Drug Synergy

Question 1

What are the benefits of drug synergy?

Answer 1

enhanced benefit, minimise toxicity, minimise chance of resistance

Question 2

What is selective toxicity?

Answer 2

maximise toxicity for other and minimise toxicity for host

Question 3

What is the mechanism of action of maraviroc?

Answer 3

allosteric modulator of CCR5 receptor to prevent fusion

Question 4

What is the mechanism of action of enfuvirtide?

Answer 4

peptide agonist of Gp41 - prevents fusion

Question 5

What is the mechanism of action of zidovudine?

Answer 5

nucleoside reverse transcriptase inhibitor

Question 6

What is the mechanism of action of nevirapine?

Answer 6

allosteric modulator of reverse transcriptase

Question 7

What is the mechanism of action of raltegravir?

Answer 7

integrase inhibitor

Question 8

What is the mechanism of action of saquinavir?

Answer 8

protease inhibitor

Question 9

In HAART are the three drugs used always from different classes?

Answer 9

no - may be from the same class

Question 10

What is the benefit of combining the protease inhibitor ritonavir with another protease inhibitor?

Answer 10

ritonavir is a potent inhibitor of Cyp3A4 which prevents the metabolism of the other protease inhibitor so the effect is increased

Question 11

What is the mechanism of action of sofosbuvir?

Answer 11

a nucleotide inhibitor of NS5B - the RNA dependent RNA polymerase in HCV

Question 12

Why are some bacteriocidal and bacteriostatic combinations of antibiotics antagonistic?

Answer 12

if the bacterostatic drug requires active bacteria

Question 13

Why is penicillin and aminoglycosides synergistic?

Answer 13

because penicillins allow entry of the aminoglycoside into the cell

Question 14

Why is flucytosine and amphotericin synergistic? (anti-fungals)

Answer 14

amphotericin breaks down the cell wall by targeting ergosterol so flucytosine can get in and inhibit DNA synthesis

Question 15

Why is sulfonamide and trimethoprim synergistic? (anti-fungals used for pneumocystis jiroveci)

Answer 15

sulfonamide inhibits conversion of PABA to folate and trimethoprim inhibits conversion of folate to tetrahydrofolate - both act on the same pathway for DNA synthesis

Question 16

Why are cisplatin/bleomycin and etoposide (drugs used for prostate cancer treatment) synergistic?

Answer 16

cisplatin/bleomycin damage the DNA and etoposide inhibits the repair of the DNA

Question 17

What is the mechanism of action of glucocorticoids for immunosupression for organ transplant?

Answer 17

negative regulator of cytokine production

Question 18

What is the mechanism of action of azathioprine for immunosupression for organ transplant?

Answer 18

it is a cytotoxic drug that blocks DNA synthesis of cell division so prevents the T cell proliferating

Question 19

What is the mechanism of action of cyclosporin for immunosupression for organ transplant?

Answer 19

inhibits calcineurin which results in a lack of transcription of IL-2 so the T cell cant be activated by antigen presentation

Question 20

What is the mechanism of action daclizumab for immunospuression for organ transplant?

Answer 20

it is an IL2 receptor antagonist - it prevents the T cell from recieving the signal it is to be divide

Question 21

What is the mechanism of action of anti-thymocyte globulin for immunosupression for organ transplant?

Answer 21

lyses T cells

Question 22

What is the mechanism of action of abatacept?

Answer 22

binds to CD80/86 to prevent the second signal for T cell activation

Question 23

What is the mechanism of action of targin?

Answer 23

targin is made up of oxycodone and naloxone. oxycodone is a mu receptor agonist and naloxone is a mu receptor antagonist. the naloxone has poor oral bioavailability so remains in the gut where it can target the side effect of constipation caused by the oxocodone.