Pharmacology

• Pharmacotherapeutics is a branch of pharmacology that refers to use of drugs to prevent, treat, or diagnose disease
• Pharmacokinetics is what the body does to the drug
• Pharmacodynamics is what the drug does to the body
• Brand name is the original drug usually protected by patents
• Generic drugs are usually off-patent substitutes for the brand names
• Preclinical phase is the initial testing usually on animals lasting 1-2 years
• Clinical phase (human testing), 5-6 years

  • three phases with progressively larger subject sizes
  • small group of healthy people
  • People with the pathology
  • Large scale study
• Postmarketing surveillance (phase IV)

  • FDA monitors for any problems after drug introduced to market
• Orphan drugs

  • drug approval may be modified by FDA
  • Smaller clinical trials, quicker approval
  • for cases under 200,000
• Adverse drug reactions (ADR) 2 ways of reporting

  • package inserts for patients = every side effect reported during testing
  • overview for health professionals = lists side effects based on percentage noted during testing
• Off-label drug use (OLDU)

  • drugs prescribed for conditions other than they were originally approved for by the FDA
  • Tricyclic antidepressants for neuropathic pain
  • Viagra originally to lower BP
• Controlled substances are drugs that have a high potential for abuse and are illegal to possess, sell, or use
• Schedule I

  • highest potential for abuse without therapeutic benefit
  • Heroin, LSD, Mescaline, Peyote
• Schedule II

  • specific therapeutic purpose but high risk for abuse
  • Morphine, Fentanyl
• Schedule III

  • therapeutic purpose with mild/moderate risk for abuse
  • Codeine, Anabolic Steroids
• Schedule IV

  • Therapeutic purpose with mild risk for abuse
• Schedule V

  • lowest relative abuse potential
• Threshold dose is the dose at which effects start to occur
• Ceiling effect is the dose at which max effect occurs, so more drug will not change effect
• Median effective dose (ED50)

  • 50% of the population responds to a specific drug
• Median Toxic Dose (TD50)

  • 50% of the population exhibits adverse effects
• therapeutic index

  • indicates the drug's safety
  • the higher the number = safer the drug
  • Acetaminophen (Tylenol) = 27
  • Meperidine (demerol) = 8
  • Diazepam (valium) = 3
• First pass effect is the significant amount of drug is absorbed and metabolized prior to reaching primary site of action

  • common meds administered via alimentary canal
  • common site of metabolism is liver
• Passive diffusion is the movement of molecules from a region of high concentration to a region of low concentration
• Active transport is membrane proteins transport across membrane
• facilitated diffusion is membrane protein assist transport without energy required
• cytosine is engulfed by the cell or encapsulated and sent outside the membrane
• Factors affecting distribution of drugs

  • tissue permeability
  • blood flow
  • binding to plasma proteins
  • binding to subcellular components
• Adipose tissue is the primary site for drug storage
• Biotransformation = drug metabolism

  • oxidation is the most common
• Drug metabolism occurs mostly in the liver

  • enters through the hepatic vein
• Kidneys are the primary site for drug excretion

  • polar is excreted through urine
  • Non-polar is reabsorbed passively through nephron wall which is fat loving
• Drug clearance is the ability of organs and tissues to eliminate a drug
• Half-life is the amount of time required for 50% of drug remaining in the body to be eliminated
• affinity is the amount of attraction between a drug and a receptor
• Allosteric modulators are regulators that can change the receptors affinity for a drug
• Allosteric activator example

  • diazepam (valium) which modulates GABA receptors
• Desensitization is overstimulation by endogenous substances (NT, hormones) or medication can lead to less active receptors and reduce the drug response
• Down-regulation is prolonged exposure to agonist leaves less receptors available
• Supersensitivity also known as up-regulation is a decrease in receptor stimulation that can lead to increased receptor sensitivity