Intro to Pharmacology

• Pharmacology


  Study of substances that interact with living systems through chemical processes
• Medical Pharmacology


  Science of substances used to prevent, diagnose, and treat disease
• Toxicology


  Branch of Pharmacology that deals with undesirable effects of chemicals on living systems
• Actions of Chemicals


  1. Medical Pharmacology and Toxicology

  2. Environmental Toxicology
• Pharmacogenomics


  Relation of the individual's genetic makeup to his or her response to specific drugs
• Epigenetics


  Area of possible manipulation of the genes that control pharmacologic responses
• Small interfering RNAs (siRNAs) and micro-RNAs (miRNAs)


  Can be therapeutic agents and can interfere with protein synthesis with extreme selectivity
• Antisense oligonucleotides (ANOs)


  Short nucleotide chains synthesized to be complementary to natural RNA or DNA, can interfere with the readout of genes and the transcription of RNA
• Nature of Drugs


  Inorganic ions, non-peptide organic molecules, small peptides and proteins, nucleic acids, lipids and carbohydrates
• Drug


  Any substance that brings about a change in biologic function through its chemical actions
• Receptor


  Target molecule that the drug interacts with
• Poison


  Drugs that have almost exclusively harmful effects
• Toxins


  Poisons of biologic origin
• Physical Nature of Drugs

  • Can be solid, liquid, or gas
  • Many organic drugs are weak acids or bases
• Drug Size


  • Vary in molecular weight from 7 to 145,000
  • Common drugs have molecular weights between 100 and 1000
• Drug Reactivity and Drug-Receptor Bonds

  • 3 major types: covalent, electrostatic, hydrophobic
  • Weaker bonds are more selective but readily detached
• All substances can under certain circumstances be toxic
• Chemicals in botanicals (herbs and plant extracts, "nutraceuticals") are no different from chemicals in manufactured drugs except for the much greater proportion of impurities in botanicals
• All dietary supplements and all therapies promoted as health-enhancing should meet the same standards of efficacy and safety as conventional drugs and medical therapies
• There should be no artificial separation between scientific medicine and "alternative" or "complementary" medicine
• Cannot move within the body

  • Must be administered directly into the compartment where they have their effect
  • Directly at the site of action
• Drug reactivity and drug-receptor bonds

  How drug interacts with receptors
• 3 major types of chemical forces/bonds

  • Covalent
  • Electrostatic
  • Hydrophobic
• Weaker bonds


  More selective bonds but readily detached
• Covalent bonds


  Very strong, not reversible under biologic conditions, formed between the acetyl group of acetylsalicylic acid (aspirin) and cyclooxygenase, involve the sharing of electrons between two atoms
• Electrostatic bonds


  Weaker than covalent bonds, more common, chemical bond in which one atom loses one electron to produce a positive ion, can be controlled/manipulated through raising or lowering pH, example: bonds between cation and an anion
• Hydrophobic bonds


  Weakest, for highly lipid soluble drugs
• Drug shape


  • The shape of a drug molecule must permit binding to its target site via the bonds described
  • In most cases, one of the enantiomers is much more potent than its mirror image enantiomer, reflecting a better fit to the receptor molecule
  • The more active enantiomer at one type of receptor site may not be more active at another receptor
• Chirality


  Stereoisomerism, exist as enantiomeric pairs, affect drug potency and duration
• Carvedidol


  • Has a single chiral center and thus two enantiomers
  • The (S)(-) isomer is a potent beta receptor blocker, the (R)(+) isomer is a weak beta receptor blocker (100-fold weaker)
• Ketamine


  • Chiral molecule with two isomers introduced as an anesthetic
  • When administered as an anesthetic, the racemic mixture is administered intravenously
  • The (S) enantiomer has recently been approved for use in nasal spray form as a rapid-acting antidepressant
  • The (+) isomer is more potent as an anesthetic and less toxic than the (-) isomer
• Rational drug design


  The ability to predict the appropriate molecular structure of a drug on the basis of information about its biological receptor, drugs are developed by random testing of chemicals or modification of drugs
• Pharmacodynamics


  Actions of the drug on the body, plays a major role in deciding whether a group is appropriate therapy for a particular symptom or disease
• Pharmacokinetics


  Actions of the body on the drug, are of great practical importance in the choice and administration of a particular drug for a particular patient
• Pharmacodynamic principles


  1. Drug (D) + receptor-effector (R) → Drug-receptor-effector complex → effect

  2. D + R → D-R complex → Activation of coupling molecule → effector molecule → effect

  3. Inhibition of metabolism of endogenous activator → Increased activator action on an effector → Increased effect
• Agonist


  Drugs that bind to and activate the receptor, which directly or indirectly brings about the effect
• Pharmacological antagonist drugs


  By binding to a receptor, compete with and prevent binding by other molecules
• Ways drugs interact with receptors

  • Alter the agonist response by activating the agonist binding site
  • Compete with the agonist
  • Act at separate (allosteric) sites
  • Increasing the response to the agonist
  • Decreasing the response to the agonist
• The lock and key mechanism explains how enzymes fit their substrate and how a drug molecule must fit into a receptor
• Agonists that inhibit their binding molecules

  Some drugs mimic agonist drugs by inhibiting the molecules responsible for terminating the action of an endogenous agent