ABX III - Miscellaneous

Question 1

TMP-SMX mechanism of action

Answer 1

Interferes with folate synthesis

Inhibits dihydrofolic acid synthesis (structural analogue of PABA)

Results in sequential enzyme inhibition**

Question 2

TMP-SMX mechanism of resistance

Answer 2

• altered enzyme targets for both TMP & SMX
• DEC sulfa accumulation
• INC production of PABA

Question 3

TMP-SMX drug interaction and CYP

Answer 3

2C9 substrate**
Moderately inhibit 2C9**
- biggest concern is Warfarin

HyperKalemia** - especially problematic mixed with ACEI/ARB/Spironolactone

Question 4

Where is TMP-SMX excreted?

Answer 4

Renally

Question 5

3 main ADRs related to TMP-SMX are…?

Answer 5

1. Hypersensitivity reaction (large dose)
   - reversible myelosuppression w/INC dose*
2. Hemolytic anemia w/G6PD pt
3. Hyponatremia, Creatinine alteration

Question 6

What is the microbial coverage of TMP-SMX?

Answer 6

• P. jiroveci (PCP)

- Most e. coli, Klebsiella, proteus, MRSA

Question 7

What are some indications for TMP-SMX?

Answer 7

Lower UTI (second line) **
PCP / PJP **

MRSA tx/suppression (not serious infection)

Question 8

Nitrofurantoin MOA?

Answer 8

Inhibits bacterial enzyme systems including acetyl coenzyme A

Interferes with metabolism and possibly cell wall synthesis

Question 9

Why is Nitrofurantoin C.I. in CrCl < 60?

Answer 9

Therapeutic levels are not attained

Renal excretion –> does not penetrate renal tissue

e.g. do NOT use for pyelo

Question 10

What are two ADRs to be aware of with Nitrofurantoin?

Answer 10

1. Acute - chronic pulmonary toxicity / fibrosis **

2. Do NOT use w/G6PD def

Question 11

What is the microbial coverage of Nitrofurantoin? What are the clinical indications?

Answer 11

• covers most urinary pathogens - GNB, enterococci

Only indications:

• Lower UTI (cystitis) **
• prophylaxis of recurrently UTI **

Question 12

What is the MOA of Fosfomycin?

Answer 12

Irreversibly binds pyuvyl transferase
- enzyme in early step of bacterial cell wall synthesis (before beta-lactams)

Single dose therapy

Question 13

Describe the cool pharmacology of Fosfomycin.

Answer 13

• excreted unchanged in urine
• bactericidal
• may DEC bacterial adhesion to urothelial cells

Well tolerated, unlikely to trigger CDI

Question 14

What is fosfomycin used for?

Answer 14

Uncomplicated cystitis

Microbial coverage: can hit some ‘big guns’ - MDR, ESBL CRE, VRE / MRSA… but only used for uncomplicated cystitis

Question 15

What is Rifaximin? What is it used for?

Answer 15

• non-absorbed PO abx derived from rifampin –> inhibits RNA synthesis

Clinically:

• E. coli traveler’s diarrhea [not effective against infections associated w/fever or bloody stool]
• chronic liver disease - prevent hepatic encephalopathy
• IBS-D (last line)

Question 16

What is Chloramphenicol?

Answer 16

Just recognize it is an abx

Rarely used because of bone marrow suppression and aplastic anemia

Question 17

What are the first line Anti-Mycobacterial agents?

Answer 17

RIPE

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

Question 18

What is the MOA/drug interactions of Rifampin?

Answer 18

Inhibits RNA polymerase –> inhibits protein synthesis

Strong INDUCER of most CYP enzymes
- remember: 2C9 and 3A4*

Question 19

What are the clinical indications of RIF?

Answer 19

• Active TB** and alternate option for latent TB

- meningococcal meningitis prophylaxis

Question 20

What are the 3 ADRs to remember with RIF?

Answer 20

• Red lobster syndrome
• hepatitis (less than INH)
• “flu-like illness”

Question 21

What is the MOA/drug interactions of Isoniazid?

Answer 21

Inhibits synthesis of mycolic acids

Strong INHIBITOR of many CYP enzymes
- remember 2D6 and 3A4*

Question 22

What cool genetics are related to INH?

Answer 22

Genetics control acetylation

1. Rapid acetylator = hepatitis with INC ETOH
2. Slow acetylator = peripheral neuropathy***
   - DEC risk w/Vit B6 (pyridoxine)

Question 23

INH indications?

Answer 23

Historic drug of choice for latent TB (9 month tx) **

Also a component of active TB tx

Question 24

What is PZA used for? What is the main ADR to remember?

Answer 24

Component of active TB tx**

ADR: arthralgias (tx w/NSAIDs to get through the pain)
- “non-gouty polyarthralgia”

Question 25

What is ETH used for? What is the common ADR?

Answer 25

Component of active TB tx**

ADR: dose related optic neuritis
- problems distinguishing red and green = red flag

Optic neuritis: DEC visual acuity, color discrimination, constricted fields, scotoma –> irreversible blindness