Chemistry in Everyday life - Drug selectivity in body

  • Introduction to drug selectivity
  • Definition of drug selectivity
  • Importance of drug selectivity in pharmacology
  • Types of drug selectivity
  • Factors affecting drug selectivity
    • Molecular size and shape
    • Binding affinity to target receptors
    • Pharmacokinetics (absorption, distribution, metabolism, excretion)
    • Drug-drug interactions
  • Mechanisms of drug selectivity
    • Receptor binding
    • Enzyme inhibition
    • Ion channel modulation
    • Transporter interactions
  • Selective drug examples
    • Aspirin (COX-1 vs. COX-2 inhibition)
    • Beta blockers (β1 vs. β2 receptors)
    • Selective serotonin reuptake inhibitors (SSRIs)
  • Non-selective drug examples
    • Acetaminophen (targets COX enzymes)
    • Non-selective NSAIDs (COX-1 and COX-2 inhibition)
    • Antihistamines (multiple histamine receptors)
  • Applications and implications of drug selectivity
    • Minimizing side effects
    • Maximizing efficacy
    • Personalized medicine
  • Challenges in achieving drug selectivity
    • Similarity of target receptors
    • Off-target effects
    • Individual variations in drug response
  • Conclusion
    • Importance of drug selectivity for effective and safe pharmacotherapy.

Mechanisms of drug selectivity

  • Receptor binding
    • Drug binds selectively to specific receptors on target cells
    • Examples: Beta blockers, antipsychotics
  • Enzyme inhibition
    • Drug selectively inhibits specific enzymes involved in biochemical pathways
    • Examples: ACE inhibitors, statins
  • Ion channel modulation
    • Drug selectively modulates ion channels to alter cellular signaling
    • Examples: Calcium channel blockers, potassium channel openers
  • Transporter interactions
    • Drug selectively interacts with specific transporters to affect drug distribution and elimination
    • Examples: Proton pump inhibitors, selective serotonin reuptake inhibitors (SSRIs)
  • Covalent modification
    • Drug selectively forms irreversible covalent bonds with target proteins
    • Example: Acetylcholinesterase inhibitors in Alzheimer’s treatment

Selective drug examples

  • Aspirin (COX-1 vs. COX-2 inhibition)
    • Aspirin selectively inhibits cyclooxygenase-1 (COX-1) to reduce inflammation and pain
    • However, at higher doses, it also inhibits cyclooxygenase-2 (COX-2) leading to undesired side effects
  • Beta blockers (β1 vs. β2 receptors)
    • Beta blockers selectively block β1 receptors in the heart, reducing heart rate and blood pressure
    • However, they may also block β2 receptors in the lungs, leading to bronchoconstriction
  • Selective serotonin reuptake inhibitors (SSRIs)
    • SSRIs selectively inhibit the reuptake of serotonin, increasing its availability in the brain
    • Used in the treatment of depression, anxiety, and other mental disorders

Non-selective drug examples

  • Acetaminophen (targets COX enzymes)
    • Acetaminophen inhibits both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes
    • However, its exact mechanism of action is not fully understood
  • Non-selective NSAIDs (COX-1 and COX-2 inhibition)
    • Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen inhibit both COX-1 and COX-2 enzymes
    • Used for relieving inflammation, pain, and fever
  • Antihistamines (multiple histamine receptors)
    • Antihistamines block various histamine receptors to alleviate allergy symptoms
    • Non-selective antihistamines may cause drowsiness, while newer selective antihistamines have fewer side effects

Applications and implications of drug selectivity

  • Minimizing side effects
    • By targeting specific receptors/enzymes, drugs can minimize off-target effects and reduce adverse reactions
  • Maximizing efficacy
    • Selective drugs can optimize therapeutic effect by acting specifically on the intended target
  • Personalized medicine
    • Understanding drug selectivity can aid in tailoring treatment based on an individual’s genetic makeup and characteristics
  • Efforts to improve drug selectivity
    • Extensive research is focused on developing drugs with higher selectivity, optimizing safety and effectiveness

Challenges in achieving drug selectivity

  • Similarity of target receptors
    • Many target receptors share structural similarities, making it challenging to design selective drugs
  • Off-target effects
    • Even drugs designed to be selective can sometimes interact with unintended targets, leading to adverse effects
  • Individual variation
    • Response to drugs varies among individuals due to genetic factors, metabolism rates, and other factors
    • One drug’s selectivity may not be applicable to all individuals

Challenges in achieving drug selectivity

  • Similarity of target receptors
    • Many target receptors share structural similarities, making it challenging to design selective drugs
  • Off-target effects
    • Even drugs designed to be selective can sometimes interact with unintended targets, leading to adverse effects
  • Individual variation
    • Response to drugs varies among individuals due to genetic factors, metabolism rates, and other factors
    • One drug’s selectivity may not be applicable to all individuals

Conclusion

  • Importance of drug selectivity for effective and safe pharmacotherapy.
  • Drug selectivity plays a crucial role in minimizing side effects and maximizing efficacy.
  • Understanding the mechanisms and challenges associated with drug selectivity can aid in the development of personalized medicine.
  • Ongoing research aims to improve drug selectivity for enhanced therapeutic outcomes.

References

  • Smith, J. D., & White, W. L. (2003). Drug selectivity: an overview. Drug Discovery Today, 8(17-18), 853-861.
  • Rang, H. P., Ritter, J. M., Flower, R. J., & Henderson, G (2012). Rang and Dale’s Pharmacology. Elsevier.
  • Katzung, B. G., Trevor, A. J., & Masters, S. B. (2018). Basic & Clinical Pharmacology. McGraw-Hill Education.

Questions for Revision

  1. Define drug selectivity and explain its importance in pharmacology.
  1. Discuss the factors that can affect drug selectivity.
  1. Describe the mechanisms of drug selectivity with examples.
  1. Provide examples of drugs that exhibit selective and non-selective actions.
  1. What are the applications and implications of drug selectivity in pharmacotherapy?
  1. Discuss the challenges associated with achieving drug selectivity.
  1. Summarize the key points discussed in this lecture on drug selectivity.
  1. How can drug selectivity contribute to personalized medicine?
  1. Explain the concept of off-target effects and its relevance in drug selectivity.
  1. What are some ongoing efforts to improve drug selectivity?