Selective toxicity

Question 1

What are the general mechanisms by which selective toxicity is achieved in chemotherapy?

Answer 1

1. Differential distribution: Pathogens have mechanisms to accumulate drug to toxic levels, but not mammalian cells.
2. Differential detoxification: Mammalian cells have mechanisms to remove drugs, but not pathogens.
3. Differential activation: Pathogens have the enzymes to convert pro-drug into drug, but not hosts.
4. Unique receptors: Drug target only present in pathogen.
5. Differential importance: Drug target present in both mammalian cells and pathogen cells, but is more important in pathogen cells.
6. Activation of host defence mechanisms: Drug activates host immune system that is already specific to pathogens and does not target own cells.

Question 2

What is an example of differential distribution?

Answer 2

Melarsoprol (treating Tyrpanosoma infections): Parasite has transporters to accumulate drugs

Question 3

What is an example of differential activation?

Answer 3

Aciclovir (antiherpes): Viral thymidine kinase needed to activate pro-drug

Question 4

What is an example of unique receptors?

Answer 4

β-lactam antibiotics: Targets bacterial cell wall which is absent in mammalian cells