Drug treatment of HIV-related opportunistic infections.

The AIDS epidemic has led to the emergence of several disease entities which in the pre-AIDS era were rare or seemingly innocuous. Experience of treating these diseases varies. In some instances, such as Pneumocystis carinii pneumonia, there is an abundance of published literature to direct our course of action. However, for many of these newly recognised diseases our treatment experience is limited. Furthermore, in many instances, well controlled trials evaluating treatment modalities in the AIDS population are lacking. We have identified 13 disease entities (P. carinii pneumonia, toxoplasmosis, cryptococcosis, histoplasmosis, Mycobacterium tuberculosis, Mycobacterium avium complex, cytomegalovirus, coccidioidomycosis, isosporiasis, candidosis, Kaposi's sarcoma, herpes simplex virus, and varicella zoster virus) and have reviewed the current literature with regard to their treatment.

Ticlopidine-induced elevated liver enzymes.

Ticlopidine is a reasonable alternative to prevent stroke and myocardial infarction when aspirin is intolerable or ineffective. It can be limited, however, by its severe adverse effect profile. The most worrisome of these is neutropenia, although clinicians must be mindful of other adverse events that may be caused by this drug. A patient experienced elevated liver function tests probably due to ticlopidine.

Comparison of the serum and intracellular pharmacokinetics of azithromycin in healthy and diabetic volunteers.

STUDY OBJECTIVE: To compare serum and intracellular pharmacokinetics of azithromycin in healthy volunteers and patients with diabetes. DESIGN: Open-label, parallel study. SETTING: Clinical research center. SUBJECTS: Twelve patients with diabetes and 12 healthy volunteers. INTERVENTIONS: Subjects were given a single 500-mg dose of azithromycin followed by 250 mg/day for 2 days. Blood samples were obtained just before and after the third dose for up to 24 hours for serum and 168 hours for intracellular measurement of azithromycin. MEASUREMENTS AND MAIN RESULTS: Pharmacokinetic parameters were calculated by noncompartmental methods and compared with a t test. The groups did not differ in maximum concentration, time to maximum concentration, or area under the concentration-time curve in serum or polymorphonuclear cells (PMNs). Differences in the PMN:serum ratio were observed at the 24-hour time point (healthy 1209 +/- 432, diabetic 859 +/- 286, p=0.051). CONCLUSION: In general, the pharmacokinetics of azithromycin are comparable in diabetics and healthy volunteers. Accumulation of drug in macrophages was slightly lower in patients.

Assessment of patients' perceptions and beliefs regarding herbal therapies.

We evaluated the demographics and beliefs regarding safety and efficacy of herbal therapy among individuals in Iowa and assessed the willingness to discuss the use of these products with health care providers. We distributed 1300 surveys to two random samples: patients attending eight clinics, and residents of the state (mailing). Data were categorized according to herb use and compared between users and nonusers. The response rate was 61% (794 people), with 41.6% of respondents reporting herb use. They were predominately white women and were likely to have had education beyond high school (p<0.05). Their use of prescription drugs was high (p<0.05). Although users rated safety and efficacy of herbs higher than nonusers (p<0.05), both groups believed that health care providers should be aware of use and would provide this information.

Metformin hydrochloride: an antihyperglycemic agent.

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of metformin hydrochloride are reviewed. Metformin is an antihyperglycemic agent; it lowers the blood glucose concentration without causing hypoglycemia. Proposed mechanisms of action include decreased intestinal absorption of glucose, increased glucose uptake from the blood into the tissues, decreased glucose production in the liver, and decreased insulin requirements for glucose disposal. Metformin is slowly absorbed from the small intestine and does not undergo hepatic metabolism. The half-life is about five hours. The major route of elimination is renal; the drug is contraindicated in patients with impaired renal function. In double-blind, placebo-controlled trials, metformin has shown efficacy in the treatment of non-insulin-dependent diabetes mellitus (NIDDM). The drug is as effective as sulfonylureas in patients with diabetes who are nonobese or obese and whose diabetes is uncontrolled by diet alone. Metformin may be useful as addon therapy in obese patients with diabetes uncontrolled by sulfonylureas and diet. Lipid profiles may be favorably influenced. The most common adverse effects are gastrointestinal. A rare but potentially fatal adverse effect is lactic acidosis. Metformin has the potential to interact with cationic drugs eliminated by the renal tubular pathway. The usual effective dosage is 1.5-2.5 g/day orally in two or three divided doses. Metformin hydrochloride is an effective alternative to sulfonylureas in obese and non-obese patients with NIDDM in whom diet alone has not achieved glycemic control, and it may be useful as addon therapy in patients whose diabetes has not responded adequately to sulfonylureas plus dietary measures.

Unsafe and potentially safe herbal therapies.

Unsafe and potentially safe herbal therapies are discussed. The use of herbal therapies is on the rise in the United States, but most pharmacists are not adequately prepared educationally to meet patients' requests for information on herbal products. Pharmacists must also cope with an environment in which there is relatively little regulation of herbal therapies by FDA. Many herbs have been identified as unsafe, including borage, calamus, coltsfoot, comfrey, life root, sassafras, chaparral, germander, licorice, and ma huang. Potentially safe herbs include feverfew, garlic, ginkgo, Asian ginseng, saw palmetto, St. John's wort, and valerian. Clinical trials have been used to evaluate feverfew for migraine prevention and rheumatoid arthritis; garlic for hypertension, hyperlipidemia, and infections; ginkgo for circulatory disturbances and dementia; ginseng for fatigue and cancer prevention; and saw palmetto for benign prostatic hyperplasia. Also studied in formal trials have been St. John's wort for depression and valerian for insomnia. The clinical trial results are suggestive of efficacy of some herbal therapies for some conditions. German Commission E, a regulatory body that evaluates the safety and efficacy of herbs on the basis of clinical trials, cases, and other scientific literature, has established indications and dosage recommendations for many herbal therapies. Pharmacists have a responsibility to educate themselves about herbal therapies in order to help patients discern the facts from the fiction, avoid harm, and gain what benefits may be available.

Oral corticosteroids for pain associated with herpes zoster.

It is apparent from published studies that corticosteroids do not prevent the development of postherpetic neuralgia. Earlier trials that indicated some benefit in both acute neuralgia and the prevention of postherpetic neuralgia are of limited use to clinicians due to problems with uncontrolled study designs, small sample sizes, and the absence of statistical analysis of the results. The lack of a consensus definition of postherpetic neuralgia, the variable agents and dosages used, and the different pain scales reported are of concern when trying to interpret the results of these studies for their clinical significance. In more recent larger and well-designed studies, similar rates of postherpetic neuralgia were observed in the corticosteroid and control groups. As a result of these findings, corticosteroids should not be recommended for the prevention of postherpetic neuralgia. Despite lack of efficacy in preventing postherpetic neuralgia, limited studies suggest corticosteroids such as prednisone (40-60 mg/d tapered over 3 wk) are well tolerated and may confer slightly significant benefits in reducing the duration of acute neuralgia and improving quality-of-life measures. However, the clinical significance and application of these findings remain to be addressed. If corticosteroids are used for acute neuralgia, clinicians are advised to select their patients carefully. The patients treated in these studies were generally healthy and free of comorbid diseases, such as hypertension, diabetes mellitus, and psychiatric disorders, which can be exacerbated in the presence of corticosteroids. Although dissemination of herpes zoster has been reported infrequently, it remains a potential risk with use of corticosteroids. Until the results of these studies are repeated in more diverse patient populations, corticosteroids appear to have a limited role in the management of acute neuralgia associated with herpes zoster.