Site Map


September 1998 Bruce H. Woolley, Pharm.D., Editor Vol. 5, No.9
Ken Hunt, Assistant Editor


The recently published results of the Heart and Estrogen/progesteroneReplacement Study (HERS) (JAMA, Aug19, 1998; 280:605-613) presents information abouthormone replacement therapy (HRT) in a population of older women with severe coronaryheart disease (CHD). The major clinical trial followed a randomized protocol whichincluded 2,763 women at 18 medical centers in the United States and evaluated HRT as atreatment for preventing CHD progression, specifically nonfatal myocardial infarction (MI)and death from CHD. The article reported that daily use of HRT did not reduce the overallrisk for MI and CHD death in postmenopausal women with established CHD. However, HRT didproduce a significant beneficial effect over time. The study was not designed to evaluateprimary prevention in a population of healthy women, which represents the most typical useof HRT. Rather, it looked a subset of women with an average age of 67 years who haveestablished CHD.

In the first year of the study, women treated with HRT experienced anincrease in second CHD events compared with placebo (RR 1.52, 95% CI 1.01-2.29). Withcontinuing treatment, this initial increase was reversed, and HRT resulted in less secondevents by the 4th and 5th years of treatment (RR 0.67, 95% CI0.43-1.04). ABasedon these findings, we don=t recommend starting estrogen plus progestin for the purpose ofpreventing heart attacks in postmenopausal women with existing heart disease,@ stated Stephen B.Hulley, MD, Professor and Chair of Epidemiology and Biostatistics at University ofCalifornia, San Francisco (UCSF) and the leader of the study. AThere was no overallbenefit during the 4 years of the trial, and the risk of heart attacks seemed to increasesoon after starting hormones. But women who are already taking estrogen plus progestincould decide to continue, given the apparent decrease in risk of heart attack afterseveral years.@



When NSAIDs were first introduced to the marketplace as agents to relievepain and inflammation, research revealed that these agents inhibit enzymes involved in thebreakdown of arachadonic acid to the prostaglandins, thromboxanes, and the leukotrienes.The two enzymes are lipoxygenase and cyclooxygenase. Most NSAIDs predominately inhibitcyclooxygenase; however this inhibition generates gastrointestinal problems due todecreased gastric mucosal protection often resulting in bleeding and/or ulcers.

Discovery of more than one physiological cyclooxygenase iosenzyme openedthe door for selective inhibition with potentially far less adverse reactions. Thereappear to be at least two cyclooxygenase isoenzymes and they are referred to as COX-1 andCOX-2. COX-1 is a constitutive isoenzyme that is produced continuously. COX-2 is aninducible enzyme produced in response to external stimuli. Both isoenzymes produce thesame prostaglandins. However, the effects of these prostaglandins differ based on thetissue of origin and the causative stimulus. Selective COX-2 inhibitors underinvestigation inhibit the inducible form of cyclooxygenase.

Selective COX-2 inhibitors are in phase III of clinical trial withcelecoxib (Celebra7/Searle) and MK-966 (Vioxx7/Merck)expected to have a filed NDA in the near future. It is expected that other companies willdevelop agents of this class. Although specific data are not available, it appears fromEuropean studies that the degree of damage to the gastric mucosa with these selectiveCOX-2 agents may be significantly lower than with older non-selective agents.

(1) Richardson C, Emery P: The clinical implications of inhibition of theinducible form of cyclo-oxygenase. Drug Saf 1996; 15(4):249-60.

(2) Cryer B, Feldman M: Cyclooxygenase-1 and cyclooxygenase-2 selectivityof widely used nonsteroidal anti-inflammatory drugs. Am J Med 1998; 104(5):413-21.

(3) Garcia Rodriguez LA: Nonsteroidal antianflammatory drugs, ulcers andrisk: A collaborative meta-analysis. Semin Arthritis Rheum 1997; 26(5 Suppl 1):16-20.



One of the dominant nutritional recommendations is for a diet high incomplex carbohydrates. This belief accounts for the foundation of the FDA=s food guide pyramidwhich suggests 6-11 servings of grains per day. The pyramid emphasizes high intakes ofbreads, cereals and potatoes. The base level of the pyramid encompasses a variety of foodsfrom a large range of refinement techniques. Recent studies suggest that grain refinementin the food industry is contributing to some of our nations health problems.

A paper by Jacobs et al (1) challenges the current generalizations made bythe food guide pyramid. They examine intakes of whole and refined grains in relation tothe risk of ischemic heart disease (IHD). In their analysis, which is part of the ongoingIowa women=shealth study, consumption of whole grains was associated with a decreased risk of IHDwhereas intake of refined grains was associated with an increased risk. Although the foodpyramid does not entirely account for differences between whole and refined grains, thesefindings are consistent with the current evidence that fiber consumption is inverselyrelated to risk for heart disease.

Widespread intake of refined grains also contributes to the sub-optimalintake of micro-nutrients in the United States (2). Many of the vitamins and mineralsinherent in whole grains are lost during refinement, and only a few are added back to theproduct via enrichment. Considerable work must be done to examine the effects of grainrefinement on health and mortality. Once more studies can provide a more precisedose-response relationship for grains, perhaps the FDA will be able to implement thisbeneficial data into their educational programs and the food guide pyramid. For now,emphasizing whole grains as the primary form of carbohydrate in the diet is a good placeto start.

(1) Jacobs DR, Meyer KA, Kushi LH, Folsom AR. Whole grain intake mayreduce the risk of ischemic heart disease death in post-menopausal women: the Iowa Women=sHealth Study. Am J Clin Nutr 1998; 68:248-57.

(2) Willet WC. The dietary pyramid: does the foundation need repair?Editorial. Am J Clin Nutr 1998; 68:218-9


The use of herbal medications is growing increasingly popular in thiscountry. Due to a widespread lack of regulation, it is often difficult to separate theserious science of herbs from the quackery which so often accompanies them. Goodinformation on the thousands of herbs available remains hard to obtain. To increase theweight on the shoulders of consumers, there are no standards to assist in judging thequality and purity of various products when choosing among them.

The United States Pharmacopeia (USP) is now taking steps to solve the lackof information and regulation. The organization has began publishing fact sheets whichsummarize the available reputable scientific data on certain herbs. For consumers, factsheets on Comfrey, Feverfew, Ginger, Hypericum (St. John=s Wort) and Valerianroot are currently available at the USP website, located at They are currently developing similar fact sheets for ginkgobiloba, saw palmetto and garlic among others. The fact sheets describe each herb=s use, precautions toconsider and side effects to watch out for.

At the beginning of the summer, the USP also began developing guidelinesfor makers of herbal products. Any product carrying the USP designation is obligated tomeet criteria for quality, strength, purity and packaging. Consumers will be assured thatthe products meet a responsible minimum standard. The letters NF (meaning NationalFormula) will denote a product with a related set of USP standards. While only a fewherbal products have standards currently applied to them, there are hundreds of productsfor which standards are currently being developed.

Adapted from: Getting Straight Facts on Herbs, Tufts University Health andNutrition Newsletter. May 1998;vol.6




Purported use



Soothes irritated membranes-coughs



External: scrapes and burns

May dec. intestinal absorption

Internal: heal ulcers

Can cause potassium depletion

Balm Plant

Diaphoretic, induces mild perspiration

Can potentiate CNS depressant effects


Astringent, diarrhea, diabetic therapy

May interfere with diabetic therapies


Upset stomachs and diarrhea.

None known

Black Cohosh

Treat hot-flashes and

Can potentiate CNS depressant effects


other menopausal symptoms

Do Not Use when pregnant


Laxative and cathartic

May cause potassium depletion


Purgative, tonic, diaphoretic

May cause potassium depletion

Castor bean

Potent laxative

Can cause potassium depletion


Mild sedative, upset stomachs

Can potentiate CNS depressant effects


Ulcers, eczema, canker sores

Can potentiate CNS depressant effects

Coffee beans

Brain stimulant, produces sleeplessness

May interfere with diabetic therapies


Prevention of urinary tract infections

None known


Mild purgative,diuretic,stimulant

May interfere with diabetic therapies


Source of minerals, diuretic

May interfere with diabetic therapies


Antiseptic, boosts immune system

Can potentiate CNS depressant effects

Evening Primrose

Eczema, arthritis, PMS

Do not use with steroids or NSAIDS


Emollient, demulcent

May decrease inestinal absorption


Produces digitalis, a cardiac stimulant

May potentiate cardiac glycoside toxicity


Lowers blood lipids, improves immunity

Do not take with anticoagulent

Ginkgo biloba

Improves memory function

May inc. cerebrovascular insufficiency


Carminitive, astringent, diuretic

May cause potassium depletion


Diuretic and astringent

Can cause potassium depletion


Blood cleanser, arthritis, skin conditions

Can cause potassium depletion

Kava - Kava

Anti-anxiety/ tension

Can potentiate CNS depressant effects


Headaches, sooths nerves, sedative

Can potentiate CNS depressant effects

Milk Thistle

Combat liver disease/ hepatits

Can potentiate laxative effects

Passion flower

CNS depressant of motor function

Can potentiate CNS depressant effects


Promotes menstrual flow

Do not use during pregnancy

Psylium seed

Laxative, demulcent

May decrease intestinal absorption

Siberian Ginseng

Raises energy level

Do not use during pregnancy

Can potentiate CNS depressants s


Nervine & antispasmodic action

Can potentiate CNS depressant effects

Slippery elm

Demulcent, expectorant, diuretic

May decrease intestinal absorption

St. John's Wort

Teat mild to moderate depression

Can potentiate CNS depressant effects

Saw Palmetto

Benign prostatic hypertrophy

None known


Sedative and sleeping aid

Can potentiate CNS depressant effects



The FDA has granted marketing approval for hepatitis B (recombinant)vaccine (Engerix B7/ SmithKline Beecham) for use in patients with chronic hepatitis Cinfection. Raymond Koff, MD of Philadelphia=s MetroWest Medical Center stated: AIt is important thatpeople with hepatitis C get vaccinated against hepatitis B...If infected with hepatitis B,hepatitis C patients are at increased risk for acute liver failure.@ The vaccine will beadministered initially, followed with addition injections at one and six months. Mostfrequent side effects are redness and swelling at the injection site.

Marketing approval has been granted for estradiol/norethindronetransdermal system (CombiPatch7/Rhone-Poulenc Rorer and Noven) for relief of moderate-to-severevasomotor symptoms in menopausal women with an intact uterus.

Approval has been granted for a combined diphtheria, tetanus, andacellular pertusis vaccine (Certiva7/North American Vaccine) for use in children aged 6 weeks to 7years. Side effects, as reported in a Swedish study of 3,450 infants, includedirritability and redness/pain at the injection site. It will be marketed by the RossProducts Division of Abbott Laboratories.



The information and opinions expressed in the Therapeutics Letter do notnecessarily reflect the official policy of the sponsoring organizations.