Complex Pharmacotherapy Research Articles

GRP-144 Potential Drug-Drug Interactions in Patients Admitted to a Trauma Hospital

BackgroundThe current complexity of pharmacotherapy in trauma patients increases the risk of drug-drug interactions (DDIs).PurposeTo identify potential DDIs (severe/moderate) and their clinical relevance in patients admitted to a tertiary trauma...

Pleiotropic effects of trimetazidine

Aim. To investigate potential pleiotropic effects of trimetazidine (PreductalMB) in patients with stable effort angina. Material and methods. This randomised controlled clinical study included 95 patients with Functional Class I–III stable effort angina and Stage 2–3 arterial hypertension. Clinical effectiveness of pharmacological therapy was assessed by expert-evaluated subjective and objective criteria, with the calculation of the treatment effectiveness index (%) (Patent No. 58859 A [8],Ukraine). Results. The complex pharmacological therapy of coronary heart disease (CHD) was twice as effective after the addition of trimetazidine, due to increased antianginal action and exercise capacity. Trimetazidine also reduced energy deficiency and tissue hypoxia in myocardial ischemia. Pleiotropic effects of trimetazidine (antiatherosclerotic, anti-inflammatory, and stress-limiting) could justify the extended indications for this medication. Conclusion. In a randomised clinical trial including patients with stable effort angina, the effectiveness of complex pharmacotherapy was doubled by additional administration of trimetazidine (Preductal MB 35 mg twice per day for 6 weeks), due to increased antianginal effects and exercise capacity.

Geriatric pharmacology and pharmacotherapy education for health professionals and students: a systematic review

The rate of medication errors is high, and these errors can cause adverse drug reactions. Elderly individuals are most vulnerable to adverse drug reactions. One cause of medication errors is the lack of drug knowledge on the part of different health professionals. Medical curricula have changed in recent years, resulting in less education in the basic sciences, such as pharmacology. Our study shows that little curricular time is devoted to geriatric pharmacology and that educational programmes in geriatric pharmacology have not been thoroughly evaluated. While interest in pharmacology education has increased recently, this is not the case for geriatric pharmacology education. Education on geriatric pharmacology should have more attention in the curricula of health professionals, given the often complex pharmacotherapy in elderly patients. Educational topics should be related to the known risk factors of medication errors, such as polypharmacy, dose adjustments in organ dysfunction and psychopharmacotherapeutics. Given the reported high rates of medication errors, especially in elderly patients, we hypothesized that current curricula do not devote enough time to the teaching of geriatric pharmacology. This review explores the quantity and nature of geriatric pharmacology education in undergraduate and postgraduate curricula for health professionals. Pubmed, Embase and PsycINFO databases were searched (from 1 January 2000 to 11 January 2011), using the terms 'pharmacology' and 'education' in combination. Articles describing content or evaluation of pharmacology education for health professionals were included. Education in general and geriatric pharmacology was compared. Articles on general pharmacology education (252) and geriatric pharmacology education (39) were included. The number of publications on education in general pharmacology, but not geriatric pharmacology, has increased over the last 10 years. Articles on undergraduate and postgraduate education for 12 different health disciplines were identified. A median of 24 h (from 15 min to 4956 h) devoted to pharmacology education and 2 h (1-935 h) devoted to geriatric pharmacology were reported. Of the articles on education in geriatric pharmacology, 61.5% evaluated the teaching provided, mostly student satisfaction with the course. The strength of findings was low. Similar educational interventions were not identified, and evaluation studies were not replicated. Recently, interest in pharmacology education has increased, possibly because of the high rate of medication errors and the recognized importance of evidence-based medical education. Nevertheless, courses on geriatric pharmacology have not been evaluated thoroughly and none can be recommended for use in training programmes. Suggestions for improvements in education in general and geriatric pharmacology are given.

Few therapy options available for carbapenem-resistant Klebsiella

Last year’s spread of deadly carbapenemase-producing Klebsiella pneumoniae (KPC) bacteria at the National Institutes of Health (NIH) Clinical Center in Bethesda, Maryland, posed complex pharmacotherapy issues for the research hospital’s pharmacy staff. The outbreak at the 243-bed Clinical Center began after the arrival of a 43-year-old lung transplant recipient from a New York hospital. According to NIH, the patient was known shortly before her arrival in June 2011 to be colonized with KPC, and contact isolation procedures were implemented to prevent the spread of the bacterium to others at the hospital. As described in a report in the August 22 issue of Science Translational Medicine, the containment plan failed. Molecular analysis confirmed that over the course of several months, resistant bacteria originating from the New York patient spread to 17 other patients. By the time the outbreak ended last December, six people had died from their infection and five died of an underlying disease while harboring the bacteria.

Patient‐reported convenience of once‐daily versus three‐times‐daily dosing during long‐term studies of pramipexole in early and advanced Parkinson’s disease

In chronic diseases including Parkinson's disease (PD), complex pharmacotherapy dosing schedules are reported to reduce adherence, perhaps leading to less-effective symptom control and, in PD, more erratic stimulation of dopamine receptors. However, blinded clinical-trial designs preclude direct comparisons of adherence to various schedules. In two double-blind (DB) studies of early PD and one of advanced PD, subjects received three-times-daily (t.i.d.) pramipexole or placebo. In open-label (OL) extensions, subjects took extended-release, once-daily (q.d.) pramipexole. At 24 or 32 OL weeks, q.d. versus t.i.d. dosing preference was surveyed by questionnaire. Of 590 DB-trial completers with early PD, 511 entered the OL extension. Of 374 survey respondents, 94.4% preferred q.d. dosing (72.2% of them found it 'very much more convenient' and 27.8%'more convenient'), 2.7% preferred t.i.d., and 2.9% chose 'no difference'. Of 465 DB-trial completers with advanced PD, 391 entered its OL extension. Of 334 survey respondents, 88.9% preferred q.d. dosing (59.9% of them found it 'very much more convenient' and 40.1%'more convenient'), 5.7% preferred t.i.d., and 5.4% chose 'no difference'. Results excluding DB-placebo recipients were highly similar. In this first direct comparison of patient preference for q.d. versus t.i.d. dopamine-agonist dosing, patients with early or advanced PD had a strong preference for q.d. rather than t.i.d. pramipexole. The high proportion of advanced-PD patients declaring this preference indicates that it does not depend on whether a patient is taking concomitant PD medications dosed more frequently than q.d.

Drug-drug interactions in patients admitted to an infectious diseases unit in a trauma hospital

BackgroundThe current complexity of pharmacotherapy in patients with orthopaedic infections increases the risk of drug-drug interactions (DDI).PurposeThe aim of this study is to identify potential DDI (severe/moderate) and its clinical...

Adverse drug events in an intensive care unit of a university hospital

Adverse drug events (ADEs) are harmful and occur with alarming frequency in critically ill patients. Complex pharmacotherapy with multiple medications increases the probability of a drug interaction (DI) and ADEs in patients in intensive care units (ICUs). The objective of the study is to determine the frequency of ADEs among patients in the ICU of a university hospital and the drugs implicated. Also, factors associated with ADEs are investigated. This cross-sectional study investigated 299 medical records of patients hospitalized for 5 or more days in an ICU. ADEs were identified through intensive monitoring adopted in hospital pharmacovigilance and also ADE triggers. Adverse drug reactions (ADR) causality was classified using the Naranjo algorithm. Data were analyzed through descriptive analysis, and through univariate and multiple logistic regression. The most frequent ADEs were ADRs type A, of possible causality and moderate severity. The most frequent ADR was drug-induced acute kidney injury. Patients with ADEs related to DIs corresponded to 7% of the sample. The multiple logistic regression showed that length of hospitalization (OR = 1.06) and administration of cardiovascular drugs (OR = 2.2) were associated with the occurrence of ADEs. Adverse drug reactions of clinical significance were the most frequent ADEs in the ICU studied, which reduces patient safety. The number of ADEs related to drug interactions was small, suggesting that clinical manifestations of drug interactions that harm patients are not frequent in ICUs.

Psychiatric comorbidity in patients with epilepsy: a population-based study

Patients with epilepsy often suffer from concomitant psychiatric disorders. Treatment patterns and the extent of comorbidity are insufficiently investigated and appropriate methods are scarce. The purpose of the study was to estimate the prevalence of psychiatric comorbidity in patients with epilepsy and to investigate prescription patterns of drugs prescribed for psychiatric disorders in epilepsy. Prescription data from the Norwegian Prescription Database (NorPD) regarding the use of CNS-active drugs included anonymous data from almost 190,000 patients and 1.1-1.3 million prescriptions per year (2004-2007). Searches were based upon use of specific drugs, defined daily doses, number of patients, prescriptions, gender, and age. Reimbursement codes related to psychiatric diagnosis were used as indicators for clinical use. The prevalence of psychiatric comorbidity in patients with epilepsy was estimated to be 32%. There were 56% women and 44% men participating in the study. Among patients using antidepressants two thirds were women, but no gender differences were seen with antipsychotic medication. Antidepressants and antipsychotics were used 3.4 (20.9%) and 5.8 (13.4%) times more frequently than in the general population, accounting for 7.88 and 1.99 defined daily doses (DDDs)/1,000 inhabitants/day/year respectively. Lamotrigine was the most commonly used antiepileptic drug (AED) in epilepsy, accounting for 33% of the use of AEDs (in total 5.65 DDDs/1,000 inhabitants/day/year). The use of benzodiazepines was 9.55 DDDs/1,000 inhabitants/day/year. The patients had complex pharmacotherapy with two to eight concomitant drugs. The present study gives an estimate of psychiatric comorbidity of 32% in patients with epilepsy in a nation-wide population. The pharmacotherapy in this patient population is complex. The results provide valuable data on prescription patterns that contribute to pharmacovigilance on a national scale.

Administrative claims data analysis of nurse practitioner prescribing for older adults

This paper is a report of a study to identify the patterns of prescribing by primary health care nurse practitioners for a cohort of older adults. The older adult population is known to receive complex pharmacotherapy. Monitoring prescribing to older adults can inform quality improvement initiatives. In comparison to other countries, research examining nurse practitioner prescribing in Canada is limited. Nurse practitioner prescribing for older adults is relatively unexplored in the international literature. Although commonly used to study physician prescribing, few studies have used claims data from drug insurance programmes to investigate nurse practitioner prescribing. Drug claims for prescriptions written by nurse practitioners from fiscal years 2004/05 to 2006/07 for beneficiaries of the Nova Scotia Seniors' Pharmacare programme were analysed. Data were retrieved and analysed in May 2008. Prescribing was described for each drug using the World Health Organization Anatomical Therapeutic Chemical code classification system by usage and costs for each fiscal year. Antimicrobials and non-steroidal anti-inflammatory drugs consistently represented the top ranked groups for prescription volume and cost. Over the three fiscal years, antimicrobial prescription rates declined relative to rates of other groups of medications. Prescription volume per nurse doubled and cost per prescription increased by approximately 20%. Prescription claims data can be used to characterize the prescribing trends of nurse practitioners. Research linking patient characteristics, including diagnoses, to prescriptions is needed to assess prescribing quality. Some potential areas of improvement were identified with antimicrobial and non-steroidal antiinflammatory selection.

Tradução e validação para o português do Medication Regimen Complexity Index

The complexity of pharmacotherapy is a result of a multiplicity of prescribed regimen factors, including the number of different drugs in the regimen, the number of dosage units per dose, the total number of prescribed doses per day and administration instructions. The Medication Regimen Complexity Index (MRCI) is a specific, reliable and valid tool used to measure the complexity of pharmacotherapy, originally developed in English language. Transcultural translation and validation of this tool into Brazilian Portuguese. A cross-sectional study was developed with 95 type-2 diabetes patients, receiving multiple medications. The validation process included translation into Portuguese, back-translation and pre-test of the tool, creating a new version called the Pharmacotherapy Complexity Index (PCI). The psychometric parameters were assessed, including convergent validity, discriminant validity and reliability (interclass and test-retest correlation). The complexity of pharmacotherapy measured by the MRCI-Brazil had an average score of 15.7 points (SD=8.36). MRCI-Brazil showed significant correlation with the number of medications (r=0.86; p<0.001) and age of patients (r=0.28, p=0.005). Interrater reliability analysis found an intra-class correlation (ICC) of 0.99 (p<0.001) and test-retest correlation was of 0.997 (p<0.001). The results have shown that the Brazilian version of the MRCI presents adequate validity and reliability, and may be useful in clinical practice and research involving the analysis of the drug regimen complexity.

Pharmacotherapy and Postdischarge Outcomes of Child Inpatients Admitted for Aggressive Behavior

: (1) To ascertain the use rates of specific pharmacotherapy strategies for child psychiatric inpatients with aggressive behavior from preadmission care through 12 months after discharge, and (2) To examine the associations between these strategies and postdischarge outcomes. : Prospective follow-up of eighty-three 5- to 13-year-old children admitted to acute inpatient care for aggressive behavior in the context of a disruptive behavior disorder. Treatment and symptom severity data were obtained at admission, discharge, and 3, 6, and 12 months after discharge between 1998 and 2001. : Utilization. The number of concurrent medications increased over assessment times. Changes in children's pharmacotherapy occurred most frequently during hospitalization and from discharge to 3 months after discharge. Treatment with antipsychotics and mood stabilizers increased over assessment times, whereas selective serotonin reuptake inhibitor (SSRI) treatment decreased. Outcomes. Children treated with stimulants and risperidone 3 months after discharge had significantly improved behavioral ratings, adjusted for admission scores and concurrent medications. Children treated with SSRIs at 6 months after discharge had higher problem severity ratings. Those who maintained lithium and SSRI treatment between 6 and 12 months showed improvements. : The complexity of pharmacotherapy for child inpatients ratchets upwards from admission through 1 year after discharge. Hospital-initiated treatment is commonly altered soon after discharge. Within the limitations of observational methodology, the postdischarge outcomes seem related to specific pharmacotherapy regimens.

Less Is More: Inpatient Management of a Child With Complex Pharmacotherapy

COMPLEX INPATIENT PHARMACOTHERAPY VIGNETTE An 11-year-old boy was admitted to an acute inpatient psychiatric setting because of a recent exacerbation of physical aggression, accompanied by long-standing problems with verbal aggression, irritability, dysphoria, and sleep disturbance. His family history was notable for domestic violence, substance abuse by his father, depression in his mother, and divorce. Initial treatment with methylphenidate 10 mg three times daily at 8 years of age improved his ability to focus, but this benefit dissipated during the next year. Two years ago, the methylphenidate was discontinued and Adderall XR was initiated and titrated up to 60 mg/day. Clonidine was subsequently added and titrated up to 0.1 mg four times daily, with an initial improvement in agitation during the day and some improvement in sleep, but these effects seemed to have waned. In light of ongoing irritability and dysphoria, sertraline was added and titrated up to a dose of 150 mg at bedtime. There were some improvements in mood noted, but the patient remained irritable and became somewhat activated. Valproic acid was added and titrated to a blood level of 105 without benefit, so quetiapine was added and titrated to a dose of 100 mg at 8:00 A.M. and 4:00 P.M. and 200 mg at bedtime. At the time of admission, the parents believed that medication was having no demonstrable benefit. On examination, the boy was hyperactive, impulsive, inattentive, and irritable, with no psychotic symptoms. Blood pressure was 90/58, with a pulse of 68. How would you approach this patient pharmacologically?

Polypharmacy in HIV: Impact of Data Source and Gender on Reported Drug Utilization

Drug use in HIV is complex and may involve multiple therapeutic and nontherapeutic agents including prescription, over-the-counter, complementary and alternative medicine, and social/recreational drugs. This study was designed to assess the extent of such drug use in HIV-infected men and women. One hundred four adults were recruited through the HIV Ontario Observational Database from HIV outpatient clinics throughout Ontario, Canada. Patient demographics and data on drug use and physician awareness of drug use were collected through in-person interviews and medical chart review. All patient interviews and 96% of medical charts revealed the use of at least one drug. Eighty-five percent of patients reported use of antiretroviral medications; nearly 70% used highly active antiretroviral therapy. Patients used significantly more drugs by patient report (15.7 +/- 7.7) than by medical chart review (8.4 +/- 5.0) reporting up to 39 drugs per person. Pill burden was substantial, averaging 20.7 +/- 12.5 and ranged up to 69 "pills-per-day." Patient-reported physician awareness of drug use was highest for prescription drugs and lowest for social/recreational drugs; correspondingly agreement between medical chart and patient report ranged from 80% for antiretrovirals to 10% for non-prescribed drugs. The drug and pill burden faced by patients with HIV is considerable. Prevalence of use for specific drug classes varied with both data source and gender while number of drugs used differed only by data source. Our findings emphasize the complexity of pharmacotherapy in HIV and the need for comprehensive drug assessment, particularly because of the risks of drug-drug interactions and decreased adherence secondary to therapeutic complexity.

Polypharmacy in HIV: Impact of Data Source and Gender on Reported Drug Utilization

Drug use in HIV is complex and may involve multiple therapeutic and nontherapeutic agents including prescription, over-the-counter, complementary and alternative medicine, and social/ recreational drugs. This study was designed to assess the extent of such drug use in HIVinfected men and women. One hundred four adults were recruited through the HIV Ontario Observational Database from HIV outpatient clinics throughout Ontario, Canada. Patient demographics and data on drug use and physician awareness of drug use were collected through in-person interviews and medical chart review. All patient interviews and 96% of medical charts revealed the use of at least one drug. Eighty-five percent of patients reported use of antiretroviral medications; nearly 70% used highly active antiretroviral therapy. Patients used significantly more drugs by patient report (15.7 ± 7.7) than by medical chart review (8.4 ± 5.0) reporting up to 39 drugs per person. Pill burden was substantial, averaging 20.7 ± 12.5 and ranged up to 69 "pills-per-day." Patient-reported physician awareness of drug use was highest for prescription drugs and lowest for social/recreational drugs; correspondingly agreement between medical chart and patient report ranged from 80% for antiretrovirals to 10% for nonprescribed drugs. The drug and pill burden faced by patients with HIV is considerable. Prevalence of use for specific drug classes varied with both data source and gender while number of drugs used differed only by data source. Our findings emphasize the complexity of pharmacotherapy in HIV and the need for comprehensive drug assessment, particularly because of the risks of drug–drug interactions and decreased adherence secondary to therapeutic complexity.

Antipsychotic medication coprescribing in a large state hospital system.

To systematically characterize antipsychotic medication coprescribing ('polypharmacy') in a large state hospital system. All antipsychotic prescriptions written for all adult in-patients (N = 8212) in New York state-run civil facilities for the year 1999 were identified using the Integrated Research Database (IRDB) created by the Information Systems Division of the Nathan Kline Institute for Psychiatric Research. Antipsychotics were considered to be intentionally coprescribed only when both were prescribed for an overlapping period of 28 days. Coprescribing of typical, atypical, and depot antipsychotics comprised 31% of antipsychotic prescribing episodes. Medications were usually coprescribed with medications from outside their own antipsychotic class. Patient factors, such as age, diagnosis, and history of prior hospitalization, affected coprescribing rates (p < 0.001 for all indicated variables). Atypical antipsychotic medications were less likely to be given with another antipsychotic than were oral or depot typical medications. Coprescribing of antipsychotic drugs is a common practice in the New York State hospital system. The analysis of large clinical databases can yield valuable information about the kinds of complex pharmacotherapy regimens actually utilized in the treatment of the most severely ill patients.

Brain natriuretic peptide-guided therapy for heart failure

The drug treatment of heart failure, once simple, has become complex. Apart from a loop diuretic and digoxin, most patients should now be receiving an angiotensin-converting enzyme inhibitor (or angiotensin II receptor blocker), a beta-blocker and spironolactone. Newer drugs, such as endothelin-receptor antagonists and combined blockers of converting-enzyme and neutral endopeptidase, might soon become available. When to introduce these drugs and what dose is optimal for any individual, are questions that currently vex clinicians. We proposed that plasma levels of the cardiac hormone brain natriuretic peptide (BNP, or better, its 1-76 amino-acid N-terminal fragment, N-BNP), would provide an objective index for guiding drug treatment in patients with established, stable cardiac failure. In a pilot study, 69 patients were randomized to drug treatment based on clinical criteria, or based on plasma levels of N-BNP. After a median follow-up of 9.6 months, those in the N-BNP group had fewer clinical end-points than those in the group managed by clinical criteria alone (19 vs 54; P= 0.02). These preliminary data encourage the concept that the increasingly complex pharmacotherapy for heart failure, both chronic (as in this trial) and acute, might best be guided by an objective measure such as plasma levels of BNP or N-BNP.

Wide Complex Tachycardia

Wide complex tachycardias present diagnostic challenges for emergency physicians. The history, physical examination, and ECG provide information required to arrive at the correct diagnosis. When a previous history of heart disease exists, VT should be suspected; however, no single clinical feature is sufficiently reliable for distinguishing VT from SVT. Patients with VT may tolerate their dysrhythmias for several hours and maintain hemodynamic stability. ECG analysis is the most useful process in differentiating SVT and VT. Characteristics suggestive of VT include evidence of AV dissociation, QRS duration of longer than 0.16 seconds, and QRS axis between -90 degrees +/- 180 degrees. Predictive QRS morphologic criteria also have been established for VT. A four-step approach to ECG analysis has been reported to accurately identify patients with VT, but prospective validation in an ED setting is lacking. The initial approach to treating patients with wide QRS tachycardias depends on hemodynamic stability. Until the identify of a dysrhythmia is certain, consider all patients to be suffering from VT. Unstable patients require immediate cardioversion. Acute treatment of stable patients includes lidocaine or procainamide. Adenosine is appropriate when wide QRS SVT is the diagnosis, and it also has been used as a diagnostic aid to identify dysrhythmias. Reports of complications with the use of adenosine as a diagnostic agent have not yet appeared but may occur after sufficient numbers of cases have accumulated. Magnesium sulfate may be useful in refractory cases of VT and torsades de pointes. Chronic treatment of patients prone to VT may include complex pharmacotherapy and AICDs. Development of new class III agents and enhancement of AICD technology may result in improved patient outcomes and the availability of more choices for emergent therapy of wide QRS tachycardias.