Antibiotics Flashcards
Rifampin
Is a rifamycin drug which is bactericidal. It binds bacterial RNA polymerase at the active center, blocking elongation of the mRNA.
Treats gm+ and gram – mycobacterium tuberculosis
Resistance:
Intrinsic Resistance-in some bacterial strains, the drug is unable to bind to the beta subunit of RNA polymerase
Acquired resistance: the strain acquires mutations in rpoB gene preventing drug binding.
Adverse effects: GI side effects, hypersensitivity-fever, can turn body fluids orange-red color
Induction of cytochrome p450 enzyme can induce the metabolism of other medicines leading to organ rejection and loss of seizure control
Deacetylation does not lead to deactivation of the drug, but it is excreted in the bile, but some is reabsorbed in the intestines the rest is passed in the feces.
Is a rifamycin drug which is bactericidal. It binds bacterial RNA polymerase at the active center, blocking elongation of the mRNA.
Treats gm+ and gram – mycobacterium tuberculosis
Rifampin
Fidaxomicin
-Better than vanco
Mechanism: Bactericidal-Inhibits RNA Polymerase by binding to sigma subunit of RNA Polymerase.
Spectrum: Narrow spectrum, particularly gram positive anaerobes, and C. difficile, is better at preventing recurring infections.
Resistance: Point mutation in RNA Polymerase.
Side Effects: Low absorbtion, nausea and vomiting
Would not expect cross resistance with Rifampin due to the two antibiotics binding two different sites on the RNA Polymerase.
Mechanism: Bactericidal-Inhibits RNA Polymerase by binding to sigma subunit of RNA Polymerase.
Spectrum: Narrow spectrum, particularly gram positive anaerobes, and C. difficile, is better at preventing recurring infections.
Fidaxomicin
Fluoroquinolones-Ciprofloxacin, levofloxacin, moxifloxacin
Mechanism: Bactericidal-Inhibit, DNA Replication by binding bacterial topioisomerase, preventing relaxing of DNA for normal transcription and translation.
Spectrum: Broad- Gm+ Gm- and atypical like mycobacteria
Resistance: efflux(multidrug resistance may occur due to the upregulation of transporters capable of effluxing many types of drugs), mutations in topioisomerase
Side effects: GI side effects, confusion, photosensitivity, tendon rupture, not for use during pregnancy
Notes: Chelates cations so don’t take with calcium, iron, aluminum, and zinc. Don’t take with dairy products, juices, and antacids.
Moxifloxacin is not excreted in the urine.
Levofloxacin has good bioavailability, and is excreted in the active state, so is very good at treating UTI’s
Folate antagonists
Sulfonamides and Trimethoprim
Sulfamethazole
Mechanism: drug is a Para-AminoBenzoic Acid PABA analog and acts as a competitive inhibitor of dihydropteroate synthetase.
Resistance: change in dehydropterate synthetase, increased efflux. Increased production of PABA.
Side effects: Rash/hypersensitivity, Stevens Johnson syndrome, cross reaction with other sulfonamide moieties. Crystalluria leading to acute renal failure
Kernicterus-Billiruben induced brain dysfunction
Trimethoprim
Mechanism: bacteriostatic, inhibits dihydrofolate reductase.
Resistance: Altered dihydrofolate reductase, increased amount of dihydrofolate reductase, alternative metabolic pathways.
Adverse effects: Bone marrow suppression, hyperkalemia(elevated K in blood)
Trimethoprim, Sulfamethazole combo
Bacteriocidal
Mechanism: sequential block of the folate synthesis pathway.
Spectrum: broad treatment of UTIs, Shigella, salmonella, Pneumocystis(fungi)
Metronidazole
Mechanism: Bacteriocidal, activated form generates free radicals leading to DNA Breaks and cell death. Only metabolized to the active form in anaerobes and not in aerobes.
Spectrum: protozoa, anaerobic bacteria including c diff
Resistance: Rare
Adverse effects: Nausea diarrhea, headache and metallic taste. Avoid during pregnancy due to free radicals
Metronidazole blocks aldehyde dehydrogenase, inhibiting the oxidation of acetaldehyde and causing a marked increase in acetaldehyde concentration after drinking, just like 2nd generation cephalosporins.
E. Coli (gm-) are resistant to beta lactam antibiotics.
Nitrofuratoin
Mechanism: Bactericidal- it is reduced by bacterial flavoproteins to reactive intermediates, which inactivate or alter bacterial ribosomal proteins and other macromolecules, leading to an inhibition of the synthesis of DNA, RNA, cell wall and protein.
Spectrum: Broad, excreted in urine in active form Usually only used for UTI
Resistance: Lack of bacterial resistance since the drug interferes with a variety of processes.
Adverse Effects: Vomiting and pulmonary toxicity
Linezolid:
Mechanism: Bacteriostatic-Inhibits protein synthesis by binding to the 23S ribosomal RNA on the 50S subunit and preventing formation of the initiation complex. Excellent Bioavailability
Spectrum: Gm+ including MRSA, Vanc resistant enterococci
Resistance: alterations or modifications in 23S ribosomal RNA, unique binding site does not result in cross-resistance with other drug classes
Adverse effects: Bone Marrow suppression, Inhibits Monoamine oxidase leading to build up of seritonin
Aminoglycosides-Gentamicin, amikacin, tobramycin
Mechanism: Bactericidal- prevents formation of initiation complex, causes misreading of mRNA, and induces early termination.
Spectrum: Gram – aerobic
Resistance: Intrinsic resistance-failure of antibiotic to enter cell(anaerobic)
Acquired resistance- Acquisition of enzymes which inactivate the drug through acetylation, phosphorylation or adenylation
Amikacin-less susceptible to enzyme inactivation and broader spectrum including pseudomonas
Adverse effects: Tubular necrosis: nephrotoxicity- drug retained in renal cortex (reversible) ototoxicity- vestibular and auditory dysfunction (irreversible) pregnancy class D- hearing loss in fetus -poor absorbtion, usually administered by IV Drugs are polar and excluded from CSF. Gentimycin is synergistic with penicillin and used in the treatment of some gm+ organisms
Tetracyclines: tetracycline, doxycycline, minocycline
Mechanism: Bacteriostatic-bind 30S preventing attachment of tRNA
Specrtum: Broad initially
Resistance: borellia, H. pylori, mycoplasma pneumoniae Intrinsic: decreased uptake
Acquired: Increased efflux Alteration of ribosomal target
Adverse effects: forms stable chelates with metal ions such as ca, mg, FE, Al. decreasing absorbtion of the drug. Gastrointestinal irritation and photosensitivity
Discoloration of teeth and inhibits bone growth in children. Pregnancy class D.
Chloramphenicol:
Mechanism: Bacteriostatic-binds 50S preventing peptide bond formation
Spectrum: extended use, but limited due to side effects
Resistance: acetyltransferase modifies drug to prevent binding to the ribosome.
Adverse effects: Toxic bone marrow depression and aplastic anemia. Grey Baby syndrome: premature infants lack the enzyme UDP-glycyronyl transferase and have decreased renal function so high levels of the drug accumulate, which can lead to cardiovascular and respiratory collapse.
Macrolides-erythroycin, azithromycin, clarithromycin
Mechanism: Bacteriostatic, inhibits translocation by binding 23S rRNA of 50S subunit
Spectrum: Broad coverage of respiratory pathogens, Chlamydia
Use of macrolides is limited by:
Resistance-Methylation of 23S rRNA binding site-also associated with clindamycin and quinupristin/dalfopristin resistance
Increased efflux, and hydrolysis of the macrolide by esterases
Adverse effects: GI discomfort, Liver failure, inhibitors of cytP450 enzymes, not safe during pregnancy
Lincosamide: Clindamycin
Mechanism: Bacteriostatic-Blocks translocation at 50S subunit
Spectrum: Gm+ including anaerobic (treat acne)
Resistance: mutation of ribosome, methylation of ribosomal RNA (D-test)-checks bacteria sensitivity to clindamycin
Adverse effects: hypersensitivity(fever and Rash)
Diarrhea, abdominal pain, mucus and blood in stool, superinfection with C. Diff.
Streptogramins: Quinupristin/Dalfopristin
Mechanism: combined action is bactericidal for some organisms, binds 50S
Spectrum: reserved for infections caused by multi-drug resistant Gm+ bacteria
Resistance: Methylation prevents binding to target. Enzymes inactivate drug. Efflux proteins pump out of cell.
Adverse effects: high incidence including arthralgias and myalgias are common. Inhibits cytP450 enzyme and is likely to have drug interactions
Decreased Uptake MOR
Primarily decreased uptake Tetracyclines Sulfonamides Aminoglycosides Chloramphenicol
Increased Efflux MOR
Cephalosporins Aztreonam Tetracyclines (most impt), minocycline the exception Macrolides Quinupristin/dalfopristin Fluoroquinolones Sulfonamides
Altered target MOR
Beta-lactams – altered penicillin binding proteins (MRSA)
Vancomycin- altered target
Rifampin - DNA dependent RNA polymerase
Fluoroquinolones - DNA topoisomerase II or IV
Sulfonamides - Dihydropteroate synthetase
Trimethoprim - Dihydrofolate reductase
Linezolid – altered ribosome
Aminoglycosides – altered ribosome (uncommon)
Erythromycin, clindamycin, quinupristin/dalfopristin – methyltransferase modified ribosome
Tetracyclines – production of proteins that interfere with ribosomal binding
Moxifloxacin
Broad spectrum gm + and -. Inhibits DNA gyrase and topoisomerase IV
