Antibacterials Flashcards
Penicillin mechanism and usage
Bind to PBPs (aka transpeptidases) and block peptidoglycan cross linking in the cell wall of bacteria.
Used for gram positives and N.meningitides and T. pallidum.
Bactericidal
Ampicillin, amoxiillin mechanism
Aminopenicillins bind to PBP and prevent cross linking of peptidoglycans. Also penicillinase sensitive.
Combine with clavulanic acid to protect against beta lactamases.
Aminopenicillin usage
Extended spectrum penicillin, includes haemophilus, e.coli, listeria, proteus, salmonella, shigella.
Aminopenicillin toxicity
hypersensitivity reactions, rash, pseudomembranous colitis.
Oxacillin, nafcillin, dicloxacillin mechanism and usage
Side effect?
Blocks transpeptidases (PBP) from cross linking peptidoglycans on cell wall. These are penicillinase resistant because of a bulky R group.
Used for S.aureus.
Cause interstitial nephritis!!!!!
Ticarcillin,piperacillin mechanism/usage.
Block PBP and cross linking of peptidoglycans. Used for pseudomonas and other gram negative rods. Best combined with beta lactamase inhibitors.
Beta lactamase inhibitors
Clavulanic acid, sulbactam, tazobactam.
How do cephalosporins work?
Beta lactam drugs that are less sensitive to penicillinases. Don’t cover listeria, mycoplasma, chlamydia, MRSA, or enterococci
First generation cephs
Cefazolin, cephalexin – used for gram + proteus, e.coli, klebsiella
Second generation cephs
Cefoxitin, cefuroxine, cefaclor. Used for Haemophilis, enterobacter, neisseria, proteus, e.coli, klebsiella, serratia.
Third generation cephs
Ceftriaxone, cefotaxime, cefazidime
Used for serious gram negatives (meningitis, gonorrhea, pseudomonas)
Fourth generation cephs
Cefepime (good activity against pseudomonas and gram positives)
Fifth generation cephs
Ceftaroline. Broad gram positive coverage, but DOES NOT cover pseudomas.
Side effects of cephalosporins
HSR’s. Vitamin K deficiency. Increases the nephrotoxicity of aminoglycosides.
Aztreonam mechanism and usage
Monobactam drug, resistant to beta lactamases. Binds to PBP3. Synergistic with aminoglycosides.
Used for gram negative rods only. No activity aginast gram positives or anaerobes.
Also used for people allergic to penicillin who can’t tolerate aminoglycosides due to renal insufficiency
Carbapenems (imipenem, carbapenem, ertapenem, meropenem) mechanism and usage
Broad sprectrum betalactamase resistant drugs.
Used for gram positive cocci, gram negative rods, anaerobes.
Lots of SE that include GI upset and seizures
Why are carbapenems (imipenem) administered with another drug? What is that drug?
Administered with cilastatin that inhibits the dihydropeptidase in renal tubules. This increases its activity.
Toxicity of carbapenems
GI upset, seizures, skin rash.
Meropenem has better profile
Vancomycin
Inhibits cell wall peptidoglycan formation by binding to the D-Ala-D-ala portion of cell wall precursors.
Used for only serious gram positive reactions
Toxicity of vancomycin
Usually trouble free, but occasionally not. Nephotoxic, ototoxic, thrombophlebitis.
Can cause red man syndrome
Protein synthesis inhibitors
Inhibit components of the 30S and 50S subunits of the 70S bacterial ribosomal complex. Human ribosome 80S is unaffected.
Include Aminoglycosides, Tetracyclines (30S)
Chloramphenicol, clindamycin
Erythromycin (macrolides)
Linezolid
(50S)
Aminoglycosides (Gentamycin, neomycin, amikacin, tobramycin, streptomycin). Anything prohibitive about them?
Bactericidal, inhibit the formation of the initiation complex and cause misreading of RNA. REQUIRE O2 FOR UPTAKE, so cannot kill anaerobes.
Used for severe gram negative infections like francisella or pseudomonas. Synergistic with beta lactams
Toxicity of aminoglycosides
Nephotoxicity (especially with cephalosporins), ototoxicity (especially with loop diuretics), neuromuscular blockade.
How are aminoglycosides inactivated?
bacteria can acetylate, or phosphorylate, or adenylate.
Tetracyclines (tetracycline, doxycycline, minocycline)
Bacteriostatic, bind to the 30S subunit and prevent attachment of aminoacyl-tRNA. Limited CNS penetration.
Doxycycline is fecally eliminated, so can be used in renal patients.
What shouldn’t patients on tetracyclines take?
Milk, antacids (ca or mg), or iron containing stuff.
Divalent cations prevent absorption of drug.
Usage of tetracyclines
Borrelia, mycoplasma, accumulates intraceullularly so very effective against rickettsia/chlamydia too.
used to treat acne
Tetracyclines toxicity
GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity.
Tetracycline resistance?
Due to decreased uptake or greater efflux out of bacterial cells by plasmid encoded pumps.
Macrolides
Include Azithromycin, clarithromycin, erythromycin.
Macrolides mechanism and usage
Include Azithromycin, clarithromycin, erythromycin. Bind to 23S of 50S subunit and block translocation (macroslides).
Use for atypical pneumonias, STDs, and gram positive cocci (strep infections in penicillin allergic patients)
Macrolides toxicity
Gastrointestinal motility issues, arrythmia (long QT), cholestatic hepatitis, rash, eosinophilia.
Increases serum concentration of theophylline, oral anticoagulants
Macrolides reistance?
Bacteria can methylate the 23S binding site of 50S.
Chloramphenicol mechanism and usage
Blocks peptidyltransferase at 50S subunit. Bacteriostatic.
Used for meningitis, ricketssiae, strep pneumo.
Limited usage because of toxicities, but low cost so used in developing countries.
Chloramphenicol toxicity
Anemia, aplastic anemia, GRAY BABY SYNDROME (because they lack UDP-glucuronyl transferase and can’t metabolize the drug) .
Chloramphenicol resistance
Plasmid encoded acetyl-transferase inactivates the drug
Clindamycin
Blocks peptide transfer (translocation) at 50S. Blocks the slide.
Used for anaerobes in aspiration pneumonia, lung abscesses, oral infections. Can be effective against GAS.
Anaerobes above the diaphragm, metronidazole treats anaerobes below the diaphragm.
Clindamycin toxicity
C. Diff, fever, diarrhea.
Sulfonamides
Sulfamethoxizole, sulfisoxizole, sulfadizine.
Inhibit folate synthesis. PABA antietabolites inhibit dihydropteroate synthase.
Prevent bacterial synthesis of RNA/DNA/protein.
Used for gram positives, gram negatives, NOCARDIA, chlamydia.
Simple utis
Sulfonamide toxicity
Hypersensitivity, hemolytic anemia if G6PD deficient. Nephrotoxic, kernicterus in infants.
Trimethoprim
Inhibits bacterial dihydrofolate reductase. Used in combination with sulfonamides to have 2 steps of blocking folate synthesis.
Used for UTIs, shigella, salmonella, PCP!!!!!!
Trimethoprim toxicity
Megaloblastic anemia, leukopenia, granulocytopenia. May alleviate with folinic acid. TMP (treats marrow poorly)
Fluoroquinolones
Ciprofloxacin, norfloxacin, etc…
Inhibits DNA gyrase (topoisomerase II) and topoisomerase IV. Can’t take with antiacids.
Fluroquinolones toxicity
GI upset, superinfections, rashes, dizzziness.
Can cause TENDONITIS, TENDON RUPTURE, CRAMPS, MYALGIAS. Fluoroquinolones hurt attachments to your bones
Don’t give to pregnant women, nursing mothers, or children under 18 because of cartilage damage.
Fluoroquinolones resistance
Chromosome-encoded mutation in DNA gyrase, plasmid mediated resistance, and efflux pumps
Metronidazole mechanism and usage
Forms free radical toxic metabolites in the bacterial cell that damage DNA. Bactericidal and anti-protozoal.
Treats anaerobic infections below the diaphragm. Giardia, entamoeba, trichomonas, gardnerella. Used with a ppi and clarithromycin for triple therapy against H.Pylori.
Metronidazole toxicity?
Disulfiram-like reaction with alcohol. Severe flushing, tachycardia, hypotension with alcohol. Headache, metallic taste
Prophylaxis for tuberculosis?
Isoniazid
RIPE for treatment
Prophylaxis for MAC
Azithromycin,rifabutin
treat with azithromycin and ethambutol.
Prophylaxis for leprosy?
None, but treat with rifampin, dapsone, clofazamine for lepromatous form.
Isoniazid
Decreases synthesis of mycolic acids. Must be activatived by a bacterial catalase-peroxidase (encoded by KatG). Used for TB.
Isoniazid toxicity
B6 deficiency, neurotoxicity, hepatotoxicity.
Injures neurons and hepatocytes (INH)
Rifamycins mechanism.
Rifampin, rifabutin
Inhibits DNA-dependent RNA polyermase.
used for MTB, delays resistance to dapsone when used in M leprae. Can by used for meningoprophylaxis and haemophilus prophylaxis.
Toxicity of rifamycins
Minor hepatotoxicity. Induces cyp450. Orange body fluids.
Pyrazinamide
Mechanism uncertain. May acidify intracellular environment, especially in phagolysosomes.
used for MTB
Pyrazinamide toxicity
Hyperuricemia
Ethambutol
Decreases carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase
Ethambutol toxicity
causes optic neuropathy and red-green color blindness.
Prophylaxis for CD4
TMP SMZ for PCP
Prophylaxis for CD4
TMPSMZ for PCP and Toxoplasmosis
Can used aerosolized pentamidine for patients who can’t tolerate TMPSMZ
Prophylaxis for CD4
Azithromycin for MAC
