Pharmacy and tobacco.

With the recognition that smoking begins in youth and that tobacco products are readily available to those under 18 years of age, new Food and Drug Administration (FDA) regulations restrict the sale, distribution, promotion, and advertising of cigarettes to minors. The objective is to decrease the use of tobacco by young people and consequently reduce the future morbidity and mortality from tobacco. Pharmacists currently have three choices with regard to the sale of tobacco in pharmacies: display and sell tobacco products, refuse to sell tobacco products, or make tobacco products available but counsel on smoking cessation. Each choice, as well as the impact of the new FDA regulations on pharmacy, is discussed.

MEDGuide and patient package inserts--again?

This article will trace the history and effects of the PPI from the time of its original concept by the FDA in the early 1970's to its current status. It will also address the response to this FDA initiative by the industry, medical community and consumer groups. Initiatives in other countries and future issues will also be discussed.

An analysis of drug information desired by the patient. (Are patients being told everything they wish to know under OBRA '90?).

The need for patient package inserts (PPI) has been a controversial issue for many years. In August 1995, the FDA proposed 'MedGuide', a mandatory PPI programme. Recent efforts to educate patients about drug therapy include the OBRA '90 (Omnibus Budget Reconciliation Act of 1990) requirement for pharmacists to offer counselling to all patients receiving prescription drugs. In order to assess if patient information needs are being met, an 18-item survey was distributed to 873 patients at eight randomly selected New Jersey pharmacies until 100 patients had anonymously responded. Seventy-five per cent or more of respondents indicated that they received the following information from a health professional: medication name, reason prescribed, how often to take and duration of therapy. Less than 50% of respondents received information concerning: storage conditions, over-the-counter (OTC) or prescription only (Rx) interactions, what happens to the body if a dose is missed and how to avoid side-effects. Using a five item scale, every item was rated as important by at least 60% of respondents. Although information was reaching the majority of patients who responded, there were still some gaps between that which they considered to be important and information actually received. Some additional intervention might be beneficial to help to bridge these informational gaps.

New York City pharmacists and OBRA '90: one year later.

New York state regulations to implement patient counseling mandated by the Omnibus Budget Reconciliation Act of 1990 took effect in December 1992, yet one year later, little was known about how successfully the counseling mandate was being implemented. To begin assessing the impact, an anonymous questionnaire was distributed to 300 New York City pharmacists and pharmacy interns in the fall of 1993; a 65% (194) response rate was achieved. The opinions of interns and pharmacists differed on whether the counseling requirement had been implemented correctly (p < 0.01). Time, personnel, and expense constraints were most frequently cited as barriers to implementation. Half of the respondents mentioned that patients had to wait for counseling. More often than not, the offer to counsel originated with the pharmacist (51%). Interns (19.5%), technicians (12%), and clerks (17%) offered counseling less frequently. Approximately 35% of patients chose not to supply counseling information. Reasons for not accepting counseling as well as methods for documentation were described and analyzed. A list of items discussed each time a prescription is dispensed revealed little agreement on what constitutes counseling.

Vitamin A as an immunomodulating agent.

Findings on the benefits and mechanism of action of vitamin A in measles and other infectious diseases and immunocompromised states are discussed. Vitamin A deficiency is one of the world's major malnutrition problems and is most commonly found in children under the age of five years. An association between vitamin A status and immune function has been suggested by community studies and animal experiments. Mortality and susceptibility to infection and diarrhea are higher in children with vitamin A deficiency. The association between increased mortality and morbidity and vitamin A deficiency is strongest in children with measles. Vitamin A supplementation reduces mortality and complications resulting from measles. Measles may increase the body's utilization of vitamin A, possibly because of the rapid destruction of epithelial surfaces. Vitamin A may boost immune responses in the elderly, persons with high exposure to ultraviolet light, patients who have undergone surgery, and persons with parasitic infection, but more studies are needed. The immune defect caused by vitamin A deficiency may be due to alterations in the glycoproteins of the lymphocyte membrane, an adverse effect on helper T-cell function, the effect on epithelial tissue, or some other mechanism. Vitamin A therapy is relatively safe, and its effectiveness in children with measles and possibly other groups appears to justify public health campaigns to eliminate vitamin A deficiency. Vitamin A apparently has important immunomodulating properties, notably in patients with measles.

Sources of regulatory information for pharmacists.

Sources of regulatory information of use to pharmacists are summarized. Regulatory information is provided by government, legal, pharmaceutical industry, nongovernment, and investigational drug sources. Databases and trade and professional organizations also provide such information. Information on legislative statutes and regulations can be found in the Federal Register, Code of Federal Regulations, and List of CFR Sections Affected. Many other government reports are also available. Various law reports are published by state and federal courts; legal textbooks, journals, and newsletters also provide pharmacy law information. Pharmaceutical industry sources supply information on U.S. drug approvals, pharmaceutical companies, and FDA enforcement actions, whereas nongovernment regulatory sources provide comprehensive regulatory and drug information. Investigational drug sources enable pharmacists to keep abreast of new drug development. Databases provide a wide variety of information, and trade newsletters supply information of interest to the organization. Knowledge of appropriate references will allow pharmacists to keep abreast of regulations that may affect them and new developments in their area of expertise.

Non-pharmacological treatment of hypertension.

This paper represents a compilation of the latest scientific research on the non-pharmacological management of hypertension to help practitioners manage this highly prevalent disease. In this regard, recent evidence suggests that nonpharmacological approaches--particularly weight reduction, salt restriction, moderation of alcohol consumption, reduction of cholesterol intake and exercise--may lower elevated pressure and improve the efficacy of pharmacological agents. Non-pharmacological therapy should be stressed for the future treatment of hypertension.

The decline in new drug development.

The future depends on innovation, not imitation. New drug development can be encouraged in a number of ways (Table 4), and the rewards are great. Who knows what dramatic drug discoveries remain to be found in a new synthetic compound, a fresh soil sample, or a plant obtained from some pristine forest? In any event, let us all hope that the molecular roulette that has governed drug development in the past will be replaced by a more rational, and less empirical, approach.

Clinical therapeutics of endometriosis, Part 2.

PIP: The 2nd part of a review on medical therapy of endometriosis discusses pseudopregnancy brought on by oral contraceptives, and pseudomenopause induced by Danazol and GnRh agonist therapy. Oral contraceptives are not FDA approved for endometriosis, but many physicians prescribe 1 tablet daily for 2 weeks, then 2 tablets daily for 6-12 months, or higher doses in case of breakthrough bleeding. Pills cause endometrial decidual changes initially then atrophy. Danazol selectively inhibits release of FSH and LH by the pituitary, resulting in anovulation and atrophy of the endometrium. It is currently the preferred and most effective medical therapy for endometriosis, and is approved for this indication. It is used in doses of 200-800 mg in 2 divided doses, or 400-800 mg/day preoperatively. Side effects are androgenic, some of which are not reversible, antiestrogenic, metabolic and nonspecific, i.e., muscle spasms. Drug interactions such as increased insulin requirements have been reported. The GnRH antagonists, nafarelin, buserelin, histrelin and leuprolide must be given subcutaneously or nasally. The anti-ovarian side effects, hot flashes, calcium loss, vaginal dryness and insomnia are more prevalent than the androgenic side effects, weight gain, edema, myalgia, and decreased libido reported with Danazol. Clinical and laparoscopic evidence of improvement is temporary with drug treatment, in contrast to surgery. Infertility is common even with mild endometriosis, and the condition may recur, even after pregnancy.^ieng

Prevention of recurrent myocardial infarction and sudden death with aspirin therapy.

In October 1985, the Food and Drug Administration approved a new indication of aspirin for the secondary prevention of recurrent myocardial infarction (MI) and death in patients with MI or unstable angina. Clinical trials have demonstrated the efficacy of this drug, especially when treatment is begun soon after the initial event. The antiplatelet actions of aspirin seem to be the most plausible explanation for its efficacy in reducing mortality and the rate of reinfarction. A single daily 325-mg tablet is effective and produces side-effect incidences of only zero to two percent above those produced by placebo. This article assesses the current state of knowledge regarding the value of aspirin therapy in survivors of acute MI and the implications for clinical practice.

A review of mechanism of action of aspirin and its potential as an immunomodulating agent.

The basic aspects of PG immune function interactions are presented and discussed herein. Specifically, the findings of many of the studies summarized suggest the possibility that pharmacologic actions of aspirin may play a role in enhancing the immune response to viral infections. Mechanisms proposed for ASA include: PG inhibition via the cyclooxygenase pathway, an interaction with cyclic nucleotides, altered cellular interactions with PG's, altered leukocyte migration, activation of complement components, stimulation of monocytopoiesis, and induction of interferon. Since dual effects for ASA have been observed for several of these mechanisms, it is clear that its role in modulating the immune response to viral infections is very complex. This delineation of a role for ASA, that would seem to constitute a defense against viral infections leads to an area worthy of study and surveillance.

Analgesic effects of antihistaminics.

The literature provides considerable evidence indicating that several, but not all antihistaminics, are indeed analgesic agents and some are analgesic adjuvants as well. Those for which effectiveness is reported includes diphenhydramine, hydroxyzine, orphenadrine, pyrilamine, phenyltoloxamine, promethazine, methdilazine, and tripelennamine. The proposed mechanisms of analgesic action of antihistaminics are reviewed and discussed. The literature suggests that more than one mechanism of action exists for them. There is considerable evidence suggesting that histaminergic and serotoninergic central pathways are involved in nociception and that antihistaminic drugs can modulate their responses (1). The evidence for a role for norepinephrine and dopamine and the effects of antihistaminics on them are less well established. Still other pathways have been proposed. A greater understanding of pain mechanisms will aid in elucidating the role of antihistaminics in analgesia.

Clinical pharmacokinetics of chlorpheniramine.

The clinical pharmacokinetics of chlorpheniramine are reviewed. Recent studies have established that the half-life of chlorpheniramine is longer than previously reported. Chlorpheniramine has a serum half-life of approximately 20 hours in adults, and elimination from the body is primarily by metabolism to monodesmethyl and didesmethyl compounds. The half-life is increased in the presence of renal dysfunction and decreased in children. The exact mechanism of the presystemic first-pass elimination and the effects of dose levels on the process presently are unclear. Biopharmaceutical and pharmacokinetic studies after single or multiple doses in humans reveal wide interindividual variations in pharmacokinetics. Age, dialysis, urinary pH and flow influence the elimination kinetics of chlorpheniramine. Attention is brought to major issues that need further clarification to optimize drug therapy with this antihistamine. The use of pharmacokinetic parameters of chlorpheniramine for clinical application is discussed.