BIOMED SCIE Lecture 4 Disease treatment Pharmacology I

• Drug


  Any (chemical) substance that causes an effect in the body
• Toxin


  Any substance that causes an unwanted effect in the body
• All drugs can be toxins! Depends on the amount
• Increase dose (amount)


  Increase response (effect)
• Dose-response relationship


  The relationship between the dose of a drug and the response it produces
• Recommended chapters: 'Pharmacology for Nurses: A pathophysiologic approach', Adams et al. (also contained in BMOL10030 book) - very relevant to Pharmacology at Stage 1
• Pharmacokinetics


  The study of the movement of drugs within the body (encompasses absorption, distribution & elimination) - i.e. how the body handles medication after it is administered
• Pharmacodynamics


  The study of the pharmacological response to a drug - i.e. what the drug does to the body

  
• Explain the applications of pharmacokinetics to clinical practice


  1. Absorption

  2. Metabolism

  3. Distribution

  4. Excretion

  
• Components of pharmacokinetics


  • Absorption
  • Metabolism
  • Distribution
  • Excretion

  
• Diffusion or passive transport


  Molecules move from higher to lower concentration, usually small, non-ionised, or lipid-soluble molecules
• Active transport


  Chemicals move against concentration or electrochemical gradient, usually large, ionised, or water-soluble molecules, co-transport involves the movement of two or more chemicals across the membrane
• Absorption is the process by which a drug moves from the site of administration across body membranes to the bloodstream

  
• The greatest barrier for many drugs is crossing many membranes. How easily a drug crosses plasma membranes determines its movement throughout the body
• Absorption depends on the size of the drug molecule, its lipid solubility, its degree of ionisation (pH of surrounding environment), and interactions with food or other medications (fatty meals)
• In acid of stomach, aspirin (acidic drug) is non-ionised and easily absorbed by bloodstream. In alkaline environment of small intestine, aspirin is ionised and less likely to be absorbed
• Metabolism (also known as biotransformation)


  Changes drug so it can be excreted, involves biochemical reactions driven by enzymes, liver is the primary site - changes in hepatic metabolism can significantly impact drug action (age, lifestyle, disease etc)
• Hepatic microsomal enzyme system

  Liver enzymes that inactivate drugs and accelerate their excretion, sometimes called the P450 system (involves cytochrome P450 oxidases), some agents, known as prodrugs, have no pharmacologic activity unless first metabolised to active form by body

  
• Oral Drugs Enter Hepatic-Portal Circulation (First-Pass Effect)


  1. Drug absorbed across the intestinal wall

  2. Drug enters into hepatic portal circulation, goes to liver

  3. Drug is metabolised to inactive form

  4. Drug conjugates with other charged species and leaves liver

  5. Drug is distributed to general circulation

  
• Many drugs rendered inactive by first-pass effect
• Drug distribution


  The methods by which drugs are transported throughout the body, simplest factor is the amount of blood flow to body tissues, depends on the formation of drug-protein complexes and special barriers like the placenta or brain barriers

  
• Drug-protein complexes


  Drug molecules form reversible complexes with plasma proteins, cannot cross capillary membranes so don't get into body tissues, only free, unbound drug can act

  
• Placenta and blood-brain barriers are special anatomic barriers that guard against many chemicals, medications and other agents from entering the brain and foetus respectively, makes brain disorders and tumours difficult to treat, foetal-placenta barrier protects foetus
• No pregnant person should be given medication without strong consideration of condition ('teratogen' – agent that can disturb foetal development)
• Thalidomide was once used widely to alleviate nausea and morning sickness during pregnancy, caused severe foetal damage
• Processes by which drugs are excreted

  • Renal excretion
  • Biliary excretion
  • Respiratory excretion
  • Excretion in glandular secretions (e.g. sweat, milk)

  
• Enterohepatic recirculation


  Drugs excreted in bile recirculate to liver, percentage of drug recirculated numerous times, prolongs activity of drug

  
• Plasma half-life (t1/2)


  The length of time required for the plasma concentration of a drug to decrease by half after administration, the greater the half-life, the longer it takes to excrete
• Therapeutic range


  The dosage range or serum concentration that achieves the desired drug effects
• Loading dose


  Comparatively large dose given at the beginning of treatment to quickly obtain the therapeutic range of a drug (plateau reached faster)
• Maintenance dose


  Dose that keeps the plasma drug concentration continuously in the therapeutic range

  
• Absorption


  The process by which a drug moves from the site of administration across body membranes to the bloodstream
• Site of drug administration

  The location in the body where a drug is introduced, such as oral, intravenous, intramuscular, or transdermal
• what studies the movement of drugs in the body


  Pharmacokinetics
• what is Pharmacodynamics?


  Study of the pharmacological response to a drug
• Drugs are excreted primarily by ...?

  the kidneys( renal execretion)
• What is the minimum effective concentration?


  Amount of drug required to produce a therapeutic effect
• What is the therapeutic range?


  The dosage range or serum concentration that achieves the desired drug effects.
• What is Toxic concentration?


  Level of drug that will result in serious adverse effects.