CYP2D6 and Pharmacogenetics Quiz

Ethnopharmacology: Understanding Drug Response Based on Race/Ethnicity

• Ethnopharmacology is a multidisciplinary field researching indigenous drugs and their biological activities.
• Key aspects are interdisciplinary scientific exploration of biologically active agents traditionally employed by people, and the study of physiological actions of plant, animal, and other substances used in indigenous medicines.

Definition

• Rivier and Bruhn define it as the observation, description, and experimental investigation of indigenous drugs and their biological activities.
• Bruhn and Holmstedt define it as the interdisciplinary scientific exploration of biologically active agents traditionally employed or observed by humans.
• The International Society of Ethnopharmacology defines it as the interdisciplinary study of the physiological actions of plant, animal, and other substances used in indigenous medicines of past and present cultures.

Definition (cont.)

• The breadth of the discipline includes the use of plants, fungi, animals, microorganisms and minerals, and their biological and pharmacological effects based on international convention.
• Ethnopharmacology welcomes interdisciplinary papers that use an ethnopharmacological, ethnobotanical, or ethnochemical approach.

Definition (cont.)

• Ethnopharmacology studies the effect of ethnicity on responses to prescribed medication, specifically drug absorption, metabolism, distribution, and excretion.
• The field includes pharmacogenetics, the study of genetic variations in responses to drugs.
• It considers how people's culture and beliefs about health issues, along with genetic and physiological characteristics of their ethnic group, impact drug effectiveness.
• Consideration of cultural attitudes and racial biases in drug prescriptions is also part of the field.

Race, Culture & Ethnicity

• Race is considered a class of people with a common lineage and often has different distributions of gene frequencies based on geography.
• Ethnicity refers to shared cultural bonds and common genetic heritage.
• Culture is an integrated system of learned beliefs, values, and customs that are typically passed down through generations.

Variation in Drug Responses

• Historically, predominantly white men were used in drug trials, leading to generalizations about responses.
• Ethnopharmacological research reveals important differences in how various ethnic groups metabolize drugs, based on differences in pharmacodynamics (drug action) and pharmacokinetics (drug movement through the body).
• Genetic variations impact the action of enzymes involved in drug responses, and factors like diet and tobacco use can play a role.

Factors Influencing Drug Response

• Biological factors are ethnicity, age, gender, genetics, and disease.
• Psychosocial-cultural factors include ethnicity.
• Environmental factors include ethnicity, diet, pollution, smoking, alcohol, and drug use.
• Factors like absorption, drug transport, systemic circulation, site of action, distribution, metabolism, and excretion influence drug responses.

Examples of Drugs with Ethnically Variable Effects

• Drugs like Warfarin, ACE inhibitors, Beta blockers, and Isoniazid have been observed to show different efficacy and side effects in different ethnic groups due to genetic variations and their metabolization.

Cytochrome P-450 (CYP) Enzymes

• Cytochrome P-450 (CYP) enzymes are vital in phase 1 metabolism of many drugs prescribed widely.
• CYPs comprise various subgroups identified by letters and numbers (e.g., CYP2C9, CYP2C19, CYP2D6, CYP3A4).

CYP Genetic Abnormalities

• Genetic abnormalities in CYP enzymes are very common, influencing drug response significantly.
• Genetic differences affect the production of enzymes and how quickly drugs are metabolized, with "ultrarapid metabolizers" processing drugs very quickly and "poor metabolizers" processing them much more slowly.

Genetic Polymorphism

• Genetic polymorphism is the existence of multiple forms of a single gene in an individual or a group varying inter-individually.
• Different subgroups of the population with distinct drug-metabolizing enzymes and varying abilities to perform drug transformations arise from genetic polymorphisms. The differences arise from variations in drug enzymes which cause changes in expression and activity due to mutations in the genes or multiple molecular mechanisms.

Drug Metabolism

• Drug metabolism is the transformation of drugs and xenobiotics into more water-soluble metabolites essential for elimination from the body and the termination of biological and pharmacological activity.
• Metabolism is classified into phases 1 (e.g., oxidation, reduction, hydrolysis) and 2 (e.g., acetylation, glucuronidation).

Polymorphisms & Drug Metabolism

• Genetic variations in metabolism of drugs are often the result of genetic polymorphism in alleles for enzymes responsible for drug metabolism.
• Abnormal allele pairs or multiples in polymorphisms lead to alterations in enzyme function.
• Differences in enzyme activity show variations related to racial groups.

Clinical Implications

• Careful monitoring is essential to prevent adverse drug effects related to dosage.
• Observation and specific questions targeting potential adverse effects should be part of medical practice.
• Considering patients' cultural background and language for effective communication is vital.

Pharmacogenomics

• Pharmacogenomics studies how genes affect responses to drugs, thus providing insight into personalized medicine tailoring treatment to individual genes.
• Differences in genetic background lead to variable responses to the same medication.