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38 Cards in this Set
- Front
- Back
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Function of folate
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provide carbon for dUMP-->dTMP and formation of purines.
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Sulfonamides inhibit...
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dihydropteorate synthase (DHPS) which is part of folate biosynthesis/metabolism.
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Mechanism of resistance of sulfonamides
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Mutation of dihydropteorate synthase (DHPS)
more prod of PABA (substrate for that enzyme) more abil to destroy/inactivate the drug using alternate metabolic pathway. Due to resistance, these are rarely used as single agents. |
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Sulfonamide we need to know
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sulfamethoxazole (will be in conj with trimethoprim)
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DHFR inhibitors
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Trimethoprim (TMP)
Compet inhibitor of dihrydofolate reductase (later in folate metabolism) - much higher affinity for the bacterial version of this enzyme. |
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THF biosynth inhibitors
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sulfamethoxazole and trimethoprim (SMX/TMP) stop formation of tetrahydrofolic acid (THF). This is formed after dihydrofolate reductase.
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Pharmacodynamics of SMX/TMP
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Bacteriostatic (can be cidal though)
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Spectrum of SMX/TMP
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GPC (e.g. strep pneum)
GNR (e.g. h inf, e coli, moxarella) Pneumocystic carinii |
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Uses of SMX/TMP
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Resp tract inf, otitis, UTIs, prostatitis, MRSA
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Pharmacokin of SMX/TMP
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abs impaired by food.
TMP has v high tissue and CSF []. And also much higher vol of distrib than SMX half life is 10-12 hours hepatic metab and renal excretion |
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AEs of TMP/SMX
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GI upset, allergy, BM suppression, avoid in 1st trimester of preg.
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Resistance to trimethoprim
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less DHFR binding affinity.
overexpression of DHFR less permeability to TMP |
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Do prokaryotes need preformed folate for RNA or DNA synthesis?
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no - but euk do.
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Fluoroquinolones
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e.g. ciprofloxacin, moxifloxacin, levofloxacin.
target bactyerial DNA gyrase (which reverses supercoiling) - the human homolog (DNA topoisomerase) is less sensitive they also target a bacterial DNA topoisomerase IV. They bind the DNA/gyrase complex and thus replication can't occur and this results in lethal double strand DNA breaks. |
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Mechanism of DNA gyrase
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binds DNA, cleaves strands with formation of the covalent complex, passes strands against each other and then ligates.
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resistance to fluoroquinolones
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less binding to DNA topo II and IV (these are both gyrases)
less permeability and more drug efflux Plasma mediated formation of new gyrases (via Qnr proteins) modification of AG-acetyltransferase (plasma-mediated as well) |
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Pharmacodynamics and psectrum of fluoroquinolones
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bacteriocidal
Ciprofloxacin - poor against GP. Good against GN (e.g. pseudomonas, e coli, legionella, mycobacteria avium intracellulare) Moxi and levofloxacin - wide spectrum (GP and GN) good against chlamydia |
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pharmacokin of fluoroquinolones
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good oral.
half life is 3-5 hours for cipro and 24 hours for the others wide distrib and high [] in tissue and CSF clearance of cipro is hepatic and renal moxifloxacin and levofloxacin have low [] in the urine. |
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clinical uses of ciprofloxacin
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UTI and STD
Good against GN (e.g. pseudomonas, e coli, legionella, mycobacteria avium intracellulare) |
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clincal uses of moxi and levofloxacin
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pneumonia
wide spectrum (GP and GN) |
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AEs of fluoroquinolones
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GI upset, rash, sz
cipro inhibits CYPs while levo and moxi do not. arthralgia and joint swelling in children. |
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Metronidazole - mech
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a DNA damaging agent
anaerobic bacterial nitroreductase reduces it so that it forms a reactive nitro-anion and radicals. then this intercalates with DNA to form single strand breaks (at A-T mainly) |
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Pharmacodyn and spectrum of metronidazole
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static
oral and bowel anaerobes good for c diff protozoal (giardia, lamblia, entamoeba, histolytica) |
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Pharmacokin of metronidazole
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food delays GI absorption.
enters CSF well half life 8 h hepatic metab (inhibits CYP3A and aldehyde dehydrogenase) |
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AEs of metronidazole
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TERATOGENIC
GI, metallic taste in mouth, ataxia and vertigo, neutropenia, dark urine, inhibition of CYP3A |
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Rifamycins
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Produced by streptomyces mediteranei
Rifampin is the one to know. |
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Rifampin
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RNA polymerase inhibitor.
Binds to beta subunit of RNA polym. At very high [], inhibits mammalian mitochondria RNA polymerase. but never gets mammalian nuclear |
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Which topos in prok vs euk
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Prok - topoisomerase I and II
Euk - topoisomerase II and IV |
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dynamics and spec of rifampin
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Cidal - inhibits growing cells.
Mycobacteria (incl TB) staph aureus - good if you wanna get to tissue quick.y legionella prophylaxis fo neisseria meningitidis |
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Pharmacokin of rifampin
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abs impaired by food
Large Vd and enters CSF well half life is 2-5 hours hepatic metab |
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resistance of rifampin
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mutations of beta subunit site of RNA polymerase (which is a rpoB gene product)
this is especially big in Myco TB therpay so never use it alone. |
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SEs and toxicity of rifampin
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GI, hepatitis, jaundice, orange-pink discoloration of tears and urine.
induces P450s |
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A 27 year-old female presents with two days of urinary frequency and burning. Urine dip stick is + for leukocyte esterase; urine culture is pending. She is allergic to TMP/SMX (Bactrim) and anaphylaxed penicillin.
Which of the following is an appropriate antibiotic choice for this patient’s cystitis? Linezolid Clindamycin Tetracycline Rifampin Ciprofloxacin |
cipro
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A 30 year-old presents with malaise, headache, and fever following participation in a golf tournament in North Carolina. She reports multiple tick exposures and has heard that ticks can carry Lyme disease, Anaplasma (formerly Erhlichiosis), and Rocky Mountain Spotted Fever.
You decide to treat her empirically for these possible tick-borne diseases with which of the following antibiotics: Clindamycin Trimethoprim-sulfamethoxizole Doxycycline Clarithromycin Linezolid |
Doxy – only one you can do for rocky mtn spotted fever
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A 10 year-old unvaccinated child presents with a classic “whooping” cough. Bordetella pertussis is confirmed on nasopharyngeal specimen PCR testing.
Which of the following antibiotics is the drug of choice to treat this infection? Clindamycin Trimethoprim-sulfamethoxizole Doxycycline Erythromycin Linezolid |
erythro
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A 10 year-old unvaccinated child presents with a classic “whooping” cough. Bordetella pertussis is confirmed on nasopharyngeal specimen PCR testing. Erythromycin is the drug of choice to treat this infection. Which of the following antibiotics is the second choice for patients with erythromycin allergy?
Clindamycin Trimethoprim-sulfamethoxizole Doxycycline Linezolid |
Correct answer is B, Bactrim (trimethoprim-sulfa) is second line for those with erythromycin allergy.
Not linez – that is for mrsa VRE and VRSA Doxy-for rocky mtn spotted fever Clinda – can give pseudomembranous colitis. |
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A 57 year-old dialysis patient presents with fever, delirium, knee pain, and S. aureus bacteremia. He is diagnosed with acute bacterial endocarditis complicated by multiple CNS abcesses as well as a prosthetic knee infection.
Which of the following agents would treat S. aureus and contribute to CNS, vegetation, and joint penetration in this patient? TMP-SMX Azithromycin Linezolid Clindamycin Rifampin |
Rifampin. Good to tx s aureus when yo uwanna get to the tissue fast.
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A 30 year-old patient presents in the emergency room with diarrhea, abdominal pain, and fever. The patient states that a week ago she finished a treatment with clindamycin for tooth abscess.
Stool analysis reveals presence of C.dificille toxin. Dx? Treatment? TMP-SMX Azithromycin Amoxicillin Metronidazole Rifampin |
What test? C diff toxin
It is positive Dx – pseudomembranous colitis So use metro |
