PHARM

• Drug


  Biologic active substance that modifies cellular function
• Placebo


  Contains no active ingredient, can modify effects through suggestion
• Chemical name


  Refers to chemical structure
• Generic name


  Nonproprietary name
• Trade or brand name

  Proprietary name
• Therapeutic effect


  Intended effect of drug
• Tolerance


  Phenomenon necessitating increase in dosage
• Tachyphylaxis


  Rapid development of tolerance
• Allergy

  Adverse immune reaction triggered by drug, food, or chemical
• Adverse reactions or side effects

  Drug effects other than those intended, may be harmful or nuisance
• Idiosyncratic reaction


  Unpredictable susceptibility to drug's action
• Teratogens


  Substances known to cause birth defects
• Carcinogens


  Substances that cause malignant neoplasms
• Drug dependence


  Continual use causes drug tolerance, withholding drug causes withdrawal symptoms, withdrawal symptoms may be due to altered physiologic state or psychological need
• Drug Development


  1. Molecule or compound identified

  2. Studied to determine mechanism

  3. Tested in animals to determine effectiveness, gather safety information, and determine absorption, breakdown, elimination

  4. Phase I studies in 20-100 healthy volunteers to determine safety and tolerability, study how drug works, learn how body responds

  5. Phase II studies in several hundred people with disease drug is intended to treat to assess whether drug effectively treats condition and assess safety and toxicity

  6. Phase III studies in large number of humans (300-3000) with the disease to confirm effectiveness and safety, test against placebo

  7. Phase IV post-marketing surveillance after approval to detect rare or long-term adverse reactions and determine if drug can treat other conditions
• Drug Development takes many years, must be approved by FDA, and is a very expensive process
• Abuse of Prescription Drugs


  Most often abused drugs are controlled by prescription, Comprehensive Drug Abuse Prevention and Control Act established drug schedules, practitioners must be registered with DEA to prescribe controlled substances
• Drug Schedules


  Drugs categorized by schedule based on drug abuse potential, pattern of abuse, risk to public health, drug's potential for dependence, and whether drug is precursor of controlled substance
• Sources of Drug Information

  • AHFS Drug Information
  • Facts and Comparisons
  • United States Pharmacopeia (USP)
  • National Formulary
  • Physicians' Desk Reference (PDR)
  • Micromedex
  • Drug Information Handbook
• 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
  • Example: general anesthetics
• Drug Ionization


  • Primarily water-soluble drug must be weak acid or weak base to be absorbed rapidly
  • Ionized drugs difficult to absorb
  • Ionized molecules poorly soluble in lipids
  • Highly charged particles repulsed by fixed charges in channels and membrane surface
  • The more neutral (un-ionized) the drug, the better its absorption
  • Absorption rate strongly influenced by tissue fluid pH
  • Henderson–Hasselbalch equation: pH = pKa + log(ionized drug/un-ionized drug)
• 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