Pharm 35: Bacterial Mass Murder Flashcards
Peptidoglycan aka
Murein
β lactam antibiotics inhibit _____ that mediate _____
β lactam antibiotics inhibit transpeptidase enzymes that mediate cross linking of sugar polymers
Fosfomycin MOA
Phophoenolpyruvate (PEP) analogue that inhibits bacterial (MurA)
Why doesn’t fosfomycin affect human cells
Structural differences in human and bacterial enzymes that act on PEP
Fosfomycin enters cells via ____
Glycerophosphate and G6P transporters
Fosfomycin is especially effective against
Gram negatives in urinary tract
Which GI bug is fosfomycin effective against
Enterococcus faecalis
Resistance to fosfomycin (common and E.coli)
Common: mutation in transporters (G6P and glycerophosphate)
E.Coli: Modification of enolpyruvate tranferase
Enolpyruvate transferase aka
MurA
Fosfomycin adverse effects
Mild and uncommon.
Headache, diarrhea, nausea
Oral fosfomycin drug interactions
Metoclopramide decreases GI absorbtion
Probenecid reduces renal clearance
Cycloserine MOA
Structural analogue of D-ALa inhibits alanine racemase and ligase
Racemase and ligase functions
Racemase: converts L-Ala to D-Ala
Ligase: joins D-Ala residues together
Cycloserine use
Second line for multidrug resistant TB
Cycloserine adverese effects
Neuro: seizures, psychosis, peripheral neuropathy
Cycloserine inhibits hepatic metabolism of _____
Phenytoin
Bacitracin MOA
Peptide antibiotic that intereferes with bactoprenol diphosphate dephosphorylation.
This makes bactoprenal lipid carrier infective and murein cannot be synthesized
Bacitracin unique amongst cell wall inhibitors because
It targets lipid and not peptide
Bacitracin requires ____ as cofactor
Divalent ions, Zn2+, Mg2+
Bacitracin use
Topical use for derm/eyes
Orally for gut decontamination prior to surgery (not absorbed)
Bacitracin systemic use
Not used systemically due to toxicity to marrow, kidney and neurons
Vancomycin activity
Bactericidal against gram-positive rods and gram positive cocci
Vancomycin, tela vancin, dalba vancin, orita vancin MOA
Lipoglycopeptides that interrupt peptidoglycan polymerization by binding to terminus of D-Ala-D-Ala murein monomer unit.
van drugs with lipid side chain
(and what does it do?)
Telavancin and oritavancin
Lipid chain anchors to bacterial membrane, enhancing drug binding
Dalbavancin has enhanced activity against
Coagulase negative staphylococci
Enteroccoci
Dalbavancin and oritavancine elimination
Long half life, once a week dosing
IV Vanco used for
MRSA pneumonia, sepsis, and endocarditis
IV telavancin used for
MRSA/Strep skin and pneumonia
Oral vanco for C.diff due to
Poor GI absorption
Vancomycin side effects
Red man syndrome: histamine release causing skin flushing and and rash
Nephrotoxicity, otoxic (esp with other meds)
Van drug without nephrotoxicity
Dalbavancin
Antibiotics that bind mess up coagulation tests results
Telavancin, oritavancin, daptomycin
van drug resistance comes from
Plasmide encoded VanH or VanA
These make D-Ala-D-lactate instead of D-Ala-D-Ala
β lactam mechanism
Inhibition of murein cross linking
β lactam ring inhibits cross linking how
Causes formation of dead-end complexes via suicide inhibition
Factor that affects β lactam bactericidalicity
Bactericidal only for actively dividing bacteria
4 β lactam families
Peniccillins
Cephalosporins
Monobactams
Carbepenems
Factor in β lactam activity against gram negs
Hydrophillics can make it through outer membrane, hydrophobics are ineffective
Hydrophilic β lactams
Ampicillin
Amoxiciillin
Piperacillin
Ticacillin
P A T A ( mete las patas en el agua)
Bugs that are inherently resistant to all β lactams (why)
Intracellular bacteria
MRSA mechanism of resistance
Transpepitidase mutations to not bind β-lactam
Main form of resistance against β-lactams
Plasmid encoded β-lactamase
Bugs that make extended spectrum β-lactamases
Klebsiella pneumonia
E. Coli
β-lactamase inhibitors
CAST
Clavulanic acid
Avibactam
Sulbactam
Tazobactam
β-lactams act synergistically with [drug class].
How
Aminoglycosides
β-lactams make holes in the mebrane to increase uptake
Most common β-lactam adverse effects
Hypersensitivities
Lupus-like drug reactions
Hemolytic anemia
β-lactam without cross reactivity to penicillins or carbapenems
Aztreonam
(cross reacts with ceftazimide)
Penicillin G vs V
G: IV
V: GI
Penicillin G common use
Pneumoccus
S. Pyogenes
Neisseria
Spirochetes
Penicillin G AEs
Hypersensitivity and rash
seizures at high doses
Anstistaphylococcal penicillins
M-DONC
Methicillin
Dicloxacillin
Oxacillin
Nafcillin
Cloxacillin
β-lactam that induces CYP3A4 enzyme
Nafacillin
Oxaccilin major AE
Reversible hepatotoxicity
Amino penicillins additional advantage
Positively charged R group facilitates diffusion through porin channels
IV ampicillin is used to treat
Invasive enterococcal infections
Listeria meningitis
Oral amoxillin use
Simple ENT infecitions
Endocarditis prevention in dentistry
H. Pylori
Amoxicillin adverse effect
Rash
Amino penicillins and corresponding β-lactamase inhibitors
Amoxicillin: Clavulanic acid
Ampicillin: Sulbactam
Ticarcillin advantages/disadvantages
Negative R chain: makes diffusion harder but increases β-lactamase resistance
To overcome diffusion, use high dose
Piperacillin use and advantages
Both positive and negative R chains
Used against Klebsiella and enterococci
Piperacillin corresponding β-lactam
Tazobactam
Cephalosporins difference to penicillins
Six member instead of five member β-lactam ring
First gen cephalosporin names
Cefazolin
Cephalexin
Cefadroxil
First gen cephalosporins use
UTIs, klebsiella
Surgical prophylaxis cephalosporin
Cefazolin
Cefuroxime use
Community pneumonias
H. Influenza
Cefotetan and Cefoxitin use
Bacteroides
PID and Intrabdominal infections
Third gen cephalosporins spectrum
Less effective against gram positive,
More effective against enterobacteria
Ceftriaxone uses
S. pneumo
Gnonorreah
Lyme dx
Ceftriaxone major AE
Cholestatic hepatitis
Ceftazidime spectrum/use
Psuedomonas aeruginosa
Hosp. acquired gram negs
Minimal use vs. gram positives
Drug used empirically for neutropenic patients with fever
Ceftazidime
Cefepime AEs
Myoclonus
Encephalopathy
Red blood cell automminunity without hemolysis
Ceftaroline use
IV use for community pneumonia and skin infections
Fifth gen cephalosporin
Ceftaroline
Disulfiram like reaction (what is it, which antibiotiocs?)
Raction that causes alcohol intolerance
Cefotetan and Cefoperazone
Antibiotics that interefere with Vitamin K
Cefotetan and Cefoperazone
Aztreonam activity
Most gram negs
No gram positive activity
Aztreonam usefulness
Usefull when penicillin allergy
Aztreonam use (plus routes)
Inhaled for CF infection prevention
IV for systemic infections
Carbapenems actvitity
Broad spectrum,
Not active against MRSA, VRE and Legionella
Imipenem dosing consideration
Deactivated by renal enzyme DHP1, must be co-administered with cilastin
Carbepenems AEs
Hypersensitivities, IV site phlebitis
Imipenem and meropenem AEs
High concentration can cause seizures
Daptomycin MOA
Specifics unknown, but integrates into gram positvie membranes, causing pores
Daptomycin activity and use
Heavy hitter
MRSA, VRE
Bacteremia
Daptomycin adveres effects
Myopathy
Eosinophilic pneuomonia
Ethambutol activity and MOA
Bacteriostatic
MOA: inhibits arbinosyl transferase to decrease arabinogalactan synthesis
When is RIP vs RIPE used
RIPE if local ionazid resistance is over 4%
Pyrazinamide and Isoniazid MOA
Inhibit mycolic acid synthesis
Pyrazinamide: Inhibits FAS1
Ionazid: Inhibits FAS2
Ethonamide MOA and use
Inhibition of FAS2
(second line INH)
Ethambutol side effects
Optic neuritis
Reversible
Pyrazinamide AEs
Arthralgias/ Hyperuricemia (gout)
Hepatotoxicity
INH AEs
Mild hepatotoxicity (no cessation needed)
Peripheral neuropathy
P450 shit
Serotonin syndrome
Ethambutol resistance by
mutations to arabinosyl transferase
Overexpression of arabinosyl transferase
INH resistance how
Inactivation of catalase peroxidase
inhA mutations
Pyrazinamide resistance
Via pyrazinamidase mutation, prodrug wont get metabolized
Pyrazinamide kinetics
Prodrug metabolised to pyrazinoic acid (active form)
IM Carbapenems
Imipenem
Ertapenem