Pharmacogenetics vs Pharmacogenomics

Definition

• Pharmacogenetics studies inherited differences in drug response
• Pharmacogenomics studies the complete spectrum of an organism's genes

Pharmacogenetics vs Pharmacogenomics

• Pharmacogenetics focuses on individual genetic variations that affect a person's response to a particular drug
• It examines single genes and their role in drug metabolism and efficacy
• Pharmacogenomics refers to all relevant genetic variations impacting drug therapy
• It studies the broader effect of entire genomes on drug response
• It considers multiple genes and their interactions to personalize medicine and optimize drug therapies for groups

How Genetics Impacts Drug Treatment

• Genetics can influence drug treatment outcomes, especially in neurologic and psychiatric disorders, by impacting the pharmacokinetic and pharmacodynamic aspects of medications
• Genetic variations can affect drug therapy in two ways:
  • Pharmacokinetics: absorption, transport, metabolism, or excretion
  • Pharmacodynamics: differences occur in the way the body responds to a drug.

Benefits of Pharmacogenetics

• Study of affecting genetic variations impacting individual drug responses leads to enhanced drug efficacy with minimized adverse effects
• Genetic variability insights allows for personalized treatment plans

Genetic Variation Impact

• Genetic variability influences how genetic variability influences drug treatment outcomes
• Understanding variations in genes could enable drug responses to be predictable

FDA Recognition

• The FDA acknowledges the importance of pharmacogenetic variation in responding to drug treatment
• The FDA includes this pharmacogenetic information on drug labels for a broad range of pharmaceuticals

Cytochrome P-450

• Cytochrome P-450 is involved in drug metabolism, affecting drug activation and breakdown
• Cytochrome P-450 helps to determine drug dosages and potential interactions
• For many drugs, cytochrome P-450 initiates detoxification, reducing drug activity for excretion
• Many drugs are inactive prodrugs requiring cytochrome P-450 conversion into an active metabolite for therapeutic effect
• The human cytochrome P-450 proteins have 56 different functional enzymes, each encoded by a different CYP gene
• CYP450 enzymes include CYP3A4, CYP2D6, CYP2C9, and CYP2C19, each metabolizing different drugs
• This also affects drug response and toxicity
• CYP genes are polymorphic, with alleles resulting in absent, decreased, or increased enzyme activity
• 6 cytochrome P-450 genes (CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) are especially important
• These six are responsible for metabolizing >90% of all commonly used drugs

CYP2D6 Codeine Metabolism

• Poor metabolizers have reduced analgesic effect
• The CYP2D6 enzyme converts codeine into its active metabolite, morphine
• In individuals with 2 inactive copies of CYP2D6 (“poor metabolizers”), pain relief may be inadequate

CYP2C19 Clopidogrel

• Poor metabolizers of CYP2C19 are at risk of clotting
• The CYP2C19 gene can influence how effective clopidogrel is ( antiplatelet)
• Clopidogrel is a commonly prescribed drug after acute coronary syndrome
• If patients have a affected varient, treatment plans can be adjusted

Pharmacodynamics

• Pharmacodynamics is concerned with the drug's effect on the body and any side effects
• Genomic factors can influence pharmacodynamics; variations can lead to an increased likelihood of serious adverse reactions
• It refers to the relationship between drug concentration and its effect
• Variable responses occur in Individuals with identical plasma and tissue concentrations
• Variable drag related responses may suggest pharmacodynamic mechanisms influence drug actions

Genetic Variation & Anesthesia

• Thermogenesis can be affected in anesthesia by genetic mutations

Malignant Hyperthermia

• Malignant hyperthermia (MH) is a condition where body temperature rises uncontrollably in response to anesthesia
• The body temperature may rapidly increase, causing symptoms that may be fatal without immediate treatment
• Patients develop life-threatening fever, sustained muscle contraction, and attendant hypercatabolism after anesthesia
• Malignant hyperthermia is frequently associated with mutations in the RYR1 gene, encoding an intracellular calcium ion channel
• Many human MH-associated mutations have been identified in the ryanodine receptor type 1 (RyR1) gene,
• These mutations cause increased calcium release from the sarcoplasmic reticulum, leading to hyperthermia

HLA

• Human leukocyte antigens (HLA) are genes in major histocompatibility complexes (MHC)
• HLA codes for proteins that differentiate between self and non-self, playing a role in disease and immune defense
• The discovery of new associations between these syndromes and specific HLA can provide a way to predict risks and reactions
• Risks can be predicted with screening to avoid morbidity and mortality

Abacavir

• Abacavir is a medication used to treat HIV/AIDS
• Abacavir-induced hypersensitivity reaction is associated with the presence of the major histocompatibility complex class I HLA-B*5701 allele
• A screening test for the HLA-B*5701 allele can assist clinicians to identify patients at risk of a hypersensitivity reaction to abacavir.
• HLA-B*5701 screening to prevent this reaction is now in widespread routine clinical use

Benefits of Pharmacogenetics

• Personalized medicine leads to tailored drug dosing
• Fewer adverse effects minimize toxicity
• Improved drug efficacy optimizes therapeutic outcomes

Challenges and Considerations

• High costs and accessibility
• Data privacy and genetic discrimination
• Clinical implementation barriers