UTI & Miscellaneous Flashcards
Sulfonamide Mechanism of Action
STATIC
-Interfere w/ microbial FOLIC ACID SYNTH (DHF)
> Competes w/ PABA
> Humans can use preformed folic acid
Sulfonamide Mechanism of RESISTANCE
- Mutation- produce increased PABA
2. R-Factor- decreased drug permeability
Sulfonamide Available Agents
Sulfisoxazole
Sulfamethoxazole
Sulfadiazine
Sulfonamide Half-Life
5+ hours
Sulfisoxazole< Sulfmethoxazole< Sulfadiazine (17hrs!)
Sulfonamide Route(s) of Administration
Oral and IV Except sulfiMETHOXAZOLE (Oral Only!).
Sulfonamide Pharmocokinetics
- Wide & excellent distribution, even CSF
- Met by liver (acetylation and glucuronidation)
- Metabolites & free drug excreted in urine
Sulfonamide Spectrum
Wide!
Strep, N. meningitis, Nocardia, Chlamydia, E. coli (urine)
Cheap too! Yay.
Sulfonamide Indications
- Uncomplicated UTI
- Nocardiosis (usually w/ trimethoprim)
- Toxoplasmosis (w/ pyrimethamine)
Sulfonamide Toxicities
- Crystalluria
- Kernicterus (displace albumin-bound substance)
- GI upset
- ALLERGIC: Stevens-Johnson/rash, Fever, (rare: Hepatic necrosis, Hemolytic anemia, Agrnulocytosis, Aplastic anemia)
This sulfonamide is used orally for ULCERATIVE COLITIS
Salicylazosulfapyridine (Azulfidine) or Sulfasalazine
These Sulfonamides are used topically for BURNS
Mafenide acetate
Silver Sulfadiazine
This Sulfonamide is used topically-ophthalmic for BACTERIAL CONJUNCTIVITIS
Sulfacetamide
Trimethoprim Mechanism of Action
STATIC
-Inhibit bacterial DIHYDROFOLATE REDUCTASE (which converts DHF to Tetrahydrofolic Acid)
Trimethoprim Mechanism of RESISTANCE
Mutation
R-Factor
Trimethoprim Pharmokinetics
- Wide & Excellent Distribution, CSF too; may concentrate in prostate
- Most excreted unchanged in urine
- T1/2= 10 hrs
Trimethoprim Route of Administration
Oral
IV (as TMP-SMX)
Trimethoprim Spectrum
-fairly wide for susceptible micro-organisms
Pretty cheap
Trimethoprim Indications
UTI due to most common urinary pathogens
Trimethoprim toxicity
Minimal
-Mimics Folic Acid Deficiency (hematologic)–give folic acid to pts!
Trimethoprim-Sulfamethoxazole Mechanism of Action
1: 5 Fixed Ratio
- Sequential blocking in FOLIC ACID SYNTH, synergistic
- Often CIDAL
Super cheap ($4 oral)
TMP/SMX toxicity
-same as individual agent
50% rate of adverse effects in AIDS PATIENTS
TMP/SMX Spectrum
Wide
Includes Strep pneumo, H. flu, most aerobic Gram (-) rods…but NOT PSEUDOMONAS
TMP/SMX Indications
- **UTI!!’*
- OM (esp for penicillinase-producing H. flu or w/ beta-lactam allergy)
- Acute exacerbations of chronic bronchitis
- Enteric infx–salmonella, shigella
- Nocardiosis
- P. jiroveci pneumonia (tx & px)
- Soft tissue & skeletal infx (gram -)
- Prophylaxis in neutropenic pts
Pyrimethamine Mechanism of Action
-Blocks DIHYDROFOLATE REDUCTASE (same as trimethoprim)
Pyrimethamine Indications
Toxoplasmosis (with sulfadiazine)
Malaria (with sulfadoxine)
Quinolone Indication
Only for UTI
Weak activity & poor pharmacokinetic profiles
Nalidixic Acid & Cinoxacin
Fluoroquiolone advantages over older quinolones
-Less toxicity
-Greater antimicrobial activity
>Broader bacterial spectrum
>Lower Inhibitory concentrations
>Lower freq of resistant mutants
>Prob involves increased interactions
w/ target site
-Better GI absorption
-Longer half-lives
-Good for systemic use
Fluoroquinolone Agents
Nor Cipro O Levo Moxi
-floxacin
In order of Older to Newer
Fluoroquinolone Mechanism of Action
- Inhibits bac DNA GYRASE (which maintains neg supercoil of xsome & facilitate DNA replication)
- Rapidly BACTERICIDAL
Fluoroquinolone Mechanisms of RESISTANCE
- R-Plasmid
- Spontaneous mutation»cross-resistance among quinolones, but not w/ other antimicrobials
- Alteration of DNA gyrase subunit
- Alteration of permeability (resist other antibiotics)
- Rate of mutation differs b/w bac= Pseudomonas>E. coli
Fluoroquinolone Spectrum
Good activity against most GRAM NEG
- Enterobac
- Proteus
- Pseudomonas!
- H. flu
- Salmonella, Shieglla, Campylobacter
- Newer fluoroquinolones increasingly active against GRAM +.
- Variable activity against mycobac, mycoplasma, Chlamydia, legionella (newer ones are better against Atypical Pneumonia)
- Not good for Anaerobes
These two antimicrobials are nicknamed “Respiratory Quinolones” because they have good activity against STREP PNEUMO (even PCN-resistant strains)
Levo & Moxi
These are newer drugs
Flouroquinolone Half-Lives
Older (Nor & Cipro): 3-6, lower absorption
Newer (O, Levo, Moxi): 10-12, high absorption
Fluoroquinolone Route of Administration
Oral IV (except for Nor)
Flouroquinolones Pharmacokinetics
- Absorption decreased w/ antacids (Mg salts), Iron & Zinc supplements, H2 blockers, milk products
- Most eliminated in urine through glomerular clearance plus tubular secretion
- Variably (<50%) met by liver & excreted into bile
- **Adjust dosage in RENAL FAILURE!
- Penetrate CSF, PROSTATE, & BILIARY TRACT very well
Norfloxacin Indications
UTI
Enteric Infx
Cipro, O, Levo, Moxi Indications
-UTI & enteric infx, like Nor
-Various GRAM NEG infx (incl. pseudomonas)
>DOC for Prostatitis
>Osteomyelitis, soft tissue infx: esp staph
> Resp tract-esp atypicals**
> Prophylaxis in neutropenic hosts
>Comm. resp infx due to S. pneumo, legionella, mycoplasma (esp levo & moxi)
>Moxi: mixed aerobic/anaerobic infx
**Cipro=most active against pseudomonas
This Fluoroquinolone is more active against Strep pneumo and less active against Pseudomonas
Moxi
Fluoroquinolone Toxicities
- Neurotoxicity (seizure @ high levels) in older quinolones
- *Contraindicated in PEDS & PREG (articular cartilage injury)
- Tendon rupture (esp Achilles): Black box warning esp in elderly
- GI
- CNS
- Skin rash
- Elevated liver enzymes
- Eosinophilia
- Sleep Disturbance
- QT prolongation (some quinolones)
- Superinfection incl. C. diff
- **Hinder elimination of theophyllines and caffeine!
This is the most widely used fluoroquinolone (esp for UTI) and is the most active drug for the most resistant GRAM NEG, esp Pseudomonas. It interacts w/ theophylline. Generic for this drug is available for very cheap.
Cipro
This drug is the L-isomer of ofloxacin and is good for resp infx (except Pseudomonas–cipro is preferred). It has a low side effect/drug interaction profile and has 1x/day dosing
Levo
This flouroquinolone is most active against S. pneumo and has fair activity against ANAEROBES
Moxi
Metronidazole Mechanism of Action
-Acts as “electron sink” by depriving cell of reducing equivalents
> metro’s nitro group is reduced by e-transport proteins w/ low redox potential
-CIDAL action against ANAEROBIC bac
-Aerobes are resistant!
Metronidazole Route of Administration
Oral
IV
Metronidazole Pharmacokinetics
- Good absorption
- T 1/2=8 hrs
- Met partially by liver (oxidation & glucuronidation)
- Metabolites and free drug excreted in urine
- Excellent BRAIN & CSF concentration!
Metronidazole Spectrum/Indications
- Protozoal Infx (esp Trichomoniasis, amebiasis, giardiasis)
- Anaerobic Infx of all types incl. BRAIN ABSCESSES (combine w/ another agent for aerobic orgs)
- Antibiotic-assoc colitis due to C. diff
- NO ACTIVITY AGAINST AEROBIC!
Metronidazole Toxicities
- GI upset, metallic taste
- Central & Peripheral neuropathy (occasional)
- Neutropenia
4. Disulfiram-like rxn (acetaldehyde syndrome)
5. Mutagenic in bac, possibly carcinogenic
6. Relatively contraindicated in PREG, AVOID IN KIDS
Nitrofurantoin Mechanism of Action
STATIC
-Cellular enzyme reduces drug, which then DAMAGES DNA
Nitrofurantoin Pharmacokinetics
- Rapid, excellent GI absorption
- Rapidly met to inactive drug in many tissues
- About 1/2 cleared into urine rapidly by glom. filtration
- No sig levels in serum
- SHORT 1/2 life!! (20 mins)
- Macrocrystalline form has slower absorption, more prolonged urine levels
Nitrofurantoin Spectrum
Good for E. coli…poor for others
Nitrofurantoin Indications
Uncomplicated, non-severe UTI
Prophylaxis of UTI
Cannot use in systemic cases/ sepsis, only local
low cost
Nitrofurantoin Toxicities
-GI upset
-Hypersensitivity (can be severe):
>Fever/chills
>Hematologic-leukopenia, hemolytic aemia
> Rashes
> Liver: cholestatic jaundice, hepatitis
> ACUTE ALLERGIC PNEUMONITIS
> SUBACUTE PULM. INTERSTITIAL FIBROSIS
> SEVERE POLYNEUROPATHIES
