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  <head>
    <title>097-03 Pharmacogenomics, adverse effects, interactions, and regulation</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Pharmacogenomics, adverse effects, regulation">
      <outline text="Variation and useful pharmacogenomics">
        <outline text="Exposure, target, disease, behaviour, chance"/>
        <outline text="Inherited and acquired genomic variation"/>
        <outline text="A useful result changes a decision">
          <outline text="Prescribe, choose, starting dose, adjust, monitor"/>
        </outline>
        <outline text="Association alone is insufficient">
          <outline text="Accurate measurement, reproducible phenotype"/>
          <outline text="Interpret in ancestry and clinical context"/>
        </outline>
      </outline>
      <outline text="Pharmacokinetic genes">
        <outline text="Absorption, transport, metabolism, elimination"/>
        <outline text="Alleles: absent to increased or altered function"/>
        <outline text="Metaboliser categories simplify a continuum"/>
        <outline text="Active parent drug: reduced metabolism, toxicity"/>
        <outline text="Prodrug: reduced activation, less efficacy">
          <outline text="Direction requires knowing the pathway"/>
        </outline>
        <outline text="Phenoconversion by enzyme inhibition"/>
        <outline text="Induction raises capacity over days"/>
        <outline text="Disease, age, diet, smoking alter expression"/>
        <outline text="Limited panels miss rare and copy-number variants"/>
      </outline>
      <outline text="Pharmacodynamic and somatic variation">
        <outline text="Receptor and signalling variants alter sensitivity"/>
        <outline text="Antigen-presenting variant presents drug antigen">
          <outline text="Strong risk of specific hypersensitivity"/>
        </outline>
        <outline text="Tumour changes predict dependence or resistance">
          <outline text="One biopsy may miss clones"/>
        </outline>
        <outline text="Germline: person and relatives; somatic: tissue"/>
      </outline>
      <outline text="Testing strategy and decision support">
        <outline text="Pre-emptive: before prescription, reusable">
          <outline text="Needs records, updates, misuse protection"/>
        </outline>
        <outline text="Reactive: at decision, may be too late"/>
        <outline text="Support states gene, phenotype, action, limits"/>
      </outline>
      <outline text="Adverse reactions and causality">
        <outline text="Intended pharmacology, off-target, immune, errors"/>
        <outline text="Predictable dose-related reactions are common"/>
        <outline text="Unpredictable reactions may still be genetic"/>
        <outline text="Classification is an aid, not a law"/>
        <outline text="An event after a drug is not automatically caused"/>
        <outline text="Timing, mechanism, dechallenge, rechallenge">
          <outline text="Rechallenge unethical after severe reaction"/>
          <outline text="Dechallenge misleads if disease resolves"/>
        </outline>
        <outline text="Scales improve consistency, not judgment"/>
      </outline>
      <outline text="Immune reactions and organ toxicity">
        <outline text="Antibody, cytotoxic, immune-complex, T-cell"/>
        <outline text="Prior uneventful exposure does not exclude it"/>
        <outline text="Severe reactions can progress after stopping">
          <outline text="Immune activation becomes self-sustaining"/>
        </outline>
        <outline text="Document culprit, phenotype, severity, certainty"/>
        <outline text="Liver: high first-pass concentrations"/>
        <outline text="Kidney: concentrated filtrate exposes tubules"/>
        <outline text="Heart: conduction, repolarisation, contractility"/>
        <outline text="Monitor by latency and mechanism"/>
      </outline>
      <outline text="Drug interactions">
        <outline text="Pharmacokinetic: one changes another&#x27;s exposure"/>
        <outline text="Absorption: binding, pH, motility, transport"/>
        <outline text="Inhibition starts as inhibitor rises"/>
        <outline text="Induction develops and resolves slowly">
          <outline text="Protein abundance must change"/>
        </outline>
        <outline text="Protein displacement alone often transient"/>
        <outline text="Pharmacodynamic: additive, synergistic, antagonistic">
          <outline text="Sedatives jointly depress ventilation"/>
          <outline text="Different mechanisms increase bleeding"/>
          <outline text="Repolarisation delay conditioned by electrolytes"/>
        </outline>
        <outline text="Databases flag, management estimates magnitude"/>
      </outline>
      <outline text="Age, pregnancy, and organ function">
        <outline text="Neonates: immature clearance pathways"/>
        <outline text="Children: maturation is nonlinear"/>
        <outline text="Older adults: reserve, frailty, sensitivity">
          <outline text="Low muscle mass hides low filtration"/>
        </outline>
        <outline text="Polypharmacy: review indication and net benefit"/>
        <outline text="Pregnancy alters volume, binding, filtration">
          <outline text="Fetal risk depends on developmental timing"/>
          <outline text="Untreated illness is not zero risk"/>
        </outline>
        <outline text="Lactation: milk transfer, infant clearance"/>
        <outline text="Loading by volume, maintenance by clearance"/>
      </outline>
      <outline text="Medication safety and regulation">
        <outline text="Errors: names, units, decimals, reconciliation"/>
        <outline text="Systems make the intended action easy"/>
        <outline text="Blame without workflow review preserves errors"/>
        <outline text="Approval: favourable benefit-risk in conditions">
          <outline text="Not complete knowledge or superiority"/>
        </outline>
        <outline text="Tools: labels, controlled distribution, studies"/>
        <outline text="Regulators can reasonably differ"/>
        <outline text="New risks weighed by absolute frequency">
          <outline text="Relative risk can sound dramatic"/>
        </outline>
      </outline>
      <outline text="Responsible pharmacology">
        <outline text="Genomics refines probability, rarely replaces"/>
        <outline text="Signals need investigation, not reflex certainty"/>
        <outline text="Choose exposure, anticipate, detect, revise"/>
      </outline>
    </outline>
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