glucose is 70 - 110 mg/dl)
* bld. glucose > 180 = sugar in urine = diuretic effects =
polyuria
- Insulin can be animal (pork or beef), or human (using
DNA technology)
- Concentration of insulin is 100 U/ml, & insulin packaged
in a 10 ml vial. For accurate dosing, insulin can be given
in insulin syringes ONLY.
 Antidiabetic Agents

- Before using insulin, need to ensure well mixed - always

roll between hands - Do NOT Shake Vial = bubbles &
inaccurate dose
- insulin CANNOT be administered orally - GI tract
secretions destroy insulin structure
- Given subcutaneous at a 45 to 90 degree angle
- Regular insulin ONLY can be given IV
- Insulin sites need to be rotated to prevent lipodystrophy
(tissue atrophy or hypertrophy) = interferes w/ insulin
absorption
 Antidiabetic Agents
Insulin
• Types of Insulin's - 3 standard types
1. Rapid-acting - Regular insulin - clear sol’n w/o added
substances to prolong insulin action
Onset = 1/2 to 1 h; Peak = 2 to 4 h; Duration = 6 to 8 h
2. Intermediate-acting - NPH, Lente - contain protamine (a
protein that prolongs the action of the insulin)
Onset = 1 to 2 h; Peak = 6 to 12 h; Duration = 18 to 24 h
3. Long-Acting - Ultralente - contain lg. crystals which
dissolve slowly to prolong duration
Onset = 4 to 8 h, Peak = 14 to 20 h; Duration = 24 to 36 h
 Antidiabetic Agents
Insulin
• Lispro Insulin (Humalog) - a new rapid acting insulin
approved in 1996
Action = 5 min.; Duration = 2 to 4 h - can be administered
5 min. before meal time
• Combination Insulin's - commercially premixed
Humulin 70/30, Novolin 70/30, Humulin 50/50
(70/30 = 70% NPH and 30% Reg)
• Reg can be mixed w/ NPH or Lente - Reg goes in first in
the syringe *Clear to Cloudy*
 Antidiabetic Agents
Insulin
• SE & adverse RXNS =
-Hypoglycemic - when more insulin is administered than
needed for glucose metabolism
- S & S = nervous, trembling, uncoordinated, cold &
clammy, incoherent (drunk)
- Rx = giving sugar orally or IV
- Ketoacidosis - An inadequate amt. of insulin = inability
to metabolize sugar = fat catabolism = use of fatty acids
(ketones) for energy
- S & S = Extreme thirst, polyria, fruity breath odor
- Rx = Insulin
 Antidiabetic Agents
Oral Agents
• Used by persons w/ NIDDM - should NOT be used by
persons w/ IDDM
• NIDDM has some degree of insulin secretion by pancreas
• Several classes of oral hypoglycemic agents
• Sulfonylureas - First & Second generation
- Chemically related to sulfonamides, but lack antibacterial
activity - stimulate the beta cells to secrete more insulin
- 1st generation divided into short, intermediate & long
acting antidiabetics
 Antidiabetic Agents
Oral Agents
- tolbutamide (Orinase) - short; Tolazamide (Tolinase) -
intermediate; Chlorpropamide (Diabinese) - long
- Action - Stimulate beta cells to secrete insulin
- Use NIDDM
- SE - similar to insulin - hypoglycemic rxn w/o adequate
food intake
- DI - ASA, anticoagulant, anticonvulsants, sulfonamides,
& some NSAIDs can inc. action of sulfonylureas an
insulin rxn
 Antidiabetic Agents
Oral Agents
• Nonsulfonylurease: Newer drugs
• Biguanides: Metformin (Glucophage)
- Decreases hepatic production of glucose from stored
glycogen = diminishes the inc. in serum glucose after a
meal
- Dec. the absorption of glucose from the small intestine
- Evidence it inc. insulin receptor sensitivity
- Does not produce hypo or hyperglycemia
- SE - N &V, anorexia, abd cramping, gas
- Can be combined w/ a sulfonylurea & insulin
 Antidiabetic Agents
Oral Agents
• Alpha-Glucosidase Inhibitor: Acarbose (Precose)
- Action - inhibits the digestive enzyme in sm. intestine
responsible for release of glucose from the complex
carbohydrates (CHO) in the diet
- By inhibiting alpha glucosidase (enzyme) - the CHO
cannot be absorbed & they pass into the lg. intestine
- does not cause a hypoglycemic rxn
- Use - for clients who do not achieve results on diet alone
 Antidiabetic Agents
Oral Agents
• Thiazolidinediones: Troglitazone (Rezulin) - unrelated to
other antidiabetic drugs
- Action - Decrease insulin resistance, helps muscle cells
respond to insulin & use glucose more effectively
- May be used w/ sulfonylurea, metformin, or insulin
- May cause serious hepatic toxicity - Not used in England
• Rapaglinide (Prandin) - classification unknown - Newest
- For use alone or w/ metfromin - short acting
- Action - similar to sulfonylureas, but does not cause
hypoglycemia
 Antidiabetic Agents
Oral Agents
• Hyperglycemic Drugs - Glucagon
- Action - A hyperglycemic hormone secreted by the alpha
cells of the islets of Langerhans - Inc. bld sugar by
stimulating glycogenolysis (breakdown of glycogen to
glucose) in the liver - protects body cells
- Use - Insulin-induced hypoglycemia when other methods
not available or not working
- Clients prone to hypoglycemia should keep in home &
family members taught how to use
- Begins to work in 5 to 20 min.
 Antidiabetic Agents
Oral Agents
• Diazoxide (Proglycem) - chemically related to thiazide
diuretics
- Action - Inc. bld sugar by inhibiting insulin release from
the beta cells & stimulating release of epi (adrenalin from
the adrenal medulla
- Use - Chronic hypoglycemia caused by hyperinsulinism
d/t islet cell Ca or hyperplasia
- Not used to Rx hypoglycemic rxns
- Parenteral form (Hyperstat) used for malignant HTN
- Oral diazoxide usually does not cause hypotension