1.2

• Pharmacology


  Study of drugs, their origin, properties, and how they work
• Pharmacology


  • Multiple factors determine drug's effects
  • Pharmacology can be subdivided into several divisions
• Areas of Pharmacology


  • Pharmacokinetics
• Common Routes of Administration

  • Oral or per os (PO)
  • Parenteral (by needle)
• Oral or per os (PO)


  • Most common and usually safest route
  • Onset usually 30 to 60 minutes
  • Multiple factors impact absorption
• Parenteral (by needle)


  Intradermal, subcutaneous, intramuscular, or intravenous
• Dose–response curve


  • Graphic representation of relationship between dose in milligrams and response to drug
  • Dose and response increase together until ceiling effect
  • Point when additional dosage stops increasing effect
  • Increasing dose may have toxic effects

  
• Potency


  • Drug that reaches effective level with smaller dose is more potent
  • More potent drug reaches toxic effects at smaller dosage
• Therapeutic dose


  Recommended amount to obtain desired effect
• Median lethal dose (LD50)

  Dose at which 50% of test animals die
• Median effective dose (ED50)

  Dose at which 50% of test animals show desired effect
• Therapeutic index (TI)


  • Ratio of LD50 to ED50
  • Gives relative safety indication
  • Formula: TI = LD50/ED50
  • The higher the TI, the safer the drug
  • The closer TI to zero, the more toxic the drug
• Drug Absorption


  Oral route: Drug must pass through GI tract membrane

  Transdermal: Drug must be absorbed through skin

  Considerations: Transport mechanisms, lipid solubility, and drug ionization
• Transport Mechanisms of Drugs Across Membranes

  1. Passive diffusion

  2. Filtration

  3. Active transport
• Fluid Mosaic Model


  Plasma cell membrane comprises two layers of lipids with integral proteins between them

  Also includes channels through which water and small water-soluble molecules can pass

  Other membranes have larger channels

  Substances pass through channels by filtration
• Lipid Solubility


  Cell membrane comprises significant amounts of lipid material

  Lipid-soluble drugs pass through rapidly

  Many drugs very lipid-soluble, e.g. general anesthetics
• Drug Ionization


  Primarily water-soluble drug must be weak acid or weak base to be absorbed rapidly

  Ionized drugs difficult to absorb

  The more neutral (un-ionized) the drug, the better its absorption

  Absorption rate strongly influenced by tissue fluid pH
• Mechanism of action


  Explains how drug produces effect

  Helps identify proper clinical application when known
• Site of action


  Location where drug exerts therapeutic effect

  Not completely identified for all drugs
• Receptor site


  Receptor is part of cell or organism that combines with drug and initiates series of events leading to drug's effect

  Usually located on cell membrane

  Specific drug usually combines with specific receptor
• Agonists


  Drugs that combine with specific receptors to cause drug action
• Antagonists (blocking agents)


  Combine with receptors and cause no action or block an effect
• Drug Distribution


  Drug gains access to blood plasma

  Carried by blood throughout body

  Combines with receptor sites

  Amount of drug that reaches receptor site influenced by plasma protein binding, tissue affinity, and blood flow
• Plasma Protein Binding


  Circulating proteins in plasma chemically attract and bind certain drugs

  Only free drug available for action

  Changes in fraction of bound drug alter degree of drug effect
• Tissue Affinity and Blood Flow


  Some drugs have strong affinity for certain tissues or organs

  Some tissues and organs receive more blood, e.g. liver, kidneys, brains exposed to largest amount of drug
• Drug Metabolism


  Process by which drugs are altered, changed, inactivated, and prepared for elimination

  Also called biotransformation

  Resulting substance called metabolite
• Enzyme induction


  Occurs when drug stimulates rate of action of microsomal enzyme system in liver

  Decreases overall time of drug's activity
• Enzyme inhibition


  Occurs when drug slows metabolism by enzymes

  Leads to increased activity or toxicity
• Pharmacokinetics


  A drug's journey through the body, broken down into four stages: absorption, distribution, metabolism, and excretion
• First-Pass Effect


  Loss of drug from metabolism before reaching its intended site of action

  Drugs with high first-pass effect may require increased oral dosages to achieve therapeutic effect

  Effect reduced through aerosol, sublingual, or parenteral administration
• Factors that Alter Drug Effects

  • Patient adherence to physician's instructions

  Placebo effect

  Pathologic state

  Administration with meals

  Gender

  Age

  Genetic variations

  Drug interaction