THERAPEUTICS REPORT
| January 1999 | Bruce H. Woolley, Pharm.D., Editor | Vol. 6, No.1 |
| Ken Hunt, Associate Editor |
ASTHMA-TRIGGERING MOLECULES FOUND
Two teams of researchers have identified a molecule that plays a key role in causing the symptoms of asthma. The finding could lead to new treatments for the breathing disorder that affects at least 15 million Americans. The two research teams have been experimenting independently with laboratory mice and have found that a reaction triggered by interleukin-13 [IL13] was a primary cause of the inflammation, clogging and restricted air flow that precipitates breathing problems in asthma attacks. The two studies appeared in the December 18th edition of the journal Science.
In one study, conducted at Johns Hopkins University, researchers treated asthma-prone mice with a drug that blocks the action of IL13. When exposed to an allergen, the animals developed no breathing problems. Mice not treated with the IL13 blocker, however, had the inflammation and restricted airways typical of asthma.
In the other study, researchers at the University of California-San Francisco applied an IL13 blocker to the nasal passages of mice and then exposed the animals to a protein known to induce asthma. Animals treated with the IL13 blocker had few asthma symptoms, the authors report. The University of California team also found that interleukin-4 [IL4] also played a role in asthma. However, investigator David Corry stated, "IL13 may be more potent."
If the mouse experiments can be duplicated in humans, they could give new targets for drugs that treat asthma at the cellular level. Such drugs, if created, would theoretically stop an asthma reaction at its source instead of treating just the symptoms of the disorder.
(1) Wills-Karp M, et al. Interleukin-13: Central Mediator of Allergic Asthma. Science Dec 18 1998: 2258-61.
(2) Grünig G. Requirement for IL-13 Independently of IL-4 in Experimental Asthma. Science Dec 18 1998: 2261-63.
FOLATE=S ROLE IN THE FIGHT AGAINST COLON CANCER
Researchers have long-since discovered that a low-fat, high-fiber diet containing plenty of fruits and vegetables appears to provide protection from colon cancer. More and more research is yielding evidence that folate found in beans and some vegetables may play an important role as well. Researchers at Tufts University and the University of Toronto found that precancerous intestinal polyps had 34% less folate surrounding them than benign tissue polyps.
At the admission of the researchers, these findings do not necessarily prove that a high folate diet will fight off colon cancer. But, the results are consistent with the results of nearly 20 epidemiological studies which have found that people who consume the most folate are least likely to get colon cancer.
So how much folate is enough? The current recommended level for adults is 400 micrograms per day, an amount rarely achieved without the help of a multivitamin supplement. In the Harvard Nurses Health Study, researchers found that women who consumed more than 400 micrograms of folate per day were about 30% less likely to end up with colon cancer than those who took less than 200 micrograms per day. Furthermore, those women who took folate-containing supplements for 15 years were 75% less likely to develop colon cancer than the other women in the study.
Folate, which has long been purported to prevent fetal toxicity and birth defects, now has a much broader role including possible prevention of colon cancer. It is certainly just as important in males as it is females. Still, the most important step in the prevention of colon cancer is early and consistent screening for the disease which is the fourth leading cause of cancer mortality in the U.S., behind lung, breast, and prostate.
Adapted from: Tufts University Health and Nutrition Newsletter. Folate May Reduce Colon Cancer Risk.16: 1,6, December 1998.
ZINC DEFICIENCY REMAINS A SIGNIFICANT PROBLEM
It was discovered more than thirty years ago that zinc deficiency occurs in humans. Since then, it has become clear that zinc deficiency is a world-wide problem, as prevalent as iron-deficiency anemia. Tremendous progress has been made recently to understand the clinical role of zinc in the body. Unfortunately, little effort has been made to correct the deficiency in populations where the disease, which affects nearly one billion people, is common.
Zinc deficiency has a severe impact on human health. Clinical trials have shown that growth retardation, male hypogonadism, neurosensory changes, delayed wound healing, abnormal immune function, and impaired cognitive functions are major effects of zinc deficiency. All of them are reversible with supplementation [1]. Two papers were published in the December 1998 edition of the Journal of the American College of Nutrition on the subject of Zinc deficiency and its impact on human health.
The first study reported that low consumption and serum levels of zinc were associated with the prevalence of coronary artery disease and diabetes [2]. If this observation is to be confirmed, zinc status would have to be considered a risk factor for the above conditions. The authors of the second paper [3] observed that decreased zinc absorption and increased urinary zinc excretion due to exocrine pancreatic insufficiency may form the basis for zinc deficiency in people with chronic pancreatic disease.
Zinc deficiency, and its characteristic illnesses, is common in both developing countries and the developed world. There are many adverse health consequences related to zinc deficiency, yet it remains a neglected problem. We can only hope that through food fortification and nutritional education programs we can solve this predicament.
(1) Prasad, AS. Zinc Deficiency in Humans: A Neglected Problem. J Am Coll Nutr, 17;6:542-543; 1998.
(2) Singh RB, et al. Current zinc intake and risk of diabetes and coronary artery disease and associated factors of insulin resistance in rural and urban populations, J Am Coll Nutr. 17:556-570, 1998.
(3) Dutta SK, et al. Zinc metabolism in patients with exocrine pancreatic insufficiency. J Am Coll Nutr. 17:556-563, 1998.
1998 APPROVED DRUG THERAPIES (as of 12-28)
Cardiology/Vascular Diseases
Cervistatin (Baycol/Bayer, SKB), high cholesterol treatment, February 1998
Candesartan (Aatacand/Astra Merck), hypertension treatment, June 1998
Diltiazem (Tiazac/Forest), chronic stable angina treatment, February 1998
Fenofibrate (Tricor/Abbott), very high triglyceride levels treatment, February 1998
Mycophenolate (CellCept/Roche), heart implant organ rejection prevention, February 1998
Propafenone (Rythmol/Knoll), paroxysmal atrial fibrillation treatment, January 1998
Valsartan/hydrochlorothiazide (Diovan HCT/Novartis) hypertension treatment, January 1998
Sildenafil (Viagra/Pfizer), impotence treatment, March 1998
Dermatology/Reconstructive Surgery
Dirithomycin (Dynabac/Sanofi), acute bacterial exacerbations treatment, March 1998
Lustra (Medicus), ultraviolet-induced skin discolorations treatment, January 1998
Mafenide (Sulfamylon/Mylan), bacterial infections on excised burn wounds control, June 1998
Metronidazole (Noritate/Dermik), rosacea treatment, January 1998
Pilocarpine (Salagen/MGI Pharma), Sjogren=s Syndrome treatment, February 1998
Thalidomide (Thalomid/Celgene), severe erythema nodosum leprosum treatment, July 1998
Tretinoin (Avita Gel/Penederm), acne treatment, February 1998
Endocrinology
Esterified estrogens (Estratab/Solvay), osteoporosis prevention & treatment, March 1998
Estrogens and progestins comgined (Prempro/Wyeth-Ayerst), hormone replacement therapy, Jan 1998
Paricalcitrol (Zemplar/Abbott), secondary hyperparathyroidism treatment, April 1998
Risedronate sodium (Actonel/HMR), Paget’s disease treatment, April 1998
Generics
Glucagon (Lilly), severe hypoglycemia assoc. with diabetes, October 1998
Glyburide (Mylan), diabetes mellitus treatment, July 1998
Gastroenterology
Lansopraxole (Prevacid/TAP), heartburn assoc. with GERD treatment, April 1998
Omeprazole (Prilosec/Astra Merck), heartburn treatment, January 1998
Generics
Cimetidine (Pharmaceutical Formulations), June 1998
Hematology
Enoxaparin (Lovenox/RPR), blood clots following hip-replacement surgery prevention, February 1998
Filgastrim (Neupogen/Amgen), slow WBC recovery post chemotherapy treatment, April 1998
Hydroxyuria (Droxia/BMS), sickle-cell anemia treatment, March 1998
Lepirudin (Refludan/HMR), heparin-induced thrombocytopenia treatment, March 1998
Immunology/Infectious Diseases
Basiliximab (Simulect/Novartis), organ transplant rejection treatment, May 1998
Ceftriaxone sodium (Rocephin/Roche), otitis media treatment, January 1998
Clindamycin (Cleocin Vaginal Cream 2%/Pharmacia & Upjohn), bacterial vaginosis, March 1998
Interferon alpha-2b recombinant & ribavirin combination (Rebetron/Schering), June 1998
Ticarcillin/clavulanate potassium (Timentin/SKB), children’s infections treatment, January 1998
Trifluridine (Viroptic/King), inflammation of cornea in children due to herpes simplex, February 1998
Generics
Clemastine fumarate syrup (Morton Grove), March 1998
Musculoskeletal
Generics
Etodolac (Faulding), May 1998
Nephrology/Urology
Finasteride (Proscar/Merck), BPH treatment, April 1998
Tolterodine tartrate (Detrol/Pharmacia & Upjohn), overactive bladder treatment, March 1998
Neurology
Lamotrigene (Lamictal/Glaxo-Wellcome), epilepsy treatment, August 1998
Naratriptan (Amerge/Glaxo-Wellcome), acute migraine treatment, February 1998
Rizatriptan (Maxalt/Merck), epilepsy treatment, June 1998
Tolcapone (Tasmar/Roche), Parkinson’s Disease treatment, January 1998
Generics
Clonazepam (Watson), January 1998
Naltrexone Hcl (Barr), May 1998
Oxycodone & Aspirin (Watson), March 1998
Obstetrics/Gynecology
Estradiol transdermal (Esclim/Fournier), menopause symptoms treatment, August 1998
Progesterone (Prometrium/Solvay), amenorrhea treatment, May 1998
Oncology
Aldesleukin [interleukin-2] (Proleukin/Chiron), metastatic melanoma treatment, January 1998
Capecitabine (Xeloda/Roche), advanced breast cancer tumors treatment, April 1998
Dolasetron mesylate (Anzemet/HMR), nausea and vomiting assoc. with chemotherapy prevention, February 1998
Filgastrim (Neupogen/Amgen), slow WBC recovery following chemotherapy, April 1998
Gemcitabine Hcl (Gemzar/Lilly), lung cancer treatment, August 1998
Herceptin (Genentech), metastatic breast cancer treatment, October 1998
Inform HER-1/neu breast cancer test (Oncor), breast cancer prediction treatment, January 1998
Ondansetron Hcl (Zofran/Glaxo-Wellcome), postoperative vomiting in adults treatment, April 1998
Porfimer sodium (Photofrin/QLT Therap.), endobronchial non-small cell lung cancer treatment, January 1998
Sterile aerosol talc (Sclerosol/Bryan), malignant pleural effusions treatment, January 1998
Ophthalmology
Dorzolamide/timolol (Cosopt/Merck), glaucoma or ocular hypertension treatment, April 1998
Fomivirsen sodium (Vitravene Injection/Isis), CMV in AIDS patients treatment, August 1998
Loteprednol etabonate (Alrex & Lotemax/Bausch & Lomb), allergic conjunctivitis & inflammation, March 1998
Pilocarpine Hcl (Salagen/MGI), Sjogren’s Syndrome treatment, February 1998
Trifluridine (Viroptic/King), inflammation of cornea in children treatment, February 1998
Pediatrics/Neonatology
Calfactant (Infasurf/ONY), respiratory distress syndrome prevention & treatment, July 1998
Desmopressin acetate (DDAVP/RPR), nocturnal enuresis treatment, March 1998
Dornase alpha (Pulmozyme Inhalation Solution/Genentech, cystic fibrosis treatment, March 1998
Montelukast sodium (Singulair/Merck), asthma treatment, February 1998
Pulmonary surfactant replacement, porcine (Curosurf/Dey), RDS in premature infants treatment, October 1998
Psychiatry/Psychology
Citalopram hydrobromide (Celexa/Forest), depression treatment, July 1998
Isocarboxacid (Marplan/Roche), depression treatment, August 1998
Generics
Clomipramine Hcl (Mylan), April 1998
Naltrexone Hcl (Barr), May 1998
Prochlorperazine (IVAX), January 1998
Pulmonary/Respiratory Diseases
Fexofenadine (Allegra-D/HMR), nasal congestion due to allergy, March 1998
Palivizumab (Synagis/Medimmune), serious lower respiratory tract disease in infants treatment, June 1998
Rifapentine (Priftin/HMR), pulmonary tuberculosis treatment, June 1998
Rheumatology
Leflunomide (Arava/HMR), rheumatoid arthritis treatment, September 1998
The information and opinions expressed in the Therapeutics Letter do not necessarily reflect the official policy of the sponsoring organizations.