Antimicrobials3 4-16-06
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- Trimethoprim How does it work?
- inhibits folic acid pathway by blocking dihydrofolate reductase which humans have as well
- Trimethoprim What are its uses?
- used in combo with Sulfamethoxazole (TMP-SMX) causing a sequential block of folate synthesis. Used for recurrent UTIs, Shigella, Salmonella, and prophylaxis for PCP in AIDS patients
- Trimethoprim Toxicities?
- Megaloblastic anemia, pancytopenia (may be alleviated with supplemental folinic acid)
- Fluoroquinolones What the most famous floroquinolone?
- Ciprofloxacin (treatment for Anthrax)
- Fluoroquinolones How does it work?
- inhibits DNA gyrase (topoisomerase II)
- Fluoroquinolones What are its uses?
- Gram neg rods or urinary and GI tract (incl. pseudomonas), Neisseria, some gram pos spp
- Fluoroquinolones What population is contraindicated for use?
- pregnancy and children
- Fluoroquinolones What are its toxicities?
- GI upset, superinfection, skin rashes, headache, dizziness and tendonitis and tendon rupture in adults. FluoroquinoLONES hurt attachment to BONES.
- Metronidazole How does it work?
- forms toxic metabolites in the bacteria. Bactericidal.
- Metronidazole What are its uses?
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antiprotazoal:
Giardia, Entamoeba, Trichomonas
GET on the Metro
anaerobes:
gardnerella vaginalis, Bacteroides, clostridium
Used with bismuth and amoxicillin (or tetracycline) for triple therapy against H pylori
BAM! - What is the role of Metronidazole in H. pylori infection?
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Used as part of triple therapy: bismuth, amoxicillin and metronidazole
BAM! - Metronidazole Main toxicity?
- disulfiram-like (antabuse) reaction to alcohol and headache
- Which drug do you use to treat anaerobic infections above the diaphram and which for below the diaphram
- anaerobes above diaphram: Clindamycin, and anaerobes below diaphram: metronidazole
- Polymyxins How does it work?
- disrupts osmotic properties of bacteria, acts like a detergent
- Polymyxins What is it used for?
- resistant gram negative infections
- Polymyxins Toxicities?
- neurotoxicity, acute renal tubular necrosis
- Isoniazid How does it work?
- decreases synthesis of mycolic acid
- Isoniazid What is it used for?
- MTB (mycobacterium tuberculosis). The only agent used as solo prophylaxis against TB
- Isoniazid Toxicities?
- Hemolysis if G6PD deficient, neurotoxicity, hepatotoxicitiy, drug induced SLE. INH, Injures Neurons and Hepatocytes
- Isoniazid What vitamin prevents neurotoxicity
- Vitamin B6 (pyridoxine)
- Isoniazid Why are toxicities particularly important to monitor in patients taking INH?
- INH half-lives are different in fast versus slow acetylators!
- Rifampin How does it work?
- inhibits DNA-dependent RNA polymerase
- Rifampin What is it used for?
- Mycobacterium tuberculosis, delays resistance to dapsone when used for leprosy, meningococcal prophylaxis
- Rifampin Toxicities?
- Minor hepatotoxicity and increases P-450
- Rifampin How can it be used for leprosy?
- rifampin delays resistance to dapsone when used for leprosy
- Rifampin What would happen if you used rifampin alone?
- get rapid resistance
- Rifampin What does it do to bodily fluids?
- makes them red/orange in color
- Rifampin What are the 4 R's of Rifampin
- RNA polymerase inhibitor, Revs up microsomal p-450, Red/Orange body fluids, Resistance is rapid if used alone
- Anti-TB Drugs What are the anti-TB drugs?
- Rifampin, Ethambutol, Streptomycin, Pyrazinamide, Isoniazid (INH) -- RESPIre
- Anti-TB Drugs What do you use for TB prophylaxis?
- INH
- Anti-TB Drugs What toxicity is common to all?
- hepatotoxicity
- Most common resistance mechanism for penicillins / cephalosporins.
- Beta-lactamase cleavage of beta-lactam ring.
- Most common resistance mechanism for aminoglycosides.
- Modification via acetylation, adenylation, or phosphorylation.
- Most common resistance mechanism for vancomycin.
- Terminal D-ala of cell wall component replaced with D-lac; decrease affinity.
- Most common resistance mechanism for Chlorampenicol.
- Modification via acetylation.
- Most common resistance mechanism for macrolides.
- Methylation of rRNA near erythromycin's ribosome-binding site.
- Most common resistance mechanism for tetracycline.
- Decrease uptake or increase transport out of cell.
- Most common resistance mechanism for sulfonamides.
- Altered enzyme (bacterial dihydropteroate synthetase), decrease uptake, or increase PABA synthesis.
- drug of choice for prophylaxis of meningococcal infection.
- Rifampin (drug of choice)
- Drug of choice for gonorrhea.
- Ceftriaxone. 3rd generation cephalosporin.
- Drug of choice for syphilis.
- Benzathine penicillin G.
- Drug of choice for meningococcal infection. Drug of choice for history of recurrent UTIs.
- TMP-SMX.
- Drug of choice for Pneumocystis carinii pneumonia.
- TMP-SMX (drug of choice), aerosolized pentamindine