Pharmacodynamics

• Pharmacodynamics


  The study of the effects of drugs on the body
• General Classification of Drug Effects

  • Change of excitability (Excitation, Inhibition)
  • Selectivity
  • Therapeutic effect (Etiological treatment, Symptomatic treatment)
  • Side effects
  • Adverse effect
  • Toxic effects
  • Allergic reaction
  • Secondary reaction
  • Tolerance
• Excitation


  Increase in function (e.g. caffeine)
• Inhibition


  Decrease in function (e.g. barbiturates)
• Selectivity


  Most prominent effects of a drug (e.g. morphine: analgesic, depresses respiration, depresses cough)
• Therapeutic effect


  Affects the functions & pathogenic processes of organisms
• Etiological treatment


  Eliminate primary pathogenic factor
• Symptomatic treatment


  Improve symptoms
• Side effects


  Produced by therapeutic doses of the drug, non-deleterious
• Adverse effect


  Noxious, unintended response
• Toxic effects


  Produced at large dosage of the drug (acute or chronic exposure), require rational & successful management
• Allergic reaction


  Results from previous sensitization to particular chemical & similar structural, produced at unexpectedly low dosage, mediated by the immune systems
• Secondary reaction


  Long time of using antibiotics, second infection appears
• Tolerance


  Larger dose is needed to bring about the same response
• Dose-effect relationship


  The magnitude of the drug effect depends on its concentration at the site of action, which in turn is determined by the dose of drug administered and by factors characteristic of the drug, such as rate of absorption, distribution, and metabolism
• Dose-response curve


  Plot of the magnitude of the response versus the dose (or the log of the dose) of the drug
• Efficacy


  The maximum effect of a drug - maximum efficacy (Emax)
• Potency


  The amount of a drug needed to produce a given effect (typical, ED50, LD50)
• Diuretics


  • Cyclopenthi azide
  • Furosemide
  • Hydrochlorothiazide
  • Chlorathiazide
• Therapeutic Index (TI)


  TI = median lethal dose / median effective dose, danger increases as TI approaches 1
• Therapeutic Index (TI)


  TI = LD50 / ED50
• Mechanisms of action of drugs

  • Change the physical and chemical properties of the cellular environment
  • Interfere or incorporate with metabolic process
  • Influence on the biological membrane
  • Influence on transmitters and hormones
  • Receptors
• Drug receptor interaction


  Drug (D) + Receptor (R) → Drug-receptor complex (DR) → Effect (E)
• Receptor occupation theory


  Receptor occupied, effects occur, the magnitude of the response of effects is proportional to number of drug-receptor complexes
• Affinity


  Tendency, or chemical forces that cause a drug to combine with the receptor
• Efficacy


  The maximal response a drug can produce
• Agonist


  A compound that binds to a receptor and produces the biological response
• Antagonist


  Binding of an antagonist to a receptor does not produce a biological effect, but it can block or reverse the effect of an agonist
• Receptor families and their transducer and effector molecules

  • Receptor as enzymes (protein Kinase)
  • Multisubunit Ligand-gated ion channels (nicotinic ACH receptor, glutamate)
  • G protein-coupled receptor systems (G Protein coupled receptors, α, β, γ subunit, Effectors)
  • Nucleus receptor (regulate the transcription of specific genes)
• Cellular response of receptor-effector linkage

  • Direct regulation of membrane permeability to ions
  • Regulation via intracellular second messengers (second messenger cAMP)
  • Direct modulation of protein phosphorylation
  • Regulation of DNA transcription
• Receptor down-regulation/Receptor desensitization


  Follow continued stimulation the cell with agonists
• Receptor up-regulation/Receptor hypersitization


  Follow continued use of antagonists, synthesis of additional receptors, connected with increase of sensitization and symptoms induced by withdrawal of drug