Diabetes and drug therapy

Nursing Homes, Jan-Feb, 1992 by James Cooper

Aside from the drugs used in the direct treatment of diabetes, there are several other pharmacologic considerations in the management of these elderly patients. Drug-disease and drug-drug interactions are of considerable concern.

Renal Complications

In addition to the physiological loss of creatinine clearance that occurs with aging, diabetes can markedly accelerate loss of kidney function. NSAIDs can worsen renal function and cause increased blood pressure, especially in the diabetic, and this is evidenced as water weight gain. Weighing the patient weekly after an NSAD is started for at least 1 to 3 months is important.

Angiotensin converting enzyme inhibitors (ACEIs) such as captopril (Capoten) and enalapril (Vasotec) may be used to prevent urinary protein losses that are associated with diabetes damage to the kidney. ACEIs should however be closely followed with at least monthly serum creatinine measurements, as paradoxical reversible worsening of renal function may occur if the patient already has renal artery stenosis. It is important that routine serum creatinines be done, and that drug dosages be adjusted in response to diminished calculated creatinine clearance and increased serum creatinine.

Since up to half of insulin is metabolized in the kidney, the patient with severe renal impairment may need less insulin. In end-stage renal disease, regular insulin action may be as prolonged in effect as the intermediate-acting insulins.

Cardiovascular Complications

High blood pressure (HBP) is more prevalent in diabetics. Diuretics and beta blockers are often initial drugs used to treat HBP, but unfortunately, both drug classes can worsen diabetic control, produce unfavorable lipid profiles and actually increase the frequency of diabetic complications, such as hypoglycemia and peripheral vascular disease.

For these reasons, the ACEIs and calcium channel blocking drugs are preferred drugs for high blood pressure and other cardiovascular complications in the diabetic.

Gastrointestinal Complications

Diabetic gastroparesis may be evident from persistent nausea, vomiting, heart-burn, persistent fullness and bloating following meals. Delayed gastric emptying may produce a mismatch of digestion with antidiabetic drugs, i.e. the nutrient may not be absorbed in time to be acted on by insulin. Metoclopramide (Reglan) may be helpful in smaller dosages than those used in the younger patient (one-half recommended dosage in CrCl <40ml/min).

However, since this drug is a phenothiazine, any concurrent neuroleptic usage should be carefully evaluated and dosage tapered or discontinued to prevent additive effects, such as sedation and extrapyramidal effects (eg, pseudoparkinsonism).

Diabetics may have chronic diarrhea, which may require anticholinergics such as glycopyrrolate (Robinul) to lessen stool frequency. If they have concurrent hypertension, usage of an antihypertensive with anticholinergic side effects, such as clonidine (Catapres), may be more helpful to control both the diarrhea and hypertension.

Painful Peripheral Neuropathy

Leg and foot pain, usually described as burning, aching and refractory to analgesics, including NSAIDs and narcotics, may be improved by continuous infusion of insulin, as well as some psychotropic drugs and anticonvulsants.

Specifically, tricyclic antidepressants and phenothiazines are used to manage chronic severe pain not adequately relieved by full-dose continuous analegesics. The tricyclics amitriptyline, nortriptyline and imipramine, in gradually increasing doses of 50 to 100mg per day, have been shown to break the chronic pain-depression-pain cycle in as little as 24-48 hours or within several weeks. Fluphenazine in doses up to 3mg/d has also been used with tricyclics for pain relief in diabetic peripheral neuropathy.

In patients unresponsive to psychotropic therapy for painful neuropathy, carbamazepine 100-200mg TID and phenytoin 100mg TID have been used with some success. Topical therapy with capsaicin 0.025% (Zostrix) or 0.075% (Axsain) ointment 3 to 4 times a day with finger cot or Q-tip to affected areas may be used, with the warning that pain may be initially worsened, and it may take several weeks for the anesthetic effect to be maximal.

Less expensive topical therapy may involve a carefully applied salicylate cream or ointment, or simply crushing a 325mg ASA tablet in two tablespoonfuls of Vaseline Intensive Care Lotion and applying to affected area several times a day, being careful to not cause enough keratolytic effect to produce a break in the skin. Americaine ointment is a 20% benzocaine product that may be needed for temporary local relief.

Peripheral Vascular Disease-Intermittent Claudication

Both an increased rate of atherosclerosis and leg pain on exertion are seen in diabetics. Pentoxyphylline (Trental), 400mg TID with meals, along with decaffeination of diet, may be beneficial, especially if combined with an enteric-coated ASA 325mg tablet twice a week and a graded walking program to improve exercise tolerance. Be careful if the patient is also taking a theophylline product, however, because in the diabetic patient this may lead to added excitation, as well as interfere with measurement of theophylline levels, raising them by as much as a third.