Inhibits cell wall CROSSLINKING (synthesis): Penicillins, Cephalosporins, Monobactams, Carbapenems
DOES THIS BY IRREVERSIBLY BINDING TRANSPEPIDASES (Penicillin Binding Proteins) PREVENTING CROSSLINKING
Restance occurs via beta-lactamases (degrades lactams) and by mutating Penicllin binding proteins so drugs no longer have affinity to PCPs
Vanco (glycopeptide) actually binds the D-ALA D-ALA parts of the cell.
Penicillin, Methicillin, Oxacillin
When do you use Naficillin?
D-ala-D-ala peptidoglycan side chain, inhibiting transpeptidase from forming crosslinks
Resistance develops vai lactamase expression. Counter with lactamase inhibitor
"Use Naf for staph" aures (not MRSA tho)
"HELPSS" kill enterococci
H Flu, E coli, Listeria monocytogenes, Proteus, Salmonella, Shigella
Combo with Tazobactam (b-lactamase)
Used specifically for Psuedomonas A.
Efficacy against G+, G-, and Anaerobes (psuedo is an aerobe than can also be a faculative anaerobe--grows very well in low/no O2)
Beta Lactmase Inhibitor. Given with Beta lactams to increase their half lives as well to be used in bacteria expressing beta-lactamases.
Beta-lactams that only have one ring. Less likely to act as haptens thus they are good to use in G- infections in ppl w/ Pencillin allergies.
Cef's don't cover?
Beta Lactams: Prefix: Cefs;
Increased resistance to beta-lactamases
Cover (2nd gen): HEN PEcKS (H flu, Enterobacter, Neisseria, Proteus, E coli, Kleb, Serratia)
Don't Cover: "LAME" Listeria, Atypicals (chlamy, Mycoplasma), MRSA, Enterococci
Worsen Nephrotoxicity of Aminoglycocides
4th Generation best for Psuedomonas (Cefepime)
Beta-lactam, Big Gun used in ICUs
ALWAYS ADMINISTERED WITH Cilastatin**** (decreases renal tubular inactivation by inhibiting renal dehydropeptidase I)
Binds PBP's like cillins.
Last Resort used for highly resistant organisms (klebseilla, serratia (red ring on toilet), enterobacter) because of GI/Seizure SEs
Glycopeptides, G+: Inhibits elongation via D-ala D-ala binding.
Enterococci have resistance by switching to D-ala-D-lactose, which can be horizontally transfered to Staph Aur via VRE plasmid
"GlycoPeptide works like Penicillin"
Glycopeptide, G+, inhibits NAG-NAM tranpsort to outer wall
Protein Synthesis Inhbitors
Aminoglycosides--Targets 30s portion of Ribosome
Strepomycin, Gentamycin, Tobramycin, Amikacin, Neomycin (GANTS)
Anti-30s subunit of Ribo; post-antibiotic effect (activity persists beyond detectable amounts)
"Aminoglycosides=small protein sugars used to inhibit the smaller part of the ribo"
ACUTE RENAL FAILURE** (made worse by Cephalosporins)
"GANTS caNNOT kill anaerobes"
N-ephrotox, N-euromuscular blockade, O-totox, T-eratogen
Competes with tRNA for A site on 30s ("with tetracyclines the ribosome never has a chance to start cycling"--prevents initiation)
Active against G+/- and protozoa
Not for children dt deposition in teeth (grey) or bone (deformation)
"Vacum the bedroom" Vibrio, Acne, chlamydia, Ureaplasma, Mycoplasma, Tuleramia, H Pylori, Borrellia, Rickettsia"
Binds 50s inhibiting translocation of ribosome
Protein synth inhibitor
Erythromycin, Azithromycin (Z-pak)
Binds 50s subunit inhibiting translocation "macrolides stop the ribo slide"
Risk of Prolonged QT**** ("z prolongs the qt")
Erythro: also has GI/Liver (p450) issues
"MACRO": Motility (GI) issues, Arrthymias (Qt), Cholestatic hepatitis, Rash, eOsinophillia
"Atypical PUS: Atyipical Pneumonia (myco and legionella), URI, STDs"
Protien synth inhibitor; binds to 23s portion of the 50s ribo subunit, causing premature tRNA dissociation
Lincosamide class: Used for skin and soft tissue infections: SE-->pseudomembranous colitis
"Clinda causes premature ejac" of the ribosome
ANAEROBIC INFECTIONS (aspiration pneumonia, lung abscesses, MRSA)
CAUSES C. DIFF INFECTION
Protein Synth Inhibitor
Blocking protein synth via Inhibits isoleucyl tRNA synthase
Used for S. Aureus skin infections
Purine Synthesis Inhibitors
DHF reductase inhibitors
DHF Reductase Inhibitors (methotrexate also hits DHFR)
"TMP" Treats Marrow Poorly (megaloblastic anemia, leukopenia, granulocytopenia)
Analog of PABA blocking PABA-->Dihydropteroate synthase inhibitors (bacteria need to make folate since they cannot absorb it)
Synergizes: TMP-SMZ (Bactrim)
Hypersensitivity reactions, Hemolysis (G6PD def), nephrotox, photosensitivity, Kernicertus (thus dont use in Preggers), Stevens Johnson Syndrome
-floxacins (cipro, gemi, levo)
inhbitis DNA topoisomerase II (DNA GYRASE) "cipro-circular-gyrase"
UTIs from pseudomonas; prophylaxis for anthrax
Associated with ruptured tendons (damages cartilage), tendonitis (particularly achilles tendon) "Fluoroquinolones hurt attachments to your bones"
Nitro group is released by bacterial metabolism and reacts with DNA
Flagyl, used for anaerobic bacteria nd protozoa
GET GAP on the Metro: Giardia, Entamoeba, Trichomona, Gardnerella, Anaerobic bacteria, h Pylori
DISULFIRAM LIKE REACTION W/ ETOH
Inhibitors of Cyp P450's
Protease Inhibitors, Isoniazid, Cimetidine/Cipro, Ketonacozle, Erythromycin, Grape Fruit Juice, Sulfonamides
Acute ETOH is inhibitor (Chronic is inducer)
Inducers of Cyp P450's
Barbiturates, Carbamazepine, Grisesofluvin, Phenytoin, Quinidine, Rifampin, St. Johns Wort
Chronic ETOH=Inudcer (acute is inhibitor)
Lipopeptide Antiobiotic. Disrupts bacterial cell membrane leading to loss of membrane potential. Also inhibits macromolecule synthesis
Good to use for very drug resistant bacteria.
Inhibits the 23s portion of the 50s ribosomal subunit.
"draws a line btwn the 50s and 30s subunits"
Can be used in MRSA VRE resistant infections
SEs: Optic Neuritis, and Thrombocytopenia; Weak MAO increasing risk for Serotonin syndrome
Decreases synth of mycolic acids.
Bacterial catalase-peroxidase needed to activate INH.
Competes with Pyridoxine (B6) causing:
1) Neurotoxicity (decreased NT/GABA synth)
2) Hepatotoxicity (needed for transaminase Rxns)
"INH=Injures Neurons and Hepatocytes"
"B6 is RIPES" for TB
Inhibits DNA-dependent RNA polymerase ("crab claw")
Used for Tb and for menignococcal and H. Influ type B** prophylaxis
Minor Hepatotox and drug interactions ("AMPs P450"---Rifabutin does not), orange body fluids.
4R's of Rifampin: 1) RNA poly inhibtior 2) Ramps up P450, 3) Red/Orange body fluids, 4) Rapid resistance if used alone.
WORKS BEST AT LOW pH*** P-yrazinamide at low p-H (works intracellularly)
Increases Acidity of Macrophage phagolysosome increasing their killing.
"PyraziMIDE causes Tb to DIE INSIDE the macros"
Inhibits Arabinosyltransferase decreasing carb polymerization of Mycobacterium. (resistance via increased arabinosyltransferase translation)
SEs: Optic neuropathy (red-green blindness) requiring periodic testing.
Etham hurts Eyes***
Inhibits Cell wall peptidoglycan formation by binding D-ala D-ala.
SEs: "NOT" trouble free: N-ephrotoxicity, O-totoxicity, T-hrombophlebitits.
RED MAN SYNDROME: release of antihistiamines causing rapid flushing when administered (treat by slowling infusion and giving antihistamine)
Restance: D-ala D-ala to D-ala D-lac
Given as IV cuz of poor absorption unless you want to target C diff (then give orally)
Binds Ergosterol forming pores.
"Amphotericin tears holes in fungi, RBCs, heart, and kidneys"
Need to supplement AND MONITOR K and Na because of altered renal tubule permeability. Risk for arrthymia (again Na/K issue). Anemia
Tx for Anaerobic bacteria?
Metronidazole and Clindamycin
Aminoglycosides cannot kill anaerobes
As you increase in Cephalosporins what you do you do to the spectrum?
First gens good for which bacteria?
As you increase generation of cephalo's you INCREASE G- coverage and DECREASE G+ coverage.
PEcK: Proteus, Ecoli, Kleb