Genetic and environmental aspects of drug metabolism relevant to side-effects in arthritic disease

The use of pharmacological agents is often a central component of medical therapy for older people. Medications can relieve symptoms, improve function, and prevent illness, but they also have the capacity to inflict great harm. Older people are at particular risk of such harms as a result of impaired homeostatic reserve, of altered drug metabolism, the presence of multimorbidity and consequent polypharmacy, which increases both exposure to potentially harmful agents and the chance of drug–drug interactions. The therapeutic priorities for older, frail people may differ when compared to younger, robust patients; limited life expectancy means that attempts to prolong life may become relatively less important than the relief of symptoms and avoidance of side effects and medication burden.

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Considering Race and Ethnicity During Psychopharmacologic Interventions

CNS Spectrums ◽

10.1017/s1092852900026535 ◽

2005 ◽

Vol 10 (S2) ◽

pp. 4-4

Author(s):

Altha Stewart

Keyword(s):

Side Effects ◽

Drug Metabolism ◽

Ethnic Groups ◽

Race And Ethnicity ◽

Clinical Decision Making ◽

Cultural Beliefs ◽

Ethnically Diverse ◽

Pharmacologic Treatment ◽

The Impact

The role of race and ethnicity in psychiatric diagnosis and treatment has received increased attention over the last 2 decades. In addition, recent studies conducted to determine the effects of psychotropic drugs among various racial and ethnic groups highlight the importance of considering race and ethnicity during psychopharmacologic interventions.Information regarding differences in drug metabolism, effectiveness, and incidence of adverse effects provides opportunities for psychiatrists to adjust pharmacologic treatment to achieve optimal treatment outcomes while minimizing intolerable side effects. These differences have been explained by inconsistencies in access, stigma, fear of medicines, differing spiritual and cultural beliefs about mental illness, and general mistrust of the healthcare system by many racial and ethnic groups.The articles in this supplement offer a significant contribution to the scientific foundation needed to minimize the patient and clinician factors contributing to the current disparities in mental health care. Recent data, such as those presented in this supplement, describe the role of ethnicity in the pharmacologic treatment of psychiatric disorders and offer hope for improved quality of care for ethnically diverse patient populations. The authors discuss differences in drug metabolism, the impact of these differences on development of various metabolic disorders, and how these differences may be useful in managing intolerable side effects and improving patient compliance and treatment outcome. The information included in these articles should assure that clinical decision making and prescribing practices include sensitivity to safety, tolerability, and dosing for an increasingly ethnically diverse population.

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Ultrarapid drug metabolism: PCR-based detection of CYP2D6 gene duplication

Clinical Chemistry ◽

10.1093/clinchem/44.5.914 ◽

1998 ◽

Vol 44 (5) ◽

pp. 914-917 ◽

Cited By ~ 49

Author(s):

Linda S W Steijns ◽

Jan Van Der Weide

Keyword(s):

Drug Therapy ◽

Side Effects ◽

Gene Duplication ◽

Drug Metabolism ◽

Therapeutic Efficacy ◽

Psychiatric Patients ◽

Clinical Importance ◽

Metabolic Capacity ◽

Cyp2d6 Gene ◽

Pcr Assays

Abstract The enzyme debrisoquine 4-hydroxylase (CYP2D6), which metabolizes many widely used drugs, is highly polymorphic. The activity of the enzyme ranges between subjects from ultrafast to a complete absence. Therefore, metabolic capacity varies, producing intersubject differences in therapeutic efficacy and side effects at standard recommended doses. Up to 7% of Caucasians may demonstrate ultrarapid drug metabolism (UM) because of inherited alleles with multiplicate functional CYP2D6 genes, causing an increased amount of enzyme to be expressed. Identification of UM subjects is of potential clinical importance for adjustment of doses in drug therapy, as well as to avoid misidentification of noncompliance. In our study, we tested recently designed PCR assays for the detection of the UM genotype. We found a 3.5% prevalence of UMs carrying duplicate active CYP2D6 genes in a population consisting of 202 psychiatric patients.

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Pharmacogenetics of Anesthetic and Analgesic Agents

Anesthesiology ◽

10.1097/00000542-200503000-00028 ◽

2005 ◽

Vol 102 (3) ◽

pp. 663-671 ◽

Cited By ~ 54

Author(s):

Stephen N. Palmer ◽

N Martin Giesecke ◽

Simon C. Body ◽

Stanton K. Shernan ◽

Amanda A. Fox ◽

...

Keyword(s):

Individual Differences ◽

Side Effects ◽

Molecular Biology ◽

Drug Metabolism ◽

Drug Response ◽

Molecular Mechanisms ◽

Genetic Profile ◽

Analgesic Agents

Predicting a patient's response to a particular drug has long been a goal of clinicians. Rapid advances in molecular biology have enabled researchers to identify associations between an individual's genetic profile and drug response. Pharmacogenetics is the study of the molecular mechanisms that underlie individual differences in drug metabolism, efficacy, and side effects. The pharmacogenetics of commonly used anesthetic and analgesic agents are reviewed.

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Pharmacology and therapeutics

Oxford Handbook of Paediatrics 3e ◽

10.1093/med/9780198789888.003.0027 ◽

2020 ◽

pp. 925-934

Keyword(s):

Drug Therapy ◽

Side Effects ◽

Drug Metabolism ◽

Medication Errors ◽

Drug Toxicity ◽

Morbidity And Mortality ◽

Physiological Differences

Medicines are an essential part of the treatment of children. They help to reduce morbidity and mortality. It is important to recognize, however, that all medicines have potential side effects and additionally medication errors can occur at any stage (prescription, dispensing, or administration). Due to physiological differences in relation to drug metabolism and the potential protein-displacing effect on bilirubin, neonates are at greater risk of drug toxicity. Drug therapy is an integral part of the management of both pain and sedation in children.

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Gastric Ulcers Produced by Cisplatin

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100099337 ◽

1981 ◽

Vol 39 ◽

pp. 582-583

Author(s):

S.K. Aggarwal ◽

J. San Antonio

Keyword(s):

Electron Microscopy ◽

Single Dose ◽

Side Effects ◽

Antitumor Agent ◽

Gastric Ulcers ◽

Enzyme Cytochemistry ◽

Intestinal Toxicity ◽

Ovarian Cancers ◽

Inner Surface

Cisplatin (cis-dichlorodiammineplatinum(II)) a potent antitumor agent is now available for the treatment of testicular and ovarian cancers. It is however, not free from its serious side effects including nephrotoxicity, gastro intestinal toxicity, myelosuppression, and ototoxicity. Here we now report that the drug produces peculiar bloating of the stomach in rats and induces acute ulceration.Wistar-derived rats weighing 200-250 g were administered cisplatin(9 mg/kg) ip as a single dose in 0.15 M NaCl. After 3 days the animals were sacrificed by decapitation. The stomachs were removed, the contents analyzed for pepsin and acidity. The inner surface was examined with a dissecting microscope after a moderate stretching for ulcers. Affected areas were fixed and processed for routine electron microscopy and enzyme cytochemistry.The drug treated animals kept on food and water consistently showed bloating and lesions (Fig. 1) with a frequency of 6-70 ulcers in the rumen section of the stomachs.

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Effects of cisplatin treatment on the rat neurohypophysis

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100142256 ◽

1986 ◽

Vol 44 ◽

pp. 122-123

Author(s):

J.M. Fadool ◽

P.J. Boyer ◽

S.K. Aggarwal

Keyword(s):

Side Effects ◽

Urine Output ◽

Morphological Changes ◽

Limiting Factor ◽

Antineoplastic Drugs

Cisplatin (CDDP) is currently one of the most valuable antineoplastic drugs available. However, it has severe toxic side effects of which nephrotoxicity is the major dose limiting factor in its use. It induces morphological changes in the kidney with hampered urine output. The present study is an effort to determine the influence of the drug on the neurohypophysis for any antidiuretic effects on the kidney.

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Severe Drooling and Treatment With Botulinum Toxin

Perspectives on Swallowing and Swallowing Disorders (Dysphagia) ◽

10.1044/sasd21.1.15 ◽

2012 ◽

Vol 21 (1) ◽

pp. 15-21

Author(s):

Merete Bakke ◽

Allan Bardow ◽

Eigild Møller

Keyword(s):

Botulinum Toxin ◽

Side Effects ◽

Health Risk ◽

Flow Rate ◽

Clinical Evidence ◽

Acetylcholine Release ◽

Psychosocial Problems ◽

Rate Reduction ◽

Local Inhibition ◽

Surgical Treatments

Severe drooling is associated with discomfort and psychosocial problems and may constitute a health risk. A variety of different surgical and non-surgical treatments have been used to diminish drooling, some of them with little or uncertain effect and others more effective but irreversible or with side effects. Based on clinical evidence, injection with botulinum toxin (BTX) into the parotid and submandibular glands is a useful treatment option, because it is local, reversible, and with few side effects, although it has to be repeated. The mechanism of BTX is a local inhibition of acetylcholine release, which diminishes receptor-coupled secretion and results in a flow rate reduction of 25–50% for 2–7 months.

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