Folic Acid Inhibitors, DNA/RNA, and Antimycobacterials

Question 1

What drug inhibits the first step of folic acid synthesis?

Answer 1

Sulfonamides

Question 2

What do sulfa drugs compete with to inhibit folic acid synthesis?

Answer 2

para-amniobenzoic acid

Question 3

What drug is highly protein bound?

What’s the significance of that?

Answer 3

Sulfa drugs

Adverse effects with drugs like warfarin and NSAIDs

Question 4

When are sulfa drugs contraindicated?

Answer 4

IN pregnant women near term and neonates under 2mo because drugs displace bilirubin from protein binding sites, which can cause kernicterus (CNS disorder)

Question 5

How do bacteria develop resistance to sulfa drugs?

Answer 5

1. reduced uptake of drug
2. develop alternate way to synthesize folic acid
3. produce excessive amounts of para aminobenzoic acid
4. alterations or mutations in dihydropteroate synthase (rate limiting step)

Question 6

How are sulfa drugs metabolized?

Answer 6

Hepatically by acetylation, oxidation, or glucoronidation. If slow acetylator, then increased risk for hypersensitivity

Question 7

After hepatic biotransformation of sulfa drugs, how are they excreted?

Answer 7

Renally

Question 8

WHat is responsible for most of the adverse effects assoc with sulfa drug?

Answer 8

oxidation

Question 9

What is trimethoprim’s MOA?

Answer 9

Inhibits DHF, last step of folic acid synthesis

Question 10

What are the resistance mechanisms for trimethoprim?

Answer 10

reduced uptake, alterations or mutations in DHF, or overproduction of DHF

Question 11

What drugs are part of the Fluoroquinolones?

Answer 11

drugs ending in -floxacin

DNA synthesis

Question 12

What do Fluoroquinolones inhibit?

Answer 12

DNA gyrase or topoisomerase IV.

Gemifloxacin is good at inhibiting both enzymes.

Question 13

What can impair absorption of Fluoroquinolones?

Answer 13

Food or cations like Ca, FE, Al, Mg, and Zn. Also sucralfate

Question 14

Where do Fluoroquinolones distribute?

Answer 14

Nearly all compartments in the body, but CNS is minimal

Question 15

Lipopeptides include what drug?

Answer 15

Daptomycin

Question 16

What is Daptomycin’s MOA?

Answer 16

Bind bacterial mbs causing rapid depolarization of of the cell. B/c is has a unique MOA, cross resistance has not been observed

Question 17

How is Daptomycin excreted

Answer 17

In the urine, primarily unchanged

Question 18

What is Metronidazole’s MOA

Answer 18

selectively absorbed by anaerobic bacteria. Reduced by reacting with pyruvate/ferropdoxcin which causes production of toxic metabolites

Question 19

Nitazoxanide MOA

Answer 19

Interferes with pyruvate/ferropdoxcin oxidoreductase

Question 20

Tinidazole MOA

Answer 20

Cytotoxic by damaging DNA and inhibiting further DNA synthesis

Question 21

When are Tinidazole and Metronidazole contraindicated?

Answer 21

1st trimester of preganancy

Question 22

Where can Metronidazole distribute in the body?

Answer 22

CNS. Absorption through skin or mucus mbs is low

Question 23

Rifaximin MOA

Answer 23

Rifampin derivative that inhibits bacterial RNA synthesis by binding to RNA polymerase

Question 24

PK properties of Rifaximin

Answer 24

Not absorbed from GI tract, therefore most of it is excreted unchanged in the feces. Does not interfere with P450s

Question 25

Why are mycobacterial infections hard to treat?

Answer 25

1. Grow slowly
2. Can lie dormant
3. Cell walls are thick and impermeable
4. Can reside within host cells
5. Become resistant to antibiotics very quickly

Question 26

Very basically, how would you treat a mycobacterial infection

Answer 26

For long periods of time and with severel different antibiotics so that you prevent resistant strains from emerging

Question 27

Isoniazid MOA

Answer 27

inhibits synthesis of mycolic acids, which are essential components of mycobacterial cell walls

Question 28

Isoniazid distribution

Answer 28

Everywhere including CNS

Question 29

Isoniazid metabolism

Answer 29

Acetylation. If fact acetylators, then Isoniazid may not reach therapeutic levels. If slow acetylator, have greater risk for toxicity

Question 30

Rifampin MOA

Answer 30

inhibits bacterial RNA polymerase, which prevents transcription by suppressing initiation of RNA chain formation

Question 31

Does Rifampin have drug interaction concerns?

Answer 31

Yes. It’s a potent inducer of drug metabolism and alters plasma levels of many drugs (digitoxin, warfarin, etc)

Question 32

Pyrazinamide MOA

Answer 32

MOA unclear. Possible that it lowers the pH in the tubercle cavity and inhibits growth of mycobacterium

Question 33

Ethambutol MOA

Answer 33

inhibits RNA synthesis and decreases replication of tubercle bacilli

Question 34

Clofazimine MOA

Answer 34

bind’s DNA and inhibits RNA plymerase actions. The bacteriocidal activities of this drug are very slow and pt’s are treated for a min of 2 yrs and possibly life

Question 35

What are mycobacteria?

Answer 35

rodlike gram -pos. aerobic bacteria that can for filamentous branching structures

Question 36

What drugs are possibly carcinogenic and/ or mutagenic because of their actions?

Answer 36

Metronidazole, nitazoxanide, and tinidazole

Question 37

Retapamulin structure?

Answer 37

Available as a Topical ointment, it’s structurally considered to be a pleuromutilin antibiotic.

Question 38

Retapamulin MOA

Answer 38

inhibit protein synthesis by interfering with peptidyl transferase. Binds a unique site on 50s subunit and blocks P site interactions

Question 39

Mupirocin MOA

Answer 39

inhibits tRNA that transports ILE. No cross resistance b/c of unique MOA
-available as topical cream and ointment

Question 40

Lineziod MOA

Answer 40

interferes with protein synthesis by binding unique site on 50s subunit, preventing formation of fnc 70s complex

Question 41

What drrugs are in streptogramins?

Answer 41

Quinupristin and dalfopristin

Question 42

Streptogramin MOA

Answer 42

acts at bacterial ribosome and interferes with protein synthesis. Quinupristin irreversibly blocks ribosomes and inhibits late phase of protein synthesis. Dalfopristin inhibits early phase. Used for vancomycin resistance MRSA