Clinical Implications of Antidepressant Pharmacokinetics and Pharmacogenetics

1996 ◽  
Vol 30 (12) ◽  
pp. 1471-1480 ◽  
Author(s):  
Lawrence J Cohen ◽  
C Lindsay DeVane
Keyword(s):  
Drug Therapy ◽  
Drug Interactions ◽  
English Language ◽  
Plasma Concentrations ◽  
Antidepressant Drug ◽  
Clinical Implications ◽  
Medline Search ◽  
Phenotypic Differences ◽  
Pharmacologic Agents ◽  
The Impact

OBJECTIVE: To review available data on pharmacokinetic and pharmacogenetic influences on the response to antidepressant therapy, analyze the mechanisms for and clinical significance of pharmacokinetic and pharmacogenetic differences, and explain the implications of pharmacokinetics and pharmacogenetics for patient care. DATA SOURCES: A MEDLINE search of English-language clinical studies, abstracts, and review articles on antidepressant pharmacokinetics, pharmacogenetics, and drug interactions was used to identify pertinent literature. DATA SYNTHESIS: The pharmacokinetic profiles of selected antidepressants are reviewed and the impact of hepatic microsomal enzymes on antidepressant metabolism is considered. How phenotypic differences influence the metabolism of antidepressant drug therapy is addressed. To evaluate the clinical implications of these pharmacokinetic and pharmacogenetic considerations, the findings of studies designed to elucidate drug interactions involving antidepressant agents are discussed. CONCLUSIONS: Differences in antidepressant plasma concentrations, and possibly safety, are caused by polymorphism in the genes that encode some of the cytochrome P450 isoenzymes that metabolize antidepressants. The isoenzymes 1A2, 2C9/19, 2D6, and 3A4 are the major enzymes that catalyze antidepressant metabolic reactions. Antidepressants can be either substrates or inhibitors of these enzymes, which also metabolize many other pharmacologic agents. Although the cytochrome enzymes that metabolize antidepressants have not been fully characterized, interaction profiles of the newer antidepressants are becoming more clearly defined. Determining patient phenotypes is not practical in the clinical setting, but an awareness of the possibility of genetic polymorphism in antidepressant metabolism may help explain therapeutic failure or toxicity, help predict the likelihood of drug interactions, and help clinicians better manage antidepressant drug therapy.

scholarly journals Update on the drug-food interactions

2014 ◽  
Vol 1 (2) ◽  
pp. 100-106
Author(s):  
Hafid Bahri ◽  
◽  
Abdelkader Douaoui ◽  
Moufida Gharbi ◽  
Djamila Amroun
Keyword(s):  
Drug Interactions ◽  
Renal Clearance ◽  
Enzyme Inhibitor ◽  
Plasma Concentrations ◽  
Public Health Problem ◽  
Therapeutic Index ◽  
Major Public Health Problem ◽  
Urine Ph ◽  
Pharmacodynamic Interaction ◽  
The Impact

Drug interactions are a major public health problem, which partly attributed to some 10,000 deaths/year in Canada. Besides the interactions between two drugs, drug interactions are also due to the effect of other substances such as foods or nutrients. The drug-food interaction will be pharmacokinetic (affecting the absorption, distribution, metabolism, and elimination) or pharmacodynamic interaction. It is in the intestine that food may have the greatest impact with mainly a change in the amount of drugs absorbed that may be clinically significant for some drugs with narrow therapeutic index (cyclosporine, phenytoin, theophylline, etc.). The absorption of the drug in the presence of food will be determined by the particular physicochemical properties of the drug but also by the impact of food on one of the parameters determining the absorption such as: modified gastric acidity and emptying, the fat content of the food, the use of common transport between the drug and nutrients, chemical reactions between elements and drugs. Fasting situations or malnutrition can affect the distribution of drugs by increasing the free drug fraction, involving sometimes the risk of overdose. Diet affects drug metabolism by changing the activity of cytochrome P450. Most often is described the increase by grapefruit juice (enzyme inhibitor) of plasma concentrations of some drugs (cyclosporine, some statins, and calcium antagonists). Other foods (garlic, smoked meats and fish, caffeine) may increase metabolism. Diet can influence two stages of renal clearance (glomerular filtration - tubular reabsorption) by modifying urine pH or renal clearance. Pharmacodynamic interactions are also monitored, especially foods rich in vitamin k or tyramine with antivitamins K or MAOIs. Finally, health professionals must mobilize against these interactions, including through patient information.

scholarly journals The use of ginkgo biloba in the treatment of dementia

2001 ◽  
Vol 25 (9) ◽  
pp. 353-356 ◽  
Author(s):  
Ian Maidment
Keyword(s):  
Side Effects ◽  
Drug Interactions ◽  
Mechanism Of Action ◽  
Ginkgo Biloba ◽  
Cholinesterase Inhibitors ◽  
Clinical Implications ◽  
Medline Search

Aims and MethodTo assess and update the available data on use of ginkgo to treat dementia. A Medline search as conducted for the period January 1985 to October 2000. The search included other aspects of the usage of ginkgo, such as side-effects, mechanism of action and drug interactions.ResultsMost of the trials using ginkgo were to treat cerebral insufficiency. Only five trials could be identified that used ginkgo to treat dementia. There are no trials comparing ginkgo to cholinesterase inhibitors such as donepezil.Clinical ImplicationsGinkgo is generally well-tolerated and appears to ease the symptoms of dementia. Although it has been suggested that the effect is comparable to donepezil, confirmation from controlled studies is required.

Rifabutin-Associated Uveitis

1995 ◽  
Vol 29 (11) ◽  
pp. 1149-1155 ◽  
Author(s):  
Alice L Tseng ◽  
Sharon L Walmsley
Keyword(s):  
Adverse Event ◽  
Drug Interactions ◽  
English Language ◽  
Case Reports ◽  
Data Extraction ◽  
Signs And Symptoms ◽  
Medline Search ◽  
Concurrent Therapy ◽  
Study Selection ◽  
Tolerance Study

Objective: To review rifabutin-associated uveitis and discuss the mechanism and potential role of drug interactions with clarithromycin and fluconazole in contributing to this adverse event. Data Sources: A MEDLINE search (1991 through September 1994) of English-language literature using the main MeSH headings “rifabutin” and “uveitis” and the subheadings “adverse effects” and “chemically induced.” Relevant articles also were selected from references of identified articles. Abstracts from recent medical conferences of infectious diseases, pharmacology, and HIV were screened for additional data. Study Selection and Data Extraction: All articles and abstracts reporting uveitis potentially related to rifabutin were considered for inclusion. Fifty-four cases were identified. Pertinent information from the case reports, as judged by the authors, was selected and synthesized for discussion. Data Synthesis: Rifabutin is being prescribed increasingly for the treatment and prophylaxis of Mycobacterium avium complex (MAC) infection in the HIV-infected population. Uveitis was initially thought to be a rare, dose-limited complication of rifabutin therapy. In an early dose-ranging tolerance study, uveitis was associated with daily doses of 1200 mg or more. Because this toxicity appeared to be dose-related, lower dosages (300–600 mg/d) of rifabutin were selected for study in subsequent clinical trials. More recent reports noting the association of uveitis with these lower dosages of rifabutin have raised concerns about the prevalence of this adverse event. In the 54 identified cases, patients presented with symptoms of unilateral or bilateral uveitis from 2 weeks to more than 7 months following initiation of rifabutin therapy. In all reported cases, patients were receiving concurrent therapy with clarithromycin and/or fluconazole, both of which have inhibitory effects on rifabutin metabolism. In most cases, uveitis resolved within 1–2 months following discontinuation of rifabutin with or without administration of topical corticosteroids. Conclusions: Rifabutin is prescribed frequently for the prophylaxis and treatment of MAC infection, especially in patients with HIV. Uveitis is a rare, dose-related toxicity of this therapy. The risk of rifabutin-associated uveitis may be increased in patients receiving concurrent therapy with clarithromycin or fluconazole because of drug interactions. Patients receiving therapy with combinations of any of these agents should be warned about signs and symptoms of uveitis and be monitored closely for the development of rifabutin toxicity. If uveitis develops, rifabutin therapy should be discontinued promptly.

Rifaximin: A New Treatment for Travelers' Diarrhea

2005 ◽  
Vol 39 (2) ◽  
pp. 284-289 ◽  
Author(s):  
Amy L Pakyz
Keyword(s):  
Adverse Effects ◽  
Drug Interactions ◽  
English Language ◽  
Data Extraction ◽  
Cross Resistance ◽  
Double Blind ◽  
Data Synthesis ◽  
Medline Search ◽  
Study Selection ◽  
New Treatment

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions and precautions, and dosing recommendations of rifaximin, a new nonabsorbed antimicrobial agent for travelers' diarrhea. DATA SOURCES: A MEDLINE search (1966–July 2004) was conducted to extract human and animal research data in the English language on rifaximin. STUDY SELECTION AND DATA EXTRACTION: Randomized, double-blind, placebo-controlled trials were reviewed and included to evaluate the efficacy of rifaximin in the treatment of travelers' diarrhea. DATA SYNTHESIS: Rifaximin is approved for the treatment of travelers' diarrhea in patients ≥12 years of age with diarrhea caused by noninvasive strains of Escherichia coli. Rifaximin was superior to placebo and trimethoprim/sulfamethoxazole and equivalent to ciprofloxacin in the primary clinical endpoint of the time to the last unformed stool passed. CONCLUSIONS: Rifaximin is a viable alternative to ciprofloxacin for the treatment of travelers' diarrhea. As rifaximin is not systemically absorbed, it offers the advantage of leading to the development of less resistance compared with systemically absorbed antibiotics, in addition to fewer systemic adverse effects and drug interactions. However, the potential for cross-resistance between rifaximin and rifampin, as well as with other classes of antibiotics, is of concern and needs to be elucidated.

Meningococcal Vaccine Use in College Students

2002 ◽  
Vol 36 (11) ◽  
pp. 1776-1784 ◽  
Author(s):  
Julia A Kelleher ◽  
Marsha A Raebel
Keyword(s):  
College Students ◽  
Meningococcal Disease ◽  
English Language ◽  
Age Groups ◽  
Meningococcal Infection ◽  
Meningococcal Vaccine ◽  
Hand Search ◽  
Medline Search ◽  
Increased Risk ◽  
The Impact

OBJECTIVE: To discuss the role of meningococcal vaccine in prevention of meningococcal disease. DATA SOURCES: A MEDLINE search (1966–June 2001) was performed to identify key literature. Search terms included, but were not limited to, meningococcal vaccines, meningococcal meningitis, meningococcal infection, and meningococcus. The search was limited to English-language literature and references dealing with humans. The MEDLINE search was supplemented by a hand search of various bibliographies. DATA SYNTHESIS: The impact of meningococcal disease has caused national and regional organizations to develop recommendations for use of meningococcal vaccine. Even though the meningococcal vaccine can provide benefit, limitations exist. The available vaccine does not cover all meningococcal strains and is not useful in all age groups. The appropriate target groups for prevention of disease through vaccination have been difficult to determine; vaccine use in college students is especially controversial. CONCLUSIONS: Although a meningococcal vaccine is available, meningococcus causes significant morbidity and mortality. Controversy exists over the meningococcal vaccine and its use. Students entering college who will be living in dormitories should be informed of the increased risk of meningococcal disease and be offered vaccination.

scholarly journals The Influence of Pharmacogenetics on the Clinical Relevance of Pharmacokinetic Drug–Drug Interactions: Drug–Gene, Drug–Gene–Gene and Drug–Drug–Gene Interactions

2021 ◽  
Vol 14 (5) ◽  
pp. 487
Author(s):  
Martina Hahn ◽  
Sibylle C. Roll
Keyword(s):  
Drug Therapy ◽  
Drug Interactions ◽  
Clinical Relevance ◽  
Adverse Drug Events ◽  
Current Evidence ◽  
Drug Event ◽  
Gene Interactions ◽  
Genetic Profile ◽  
The Impact ◽  
Pharmacokinetic Drug

Drug interactions are a well-known cause of adverse drug events, and drug interaction databases can help the clinician to recognize and avoid such interactions and their adverse events. However, not every interaction leads to an adverse drug event. This is because the clinical relevance of drug–drug interactions also depends on the genetic profile of the patient. If inhibitors or inducers of drug metabolising enzymes (e.g., CYP and UGT) are added to the drug therapy, phenoconcversion can occur. This leads to a genetic phenotype that mismatches the observable phenotype. Drug–drug–gene and drug–gene–gene interactions influence the toxicity and/or ineffectivness of the drug therapy. To date, there have been limited published studies on the impact of genetic variations on drug–drug interactions. This review discusses the current evidence of drug–drug–gene interactions, as well as drug–gene–gene interactions. Phenoconversion is explained, the and methods to calculate the phenotypes are described. Clinical recommendations are given regarding the integratation of the PGx results in the assessment of the relevance of drug interactions in the future.

scholarly journals Chemotherapy of Drug-Resistant Malaria

1996 ◽  
Vol 7 (1) ◽  
pp. 25-33 ◽  
Author(s):  
Kevin C Kain
Keyword(s):  
English Language ◽  
Multidrug Resistant ◽  
Parasite Development ◽  
Mosquito Vector ◽  
Drug Resistant ◽  
Medline Search ◽  
Artemisinin Derivatives ◽  
Drug Regimens ◽  
High Doses ◽  
The Impact

OBJECTIVE: To review the impact of drug-resistant malaria on current management of plasmodial infections.DATA SOURCES: A MEDLINE search of the English-language medical literature from 1985 to 1995; bibliographies of selected papers; international malaria advisory experts.DATA SYNTHESIS: Combinations of artemisinin derivatives and mefloquine or atovaquone plus proguanil appear to be the most active drug regimens against multidrug-resistant falciparum malaria from Southeast Asia. The optimal therapy for chloroquine-resistantPlasmodium vivaxis unknown, but recent data indicate that halofantrine or chloroquine plus high doses of primaquine are efficacious.CONCLUSIONS: The incidence of drug-resistant malaria continues to increase at a rate that exceeds new drug development. Ultimately the control of malaria will require more creative approaches than just the development of additional inhibitory drugs. These might include the identification of biochemical pathways unique to the parasite (such as drug efflux and heme polymerization), making it possible to design new classes of antimalarial agents that are selectively toxic to the parasite; methods to block parasite development in the mosquito vector; and multistage vaccines against asexual and sexual stages to block both the pathophysiology and the transmission of disease.

Stereoselective Pharmacokinetics and Pharmacodynamics of Anti-Asthma Agents

2002 ◽  
Vol 36 (4) ◽  
pp. 693-701 ◽  
Author(s):  
Majid Vakily ◽  
Reza Mehvar ◽  
Dion Brocks
Keyword(s):  
English Language ◽  
Data Extraction ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Chiral Drugs ◽  
Medline Search ◽  
Secondary Sources ◽  
Asthmatic Patients ◽  
Stereoselective Pharmacokinetics

OBJECTIVE: To review the previously published studies on pharmacokinetics and pharmacodynamics of chiral drugs used in the treatment of asthma. DATA SOURCES: Primary and review articles were identified with a MEDLINE search (1980–May 2001) and through secondary sources. STUDY SELECTION AND DATA EXTRACTION: All English-language studies and reviews obtained from the MEDLINE search pertaining to stereoselective pharmacokinetics and pharmacodynamics of chiral anti-asthma drugs were assessed. DATA SYNTHESIS: Several anti-asthma drugs (e.g., β2-adrenergic agonists, leukotriene modifiers) are chiral and marketed as racemates, which consist of equal proportions of 2 enantiomers. Significant stereoselectivity has also been reported in pharmacodynamics and pharmacokinetics of the β2-agonists. The enantiomers of β2-agonists in the R configuration are primarily responsible for the bronchodilating effects of the racemate. The plasma concentrations of the enantiomers of anti-asthma drugs may differ as a reflection of stereoselectivity in clearance, volume of distribution, and route of administration. CONCLUSIONS: Stereoselectivity in the pharmacokinetics of anti-asthma drugs may complicate the relationship between dose and/or plasma concentration of racemic drug versus effect relationship. An appreciation of the stereoselective pharmacokinetics and pharmacodynamics of chiral anti-asthma drugs may optimize the use of these agents in asthmatic patients.

Management of Drug Interactions in Patients with HIV

1997 ◽  
Vol 31 (9) ◽  
pp. 1040-1058 ◽  
Author(s):  
Alice Lin-In Tseng ◽  
Michelle M Foisy
Keyword(s):  
Drug Therapy ◽  
Drug Interactions ◽  
Drug Disposition ◽  
Opportunistic Infections ◽  
Data Extraction ◽  
Management Strategies ◽  
Relevant Information ◽  
Management Options ◽  
Medline Search ◽  
Clinically Significant

Objective To provide a compilation of relevant information on drug interactions to assist healthcare practitioners in managing complex HIV-related pharmacotherapy. Data Sources Information was retrieved via a MEDLINE search (January 1966–December 1996) using MeSH headings “human immunodeficiency virus,” “drug interactions,” and names of medications commonly prescribed for the management of HIV infection and related opportunistic infections. Abstracts of international and national conferences, review articles, textbooks, and references of all articles were also searched. Study Selection and Data Extraction All literature on pharmacokinetic or pharmacodynamic interactions was considered for inclusion. Pertinent information, as assessed by the authors, was selected and summarized for discussion. Data Synthesis Drug disposition and/or pharmacologic effect may be affected either by HIV-related physiologic changes or by the presence of concomitant drug therapy. Modifications in drug selection, dosage, dosing regimen, or route of administration may be needed to avoid or manage drug–disease, drug–drug, or drug-food interactions. Management options may depend on the mechanism and the clinical significance of the interaction, the availability of therapeutic alternatives, patient convenience, and cost restrictions. In the absence of specific data, consideration of pharmacokinetic and pharmacodynamic characteristics to assist practitioners in predicting the likelihood of possible interactions was included. Results A comprehensive table of clinically significant drug interactions is provided. Drug interaction principles and practical management strategies are also discussed. Conclusions The potential for drug interactions is extremely common, given the increasing complexity of managing patients infected with HIV. To avoid compromising therapeutic efficacy or increasing drug toxicity, practitioners need to be aware of potential interactions and are encouraged to use a systematic approach when managing patient drug therapy.

1993 Bibliography: A 32-Year Literature Review on the Value and Acceptance of Ambulatory Care Provided by Pharmacists

1993 ◽  
Vol 27 (9) ◽  
pp. 1106-1119 ◽  
Author(s):  
Hind T. Hatoum ◽  
Kasem Akhras
Keyword(s):  
Ambulatory Care ◽  
English Language ◽  
Negative Impact ◽  
Positive Impact ◽  
Research Data ◽  
Care Quality ◽  
Pharmaceutical Services ◽  
Original Research ◽  
Medline Search ◽  
The Impact

OBJECTIVE: To review the published literature on the value and acceptance of pharmaceutical services provided by pharmacists in ambulatory care settings. DATA SOURCES AND METHODS: Articles published between 1960 and 1992. A MEDLINE search of the English-language literature was conducted using the terms pharmacists, services, and ambulatory settings. Studies were selected for inclusion if they addressed services provided by pharmacists in ambulatory settings and dealt with the cost of patient care, quality of care, or attitudinal surveys. Original research reports were summarized according to objectives, sample size, duration of study, methods, and findings. Summaries were categorized according to reported positive impact, negative impact, or investigational reports with no outcome. RESULTS: One hundred seventy articles were identified; 104 of them reported research data and were summarized. The 1970s was the most prolific decade for publication of articles reporting positive, negative, or no impact, which numbered 47, 20, and 37, respectively. Positive correlation was found among studies conducted according to predetermined protocol and reporting positive impact. Moreover, academic interest in pharmacy varied for the different decades. CONCLUSIONS: Collectively, this article provides references of the published reports on pharmacy professional services in ambulatory care settings, and a summary of the articles reporting research data. Additional and more focused research on pharmaceutical services in the community is needed. Emphasis is required on practicing pharmacists' attitudes toward nondispensing, patient-oriented pharmaceutical services; the impact of educational changes on the practice of pharmacy and consumers' attitudes and willingness to pay for services; and the link between patient outcome and pharmaceutical services.

Sign in / Sign up

Export Citation Format

Share Document