Tetracyclines + Other Cyclins Flashcards
Tetracycline + Glycylclines: MOA
REVERSIBLY Inhibits protein synthesis at 30 S ribosome by preventing the binding of tRNA to A site –> no elongation
bacterioSTATIC
Tetracyclines + glyclyclines: MOR
Three MOR:
- Efflux protein channels
- Ribosomal proteins that protect the ribosome
- Enzymatic inactivation of drugs
*MOR is acquired via mobile genetic elements
Tigecycline is RESISTANT to all forms of MOR
Tetracyclines + glyclyclines: Spectrum of Activity
4 catergories
Gram + Aerobes
MSSA
Gram - Aerobes
Burkholderia Pseudomallei
Anaerobes
Others-
brucella, legionella, coxiella, Borrelia, chlamydias, mycoplasm, ureaplasma, Rickettsia
Tigecycline: Spectrum of Activity
Gram +, Gram -, anaerobes
bacteriodes group
NO: proteus, no pseudomonas
Tetracyclines + glyclyclines, tigecycline: Clinical uses
Reserved for treatment of infections due to unusual organisms
Respiratory infections - pertussis
STDS
Prophylaxis for malaria
Rocky MTN spotted fever, Q fever, lyme disease (Borrelia)
Polymicrobial infections
Acne, SSTI, intra-abdominal infections, SIDAH
Tigecycline is NOT used for UTIs or bacteremias
Tetracyclines + glyclyclines, tigecycline: AEs (6)
GI - N/V in 30% of the people, increased in Tigecycline
Hypersensitivity
Photosensitivity
Renal - fanconi-like syndrome, renal failure in outdates tetracyclines
Hepatic - increased liver enzymes
*Pregnancy NO NO - category D
Discoloration of permanent teeth, decrease bone growth in kids
Tetracyclines + glyclyclines, tigecycline: Pharmocology
Absorption:
Distribution: widely distrubuted, good penetration in synovial fluid, seminal fluid, PROSTATE
NO CSF
Elimination:
Tetra - renal, unchanged
Doxy and minocycline - metabolically eliminated, no RI adj
Tigecycline - biliary adjust for liver disease
Minimally removed via HD
TMP- SMX Bactrim: MOA
Synergistically bacterioCIDAL
Inhibition of PURINE synthesis via blocking two different enzymes in the pathway:
PABA (1)—>Dihydrofolic Acid (2) –>tetrahydrofolic acid –> purines
“Sulfas”
SMX inhibits enz 1 : dihydropteroate synthetase
TMP inhibits enz 2: dihydrofolate reductase
TMP- SMX Bactrim: MOR
decrease emergence of resistance
Sulfa resistance is widespread
- PABA overproduction
- structural change to enz 1 dihydropteroate synthetase
- PLASMID mediated prod of drug resistance, or decrease permeability
Trimethoprim:
- chromosomal or plasmid mediated
- plasmid mediated resistance to the drug
- changes in cell permeability
TMP- SMX Bactrim: Spectrum of Activity
Gram negative aerobes:
Stenotropomas Maltophilia
Gram + aerobes: * S. Aureus, CA-MRSA* S. pyogenes Nocardia Listeria
others:
*pneumocystis carinni
NO anaerobe activity
TMP- SMX Bactrim: Clinical Use
UTIs
Prostatis
Skin infections due to CA-MRSA
TMP- SMX Bactrim: Adverse Effects
GI - NVD, glossitis, jaundice, hepatic necrosis
Hypersensitivity - RASH
Hematology: leukopenia, thrombocytopenia
Renal
CNS - H/A, aseptic meningitis, seizures
Others- drug induces lupus, serum sickness like syndrome, crystaluria
TMP- SMX Bactrim: Pharmocology
Absorption:
IV and oral, good bioavailability
Distribution:
70% protein bound
Wide, good penetration
lungs, urine, PROSTATE, CSF
Elimination: Renal and hepatic
**RI adjustment with CrCl
TMP- SMX Bactrim: Drug interactions (3)
Drug Interactions
[PHENYTOIN] INCREASES
[WARFARIN] INCREASES = increase anticoag effect
[METHOTREXATE] INCREASES, decreases renal clearance
Chlorampheniocol: MOA
Inhibits the 50S subunit, blocking peptide synthesis
bacterioSTATIC
exception bacteriocidial w:
H. influenzae
S. pneumo
N. meningitis
Chlorampheniocol: Mechanism of resistance (3)
Ribosomal mutations
decrease cellular permeability / uptake
direct inactivation of drug by ACETYLTRANSFERASE
can lead to massive outbreaks of typhoid fever and shigella
(central and south america, vietnam, india; not used in US)
Chlorampheniocol: Spectrum of Activity
Gram positive:
NO- S. Aureus, or enterococci
Gram negatives:
NO - Pseudomonas aeruginosa
Anaerobes - both gram - and +
Ricekettsiae
Spirochetes
Chlamydia
Mycoplasm
Chlorampheniocol: Clinical Uses
None in the US
Rocky MTN spotted fever
penumo, meningitis, typhoid
Chlorampheniocol: AEs
Gray Baby Syndrome in neonates
(abdominal distension, vomiting, flaccidity, cyanosis, circulatory colapse/death)
Hematologic:
REV. bone marrow suppression
aplastic anemia
Others: Optic neuritis hypersen rxn anaphylaxis GI stomatitis porphyria
Chlorampheniocol: pharmocology
Absorption - well absorped via GI tract
Distribution: lipid soluble
not highly protein bound
CSF levesl about 30-50%
Elimination:
metabolized by the liver
enterhepatic ciruculation
excreted y the kidneys
- DECREASE dose in liver failure
- not required for RI
Nitrofuranton: MOA
poorly understood
binds ribosomal proteins, inhibits translation, inhibits bacterial respiration and pyruvate metabolism
Nitrofuranton: Mxn of Resistance
RARE
Ecoli does make nitrofuranton reductase
Nitrofuranton: Spectrum of Activity
E. coli citrobacter spp Group B strep Staph saprophyticus Enterococcus (including some strains of VRE)
NO: pseudomonas, proteus, providencia, morganella, serratia, acinetobacter
Nitrofuranton: Clinical Uses
Acute, UNCOMPLICATED UTIs
NOT for:
pyelonephritis
complicated UTIS
