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  <head>
    <title>005-01 Foundations</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Pharmacokinetics, pharmacodynamics, and safe prescribing">
      <outline text="Orientation">
        <outline text="Dose to target concentration to response"/>
        <outline text="Pharmacokinetics: what the body does to the drug">
          <outline text="Absorption, distribution, metabolism, excretion"/>
        </outline>
        <outline text="Pharmacodynamics: what the drug does to the body">
          <outline text="Receptors, enzymes, channels, transporters"/>
        </outline>
        <outline text="Safe prescribing adds indication, monitoring, stop plan"/>
      </outline>
      <outline text="Routes and absorption">
        <outline text="Intravenous: complete bioavailability"/>
        <outline text="Oral: convenient but many barriers">
          <outline text="Dissolution, stability, membrane passage"/>
          <outline text="Intestinal and hepatic first-pass metabolism"/>
        </outline>
        <outline text="Bioavailability: fraction reaching circulation unchanged"/>
        <outline text="Absorption depends on formulation, flow, food, pH"/>
        <outline text="Lipid-soluble uncharged molecules cross readily">
          <outline text="Many drugs still rely on transporters"/>
        </outline>
        <outline text="Ionisation follows pH and dissociation constant">
          <outline text="pH alone cannot predict clinical behaviour"/>
        </outline>
        <outline text="Inhaled rapid, transdermal slow and sustained"/>
        <outline text="Intramuscular and subcutaneous unreliable in shock"/>
      </outline>
      <outline text="Distribution">
        <outline text="Perfusion, permeability, tissue and plasma binding"/>
        <outline text="Albumin binds acids, alpha one acid glycoprotein bases"/>
        <outline text="Only unbound drug crosses, acts, is filtered">
          <outline text="Bound drug dissociates as a reservoir"/>
        </outline>
        <outline text="Volume of distribution relates amount to concentration">
          <outline text="Small: mainly plasma; large: tissue binding"/>
          <outline text="Proportional concept, not an anatomical space"/>
        </outline>
        <outline text="Older adults: less water and lean mass, more fat"/>
        <outline text="Oedema, pregnancy, burns, obesity alter distribution"/>
        <outline text="Blood-brain barrier restricts polar compounds">
          <outline text="Tight junctions and active efflux"/>
        </outline>
      </outline>
      <outline text="Clearance, metabolism, and half-life">
        <outline text="Clearance: plasma volume cleared per unit time">
          <outline text="Elimination rate equals clearance times concentration"/>
        </outline>
        <outline text="Half-life depends on volume divided by clearance"/>
        <outline text="Hepatic: blood flow, enzymes, biliary transport, binding"/>
        <outline text="Phase one oxidation, reduction, hydrolysis"/>
        <outline text="Phase two conjugation with polar groups"/>
        <outline text="Metabolism inactivates, activates prodrugs, or intoxicates"/>
        <outline text="Inhibition acts quickly, induction takes days">
          <outline text="New enzyme protein must be produced"/>
        </outline>
        <outline text="Grapefruit effect is drug-specific"/>
        <outline text="Renal filtration, secretion, reabsorption">
          <outline text="Only unbound drug is filtered"/>
        </outline>
        <outline text="Estimated filtration imperfect at extremes"/>
        <outline text="Dialysis removal: size, binding, volume, membrane"/>
      </outline>
      <outline text="Dosing over time">
        <outline text="Loading dose follows volume of distribution"/>
        <outline text="Maintenance dose follows clearance"/>
        <outline text="Steady state after four to five half-lives, any dose"/>
        <outline text="Short intervals reduce peak-to-trough fluctuation"/>
        <outline text="Modified release must not always be crushed"/>
        <outline text="Zero-order elimination saturates capacity">
          <outline text="Small dose rise, disproportionate concentration rise"/>
        </outline>
        <outline text="Therapeutic drug monitoring for narrow ranges">
          <outline text="Level needs timing, dose history, clinical context"/>
        </outline>
        <outline text="Worked model: concentration times volume gives amount">
          <outline text="Concentration times clearance gives amount per time"/>
          <outline text="Halved clearance halves maintenance, not loading"/>
          <outline text="Half bioavailability doubles the oral input"/>
        </outline>
      </outline>
      <outline text="Receptors and response">
        <outline text="Full agonist reaches the system maximum"/>
        <outline text="Partial agonist can oppose a full agonist"/>
        <outline text="Competitive antagonism overcome by more agonist">
          <outline text="Irreversible effects lower achievable response"/>
        </outline>
        <outline text="Potency is dose needed, efficacy is maximum effect">
          <outline text="More potent is not more effective or safer"/>
        </outline>
        <outline text="Spare receptors and amplification break linearity"/>
        <outline text="Tolerance from desensitisation, metabolism, compensation"/>
        <outline text="Physical dependence differs from substance-use disorder"/>
      </outline>
      <outline text="Variability and interactions">
        <outline text="Genetics, age, organ function, adherence vary response"/>
        <outline text="Children not scaled simply from adult weight"/>
        <outline text="Frail older adults: falls, delirium, bleeding"/>
        <outline text="Pharmacokinetic interactions change concentration"/>
        <outline text="Pharmacodynamic interactions change combined effect">
          <outline text="Sedatives, QT prolongers, bleeding, potassium"/>
        </outline>
        <outline text="Medication reconciliation: what is actually taken"/>
      </outline>
      <outline text="Adverse reactions and safety">
        <outline text="Predictable dose-related versus unpredictable reactions"/>
        <outline text="Side effect is not automatically allergy">
          <outline text="Mislabelled allergy denies useful treatment"/>
        </outline>
        <outline text="Before prescribing: goal, contraindications, interactions"/>
        <outline text="Explain benefit, risks, timing, warning symptoms"/>
        <outline text="Plan monitoring, duration, deprescribing"/>
        <outline text="Errors from names, decimals, units, transitions">
          <outline text="Leading zeros, no trailing zeros"/>
        </outline>
        <outline text="Deterioration: review new drugs and dose changes"/>
      </outline>
    </outline>
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