Lucinda G. Miller

Metoclopramide-Induced Movement Disorders Clinical Findings With a Review of the Literature

Metoclopramide, a dopamine-2 receptor antagonist used for various gastrointestinal disorders, may cause or exacerbate a variety of extrapyramidal movement disorders. To draw attention to the frequent occurrence of metoclopramide-induced movement disorders, we identified and studied 16 patients who had been exposed to this neuroleptic. The average age at onset was 63 years (range, 24 to 85 years), and women outnumbered men 3 to 1. Tardive dyskinesia was the most common movement disorder (n = 10 [63%]). Five patients had metoclopramide-induced parkinsonism, 1 patient had tardive dystonia, and 1 patient had akathisia. The average duration of exposure prior to onset of movement disorders was 12 months (range, 1 day to 4 years). Therapy was continued for an average of 6 months (range, 1 day to 2 years) after the onset of symptoms, reflecting clinical nonrecognition of the movement disorder and its relationship to metoclopramide. To prevent persistent and disabling movement disorders, long-term use of metoclopramide should be avoided, and patients should be carefully observed for potential neurologic reactions.

White Paper on Herbal Products

: Individuals increasingly are taking a more active role in their health care, and herbal products have emerged as a common choice among self-care therapies. Pharmacists are active participants in the care of patients who are taking herbal products. Currently, most pharmacists are not educated adequately about herbal products and other types of alternative medicine. Furthermore, good information about many of these products is not available. These combined factors present a challenge for pharmacists as they seek to provide optimal care and counseling to patients who use herbs or supplements. We recommend the following actions to place pharmacists in better positions as effective agents protecting public safety: Regulations should be implemented at a federal level to require basic levels of standardization and quality control in the manufacture of herbal products. Indexing terms in medical bibliographic systems should be expanded to target herbal products. Funding should be increased for scientific research evaluating herbal products. Pharmacy schools should include a competency statement in their curricula regarding herbal medicines. Continuing education in herbal products should be available and encouraged for all pharmacists. Pharmacists should approach the use of all therapeutic interventions with scientific rigor, whether they are traditional or complementary in nature. Patients will benefit as more information is known and widely disseminated. By actively embracing the responsibility for counseling individuals on the appropriate use of herbal products, pharmacists will become a recognized source of expert information in this rapidly growing area, yielding important improvements in the quality of care.

Recent Developments in the Study of the Effects of Cigarette Smoking on Clinical Pharmacokinetics and Clinical Pharmacodynamics

SummaryWith the ever-increasing population of cigarette smokers, the potential for cigarette smoke to affect drug therapy both pharmacokinetically and pharmacodynamically is significant. The overriding pharmacokinetic effect is increased drug metabolism through the induction of liver enzymes. The constituents of tobacco smoke, primarily nicotine, have their own pharmacological effects which may potentiate or antagonise the desired pharmacological effect of a particular drug, thereby affecting its efficacy. Furthermore, end-organ responsiveness may also be altered by tobacco. These latter 2 aspects constitute altered clinical pharmacodynamics.Approximately 30 drugs have been evaluated in terms of cigarette smoking. Induction of liver enzymes has been shown to increase the metabolism of imipramine, meprobamate, oestrogens, pentazocine, phenylbutazone, theophylline and warfarin. Nicotine has been shown to inhibit diuresis, alter ulcer healing, impair subcutaneous absorption, affect protein binding and stimulate catecholamine release; these effects have been evaluated in terms of therapy with frusemide (furosemide), histamine H2-antagonists, insulin, lignocaine (lidocaine) and α-blockers, respectively. The interactions have not been correlated with clinical significance in all cases. Diminished end-organ responsiveness may account for reduced drowsiness in smokers receiving chlorpromazine and benzodiazepines, compared with non-smokers. Smoking has been associated with diminished pain tolerance, requiring increased dosages of morphine, pethidine (meperidine) and propoxyphene. Enzyme-inducers such as carbamazepine, Phenytoin and phenobarbitone appear to be minimally affected by cigarette smoke, perhaps because hepatic enzymes are already maximally stimulated. Codeine, corticosteroids and nortriptyline do not appear to be affected by cigarette smoke. The bioavailability of glutethimide is higher in smokers, but this has not been associated with greater efficacy. The effect of smoking on paracetamol (acetaminophen) has been variable, depending on the extent of smoking, and does not appear to be of clinical significance.

Application of Actigraphy in the Clinical Setting: Use in Children With Attention-Deficit Hyperactivity Disorder

Clinicians rely primarily on subjective behavioral questionnaires in assessing attention‐deficit hyperactivity disorder (ADHD). The new mini‐motion logger actigraph, which is a wrist‐worn minicomputer, can add an objective element to this assessment and is especially useful in children due to its small size. We applied this technology as an outcome measure in evaluating drug therapy in two children with ADHD who were receiving methylphenidate and pemoline, respectively. We also assessed preliminary findings from an additional 13 children.

Effect of concurrent sucralfate administration on the absorption of erythromycin.

To determine the influence of sucralfate on the absorption of erythromycin, prior to evaluating its efficacy in decreasing erythromycin‐associated gastrointestinal (GI) intolerance, we assessed pharmacokinetic parameters in six healthy adult volunteers. Erythromycin ethylsuccinate administered alone or with sucralfate as a single dose was compared. Sucralfate did not significantly alter the elimination rate constant, half‐life, or area under the curve for erythromycin ethylsuccinate. It is therefore unlikely that efficacy of erythromycin ethylsuccinate will be altered when sucralfate is coadministered.

Disposition of Olsalazine and Metabolites in Breast Milk

This study examined the disposition of olsalazine and its metabolites into breast milk after the ingestion of a single dose of 500 mg olsalazine. Blood and serum samples were obtained for 48 hours after the ingestion of 500 mg olsalazine in a 39‐year‐old lactating woman. Blood samples were obtained at .0, .5, 1, 2, 4, 6, 24.5, 26, and 48 hours. Maternal milk samples were obtained at .0, .5, 2, 4, 6, 14, 24, 28, 36, and 48 hours. Olsalazine and olsalazine‐S underwent high‐pressure liquid chromatography analysis, and 5‐ASA and Ac 5‐ASA underwent fluorometric detection. Acetylated‐5‐ASA achieved concentrations of .8, .86, and 1.24 μmol/L in breast milk at 10,14, and 24 hours, respectively. Olsalazine, olsalazine‐S, and 5‐ASA were undetectable in the breast milk for 48 hours after drug administration. Clinically significant drug exposure in the breast‐fed infant is unlikely after a maternal single dose of olsalazine. Idiosyncratic hypersensitivity, however, remains a possibility even if the infant is exposed to only minute quantities.

Selecting nonsteroidal anti-inflammatory drugs: pharmacologic and clinical considerations.

An increasing number of nonsteroidal anti-inflammatory drugs (NSAIDs) are available to treat a variety of conditions. There exist little comparative data examining efficacy for all NSAIDs for a particular illness. The major factors governing selection of these agents relate to the patients condition and the drugs characteristics. Once efficacy has been established, selection of an NSAID is then determined by side-effect profile, potential for drug interactions, dosing frequency, and cost. This review presents a listing of commercially available NSAIDs, cost comparisons for average daily doses of NSAIDs, and the conditions and drug characteristics that might influence the choice of an NSAID.

Physician Assistants and Nurse Practitioners

TO THE EDITOR: The American College of Physicians recently voiced its position on the role of nonphysician health care providers [1]. The College recognizes the need for an expanded role of nonphysicians to meet future demands for primary health care. The debate on midlevel practitioners has previously focused on physician assistants and nurse practitioners. I suggest that a third group of practitionersclinical pharmacistsalso be considered. Equipped with extensive didactic and clinical pharmacology training, PharmDs and other clinical pharmacists are often called on by physicians, physician assistants, and nurse practitioners for therapeutic consultations. (At our institution, 9 hours of pharmacology and 10 hours of applied therapeutics and pharmacology are required, in addition to other pharmacy-related courses such as biopharmaceutics and pharmacokinetics.) A logical extension of a clinical pharmacists professional expertise would be to acknowledge and formalize this relationship by extending prescriptive authority under physician protocol. Seven states currently authorize prescriptive authority for pharmacists, and other states are considering similar legislation [2]. In these models, only clinical pharmacists interested in this role apply to a state authority for credentialing for prescriptive authority under protocol or under the auspices of an attending physician or health care facility. For those physicians who have worked with PharmDs or other clinical pharmacists, the model would offer a welcome relief. Working with physician assistants and nurse practitioners who have diagnostic prowess, the pharmacy practitioners, if allowed to handle the treatment issues (for example, drug therapy selection, monitoring, and modifying and surveillance of adverse effects, drug therapy, and patient counseling), could allow more patients to be seen within a given period. Any professional with prescribing authority should participate in a checks-and-balances system whereby the prescription is checked by another professional before it is dispensed. To date, this role has been filled by dispensing pharmacists. The Colleges sixth policy position statement advocates a system in which physician assistants and nurse practitioners dispense their own prescription drugs [1]. It is interesting that an association representing physicians has ignored the daily telephone calls physicians receive from pharmacists correcting inaccurate and sometimes dangerous prescriptions that the physician assistants and nurse practitioners have written. To deny these professionals the value of this check system would be a disservice not only to these midlevel practitioners but, more importantly, to the patients they serve. I strongly urge the College to reconsider their position on this matter. Health care reform is upon us, whether legislated or not. An increased role for nonphysician health care providers is one of the few possible solutions to meet the need for primary care, especially in rural areas. Clinical pharmacists with prescriptive authority should be considered a part of the solution.

Selective Effect of Diclofenac in the Treatment of Osteoarthritis Versus Dysmenorrhea

D iclofenac, a phenylacetic acid derivative, is the newest of the nonsteroidal anti-inflammatory drugs (NSAID5) to be marketed in the United States.1 Diclofenac is sequestered into the synovial fluid where it imparts an extended duration of action despite its short half-life of 2 hours.1 Because of this pharmacokinetic principle, diclofenac may offer a focused effect of enhanced anti-inflammatory effect in conditions involving the synovial fluid such as osteoarthritis and rheumatoid arthritis. Conversely, because of its rapid excretion, its efficacy for a nonsynovial condition such as dysmenorrhea may be diminished. We report herein a case which appears to support this theory.

Ibuprofen and Antihypertensive Drugs

Excerpt To the editor: I read with interest the article by Radack and associates (1) on the interaction of Ibuprofen and antihypertensive drugs. Although the dosage studied was that normally used v...