Antibiotics Flashcards
Penicillin forms
G = IV, IM V = oral
Mechanism of penicillin
bind penicillin-binding proteins (transpeptidases)
block transpeptidase cross-linking of peptidoglycan in cell wall
activates autolytic enzymes
Use of penicillin
Mostly used for gram positive organisms (S. aureus - MSSA; Group A strep, Group B strep, Actinomyces)
Some gram negative cocci - N. meningitidis)
Spirochetes (T. pallidum)
Bactericidal for gram-positive cocci, gram-positive rods, gram-negative cocci, and spirochetes that are penicillinase sensitive
Toxicity of penicillin
hypersensitivity reactions, hemolytic anemia
Resistance to penicillin
penicillinase in bacteria (a type of beta-lactamse) cleaves beta-lactam ring
Mechanism of amoxicillin/ampicillin
same as penicillin; wider spectrum; penicillinase sensitive
can combine with clavulanic acid to protect against destruction by beta-lactamase
amoxicillin (more oral bioavailability)
Mech: bind penicillin-binding proteins (transpeptidases)
block transpeptidase cross-linking of peptidoglycan in cell wall
activates autolytic enzymes
Use of amoxicillin/ampicillin
Extended-spectrum penicillin (gram-positive cocci, gram-negative cocci, gram-positive rods, spirochetes)
PLUS
H. influenzae, H. pylori, E. coli. Listeria, Proteus, Salmonella, Shigella, enterococci
HHELPSS kill enterococci
Toxicity of amoxicillin/ampicillin
Hypersensitivity reactions; rash; pseudomembranous colitis
Resistance to amoxicillin/ampicillin
penicillinase in bacteria (a type of beta-lactamase) cleaves beta-lactam ring
Name the penicillinase-resistant penicillins
dicloxacillin, nafcillin, oxacillin
Mechanism of dicloxacillin/nafcillin/oxacillin
same as penicillin: bind penicillin-binding proteins (transpeptidases); block transpeptidase cross-linking of peptidoglycan in cell wall; activates autolytic enzymes
narrow spectrum
penicillinase resistant because bulky R group blocks access of beta-lactamase to beta-lactam ring
Use of dicloxacillin/nafcillin/oxacillin
S. aureus (MSSA only)
MRSA is still resistant to these because of altered penicillin binding protein target site
Toxicity of dicloxacillin/nafcillin/oxacillin
Hypersensitivity rxn; interstitial nephritis
Name the antipseudomonal penicillins
Piperacillin and ticarcillin
Mechanism of piperacillin/ticarcillin
same as penicillin: bind penicillin-binding proteins (transpeptidases); block transpeptidase cross-linking of peptidoglycan in cell wall; activates autolytic enzymes
extended spectrum
Use of piperacillin/ticarcillin
pseudomonas spp. and gram-negative rods
susceptible to penicillinase; use with beta-lactamase inhibitors
Toxicity of piperacillin/ticarcillin
hypersensitivity rxn
Name the beta-lactamase inhibitors
Clavulanic acid, sulbactam, tazobactam
add to penicillin antibiotics to protect the antibiotic from destruction by beta-lactamase (penicillinase)
CAST
Amox/Clav
Amp/Sul
Pip/Tazo
Mechanism of the cephalosporins
beta-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases
bactericidal
Organisms that are NOT covered by cephalosporins
LAME: listeria, atypicals (chlamydia, mycoplasma), MRSA and enterococci
Exception: ceftaroline covers MRSA
Name the first generation cephalosporins
cefazolin, cephalexin
Use of the first generation cephalosporins
gram-positive cocci; Proteus, E. coli, Klebsiella (PEcK)
cefazolin used prior to surgery to prevent S. aureus wound infections
Name the second generation cephalosporins
cefoxitin, cefaclor, cefuroxime
Use of the second generation cephalosporins
gram-positive cocci; H. influenzae, Enterobacter, Neisseria species, Proteus, E. coli, Klebsiella, Serratia (HEN PEcKS)
Name the third generation cephalosporins
ceftriaxone, cefotaxime, ceftazidime
Use of the third generation cephalosporins
serious gram-negative infections resistant to other beta-lactamse
Use of ceftriaxone specifically
Neisseria meningitis, gonorrhea; alpha hemolytic streps, disseminated lymes disease
Use of ceftazidime specifically
pseudomonas
Name the fourth generation cephalosporins
cefepime
Use of fourth generation cephalosporins
gram-negative organisms, with increased activity against pseudomonas and gram-positive organisms
Name the fifth generation cephalosporins
ceftaroline
Use of the fifth generation cephalosporins
broad gram-positive and gram-negative organism coverage, including MRSA; does NOT cover pseudomonas
Toxicity of the cephalosporins
hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency
Exhibit cross-reactivity with penicillins
increased nephrotoxicity with aminoglycosides
Resistance to cephalosporins
structural changes in penicillin-binding proteins (transpeptidases)
Name the carbapenems
imipenem, meropenem, ertapenem, doripenem
Mechanism of imipenem
broad-spectrum, beta-lactamase-resistant carbapenem
What is imipenem administered with?
also with cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules
Which are the newer carbapenems?
Ertapenem (limited pseudomonas coverage)
Doripenem
Use of the carbapenems
gram-positive cocci, gram-negative rods, and anaerobes
wide spectrum, use in LIFE-THREATENING infections after other drugs have failed
Toxicity of the carbapenems
GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels
Specific about meropenem
has a decreased risk of seizures and is stable to dehydropeptidase I
Name the monobactams
aztreonam
Mechanism of aztreonam
less susceptible to beta-lactamases
prevents peptidoglycan cross-linking by binding to penicillin-binding protein 3
synergistic with aminoglycosides
NO cross-allergenicity with penicillins
Use of aztreonam
gram-negative rods ONLY
use in penicillin-allergic pts and those with renal insufficiency who cannot tolerate aminoglycosides
Toxicity of aztreonam
usually nontoxic; occasional GI upset
Mechanism of vancomycin
inhibits cell wall peptidoglycan formation by binding to D-ala D-ala portion of cell wall precursors
bactericidal
not susceptible to beta-lactamases
Use of vancomycin
gram-positive bugs ONLY
use in serious, multi-drug resistant organisms, including MRSA, S. epidermidis, sensitive Enterococcus species and C. difficile (oral only for pseudomembranous colitis)
Toxicity of vancomycin
well tolerated in general but NOT trouble free - Nephrotoxicity, Ototoxicity, Thrombophlebitis
diffuse flushing - RED MAN SYNDROME
Prevent Red Man Syndrome
occurs because of too fast infusion of vancomycin
prevent with antihistamines and SLOW infusion rate
Resistant to vancomycin
occurs in bacteria via amino acid modification of the D-ala D-ala motif to D-lac D-lac
see this in enterococcus species (VRE)
Name the 30S inhibitors
aminoglycosides (bactericidal)
tetracyclines (bacteriostatic)
Name the 50S inhibitors
chloramphenicol, clindamycin (bacteriostatic)
erythromycin (macrolides) (bacteriostatic)
linezolid (variable)
Name the aminoglycosides
Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin
Mechanism of aminoglycosides
bactericidal
irreversible inhibition of initiation complex through binding of the 30S subunit
can cause misreading of the mRNA
blocks translocation
requires O2 for uptake (therefore ineffective against anaerobes)
Use of aminoglycosides
severe gram-negative rod infections
synergistic with beta-lactam antibiotics
Specific use of neomycin
neomycin for bowel surgery
Toxicity of aminoglycosides
Nephrotoxicity, Neuromuscular blockade, Ototoxicity (esp when used with loop diuretics)
Teratogen
Resistance to aminoglycosides
bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation or adenylation
Name the tetracyclines
tetracycline, doxycycline, minocycline
Mechanism of tetracyclines
bacteriostatic; limited CNS penetration
binds to 30S and prevent attachment of aminoacyl-tRNA
Specific pharmacokinetic property of doxycycline
it is eliminated fecally and thus can be used in patients with renal failure
Interaction of tetracycline and what?
Divalent cations
Tetracyclines should not be taken with milk (Ca2+), antacids (Ca2+ or Mg2+) or iron-containing preparations because divalent cations inhibit drugs absorption in the gut
Use of tetracyclines
Borrelia burgdorferi (lymes), M. pneumoniae
drug can accumulate intracellularly so good against Rickettsia and Chlamydia
also used to treat acne
Toxicity of tetracyclines
GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity
contraindicated in PREGNANCY
Resistance to tetracyclines
decreased uptake or increased efflux out of bacterial cells by plasmid-encoded transport pumps
Mechanism of chloramphenicol
blocks peptidyltransferase at 50S ribosomal subunit
bacteriostatic
Use of chloramphenicol
Meningitis (H. influenzae, Neisseria meningitidis, S. pneumoniae)
Rocky Mountain Spotted Fever (Rickettsia rickettsii)
limited use owing to toxicities, used in developing countries because cheap
Toxicity of chloramphenicol
Anemia (dose dependent), aplastic anemia (dose independent), gray baby syndrome (in premature infants because they lack the liver UDP-glucoronyl transferase)
Resistance to chloamphenicol
plasmid-encoded acetyltransferase inactivates the drug
Mechanism of clindamycin
blocks peptide transfer (translocation) at 50S ribosomal subunit
bacteriostatic
Use of clindamycin
ABOVE THE DIAPHRAGM ANAEROBES anaerobic infections (e.g. Bacteroides, Clostridium perfringens) in aspiration pneumonia, lung abscesses, and oral infections
also effective against invasive group A strep infections
Toxicity of clindamycin
pseudomembranous colitis (C. diff overgrowth), fever, diarrhea
Name the oxazolidinones
linezolid
Mechanism of linezolid
inhibit protein synthesis by binding to 50S subunit and preventing formation of the initiation complex
Use of linezolid
gram-positive species including MRSA and VRE
Toxicity of linezolid
bone marrow suppression (esp. thrombocytopenia), peripheral neuropathy, serotonin syndrome
Resistance to linezolid
point mutation of ribosomal RNA
Image of the site of action of the protein synthesis/ribosomal subunit inhibitors
insert image
Name the macrolides
azithromycin, clarithromycin, erythromycin
Mechanism of macrolides
inhibit protein synthesis by blocking translocation
bind to the 23S rRNA of the 50S ribosomal subunit
bacteriostatic
Use of macrolides
atypical pneumonia (Mycoplasma, chlamydia, legionella), STIs (chlamydia), gram-positive cocci (strep. pneumo/strep viridans esp in pts allergic to penicillins), and B. pertussis
Toxicity of macrolides
MACRO: gi Motility issues, Arrhythmia caused by prolonged QT interval, acute Cholestatic hepatitis, Rash, eOsinophilia
increases serum concentration of theophyllines, oral anticoagulants
clarithromycin and erythromycin inhibit cytochrome p450
Resistance to macrolides
Methylation of 23S rRNA-binding site prevents binding of drug
Mechanism of trimethoprim
inhibits bacterial dihydrofolate reductase
bacteriostatic
Use of trimethoprim
used in combination with sulfonamides (TMP-SMX), causing sequential block of folate synthesis
Combination used for UTIs, shigella, salmonella, pneumocystis jirovecii pneumonia treatment and prophylaxis, toxoplasmosis prophylaxis
Toxicity of trimethoprim
Megaloblastic anemia, leukopenia, granulocytopenia (may alleviate with supplemental folinic acid)
TMP Treats Marrow Poorly
Name the sulfonamides
sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine
Mechanism of sulfonamides
inhibit folate synthesis
para-aminobenzoic acid (PABA) antimetabolites inhibit dihydropteroate synthase
bacteriostatic (bactericidal when with TMP)
What is a closely related drug to sulfonamides and what is it used to treat?
Dapsone and it also inhibits folate synthesis
used for lepromatous leprosy
Use of sulfonamides
gram-positives, gram-negatives, Nocardia, chlamydia
Triple sulfas or SMX for simple UTI
Toxicity of sulfonamides
hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (tubulointerstitial nephritis), photosensitivity, kernicterus in infants, displace other drugs from albumin (e.g. warfarin)
Resistant to sulfonamides
altered enzyme (bacterial dihydropteroate synthase), decreased uptake or increased PABA synthesis
Name the fluoroquinolones
ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, moxifloxacin, gemifloxacin, enoxacin
Mechanism of fluoroquinolones
inhibit prokaryotic enzymes topoisomerase II (DNA gyrase) and topoisomerase IV
bactericidal
must NOT be taken with antacids
Use of fluoroquinolones
gram-negative rods of urinary and GI tracts (including pseudomonas), Neisseria, some gram-positive organisms
Toxicity of fluoroquinolones
GI upset, superinfections, skin rashes, headache, dizziness
less common: leg cramps and myalgias
may prolong QT interval
may cause tendonitis or tendon rupture in people >60 years old and in patients taking prednisone
Contraindications to fluoroquinolone use
pregnant women, nursing mothers, and children
Resistance to fluoroquinolones
chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps
Mechanism of daptomycin
lipopeptide that disrupts cell membrane of gram-positive cocci
Use of daptomycin
S. aureus skin infections (especially MRSA), bacteremia, endocarditis, VRE
Do not use daptomycin in?
pneumonia because avidly binds to and is inactivated by surfactant
Toxicity of daptomycin
myopathy and rhabdomyolysis
Mechanism of metronidazole
Forms toxic free radical metabolites in the bacterial cell that damage DNA
bactericidal, antiprotozoal
Use of metronidazole
BELOW THE DIAPHRAGM ANAEROBES
treats Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (Bacteroides, C. difficile)
used with PPIs and clarithromycin for “triple therapy” against H. Pylori
GET GAP on the metro
Toxicity of metronidazole
disulfiram-like reaction (severe flushing, tachycardia, hypotension) with alcohol; headache, metallic taste