Psych Map

May 2000 Bruce H. Woolley, Pharm.D., Editor Vol. 7, No. 5
Kenneth J. Hunt, Associate Editor

Lipid Lowering Drugs and Osteoporosis

A recent study demonstrated that treatment with HMG-CoA reductase inhibitors increases bone mineral density in patients with type II diabetes. These findings elaborate on recent reports that these drugs increase bone mineral density in mice.

The investigators treated 36 of 69 type II diabetic patients with the HMG-CoA reductase inhibitors for hypercholesterolemia. The remaining 33 patients did not take HMG-CoA reductase inhibitors and had normal cholesterol levels. After approximately 14 months, spinal bone mineral density decreased significantly in patients not using HMG-CoA reductase inhibitors, while bone mineral density at the femoral neck increased significantly in those taking the drugs.

Men in the study who were taking the drugs experienced a significant increase in bone mineral density at the femoral trochanter compared to controls. In both men and women, bone mineral density of the femoral neck increased significantly in treated patients. Researchers concluded that HMG-CoA reductase inhibitors may increase BMD in male patients with type II diabetes mellitus.

While improvement is also seen in females, it is more prominent in male subjects, perhaps due to physiological differences in male and female bone loss. They also site prior in vitro studies that demonstrate these medications to affect osteoclast apoptosis and decrease bone resorption. These findings present a possible step toward the treatment of osteoporosis in diabetic men (see April newsletter)

J Clin Endocrinol Metab 2000;85:1137-1142

The Future of the Herbal Industry

When congress passed the Dietary Supplement Health and Education Act of 1994 (DSHEA), a six year period of unprecedented growth in the herbal and nutritional supplement industry ensued. Though there is evidence that this trend is slowing, the US public is using increasing numbers of herbal and nutritional products in conjunction with or as replacements for conventional medicine. As the primary providers of health information, physicians and pharmacists face scores of questions about the safety and efficacy of these substances.

The principal concern among patients and health professionals is the quality and reliability of the products available. Plant products present challenges from a regulatory and safety perspective due to the wide variety of potentially active constituents contained within them. There is variation in quality and content of botanicals based on the source of raw materials and the manufacturing process. Potential problems include both contamination and inconsistent concentration of active ingredients. These facets of botanical preparations are not currently regulated in the United States.

Each month, new trials and data are released on safety and efficacy issues for particular herbs and alternative medicines. Furthermore, alternative therapies are a dynamic industry that has a tremendous impact on health care and continues to be a source of legislative measures. In the absence of regulatory changes at the government level, health professionals must be familiar with the quality of popular botanical product in order to speak confidently about product to a patient.

This and future newsletter issues will contain information and updates on the most popular herbal supplements. Information will be based on published findings of safety, efficacy, and dosage for each herbal product. All health professionals should take time to learn about the major issues involved and begin to learn about the quality standards of herbal products that their patients are taking. This becomes a difficult task for busy clinicians. The monthly updates will serve as a concise look at herbal products as we hope the nation progresses toward a higher standard of assuring safe use of herbal products.

Popular Herbal Products: Garlic for Hyperlipidemia

Alternative medicine continues to hit the nation like a storm. Sales of herbal medications exceed $1.5 billion a year and are still increasing. Patients and consumers are seeking alternative therapies to supplement or even replace modern conventional medicine. The safety and efficacy of these products, however, remain a troubling problem in the herbal world. While some alternative medicines have been scientifically demonstrated, many are either controversial or unproven.

Garlic is the one currently marketed herbal product whose effects are well supported by scientific and clinical evidence. Allicin, garlic’s biologically active constituent, is a product formed by enzymatic action from alliin - a crystalline amino acid occurring in garlic oil. Common indications for garlic include use as therapy for atherosclerosis and as an antibacterial, antiviral, and antifungal agent. It is also used to treat mild hypertension and hypercholesterolemia. It is most effective in reducation of blood lipids.

More than 32 human studies since 1975 have demonstrated the lipid-lowering effects of garlic. The majority of these were completed with the most common garlic powder tablet that is standardized to 1.3% alliin. Meta-analyses have indicated that doses from 600 to 900mg of garlic powder daily for 1 to 3 months reduces total serum cholesterol by 9% to 12% and lowers serum triglycerides by 8% to 27%. However, the overall design of most studies weakens the validity of their findings. Future studies should include placebos that look, taste, and smell like garlic and also incorporate dietary habits or restrictions. Look for LDL to be used as a more precise marker of cardiovascular risk than total cholesterol.

Daily consumption of moderate quantities of garlic should not pose any health risk to healthy people. Larger doses of more than one clove per day can cause heartburn, and certain mild gastrointestinal problems. As garlic reduces blood-clotting time, patients taking aspirin or anticoagulant drugs should avoid consuming large amounts. There are no other known contraindications to the use of garlic.

Future newsletters will contain similar articles on herbs and alternative therapies. The purpose of these articles is to update health professionals on current research and legislation involving safety and efficacy for therapies that our patients are commonly using.

Thanks to Drug Benefit Trends 10(5):43-50, 1998

Propulsid Withdrawn From the Market

New Jersey based Janssen Pharmaceuticals recently announced that it will stop marketing cisapride (Propulsid) in the United States as of July 14, 2000. The effective date of the voluntary action is intended to provide adequate time for patients and physicians to make alternative treatment decisions. Cisapride approved only for the severe nighttime heartburn experienced by adult patients with gastroesophageal reflux disease (GERD) that does not adequately respond to other therapies.

As of January, 2000, use of cisapride has been associated with more than 340 reports of heart rhythm abnormalities including 80 reports of deaths. Most of these adverse events occurred in patients who were taking other medications or suffering from underlying conditions known to increase risk of cardiac arrhythmia. Patients who are currently taking cisapride are urged by Janssen and the FDA to promptly contact their health care providers to discuss alternative treatments.

Physicians who are treating patients with severely debilitating conditions for whom they believe the benefits of the cisapride may still outweigh its risks are encouraged to contact Janssen at 1-800-JANSSEN. The company will continue to make the drug available to patients who meet specific clinical eligibility criteria for a limited-access protocol.

Since the drug was approved 1993, Cisapride’s labeling has been revised several times to inform health care professionals and patients about the drug’s risks. Still, the company decide that continued general prescription access to the drug poses unacceptable risks.

See letter from Janssen:

Determining Longevity of Hepatitis C Infections

Hepatitis C currently affects around 3.5 million Americans, more than five times as many as are infected with HIV. Yet, research appropriations in the U.S. for hepatitis C are 255 times smaller than those for HIV. There is no funding for the treatment of chronic hepatitis, but $500 million is spent annually for AIDS treatment. It appears, however, that we are making strides toward the diagnosis and prognosis of Hepatits C infection.

According to the April 12 issue of Science, it is now possible to determine whether hepatitis C virus (HCV) infection will become chronic or resolve by examining the genetic diversity of the virus during the early stages of infection. In a prospective study of 12 patients with acute HCV infection, an Italian research group detected a dramatic increase in the genetic diversity of a region (HVR1) of the viruses genome patients with hepatitis that proved to be slowly or rapid progressive. Patients whose infection eventually resolved showed a decrease in genetic diversity of HVR1.

The researchers note that acute hepatitis progressing to chronicity correlates with the genetic evolution of HCV within the first 4 months of infection. The direct implication of HVR1 in the development of chronic HCV infection poses a major challenge for devising preventive and therapeutic strategies against the virus. The hope is to reduce mortality and morbidity associated with Hepatits C infections, an emerging global health issue.

Science 2000;288:339-344.

Interaction with Warfarin and Celecoxib

After recent reports of patients experiencing potentially dangerous changes anticoagulation activity in elderly patients, those taking both warfarin and celecoxib should have blood clotting times closely monitored.

Though the two drugs are primarily metabolized through the same pathway, it is not certain whether this causes a competitive inhibition of either or both drugs. A short-term study of healthy subjects found that co-administration of celecoxib and warfarin did not significantly affect prothrombin times. However, in response to several reports of increased prothrombin times, especially in the elderly, the FDA has recommended a product labeling change for celecoxib.

Nurses' Drug Alert 24(4):27, 2000

The information and opinions expressed in the Therapeutics Letter do not necessarily reflect the official policy of the sponsoring organizations