ABX III - Miscellaneous Flashcards
TMP-SMX mechanism of action
Interferes with folate synthesis
Inhibits dihydrofolic acid synthesis (structural analogue of PABA)
Results in sequential enzyme inhibition**
TMP-SMX mechanism of resistance
- altered enzyme targets for both TMP & SMX
- DEC sulfa accumulation
- INC production of PABA
TMP-SMX drug interaction and CYP
2C9 substrate**
Moderately inhibit 2C9**
- biggest concern is Warfarin
HyperKalemia** - especially problematic mixed with ACEI/ARB/Spironolactone
Where is TMP-SMX excreted?
Renally
3 main ADRs related to TMP-SMX are…?
- Hypersensitivity reaction (large dose)
- reversible myelosuppression w/INC dose* - Hemolytic anemia w/G6PD pt
- Hyponatremia, Creatinine alteration
What is the microbial coverage of TMP-SMX?
- P. jiroveci (PCP)
- Most e. coli, Klebsiella, proteus, MRSA
What are some indications for TMP-SMX?
Lower UTI (second line) ** PCP / PJP **
MRSA tx/suppression (not serious infection)
Nitrofurantoin MOA?
Inhibits bacterial enzyme systems including acetyl coenzyme A
Interferes with metabolism and possibly cell wall synthesis
Why is Nitrofurantoin C.I. in CrCl < 60?
Therapeutic levels are not attained
Renal excretion –> does not penetrate renal tissue
e.g. do NOT use for pyelo
What are two ADRs to be aware of with Nitrofurantoin?
- Acute - chronic pulmonary toxicity / fibrosis **
2. Do NOT use w/G6PD def
What is the microbial coverage of Nitrofurantoin? What are the clinical indications?
- covers most urinary pathogens - GNB, enterococci
Only indications:
- Lower UTI (cystitis) **
- prophylaxis of recurrently UTI **
What is the MOA of Fosfomycin?
Irreversibly binds pyuvyl transferase
- enzyme in early step of bacterial cell wall synthesis (before beta-lactams)
Single dose therapy
Describe the cool pharmacology of Fosfomycin.
- excreted unchanged in urine
- bactericidal
- may DEC bacterial adhesion to urothelial cells
Well tolerated, unlikely to trigger CDI
What is fosfomycin used for?
Uncomplicated cystitis
Microbial coverage: can hit some ‘big guns’ - MDR, ESBL CRE, VRE / MRSA… but only used for uncomplicated cystitis
What is Rifaximin? What is it used for?
- 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)
What is Chloramphenicol?
Just recognize it is an abx
Rarely used because of bone marrow suppression and aplastic anemia
What are the first line Anti-Mycobacterial agents?
RIPE
Rifampin (RIF)
Isoniazid (INH)
Pyrazinamide (PZA)
Ethambutol (ETH)
What is the MOA/drug interactions of Rifampin?
Inhibits RNA polymerase –> inhibits protein synthesis
Strong INDUCER of most CYP enzymes
- remember: 2C9 and 3A4*
What are the clinical indications of RIF?
- Active TB** and alternate option for latent TB
- meningococcal meningitis prophylaxis
What are the 3 ADRs to remember with RIF?
- Red lobster syndrome
- hepatitis (less than INH)
- “flu-like illness”
What is the MOA/drug interactions of Isoniazid?
Inhibits synthesis of mycolic acids
Strong INHIBITOR of many CYP enzymes
- remember 2D6 and 3A4*
What cool genetics are related to INH?
Genetics control acetylation
- Rapid acetylator = hepatitis with INC ETOH
- Slow acetylator = peripheral neuropathy***
- DEC risk w/Vit B6 (pyridoxine)
INH indications?
Historic drug of choice for latent TB (9 month tx) **
Also a component of active TB tx
What is PZA used for? What is the main ADR to remember?
Component of active TB tx**
ADR: arthralgias (tx w/NSAIDs to get through the pain)
- “non-gouty polyarthralgia”
What is ETH used for? What is the common ADR?
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
