Page 782 - Basic _ Clinical Pharmacology ( PDFDrive )

768 SECTION VII Endocrine Drugs

correction of these variables must be monitored closely. Low-dose state subsequent to the onset of puberty and glycemic control. In
insulin therapy may be required. type 1 diabetes, end-stage chronic kidney disease develops in up
to 40% of patients, compared with less than 20% of patients with
Chronic Complications of Diabetes type 2 diabetes. Proliferative retinopathy ultimately develops in
both types of diabetes but has a slightly higher prevalence in type
Late clinical manifestations of diabetes mellitus include a number of 1 patients (25% after 15 years’ duration). In patients with type 1
pathologic changes that involve small and large blood vessels, cranial diabetes, complications from end-stage chronic kidney disease are
and peripheral nerves, the skin, and the lens of the eye. These lesions a major cause of death, whereas patients with type 2 diabetes are
lead to hypertension, end-stage chronic kidney disease, blindness, more likely to have macrovascular diseases leading to myocardial
autonomic and peripheral neuropathy, amputations of the lower infarction and stroke as the main causes of death. Cigarette use adds
extremities, myocardial infarction, and cerebrovascular accidents. significantly to the risk of both microvascular and macrovascular
These late manifestations correlate with the duration of the diabetic complications in diabetic patients.

SUMMARY Drugs Used for Diabetes

Mechanism of Clinical Pharmacokinetics,
Subclass, Drug Action Effects Applications Toxicities, Interactions

INSULINS
• Rapid-acting: Lispro, aspart, Activate insulin receptor Reduce circulating glucose Type 1 and type 2 Parenteral (SC or IV) • duration
glulisine, inhaled regular diabetes varies (see text) • Toxicity:
• Short-acting: Regular Hypoglycemia, weight gain,
• Intermediate-acting: NPH lipodystrophy (rare)
• Long-acting: Detemir, glargine,
degludec
SULFONYLUREAS
• Glipizide Insulin secretagogues: Reduce circulating glucose in Type 2 diabetes Orally active • duration 10–24 h
+
• Glyburide Close K channels in patients with functioning • Toxicity: Hypoglycemia, weight
• Glimepiride beta cells • increase beta cells gain
• Gliclazide 1 insulin release
• Tolazamide, tolbutamide, chlorpropamide, acetohexamide: Older sulfonylureas, lower potency, greater toxicity; rarely used
MEGLITINIDE ANALOGS; d-PHENYLANALINE DERIVATIVE
• Repaglinide, nateglinide Insulin secretagogue: In patients with functioning Type 2 diabetes Oral • very fast onset of action
• Mitiglinide 1 Similar to sulfonylureas beta cells, reduce circulating • duration 5–8 h, nateglinide • 4 h
with some overlap in glucose • Toxicity: Hypoglycemia
binding sites
BIGUANIDES
• Metformin Activates AMP kinase Decreases circulating Type 2 diabetes Oral • maximal plasma
• reduces hepatic and glucose concentration in 2–3 h • Toxicity:
renal gluconeogenesis Gastrointestinal symptoms, lactic
acidosis (rare) • cannot use if
impaired renal/hepatic function
• congestive heart failure (CHF),
hypoxic/acidotic states, alcoholism
ALPHA-GLUCOSIDASE INHIBITORS
• Acarbose, miglitol Inhibit intestinal Reduce conversion of starch Type 2 diabetes Oral • rapid onset • Toxicity:
• Voglibose 1 α-glucosidases and disaccharides to Gastrointestinal symptoms • cannot
monosaccharides • reduce use if impaired renal/hepatic
postprandial hyperglycemia function, intestinal disorders
THIAZOLIDINEDIONES
• Pioglitazone, rosiglitazone Regulate gene Reduce insulin resistance Type 2 diabetes Oral • long-acting (>24 h) • Toxicity:
expression by binding Fluid retention, edema, anemia,
to PPAR-γ and PPAR-α weight gain, macular edema, bone
fractures in women • cannot use if
CHF, hepatic disease
(continued)