Nursing Pharmacology Chapter 29: Diabetes
Atherosclerosis: more extensive and occurs earlier (accelerated course)
Lesions initiated by oxidized LDL
Increased platelet adhesiveness
Increase secretion of endothelin-1
Endothelin-1is both a powerful vasoconstrictor and avascular smooth muscle mitogen.
Decreased nitric oxide production
Nitric oxide: is both a vasodilator and anti-mitogenic in vascular smooth muscle.
Diabetes: procoagulant state
Increased levels of tissue factor
Deficiency of tissue factor pathway inhibitor type 1
Factor VIII elevated
Impaired fibrolysis: (probably as a result of increased tPA inhibitor, type 1)
Intermittent claudication, gangrene, impotence (vascular)
Coronary artery disease; stroke:common
Silent myocardial infarction
Diabetic retinopathy: leading cause of blindness in the U.S.
Increased capillary permeability
Retinal capillary occlusion (saccular and fusiform aneurysms)
Vascular lesions associated with:
Proliferation of lining endothelial cells
Pericyte loss around vessels
Proliferative retinopathy: new vessel formation and scarring.
Renal disease: leading cause of death and disability due to diabetes.
50% of end-stage renal disease in United States: diabetic nephropathy
35% of IDDM patients
15 to 60% of NIDDM patients (ethnic background dependent; highest -- Pima Indians;lowest- Europeans)
Two pathologic patterns
Diffuse (more common)
Widening of glomerular basement membrane
Periodic acid-Schiff-positive material: deposited at glomerular tuft periphery
Hyalinization of afferent and efferent arterioles
Deposition of albumin and other proteins in tubules and glomeruli
Major cause of morbidity
Peripheral Polyneuropathy: most common
Bilateral, characterized by:
Pain (deep-seeded, severe)
Mononeuropathy: characterized by:
Paralysis of third, fourth or sixth cranial nerve
Sensory syndrome involves pain distribution of one or more spinal nerves, usually in chest wall or abdomen.
Significant target is the gastrointestinal tract with symptoms symptoms including:
Delayed gastric emptying
Constipation or diarrhea
Cardiopulmonary arrest; sudden death
Bladder dysfunction (may require chronic catheter drainage)
Pain: Although opioids may be used (e.g. tramadol (Ultram) side effects make these agents problematic for long-term therapy.
Other options include:
Gabapentin, prgabalin and carbamazepine (from the anti-seizure medication class)
Amitriptyline, imipramine, desipramine and nortriptyline from the tricycylic antidepressant class.
Secondary to diabetic neuropathy an associated with an abnormal pressure distribution.
Vascular disease (decreased perfusion) augments ulcer development.
Infection is common and may involve multiple bacterial organisms.
Possible initial antibiotic treatment until culture results are available
Ampicillin-sulbactam plus gentamycin or aztreonam
Autonomic Dysfunction: Diabetes Mellitus
Initial finding: often asymptomatic abnormal vagal function manifesting as reduced heart rate variation with deep breathing.
Loss of myelinated and non-myelinated small nerve fibers are noted in splanchnic distribution, carotid sinus, and vagus nerve.
Disturbances and gut motility.
Symptoms of hypoglycemia -- blunted or detectable because damage to sympathetic adrenal gland innervation prevents epinephrine release.
Autonomic dysfunction may lengthen Q-T interval, an effect which may be associated with sudden cardiac death.
Karam, J. H., Pancreatic Hormones and Antidiabetic Drugs, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 684-703
Foster, D. W., Diabetes Mellitus, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 2060-2080