Miscellaneous ABX

Question 1

What is the antimetabolite ABX?

Answer 1

TMP-SMX

Question 2

Sulfa MOA

Answer 2

Inhibit dihydrofolic acid synthesis (structural analogue of PABA) -> interferes with bacterial folate synthesis

Question 3

Trimethoprim MOA

Answer 3

Inhibits dihydrofolic acid reduction to tetrahydrofolate

Question 4

TMP-SMX MOR

Answer 4

• Altered enzyme targets
• ↓ sulfa accumulation
• ↑ production of PABA

Question 5

TMP & SMX are substrates of and moderate inhibitors of CYP___

Answer 5

CYP2C9

Question 6

Drug interactions for TMP-SMX

Answer 6

Drugs that cause hyperkalemia (ACEI/ARB/spironolactone)

Question 7

TMP-SMX pharmacology

Answer 7

• Renal excretion

- Bacteriostatic

Question 8

TMP-SMX ADRs

Answer 8

• Hypersensitivity, esp. reversible myelosupression (w/ larger dose)
• Hemolytic anemia in G6PD pts. (AA male)
• hyperkalemia

Question 9

Microbial coverage of TMP-SMX

Answer 9

• P. jiroveci

- Most E. coli, Klebsiella, Proteus, MRSA

Question 10

Clinical indications for TMP-SMX

Answer 10

• Lower UTIs (2nd line)
• PCP/PJP
• MRSA treatment/suppression (not serious infections)

Question 11

Nitrofurantoin MOA

Answer 11

Inhibits bacterial enzyme systems, including acetyl CoA, interfering with metabolism & possibly cell wall synthesis

Question 12

Nitrofurantoin pharmacology

Answer 12

Renal excretion (does NOT penetrate renal tissue)

Question 13

Nitrofurantoin contraindication

Answer 13

CrCl <60

- BUT new data suggests short term use is safe & effective if CrCl >30

Question 14

Nitrofurantoin ADRs

Answer 14

Acute -> chronic pulmonary toxicity/fibrosis

Question 15

Microbial coverage of nitrofurantoin

Answer 15

GNB & enterococci

Question 16

Microbial resistance to nitrofurantoin

Answer 16

• E. coli <2%

- Klebsiella 1/3

Question 17

Clinical indications for nitrofurantoin

Answer 17

• Lower UTI (cystitis)

- Prophylaxis of recurrent UTI

Question 18

Fosfomycin MOA

Answer 18

Irreversibly binds pyuvyl transferase (enzyme in early step of bacterial cell wall synthesis)

Question 19

Fosfomycin pharmacology

Answer 19

• Excreted unchanged in the urine
• Bacteriocidal
• May ↓ bacterial adhesion to urothelial cells

Question 20

Microbial coverage of fosfomycin

Answer 20

GNB & enterococci / staph

- Includes MDR/EBSL CRE (GNBs) & VRE/MRSA; +/- for pseudomonas

Question 21

Most E. coli is resistant OR susceptible to fosfomycin

Answer 21

Susceptible!

Question 22

Clinical indications for fosfomycin

Answer 22

Uncomplicated cystitis (3g powder dissolved in water)

Question 23

Two ABX derived from rifampin

Answer 23

• Rifaximin

- Rifamycin

Question 24

Route of rifaximin, rifamycin

Answer 24

PO (non-absorbed)

Question 25

Rifaximin, rifamycin MOA

Answer 25

Inhibit bacterial RNA synthesis

Question 26

Clinical indications for rifaximin, rifamycin

Answer 26

- Noninvasive E. coli causing traveler's diarrhea (NOT effective if bloody stool or fever) - Prevention of hepatic encephalopathy in pts. w/ CLD - IBS-D

Question 27

Microbial coverage of chloramphenicol

Answer 27

- H. flu - S. pneumo - N. meningitides - Some anaerobes

Question 28

Chloramphenicol pearl

Answer 28

Reaches therapeutic levels in the CNS (used as last resort in CNS infections)

Question 29

Why is chloramphenicol rarely used?

Answer 29

Toxicities: bone marrow suppression and possibly fatal aplastic anemia

Question 30

1st gen anti-mycobacterial agents

Answer 30

- Rifampin (RIF) - Isoniazid (INH) - Pyrazinamide (PZA) - Ethambutol (ETH)

Question 31

2nd gen anti-mycobacterial agents

Answer 31

- Streptomycin - Kanamycin - Amikacin - Levofloxacin - Moxifloxacin - Capreomycin - Cycloserine - Ethionamide - Aminosalicyclic acid

Question 32

Rifampin MOA

Answer 32

Inhibits RNA polymerase (protein synthesis)

Question 33

Rifampin is an INDUCER of

Answer 33

MOST CYP enzymes (remember: 2C9, 3A4)

Question 34

Clinical indications of rifampin

Answer 34

- Active Tb - Latent Tb (alternative option) - Meningococcal meningitis prophylaxis

Question 35

Rifampin ADRs

Answer 35

- Red lobster syndrome - Hepatitis - Flu-like illness

Question 36

Isoniazid MOA

Answer 36

Inhibits synthesis of mycolic acids

Question 37

Isoniazid is an INHIBITOR of

Answer 37

MOST CYP enzymes (remember: 2D6, 3A4)

Question 38

Acetylation determines blood concentration of isoniazid and is controlled by

Answer 38

Genetics

Question 39

Rapid acetylators of isoniazid are more likely to get...

Answer 39

Hepatitis (↑ w/ ETOH)

Question 40

Slow acetylators of isoniazid are more likely to get...

Answer 40

Peripheral neuropathy (↓ risk w/ vitamin B6)

Question 41

Clinical indications of isoniazid

Answer 41

- Latent Tb (drug of choice) | - Component of active Tb tx

Question 42

Clinical indication of pyrazinamide

Answer 42

Component of active Tb tx

Question 43

Pyrazinamide ADRs

Answer 43

- Non-gouty polyarthralgias (tx w/ NSAIDs) - Asymptomatic hyperuricemia - Dose-related hepatitis

Question 44

Ethambutol MOA

Answer 44

Inhibits cell wall synthesis

Question 45

Clinical indications of ethambutol

Answer 45

Component of active Tb tx

Question 46

Ethambutol ADR

Answer 46

Dose-related optic neuritis

Question 47

Pathogenesis of ethambutol-induced optic neuritis

Answer 47

ETH is a metal chelator - Chelation of copper or zinc though to play a role - Supplementation does not help

Question 48

Sx of ethambutol-induced optic neuritis

Answer 48

- ↓ visual acuity/color discrimination (red, green) - Constricted fields - Scotoma * can lead to irreversible blindness

Question 49

Management of pt. on ethambutol

Answer 49

Monthly f/u with ophthal for monthly visual acuity & color perception checks