Essential pharmacology

• What is pharmacology?


  .•The study of the way living systems are affected by chemical agents 

  •Can be endogenous and made by the body e.g. neurotransmitters and hormones

  •Can also be exogenous – i.e. drugs
• What is a drug?


  .•Any chemical agent that affects a biological system

  •Sources include:

  •Natural products from plants

  •Synthetic drugs generated by pharmaceutical industry

  •Biotechnology using living systems to make therapeutic agents

  •Gene therapy?
• What is a receptor?


  .•Drugs act by interacting with a binding site - a receptor

  •Examples of receptors include:

  •Cell surface receptors e.g. β-adrenergic receptors

  •Intracellular receptors e.g. steroid receptors

  •Ion channels e.g. TTX blocks Na+ channels

  •Carriers e.g. ouabain inhibits Na+/K+-ATPase

  •Enzymes e.g. aspirin and ibuprofen inhibit cyclooxygenase

  •Nucleic acids e.g. tumour promoters bind to DNA
• Drug-receptor interactions pt1


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• Drug-receptor interactions pt2


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• Drug-receptor interactions pt3


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• Drug-receptor interactions pt4


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• Concentration-response curves pt1


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• Concentration response curves pt2


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• What determines the size of a drug's response at a receptor?

  .The size of the response depends on:

  1. Drug Affinity: The ability of the drug to bind to the receptor.
  2. Drug Efficacy: The ability of the drug to activate the receptor.

  Additional Notes:

  • Agonists: Mimic the normal effects of the receptor.
  • Antagonists: Block the normal action of the receptor.

  
• Antagonists are still useful?


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• Antagonists graph


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• Summary

  .•Drugs come from a range of sources

  •They act by binding to a specific site (the “receptor”)

  •This explains the characteristic concentration–response curve

  •Properties of affinity vs efficacy explain their effects
• 1.Why does increasing drug concentration have a much smaller effect at very low concentrations, compared to very high concentrations?


  .At very low drug concentrations, only a few receptors are occupied, leading to a minimal response. As concentration increases, more receptors are activated, resulting in a greater effect. At high concentrations, most receptors are occupied, and the response plateaus due to saturation, causing diminishing returns with further increases in concentration.
• 2.Most drugs have a maximal therapeutic dose, above which no further beneficial effect is seen. Why?


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  1. Receptor Saturation: All receptors are occupied, so increasing the dose doesn't enhance effects.
  2. Biological Limits: The body can only respond up to a certain level.
  3. Toxicity Risk: Higher doses may cause harmful side effects.
  4. Homeostasis: The body may counteract excessive drug effects.

  These factors create a ceiling effect, beyond which no additional benefits are seen.
• 3.One of the body’s responses to repeated administration of a drug may be down-regulation of the receptor that drug acts on. What effect will this have on the effectiveness of the drug?


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  • Receptor down-regulation from repeated drug use decreases effectiveness by:

  1. Fewer Receptors: Less receptor availability results in a weaker response.
  2. Tolerance: Higher doses may be needed for the same effect.
  3. Reduced Efficacy: The drug can’t activate enough receptors to produce the desired effect.

  Overall, this leads to diminished therapeutic response.
• 4.I have a high affinity and zero efficacy at my receptor. What am I?


  .You are an antagonist. Antagonists have high affinity for receptors, meaning they bind well, but they do not activate the receptor, resulting in zero efficacy. They block the receptor's normal function without producing a physiological response.
• 5.In the presence of competitive antagonist, the agonist concentration response curve is shifted to the right. Why?


  .In the presence of a competitive antagonist, the agonist concentration-response curve shifts to the right because the antagonist competes with the agonist for binding to the same receptors. This requires a higher concentration of the agonist to achieve the same response, indicating reduced effectiveness at lower concentrations.
• 6.Some antagonists are called non-competitive, because they stop the receptor working but by binding to a different site to the agonist. What effect do you predict the presence of such a non-competitive antagonist would have on the agonist concentration response curve?


  .The presence of a non-competitive antagonist would reduce the maximum response of the agonist concentration-response curve. This is because the antagonist inhibits receptor function regardless of agonist concentration, lowering the maximum effect (Emax) achievable by the agonist.