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Flashcards in Selective Toxicity Mechanisms Deck (17)
1

At what levels can selectivity occur?

Species level, organ level, cell level

2

What is species level selectivity?

Drugs which are designed to target a certain species (e.g. bacteria and not humans)

3

What is sulfanilamide?

An antibiotic which resembles p-amino benzoic acid which is part of folic acid. It binds to the enzyme dihydropteroate synthase to inhibit DNA synthesis.

4

What is trimethoprim?

An antibiotic which binds to dihydrofolate reductase to inhibit DNA synthesis.

5

What is cotrimoxyzol?

A combination of sulfanilamide and trimethoprim - achieves a synergistic effect even though they both work on enzymes in the same pathway

6

What is cell level selectivity?

Drugs which are designed to target certain cells e.g. target cancer cells which are replicating more quickly than other cells

7

What is methotrexate?

A drug which resembles folic acid and binds to the human enzyme dihydrofolate reductase to inhibit DNA synthesis - this specifically targets cells which are making a lot of DNA i.e. cancer cells

8

What are the side effects of methotrexate?

It also suppresses blood synthesis, WBC synthesis, growth of endometrium and other processes involving a lot of DNA synthesis

9

What other disease is methotrexate used for other than cancer?

rheumatoid arthritis and psoriasis - because it suppresses the body’s ability to make immune cells - used at lower doses than when used as a cytotoxic cancer agent

10

What else can methotrexate be used for?

To terminate ectopic pregnancies because it is teratogenic

11

What is the half life of methotrexate?

Long - normal dose is once weekly

12

What is organ level toxicity?

Drugs which a selectively toxic to a particular organ e.g. the kidney

13

Why are kidneys particularly susceptible to toxicity?

Because they require a lot of oxygen but are set up for countercurrent exchange so can have lowered oxygen concentration

14

What is the triple whammy?

A combination of a diuretic, an ACE inhibitor or AT1 receptor antagonist and an NSAID

15

Why does a triple whammy cause renal failure?

Because the diuretic and ACE inhibitor would normally lead to lower renal blood flow but the action of prostaglandin preserves renal blood flow so adding an NSAID will remove the prostaglandin and the patient will be at risk of renal failure

16

What is gentamicin?

A broad spectrum antibiotic which causes nephrotoxicity and ototoxicity

17

What is paraquat?

A herbicide which when activated by reduction becomes a free radical and produces ROS - destroys cell membranes, proteins and DNA