Pharmacodynamics

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Pharmacodynamics

• Drug-receptor interactions
• Receptor complexes and the action of ligands
• Transmembrane potential changes via receptor
  complex
• Change is proportional to receptors occupied or
  by rate of reversible binding (attachment) of
  ligand
• Effects are agonistic or antagonistic

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Ways a drug may act on a neuron or synapse

• Manufacture Increase or block
• Packaging Make vesicles leaky
• Transport Block or facilitate vesicle movement
• In the synapse
• After reversible binding

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Pharmacodynamics

• Drug-receptor affinity
• Governed by stereochemical fit
• Effects on brain determined by location of
  receptor types
• The dose-response relationship
• Dose
• Potency
• Efficacy or maximum effect
• Slope

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The dose-response curve

• The dose-response curve relates the amount
  administered to the response.
• Response may be measured as responding or as
  intensity of response

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The dose-response curve Effectiveness and safety
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Drug variability and toxicity assessment

• ED50 Effective dose for 50 of subjects
• LD50 Lethal dose for 50 of subjects
• The therapeutic index
• TI LD50 / ED50
• No drug is 100 safe
• Placebo effects
• The FDA and drug development

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FDA rules

• Pure Food and Drug Act, 1906 Labeling accuracy
  to eliminate adulteration
• Cuforhedake Brane-Fude, labeled 30 alcohol
• Sherley Amendment, 1912 False and fraudulent
  therapeutic claims on the label
• Harrison Narcotics Act, 1914 Trade controls and
  taxation (Dr. Hamilton Wright)
• Agriculture Department vs. Treasury Dept.

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Expansion of FDA concerns

• Purity (1906)
• Safety (1938) The Food, Drug, and Cosmetics Act
• Toxicity assessment before marketing
• Instructions for use on the label
• Effectiveness (1962) Kefauver-Harris amendments
• Carters Little Liver Pills

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Current FDA Approval Process

• Safety Pre-clinical testing of several dosages
  over relevant time periods on at least two
  species
• Carefully planned clinical trials with signed
  informed consent and annual reports
• Phase 1 clinical trials Small doses on healthy
  volunteers Pharmacokinetics and side effects
• Phase 2 Small sample of hospital patients
• Phase 3 Broader clinical trials on patients

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More recent legislation

• The Orphan Drug Act, 1983
• Prescription Drug Marketing Act, 1987
• Analogue (Designer Drug) Act, 1986
• Anti-Drug Abuse Act, 1988 (ONDCP)
• Anabolic Steroids Control Act, 1990
• http//www.druglibrary.org/schaffer/History/drug_l
  aw_timeline.htm