Pt1445

• The medicinal use of drugs includes:

  • Alleviate symptoms
  • cure disease
  • Prevent disease
  • Aid other procedures(anesthetics during surgery)
  • Lifestyle aids (contraceptives, vitamins)
• Pharmacodynamics


  How the drug interacts with the body to produce biochemical/physiological effects
• Pharmacokinetics


  How the body interacts with the drug (absorption, delivery, metabolism, excretion)
• Receptors


  • Molecular components of the body with which a drug interacts to bring about its effect
• Non-receptor mechanisms by which drugs work


  1. Antacids

  2. Mannitol

  3. Bulk & lubricating laxatives

  4. Bile acid binding resins

  5. Metal chelators

  6. Purine/pyrimidine or folic acid structural analogues
• Receptor mechanisms by which drugs work


  1. Agonists mimic endogenous ligand

  2. Antagonists lack intrinsic activity but occupy receptor so reduce agonist binding (& effect)
• Medicinal use of drugs


  • Alleviate symptoms (e.g. analgesics)
  • Cure disease (e.g. antibiotics)
  • Prevent disease (e.g. vaccines)
  • Aid other procedures (e.g. general anaesthetics during surgery)
  • Lifestyle aids (e.g. contraceptives, vitamins)
• Desirable drug properties


  • Specific action
  • Potent
  • Appropriate duration of action
  • Easy to administer/convenient for patient
  • Minimal side-effects/toxicity at therapeutic doses
  • Low cost; ready availability
• Undesirable drug properties


  • Adverse effects
  • High dose needed
  • Organ toxicity
  • Teratogenic
  • Difficult to administer
  • Poor tissue access
  • Expensive; poor availability
• Rational approach to prescribing & therapeutics


  1. Correct clinical diagnosis

  2. Underlying pathophysiology

  3. Drugs with potentially useful action

  4. Monitoring therapeutic response

  5. Risks vs benefits

  6. Communication with patient in making decision to treat
• Clinical Pharmacology


  Use of drugs for diagnosis, prevention & treatment of disease
• Toxicology


  Study of the undesirable effects of chemical agents on living systems (organisms, ecosystems, etc.) - therapeutic agents, industrial pollutants, natural organic & inorganic poisons, other chemicals
• Pharmacology


  Study/knowledge of drugs or poisons
• Drug molecules


  • Size (molecular mass usually 300-500 daltons)
  • Shape & charge that complements binding site on receptor
  • Chemistry (many are weak acids or weak bases)
• Receptor


  Proteins that mediate cell response to chemical signals
• Other protein/nucleic acid targets


  Enzymes, transporters, structural proteins, DNA, RNA
• Drug-receptor interaction


  1. Based on 3D-fit 'lock and key'

  2. Involves various chemical interactions (non-covalent, covalent, ionic, hydrogen bonding, van der Waals, hydrophobic)

  3. Usually reversible

  4. Random/Brownian motion to binding site

  5. Nature of interactions determines binding & dissociation rates
• Dynamic (near) equilibrium occurs, where [DR] is proportional to [D] (& [R])
• For a receptor molecule, the proportion of time it spends in the DR form ('switched on') will be related to the size of the cell response
• If 2 ligands bind at the same site on the receptor, competition will reduce the time spent receptor-bound by each individually
• Agonists


  Mimic endogenous ligand
• Antagonists


  Lack intrinsic activity but occupy receptor so reduce agonist binding (& effect)
• Agonists & competitive antagonists acting at a particular receptor are often closely related in structure
• Receptor response to drug

  Binding of drug causes the receptor protein to undergo conformational change, which in turn affects receptor interaction with other proteins (e.g. signalling pathways), ion channel open probability, or enzyme activity
• Direct drug effects


  Drug mimics endogenous ligand (agonist) or competes with it for the binding site on the receptor (competitive antagonist)

  Drug binding obstructs substrate access to enzyme active site (competitive inhibitor)
• Indirect drug effects


  Binding elsewhere on receptor, leading to conformational change that in turn modulates receptor function or enzyme activity (allosteric regulation: indirect agonism / non-competitive antagonism)

  Modulation of downstream event(s)
• Drug specificity is usually incomplete - drug interacts not only with target receptor(s) (intended effects) but also with other ('non-target') receptors (side effects)
• Drug affinity (KA) for target receptors > affinity for other receptors
• The extent of binding to non-target receptors increases with drug concentration, so drug side effects tend to increase with dose
• Affinity is the extent or fraction to which a drug binds to receptors at any given drug concentration or the firmness with which the drug binds to the receptor.
• Potency is the amount of drug required to elicit a certain effect.
• Teratogenic is when the medication interferes with fetal development and causes birth defects
• A drug is a substance acting on living systems at a molecular level
• A receptor is a molecular component of the body that a drug interacts with to bring about its effect
• Pharmacokinetics patient response to drug:

  (A)bsorption form site of administration

  (D)elivery to site of action

  (M)etabolism

  (E)xcretion

  Time to onset of effect

  Duration of effect

  Accumalation on repeat dosing
• First pass metabolism occurs when drugs are absorbed into the portal vein from the gut and then travel through the liver where they may be broken down by enzymes
• Pharmacokinetics is body to drug
• Pharmacodynamics is drug to body
• Drug molecules vary in size, shape, and polarity.
• Many drugs are weak acids or weak bases

  -ionization depends on local pH

  -unionized form crosses membranes more readily