Anti-fungal drugs

Question 1

What drug binds to membrane ergosterol?

Answer 1

amphotericin B

Question 2

How is amphotericin B administered?

Answer 2

topical or IV (not oral)

Question 3

Which class of drug inhibits lanosterol demethylase? Results?

Answer 3

• azole drugs

- inhibits ergosterol synthesis

Question 4

Which azole drug subtype inhibits CYP450 proteins?

Answer 4

triazoles

Question 5

Which drug directly disrupts the cell wall? When is it used?

Answer 5

• caspofungin

- IV for azole-resistant infections

Question 6

What drugs inhibit enoyl reductase? What is disrupted?

Answer 6

• Isoniazid, ethionamide

- mycolic acid synthesis

Question 7

Two AE’s associated with isoniazid?

Answer 7

• neuritis

- hepatotoxicity

Question 8

What enzyme is inhibited by rifampin?

Answer 8

DNA-dependent RNA polymerase

Question 9

What is induced by rifampin?

Answer 9

CYP450

Question 10

Difference between effectiveness of fluconazole and itraconazole?

Answer 10

similar, but flu is less effective in the lungs

Question 11

How are blast patients typically treated?

Answer 11

• itra/keto

- ampho

Question 12

Benefits of triazoles over imidazoles?

Answer 12

• tri’s last longer and have fewer cross-reactions

Question 13

How do azole drugs work?

Answer 13

• inhibit lanosterol demethylase, a CYP450 enzyme that is important in membrane structure and O2 transport in fungi

Question 14

What effects can azole drugs have in humans?

Answer 14

• inhibition of human CYP450 lanosterol demethylase

- inhibit human sterol synthesis and can alter metabolism of other drugs

Question 15

What is a common chemotherapeutic agent whose effectiveness is decreased by azole drugs?

Answer 15

• cyclophosphamide

- activated by CYP450

Question 16

What class of anti-fungals are teratogens?

Answer 16

azole drugs - disrupts hormonal synthesis and inhibits aromatase

Question 17

Differences between ketoconazole and itraconazole?

Answer 17

• older imidazole with lots of drug interactions

- itra is newer triazole with less severe interactions

Question 18

What 6 drugs have significant interactions with azoles?

Answer 18

• warfarin, cyclosporine, phenytoin

- lovastatin, oral hypoglycemics, protease inhibitors

Question 19

What drug binds to ergosterol in the fungal cell membrane and disrupts the membrane?

Answer 19

amphotericin B

Question 20

What anti-fungal is pretty useful against a BROAD spectrum of fungi?

Answer 20

amphotericin B AND it crosses the BBB

Question 21

What is the principal dose-limiting toxicity with amphotericin B?

Answer 21

renal dysfunction - also hypotension, hypokalemia, reversible normocytic anemia, thrombophlebitis

Question 22

Pharmacodynamics of azoles?

Answer 22

• Itra and keto are highly protein-bound in the bloodstream

- Flu crosses BBB readily

Question 23

How is cocci treated? What other types of drugs should be avoided with this treatment?

Answer 23

• amphotericin B

- anti-virals also cause renal toxicity

Question 24

What is the new SOC for invasive aspergillosis?

Answer 24

voriconazole (traditionally amphotericin)

Question 25

What class of drug is caspofungin? How does it work?

Answer 25

- echinocandin | - non-competitively inhibits synthesis of fungal cell wall by being a lipopeptide that causes fungal cells to lyse

Question 26

What two diseases is caspofungin approved for?

Answer 26

- invasive aspergillosis - esophageal candidosis - WHEN ampho/fluconazole have failed

Question 27

How is caspofungin administered and why?

Answer 27

- IV | - not absorbed by GI tract

Question 28

Why must TB treatments last 6 months?

Answer 28

- granulomatous immune response | - organisms have thick waxy coats and can form resistant little masses in the lungs

Question 29

When is ethambutol included in a TB regimen?

Answer 29

when isoniazide resistance exceeds 4%

Question 30

Standard 4 drug TB regimen?

Answer 30

- PIER | - pyrazinamide, isoniazide, ethambutol, rifampin

Question 31

MOA of isoniazid?

Answer 31

- inhibits enoyl reductase blocking my colic acid synthesis

Question 32

What enzyme activates isoniazid?

Answer 32

KatG - catalase/peroxidase

Question 33

What drug may inhibit uptake of isoniazid?

Answer 33

Al-containing antacids

Question 34

What enzyme metabolizes isoniazid? Who is this a problem in?

Answer 34

- liver N-acetyl transferase | - 50% of American Caucasians and 15% of Asians are slow acetylators

Question 35

How is neuritis associated with isoniazid administration treated?

Answer 35

- pyridoxine | - isoniazid looks like Vit B6 so large doses of B6 can displace it from non-target sites

Question 36

3 TB drugs associated with hepatotoxicity?

Answer 36

- isoniazid - rifampin - pyrazinamide (hepatitis)

Question 37

What 4 drugs are affected by induction of CYP450 by rifampin?

Answer 37

- prednisone, digitoxin, quinidine, propanalol

Question 38

What are the anti-TB effects of pyrazinamide?

Answer 38

- unknown MOA | - inhibits my colic acid biosynthesis

Question 39

What are the anti-TB effects of ethambutol?

Answer 39

- unknown MOA | - interferes with metabolism, replication

Question 40

AE associated with ethambutol?

Answer 40

- optic neuritis = blurring, red-green perception loss | - reversible

Question 41

What TB drugs are associated with high rates of resistance?

Answer 41

isoniazid and rifampin

Question 42

What three drugs are added in second-line anti-TB therapy?

Answer 42

- streptomycin - ethionamide - p-aminosalicylate

Question 43

How does p-aminosalicylic acid work in an anti-TB regimen?

Answer 43

- competitive inhibitor of PABA (folate synthesis) | - specific for tubercle bacilli but has severe GI and hypersensitivity effects

Question 44

How does ethionamide work?

Answer 44

- pro-drug that inhibits the same step as isoniazid (enoyl reductase) but by a different mechanism - inhibition of my colic acid synthesis

Question 45

AE's associated with ethionamide?

Answer 45

GI effects (vs. neuritis, hepatotoxicity, rash, fever, hypersensitivity)