pharmacokinetics

• Diffusion → Passive transport through cell membrane, 
• Pinocytosis → Passive movement , mostly of liquid, by the budding of small vesicles from the cell membrane,
• Aqueous pores → Very small channels only useful for some ions
• Carrier mediated transport → Active and specific transport of molecules,
• Brain → Continuous Endothelium with tight junctions
• Gastrointestinal tract → Fenestrated endothelium,
• Muscle → Continuous endothelium
• Heart → Continuous endothelium,
• Liver → Discontinuous endothelium
• Which drug will cross a cell (plasma) membrane more easily? Select (i) or (ii) for each scenario below.

  (i) A 400Da drug or (ii) a 1500Da drug?

  (i) A 400Da drug
• Which drug will cross a cell (plasma) membrane more easily? Select (i) or (ii) for each scenario below. A weakly basic drug or (ii) a weakly acidic drug in a low pH environment

   (ii) a weakly acidic drug in a low pH environment
•  Which drug will cross a cell (plasma) membrane more easily? Select (i) or (ii) for each scenario below.

  A strongly acidic drug or (ii) a neutral drug? 


  (ii) a neutral drug?
• Which drug will cross a cell (plasma) membrane more easily? Select (i) or (ii) for each scenario below. (i) A protonated weak acid or (ii) a protonated weak base?

  (i) A protonated weak acid
• Which drug will cross a cell (plasma) membrane more easily? Select (i) or (ii) for each scenario below

  A lipophilic drug or (ii) a water soluble drug via passive diffusion?

  (i) A lipophilic drug
• Which drug will cross a cell (plasma) membrane more easily? Select (i) or (ii) for each scenario below.

  A lipophilic drug or (ii) a water soluble drug via pinocytosis


  a water soluble drug via pinocytosis
• Rapid systemic administration in a horse →

  Intravenous
•  Specifically targeting bronchi in a cat

  Inhalation
• Long-term epileptic treatment in a dog →

  Oral
• Administration of a drug with a high hepatic metabolism →

  Rectal
• Treatment of conjunctivitis in a rabbit →

  Topical solution
• Vaccination of a dog →

  Subcutaneous,
• Treatment of eczema in a cat → Topical cream
• Which of these are examples of drug trapping

  Drug binding to non-target proteins in tissue

  Change in ionisation state in tissue that reduces the rate the drug can move out of the tissue
• Liver → Metabolism,
• Kidney → Excretion and a little metabolism
• Gastrointestinal tract → Metabolism,
• Metabolism, Lung → Metabolism and a little excretion,
• Plasma  → Metabolism
• Bile → Excretion
• Because the elimination mechanism is saturated, the half life changes with higher doses= zero order
• Tolerance → Reduced drug efficacy due to short-term changes in drug-target binding, e.g. increased receptor internalisation
• Irreversible antagonism → 'Permanent’ binding of a antagonist to a receptor, preventing drug binding within the life-time of the cell,
• Physiological antagonism → Targeting of pathway producing opposite effect to that produced by a pre-existing agonist,
• Non-competitive antagonism → Blocking downstream pathways that prevent the effects of an agonist being realised,
• Resistance → Long-term adaptions at the cell or organism level that stop a drug having an effect,
• Pharmacokinetic antagonism → Drug induced alterations (typically in liver enzymes) that increase the removal of a drug from the body, preventing/reducing a therapeutic effect,
• Competitive antagonism → A direct competition with agonist for binding to the receptor