... ALL RIGHTS RESERVED Manufactured in the United States of America on acid-free paper 11 10 09 ... more ... ALL RIGHTS RESERVED Manufactured in the United States of America on acid-free paper 11 10 09 08 07 5 4 3 2 1 First ... Marcucci, MD Jessica R. Oesterheld, MD Steven Ruths, MD Joseph Sokal, MD Susan Strahan, MD Ken Walters, Pharm.D. Edward Zuzarte, MD vii ...
This edition of DDI Update will review reports about St. John's Wort (SJW) and the concerns about... more This edition of DDI Update will review reports about St. John's Wort (SJW) and the concerns about its interactions at cytochrome P450 3A4. We will also review the demise of cisapride, a strong reminder that postmarketing surveillance and the report of adverse drug reactions is a responsibility of us all.
Parkinson's disease belongs to the most prevalent neurodegenerative disorders and manifests both ... more Parkinson's disease belongs to the most prevalent neurodegenerative disorders and manifests both with motor and non-motor symptoms. Symptomatic treatment of this disorder became more multifaceted over the past years: besides classical dopaminergic drugs and physiotherapy, novel invasive escalation treatment strategies became gold standard in many countries. On the other hand, non-motor symptoms significantly impacts quality of life in many patients which necessitates initiation of adequate therapy.
Antihistamines and their drug-drug interactions are reviewed in depth. The metabolism of classic ... more Antihistamines and their drug-drug interactions are reviewed in depth. The metabolism of classic or sedating antihistamines is coming to light through in vivo and in vitro studies. The polymorphic CYP 2D6 metabolic enzyme appears to be potently inhibited by many of these over-the-counter medications. The history of the discontinued second-generation antihistamines terfenadine and asteittizole is reviewed to remind the reader why the understanding of the cytochrome P450 system became increasingly important when the cardiotoxicity of these drugs became apparent. The third-generation nonsedating antihistamines are also listed and compared. They have been exhaustively scrutinized for drug-drug interactions and cardiotoxicity. and they appear to have no serious drug-drug interactions at recommended doses.
The literature on pharmacokinetic drug-drug interactions usually focuses on various interactions ... more The literature on pharmacokinetic drug-drug interactions usually focuses on various interactions relating to the cytochrome P450 system, phase II glucuronidation, and P-glycoprotein function. However, there has been relatively little examination of how the modes or patterns that govern these interactions can be systematically characterized to better anticipate drug-drug interactions in clinical practice. This article details a schema of six core patterns of pharmacokinetic drugdrug interaction relating to processes of induction and inhibition and the action of substrates. Case examples illustrating each pattern are provided.
Drug-drug interactions or genetic variability may require using doses different from those recomm... more Drug-drug interactions or genetic variability may require using doses different from those recommended for atypical antipsychotics. Dosage alterations of olanzapine and clozapine, dependent on cytochrome P450 1A2 (CYP1A2) for clearance, and quetiapine, dependent on cytochrome P450 3A (CYP3A), may be necessary when used with other drugs that inhibit or induce their metabolic enzymes. Smoking cessation can significantly increase clozapine, and perhaps olanzapine, levels. Ziprasidone pharmacokinetic drug-drug interactions are not likely to be important. Genetic variations of cytochrome P450 2D6 (CYP2D6) and drug-drug interactions causing inhibition (CYP2D6 and/or CYP3A) or induction (CYP3A) may be important for risperidone, and perhaps for aripiprazole, dosing. Adding inhibitors may cause side effects more easily in drugs with a narrow therapeutic window, such as clozapine or risperidone, than in those with a wide therapeutic window, such as olanzapine or aripiprazole. Adding inducers may be associated with a gradual development of lost efficacy.
Attention to pharmacokinetics and pharmacodynamics and an understanding of intended effects, side... more Attention to pharmacokinetics and pharmacodynamics and an understanding of intended effects, side effects, toxicities, and drug interactions are imperative when treating persons with HIV/AIDS. This chapter includes an essential review of drug interaction principles and an overview of current antiretroviral treatment (ART) and known side effects, toxicities, and drug interactions, in text and table format. The chapter concludes with a presentation of psychotropic-antiretroviral treatment issues. Most psychotropics are effective in the treatment of persons with HIV, but some, particularly the pan-inducing antiepileptics, are best avoided or at least should be very carefully monitored. Recognizing the potential for drug–drug interactions allows for more careful monitoring and for consideration of alternative treatments or precautions. Being a pharmacologically knowledgeable multidisciplinary team member can reduce morbidity and mortality in patients. An understanding of antiretroviral therapy and psychopharmacological treatment issues prevents morbidity, supports adherence to medications, and improves quality of life for persons with HIV.
The use of the immunosuppressant drug cyclosporin A (C5A) as a biochemical tool to study the sign... more The use of the immunosuppressant drug cyclosporin A (C5A) as a biochemical tool to study the signal transduction pathway in T cells has led to the discovery of a first family of immunosuppressant-binding proteins or "immunophilins' the cyclophiins (Cyp). Another, chemically unrelated immunosuppressant molecule, FK506, was then found to be related to a second class of immunophilins, the FK506-binding proteins (FKBPs). This paper reviews the existing structural information on these immunophiins in the context of present knowledge of the biochemical mechanisms for immunosuppression. The formation of Cyp-CsA and FKBP-FK506 complexes, and the subsequent specific interaction of these complexes with the serine/threonine phosphatase calcineurin (CN), are key steps in the cascade of events that result in the desired immunosuppression. Knowledge of the conformation of the Cyp-CsA-CN and FKBP-FK506-CN ternary complexes is of significant biomedical interest, because mimics of the composite contact surfaces of, for example, Cyp-CsA or FKBP-FK506, could provide immunosuppressant drugs with improved pharmacological profiles.-Braun,
This article is one of a series coordinated by APA’s Council on Consultation-Liaison Psychiatry a... more This article is one of a series coordinated by APA’s Council on Consultation-Liaison Psychiatry and the Academy of Consultation-Liaison Psychiatry.
At "raves," young people dance and ingest illicit drugs, the most common of which is MDMA (N-meth... more At "raves," young people dance and ingest illicit drugs, the most common of which is MDMA (N-methyl-3,4,-methylenedioxymethamphetamine) or "ecstasy." This drug is metabolized principally through the cytochrome P450 (CYP450) 2D6 enzyme. Pharmacokinetic drug-drug interactions can occur if MDMA is combined with other recreational or therapeutic drugs that are 2D6 inhibitors. Ecstasy concentration may increase to cause toxicity. Since ecstasy is pro-serotonergic, it may also be involved in pharmacodynamic drug-drug interactions when other pro-serotonergic drugs are combined with it, leading to a central serotonin syndrome. Some drugs are both proserotonergic and CYP450 2D6 inhibitors and, if co-administered with ecstasy, may cause both pharmacokinetic and pharmacodynamic drug-drug interactions.
This chapter was developed as a basic reference list of resources for HIV clinicians to help them... more This chapter was developed as a basic reference list of resources for HIV clinicians to help them meet the various needs of persons with AIDS throughout the lifespan. The resources listed are by no means exhaustive or comprehensive, as there is a plethora of relevant literature, Web sites, and interest groups—too many to fit into a single chapter! Instead, this is a set of resources that the authors have found particularly useful when seeking answers to treatment-and social services–related questions at the bedside as well as in ambulatory and community settings. At the time of publication, these resources had been updated regularly and consistently; technology related to HIV evolves on an almost daily basis. A mixture of print and Internet-based resources is provided here—some will be useful to keep in the office setting for perusal or for patients, and some can be obtained on the Internet at a moment’s notice when the need arises. Many of the listings are for Web sites that can ai...
... ALL RIGHTS RESERVED Manufactured in the United States of America on acid-free paper 11 10 09 ... more ... ALL RIGHTS RESERVED Manufactured in the United States of America on acid-free paper 11 10 09 08 07 5 4 3 2 1 First ... Marcucci, MD Jessica R. Oesterheld, MD Steven Ruths, MD Joseph Sokal, MD Susan Strahan, MD Ken Walters, Pharm.D. Edward Zuzarte, MD vii ...
This edition of DDI Update will review reports about St. John's Wort (SJW) and the concerns about... more This edition of DDI Update will review reports about St. John's Wort (SJW) and the concerns about its interactions at cytochrome P450 3A4. We will also review the demise of cisapride, a strong reminder that postmarketing surveillance and the report of adverse drug reactions is a responsibility of us all.
Parkinson's disease belongs to the most prevalent neurodegenerative disorders and manifests both ... more Parkinson's disease belongs to the most prevalent neurodegenerative disorders and manifests both with motor and non-motor symptoms. Symptomatic treatment of this disorder became more multifaceted over the past years: besides classical dopaminergic drugs and physiotherapy, novel invasive escalation treatment strategies became gold standard in many countries. On the other hand, non-motor symptoms significantly impacts quality of life in many patients which necessitates initiation of adequate therapy.
Antihistamines and their drug-drug interactions are reviewed in depth. The metabolism of classic ... more Antihistamines and their drug-drug interactions are reviewed in depth. The metabolism of classic or sedating antihistamines is coming to light through in vivo and in vitro studies. The polymorphic CYP 2D6 metabolic enzyme appears to be potently inhibited by many of these over-the-counter medications. The history of the discontinued second-generation antihistamines terfenadine and asteittizole is reviewed to remind the reader why the understanding of the cytochrome P450 system became increasingly important when the cardiotoxicity of these drugs became apparent. The third-generation nonsedating antihistamines are also listed and compared. They have been exhaustively scrutinized for drug-drug interactions and cardiotoxicity. and they appear to have no serious drug-drug interactions at recommended doses.
The literature on pharmacokinetic drug-drug interactions usually focuses on various interactions ... more The literature on pharmacokinetic drug-drug interactions usually focuses on various interactions relating to the cytochrome P450 system, phase II glucuronidation, and P-glycoprotein function. However, there has been relatively little examination of how the modes or patterns that govern these interactions can be systematically characterized to better anticipate drug-drug interactions in clinical practice. This article details a schema of six core patterns of pharmacokinetic drugdrug interaction relating to processes of induction and inhibition and the action of substrates. Case examples illustrating each pattern are provided.
Drug-drug interactions or genetic variability may require using doses different from those recomm... more Drug-drug interactions or genetic variability may require using doses different from those recommended for atypical antipsychotics. Dosage alterations of olanzapine and clozapine, dependent on cytochrome P450 1A2 (CYP1A2) for clearance, and quetiapine, dependent on cytochrome P450 3A (CYP3A), may be necessary when used with other drugs that inhibit or induce their metabolic enzymes. Smoking cessation can significantly increase clozapine, and perhaps olanzapine, levels. Ziprasidone pharmacokinetic drug-drug interactions are not likely to be important. Genetic variations of cytochrome P450 2D6 (CYP2D6) and drug-drug interactions causing inhibition (CYP2D6 and/or CYP3A) or induction (CYP3A) may be important for risperidone, and perhaps for aripiprazole, dosing. Adding inhibitors may cause side effects more easily in drugs with a narrow therapeutic window, such as clozapine or risperidone, than in those with a wide therapeutic window, such as olanzapine or aripiprazole. Adding inducers may be associated with a gradual development of lost efficacy.
Attention to pharmacokinetics and pharmacodynamics and an understanding of intended effects, side... more Attention to pharmacokinetics and pharmacodynamics and an understanding of intended effects, side effects, toxicities, and drug interactions are imperative when treating persons with HIV/AIDS. This chapter includes an essential review of drug interaction principles and an overview of current antiretroviral treatment (ART) and known side effects, toxicities, and drug interactions, in text and table format. The chapter concludes with a presentation of psychotropic-antiretroviral treatment issues. Most psychotropics are effective in the treatment of persons with HIV, but some, particularly the pan-inducing antiepileptics, are best avoided or at least should be very carefully monitored. Recognizing the potential for drug–drug interactions allows for more careful monitoring and for consideration of alternative treatments or precautions. Being a pharmacologically knowledgeable multidisciplinary team member can reduce morbidity and mortality in patients. An understanding of antiretroviral therapy and psychopharmacological treatment issues prevents morbidity, supports adherence to medications, and improves quality of life for persons with HIV.
The use of the immunosuppressant drug cyclosporin A (C5A) as a biochemical tool to study the sign... more The use of the immunosuppressant drug cyclosporin A (C5A) as a biochemical tool to study the signal transduction pathway in T cells has led to the discovery of a first family of immunosuppressant-binding proteins or "immunophilins' the cyclophiins (Cyp). Another, chemically unrelated immunosuppressant molecule, FK506, was then found to be related to a second class of immunophilins, the FK506-binding proteins (FKBPs). This paper reviews the existing structural information on these immunophiins in the context of present knowledge of the biochemical mechanisms for immunosuppression. The formation of Cyp-CsA and FKBP-FK506 complexes, and the subsequent specific interaction of these complexes with the serine/threonine phosphatase calcineurin (CN), are key steps in the cascade of events that result in the desired immunosuppression. Knowledge of the conformation of the Cyp-CsA-CN and FKBP-FK506-CN ternary complexes is of significant biomedical interest, because mimics of the composite contact surfaces of, for example, Cyp-CsA or FKBP-FK506, could provide immunosuppressant drugs with improved pharmacological profiles.-Braun,
This article is one of a series coordinated by APA’s Council on Consultation-Liaison Psychiatry a... more This article is one of a series coordinated by APA’s Council on Consultation-Liaison Psychiatry and the Academy of Consultation-Liaison Psychiatry.
At "raves," young people dance and ingest illicit drugs, the most common of which is MDMA (N-meth... more At "raves," young people dance and ingest illicit drugs, the most common of which is MDMA (N-methyl-3,4,-methylenedioxymethamphetamine) or "ecstasy." This drug is metabolized principally through the cytochrome P450 (CYP450) 2D6 enzyme. Pharmacokinetic drug-drug interactions can occur if MDMA is combined with other recreational or therapeutic drugs that are 2D6 inhibitors. Ecstasy concentration may increase to cause toxicity. Since ecstasy is pro-serotonergic, it may also be involved in pharmacodynamic drug-drug interactions when other pro-serotonergic drugs are combined with it, leading to a central serotonin syndrome. Some drugs are both proserotonergic and CYP450 2D6 inhibitors and, if co-administered with ecstasy, may cause both pharmacokinetic and pharmacodynamic drug-drug interactions.
This chapter was developed as a basic reference list of resources for HIV clinicians to help them... more This chapter was developed as a basic reference list of resources for HIV clinicians to help them meet the various needs of persons with AIDS throughout the lifespan. The resources listed are by no means exhaustive or comprehensive, as there is a plethora of relevant literature, Web sites, and interest groups—too many to fit into a single chapter! Instead, this is a set of resources that the authors have found particularly useful when seeking answers to treatment-and social services–related questions at the bedside as well as in ambulatory and community settings. At the time of publication, these resources had been updated regularly and consistently; technology related to HIV evolves on an almost daily basis. A mixture of print and Internet-based resources is provided here—some will be useful to keep in the office setting for perusal or for patients, and some can be obtained on the Internet at a moment’s notice when the need arises. Many of the listings are for Web sites that can ai...
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