Annals of Pharmacotherapy

Raggi, Paolo; Dickson, Natalie R; Boyne, Michael; Pereira, Roberto; Cooil, Bruce; Wattanasuwan, Norrapol; Russell, Douglas C

doi: 10.1345/aph.18071pmid: 9825077

BACKGROUND:Angiotensin-converting enzyme inhibitor (ACE-I) therapy reduces complications of acute myocardial infarction (MI) even when the therapy is started very early after an acute event. This study sought to determine whether administration of ACE-I therapy prior to acute MI is related to subsequent patient morbidity and mortality.METHODS:Chart review of 318 consecutive patients admitted between September 1995 and December 1996 with a diagnosis of acute MI. Outcome data were compared between patient groups receiving ACE-I therapy prior to infarction and those who were not.RESULTS:Sixty-four patients (20%) were receiving prior ACE-I therapy. They experienced smaller MIs, as determined by peak creatine kinase elevation (1066 ± 134 vs. 1510 ± 95 IU; p < 0.05), and fewer Q-wave infarctions (p < 0.05) than did patients who were not receiving prior treatment. The severity of coronary artery disease, defined by an angiographic score, was similar for the two groups. Mortality rates, including patients resuscitated from ventricular fibrillation, were similar within the first 72 hours of admission (3% vs. 2%; p = NS), but patients receiving prior ACE-I therapy showed a greater long-term in-hospital mortality rate (14% vs. 5%; p < 0.05) related to more heart failure deaths. Multivariate logistic regression analysis identified age, treatment with digoxin prior to acute MI, and left ventricular ejection fraction after infarction, but not ACE-I therapy taken prior to infarction, as significant independent predictors of mortality and combined morbidity and mortality.CONCLUSIONS:In a group of patients experiencing an acute MI, those receiving prior ACE-I therapy were more likely to sustain fewer transmural MIs and smaller infarcts. Chronic ACE-I therapy may have cardioprotective effects during acute myocardial ischemia.

Silvestri, Rosalia C; Bromfield, Edward B; Khoshbin, Shahram

doi: 10.1345/aph.18062pmid: 9825078

OBJECTIVE:To examine the seizure characteristics and electroencephalogram (EEG) abnormalities in psychiatric patients taking clozapine, given the estimate of a 10% cumulative risk of generalized seizures in this population.DESIGN:We reviewed all consecutive EEGs of ambulatory psychiatric patients taking clozapine performed at our laboratory during 1996 and 1997.SETTING:A university-affiliated urban teaching hospital.SUBJECTS:Twelve patients (4 F/8 M; mean age 40.1 y, range 20–63) had either presented with de novo ictal events within the first month of clozapine therapy (n = 8) or had EEGs recorded to assess seizure risk (n = 4).RESULTS:According to clinical history and interictal EEG findings, the patients were subdivided as follows: three patients with generalized tonic–clonic seizures, two with generalized myoclonic jerks (1 associated with simple partial seizures), two with complex partial seizures, and one with simple partial seizures. The EEGs revealed interictal epileptiform abnormalities (IEDs) in eight patients, two of whom had not had seizures. IEDs were focal or multifocal, with a predominance of left temporal foci. One patient showed a paroxysmal response to photic stimulation.CONCLUSIONS:Patients taking clozapine may be prone to partial seizures and focal EEG abnormalities as well as to generalized seizures and EEG abnormalities, as previously reported.

Kozyrskyj, Anita L; Mustard, Cameron A

doi: 10.1345/aph.18117pmid: 9825079

BACKGROUND:The Drug Programs Information Network (DPIN), Manitoba's (Canada) new electronic prescription database, is a valuable data source for pharmacoepidemiologic research. Pharmacies are required to submit to the DPIN all prescriptions for Pharmacare, the province's drug insurance plan, but submission of prescriptions for social assistance recipients and treaty status Indians is discretionary.OBJECTIVE:The completeness of the DPIN prescription database was assessed to determine whether treaty status Indians and social assistance recipients were underrepresented.DESIGN:Prescriptions dispensed during March 13–17, 1995, in a stratified sample of Manitoba pharmacies were linked to DPIN by prescription number to determine the proportions submitted for Indian Affairs, Social Services, and Pharmacare recipients. Pharmacare records in the DPIN were compared with original pharmacy records to evaluate data accuracy.RESULTS:Of 2196 Indian Affairs and 1879 Social Services prescriptions dispensed in 58 pharmacies, a corresponding prescription was found in the DPIN for 79.7% (98% CI 78.0% to 81.4%) and 90.1% (98% CI 88.8% to 91.4%) of prescriptions, respectively. These proportions were significantly lower than the estimated proportion of Pharmacare prescriptions submitted (93%, 98% CI 92.4% to 93.6%). Ninety-two percent of 8012 DPIN Pharmacare prescriptions matched the original prescription on the drug name, quantity, and days' supply.CONCLUSIONS:This study established that the DPIN is a valid and reliable data source for studying prescription use among the majority of Manitoban residents. However, the DPIN database has differential validity and underrepresents prescriptions dispensed for the aboriginal population.

Filice, Gregory A; McDougall, Beth C; Ercan-Fang, Nacide; Billington, Charles J

doi: 10.1345/aph.18151pmid: 9825080

OBJECTIVE:To report a case of neuroleptic malignant syndrome (NMS) associated with the use of olanzapine.CASE SUMMARY:A 67-year-old white man with bipolar disorder developed nausea and vomiting. After 12 days, he became confused, delirious, and manic. His only medications were olanzapine 10 mg/d and divalproex sodium 500 mg bid. He was admitted to a hospital and treated for dehydration and mania. Olanzapine was given on 6 of the first 7 hospital days. On hospital day 6, typical NMS developed with the body temperature increasing to 39.9 °C, obtundation, rigidity, tremor, diaphoresis, fluctuating pupillary diameter, labile tachycardia and hypertension, hypernatremia, and elevated serum creatine kinase. Olanzapine was stopped after hospital day 7, and the syndrome resolved by hospital day 12.DISCUSSION:The patient had all of the major manifestations of NMS. There was no other likely explanation for his illness and he received no other drug likely to be associated with the syndrome. This is the first case reported in which NMS was associated with olanzapine.

Wai, Amy O; Lo, Agnes MS; Abdo, Ayman; Marra, Fawziah

doi: 10.1345/aph.17448pmid: 9825081

OBJECTIVE:To report a case of acute interstitial nephritis (AIN) related to administration of vancomycin for the treatment of Staphylococcus aureus sternal wound infection, osteomyelitis, and infective endocarditis.CASE SUMMARY:Reports in the literature regarding vancomycin-induced AIN are scarce. We describe the fifth known case of AIN, in a 64-year-old white man who developed fever, maculopapular rash, acute renal failure, eosinophilia, and eosinophiluria after approximately 1 month of vancomycin treatment. The results of the renal biopsy were consistent with an allergic drug reaction. Four months after his initial episode of AIN, the patient was rechallenged with vancomycin for the treatment of S. aureus septic arthritis. One day after initiation of vancomycin, serum eosinophils started to rise, his urine tested positive for eosinophils, but his serum creatinine remained stable.CONCLUSIONS:Our case report and others from the literature suggest vancomycin causes allergic AIN. Clinicians should be aware of this adverse effect in an era of increasing use of vancomycin for treatment of resistant gram-positive organisms.

Phillips, Beth Bryles; Muller, Barbara A

doi: 10.1345/aph.18082pmid: 9825082

OBJECTIVE:To document a case of severe, progressive myopathy, myalgias, arthralgias, and weakness possibly caused by amlodipine in a patient with benign essential hypertension.CASE SUMMARY:A 52-year-old white woman with asthma and newly diagnosed hypertension was initiated on zafirlukast therapy for asthma and amlodipine therapy for hypertension. Two months later, the patient reported severe, generalized muscle and joint pain, muscle stiffness, and weakness. The zafirlukast was discontinued without resolution of symptoms. Laboratory tests revealed an elevated C-reactive protein. The amlodipine dosage was increased. Her symptoms persisted and further laboratory tests revealed a positive anti-nuclear antibody screen, and negative single- and double-stranded DNA antibody tests. After another amlodipine dosage increase, the patient experienced a sudden onset of left-sided facial numbness, facial weakness, and a severe headache. The patient was admitted to rule out a possible cerebrovascular event or a metabolic neurologic process. Magnetic resonance imaging showed no abnormalities. The patient discontinued the amlodipine and reported complete resolution of the neurologic symptoms after 4 days. One month later, zafirlukast was reinitiated without a return of symptoms.CONCLUSIONS:Amlodipine was not initially suspected as a cause of these symptoms because these effects are not commonly associated with amlodipine therapy. However, due to the temporal relationship and progression of symptoms with increasing amlodipine dosage, drug-related causes were eventually explored. Review of the medical literature suggests myalgias and arthralgias may be adverse effects common to dihydropyridine calcium-channel antagonists.

Stecker, Mark M; Kita, Mariko

doi: 10.1345/aph.18039pmid: 9825083

OBJECTIVE:To report a patient who developed the paradoxical effect of increasing electrical seizure activity and confusion with initiation of valproic acid therapy.CASE SUMMARY:A 25-year-old African-American woman with a hypothalamic hamartoma had an electroencephalogram (EEG) that demonstrated frequent bursts of generalized spike and wave activity. The prevalence of spike and wave activity increased dramatically and the patient became increasingly somnolent as valproic acid was added to carbamazepine and phenobarbital therapy. Her EEG and mental status changes resolved when the valproic acid was discontinued. There was a strong positive correlation between the prevalence of spike and wave activity and the valproic acid concentration, but not between spike and wave activity and the concentrations of carbamazepine or phenobarbital.DISCUSSION:Although this is a complex case, it is clear that the addition of valproic acid produced an increase in spike and wave activity. Possible mechanisms and pathophysiologic significance of this paradoxical effect are discussed in light of the differences between this epileptic syndrome and the primary generalized epilepsies.

Luer, Mark S; Rhoney, Denise H

doi: 10.1345/aph.18053pmid: 9825084

OBJECTIVE:To provide a comprehensive review of tiagabine, including its pharmacology, toxicology, pharmacokinetics, drug interactions, efficacy, adverse effects, and dosing recommendations.DATA SOURCES:A computerized search of the MEDLINE database from 1966 to December 1997 was used to identify publications related to tiagabine and nipecotic acid derivatives. Included in this review was information gathered from scientific meetings. Manufacturer's information was used when there was no primary literature.DATA SYNTHESIS:Tiagabine amplifies γ-aminobutyric acid (GABA) neurotransmission, the predominant inhibitory neurotransmitter in the brain. Its mechanism of action is selective and has shown promise as an antiepileptic drug (AED) in patients with seizures refractory to other pharmaceutical products. Tiagabine exhibits dose-independent absorption, 90–95% bioavailability, high protein binding (96%), metabolism via hepatic cytochrome P450 enzymes (CYP3A subfamily), and displays first-order elimination pharmacokinetics. The mean plasma half-life is 5–8 hours. Concomitant medications that induce hepatic metabolism enhance tiagabine elimination; metabolism is reduced in patients with hepatic dysfunction. Adverse events of tiagabine typically involve the central nervous system, have been mild to moderate in intensity, and also have been transient in nature.CONCLUSIONS:Tiagabine has demonstrated a good safety profile and, while it has not been demonstrated to be superior to other second-line AEDs for partial seizures, its safety and select mechanism of action warrant its further evaluation in the clinical setting. Tiagabine should be a good alternative add-on agent for patients with unsatisfactory seizure control or intolerable adverse effects of traditional therapies; thus, this agent should be made available to these patients.

Kendle, Julie B; Fan-Havard, Patty

doi: 10.1345/aph.17312pmid: 9825085

OBJECTIVE:To review the clinical pharmacology and microbiology of cidofovir in the therapy of cytomegalovirus (CMV) disease.DATA SOURCES:Pertinent literature was identified via a MEDLINE search (October 1986–February 1997), and data from abstracts presented at recent scientific meetings were also included; unpublished information was provided by the manufacturer.STUDY SELECTION:Antiviral activity data were included if widely accepted methodology was used. All clinical data currently available from human studies were also included.DATA SYNTHESIS:Cidofovir is similar to ganciclovir in mechanism of action; however, cidofovir does not require viral enzymes for activation. Although the half-life of cidofovir in plasma is only 2.6 hours, the intracellular half-life may be much longer, allowing efficacy with biweekly maintenance dosing. In vitro, cidofovir appears to be equally or more effective than the other agents currently available for the treatment of CMV. In vivo, cidofovir appears to be effective in delaying the progression of CMV retinitis, although no clinical trials to date have directly compared cidofovir with either ganciclovir or foscarnet. Current intravenous dose recommendations are 5 mg/kg once weekly for two doses (induction), and then 5 mg/kg once every other week (maintenance). Since cidofovir is cleared almost entirely by the kidneys, dosage adjustments must be made in patients with impaired renal function. Disadvantages of cidofovir primarily include its risks of adverse drug reactions, such as nephrotoxicity, which is likely to occur in up to 50% of patients if appropriate preventative measures are not taken. Neutropenia and constitutional reactions to probenecid are also commonly encountered during the course of cidofovir therapy.CONCLUSIONS:Cidofovir is the first acyclic phosphonate nucleoside antiviral agent to be approved for general use in the US. In addition to delaying the progression of CMV retinitis, cidofovir may provide some protective benefits to patients at risk for developing the disease and may be active against certain strains of virus resistant to other currently available therapies. Another advantage of cidofovir is its infrequent dosage schedule, which may prove beneficial in patients who are not compliant with daily intravenous dosing regimens. When determining the appropriate treatment for a patient with CMV retinitis, the benefits of using cidofovir must be weighed carefully against the risk of potentially serious adverse effects.

Etminan, Mahyar; Wright, James M; Carleton, Bruce C

doi: 10.1345/aph.17333pmid: 9825086

OBJECTIVE:To introduce concepts that may assist pharmacists in the use and application of scientific evidence in clinical practice. These concepts are followed by examples of clinical trials as well as case scenarios that guide the reader through solving clinical problems using the tools discussed in the article.BACKGROUND:The introduction of evidence-based practice in the 1990s has had a positive impact on the practices of medicine and pharmacy. Part of this impact has been in the area of drug therapy. Although much literature has been published on the principles of evidence-based practice in the past few years, most of this material was intended for practicing physicians. We are not aware of any articles on the use of the evidence-based principles intended for clinical pharmacists. We are also aware that discussing all of these principles is an enormous task and thus beyond the scope of this article. Therefore, we focused this discussion on a brief summary of different study designs, factors affecting the strength of scientific evidence, and interpretation of the data. An approach in the use of these concepts is discussed through the use of case scenarios.RECOMMENDATIONS:Clinical pharmacists must use concepts in evidence-based practice when making pharmacotherapeutic decisions.