PCT312 Pharmacology I - Week 3

PCT312 Pharmacology I (Week 3)

• General Pharmacology - Pharmacokinetics & Pharmacodynamics
• Focuses on the concepts of plasma steady state and clearance.
• Importance of half-life (t1/2):
  • Determines frequency of dosing
  • Estimates time to reach steady state
  • Estimates time needed for drug removal after stopping
• Steady State:
  • Initial administration rate is much higher than elimination rate, leading to low plasma concentration.
  • As administration continues, elimination rate increases, while administration rate remains constant.
  • Eventually, elimination rate equals administration rate, and a steady-state equilibrium is achieved
  • Time to reach steady state is roughly 4-5 half-lives.
• Factors affecting steady state:
  • Admin rate/dose
  • Rate of elimination (e.g., liver/kidney function)
• Drug Excretion:
  • Primarily through urine, but also via bile, sweat, saliva, tears, feces, breast milk, and exhaled air.
• Glomerular filtration:
  • Rate (GFR) is 90-120 mL/min
  • Affected by renal disease
  • Lipid solubility and pH don't influence passage.
  • Drug binding to proteins can affect filtration.
• Proximal tubular secretion:
  • Energy-requiring active transport systems for anions and cations
• Distal tubular reabsorption:
  • Drug concentration increases as passing distal tubule
  • If uncharged, drug may diffuse out back into blood.
  • pH manipulation (ion trapping) can influence drug elimination.
• Total Body Clearance (Cl):
  • Volume of body fluid (blood/plasma) eliminating a drug per unit of time
  • Factors include intestines, bile, lungs, and breast milk
  • CL_total = CL_hepatic + CL_renal + CL_pulmonary + CL_other
• Biliary excretion:
  • Favors compounds with high molecular weight
  • Conjugation (e.g., with glucuronate) enhances biliary excretion
  • Enterohepatic cycling (reabsorption and return to liver) is possible.
• Renal Clearance:
  • Clearance rates can be used to assess a drug's renal elimination.
  • Clearance = 100ml/min with normal kidneys
• Dosage calculations:
  • Loading dose: Used to obtain desired plasma levels rapidly (e.g., serious infections)
  • Maintenance dose: Administered to maintain a desired steady-state plasma concentration
  • Rate of drug elimination = average Css × Cl / dosage interval

Pharmacodynamics

• Definition: Study of the biological and therapeutic effects of drugs (how drugs affect the body).
• Main Targets for Drug Action:
  • Receptors
  • Ion channels
  • Enzymes
  • Carrier molecules
• Drug Receptors: Sensing elements, usually macromolecules. Binding initiates a series of events leading to physiological effect. The magnitude of response is proportional to the number of drug-receptor complexes
• Agonists: drugs that stimulate receptors to initiate changes in cell function (e.g. increasing or decreasing cell signaling).
• Antagonists: drugs that bind to receptors without eliciting a response, blocking the action of agonists.
• Drug-receptor classification:
  • Ligand-gated ion channels, G protein-coupled receptors, enzyme-linked receptors, intracellular receptors