Antimicrobial Drugs Flashcards
Block cell wall synthesis by inhibition of peptidoglycan cross-linking
Penicillin, Methicillin, Ampicillin, Piperacillin, Cephalosporins, Aztreonam, Imipenem
Block peptidoglycan synthesis
Bacitracin, Vancomycin
Block nucleotide synthesis by inhibiting folic acid synthesis (involved in methylation)
Sulfonamides, trimethopram
Block DNA topoisomerases
Fluoroquinolones
Block mRNA synthesis
Rifampin
Damage DNA
Metronidazole
Block protein synthesis at 50S ribosomal subunit
Chloramphenicol, Macrolides, Clindamycin, Streptogramins (Quinupristin, Dalfopristin, Linsezolid)
Block protein synthesis at 30S ribosomal subunit
Aminoglycosides, Tetracyclines
Penicillin
Penicillin G (IV and IM form), penicillin V (oral), Prototype B-lactam antibiotics
Penicillin Mechanism
Bind penicillin-binding proteins (transpeptidases)
Block transpeptidase cross-linking in peptidoglycan
Activate autolytic enzymes
Penicillin Clinical Use
Mostly used for gram-positive organisms (S. pneumoniae, S. pyogenes, Actinomyces)
Bacterocidal for gram-positive rods, gram-negative cocci, and spirochetes
Penicillin: Penicillinase resistant?
No. Duh!
Penicillin Toxicity
Hypersensitivity reactions, Hemolytic anemia
How does penicillin resistance occur?
B-lactamases cleave B-lactam ring
Penicillinase resistant penicillins
Oxacillin, Nafcillin, Dicloxacillin
Penicillinase resistant penicillins Mechanism
Narrow spectrum Bind penicillin-binding proteins (transpeptidases)
How are the “-cillins” penicillinase resistant?
Bulky R group blocks access of B-lactamase to B-lactam ring
Penicillinase resistant penicillins Clinical Use
S. aureus (except MRSA; resistant because of altered penicillin-binding protein target site)
Penicillinase resistant penicillins Toxicity
Hypersensitivity reactions, interstitial nephritis
Aminopenicillins
Ampicillin, Amoxicillin
Aminopenicillins: Mechanism
Same as penicillin but wider spectrum
Aminopenicillins: Penicillinase resistant or penicillinase sensitive
Penicillinase sensitive Also combine with clavulanic acid to protect against B-lactamase
Which has greater oral bioavailability? Amoxicillin or Ampicillin
Amoxicillin
Aminopenicillins (Ampicillin, Amoxicillin) : Clinical Use
Extended spectrum penicillin - (HELPSS) Haemophilus influenzae, E.coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci
Aminopenicillin (Ampicillin, Amoxicillin) Toxicity
Hypersensitivity reactions; ampicillin rash; pseudomembranous colitis
Aminopenicillin (Ampicillin, Amoxicillin) Resistance
B-lactamases cleave B-lactam ring
Antipseudomonals
Ticarcillin, Piperacillin
Antipseudomonals (Ticarcillin, Piperacillin) Mechanism
Same as penicillin Extended spectrum
Ticarcillin, Piperacillin Clinical Use
Pseudomonas spp. and gram-negative rods
Ticarcillin, Piperacillin: Penicillinase resistant or Penicillinase sensitive?
Penicillinase sensitive Use with clavulanic acid to protect against B-lactamase
B-lactamase inhibitors
CAST - Clavulanic Acid Sulbactam, Tazobactum
Cephalosporins: Mechanism
B-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases. Bactericidal
Which organisms are not covered by cephalosporins?
Organisms typically not covered by cephalosporins are LAME:
Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci
Which cephalosporin is the exception to the LAME organism rule?
Ceftaroline covers MRSA
1st generation cephalosporins
Cefazolin, Cephalexin
1st generation cephalosporins coverage
1st generation - PEcK
Proteus
E.Coil
Klebsiella
2nd generation cephalosporins
Cefoxitin, Cefaclor, Cefuroxime
2nd generation cephalosporin coverage
2nd generation cephalosporins - *HEN PEckS* H.influenza Enterobacter Neisseria Proteus E.Coli Klebsiella
3rd generation cephalosporins
Ceftriaxone, Cefotaxime, Ceftazidime
3rd generation cephalosporins coverage
Serious gram-negative infections resistant to other B-lactams
4th generation cephalosporins
Cefepime
4th generation cephalosporin coverage
Cefepime - increased activity against Pseudomonas and gram-positive organisms
Cephalosporin Toxicity
Hypersensitiity reactions, vitamin K deficiency.
Aztreonam: Mechanism
A monobactam resistant to B-lactamases. Prevents peptidoglycan cross-linking by binding to PBP3
Synergistic with aminoglycosides. No cross-allergy with penicillins
Aztreonam: Clinical Use
Gram-negative rods only - No activity against gram-positives or anaerobes. For penicillin-allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides
Imipenem/Cilastatin, Meropenem: Mechanism
Imipenem is a broad-spectrum, B-lactamase-resistant carbapenem. Always administered with cilastatin (inhibitor of renal dehydropeptidase I) to decreased inactivation of drug in renal tubules.
Imipenem/Cilastatin, Meropenem: Clinical Use
Gram-positive cocci, gram-negative rods, and anaerobes.
Discuss Meropenem and seizure risk
Unlike imipenem/cilastatin, meropenem has reduced risk of seizures, and is stable to dehydropeptidase I
Imipenem/Cilastatin, Meropenem: Toxicity
GI distress, skin rash, and CNS toxicity (seizures at high plasma levels)
Vancomycin: Mechanism
Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors. Bactericidal
Vancomycin: Clinical Use
Gram-positive only - serious, amultidrug-resistant organisms, including MRSA, enterococci, and Clostridium difficile (oral dose for pseudomembranous colitis)
Vancomycin: Toxicity
Well tolerated in general - does *NOT* have many problems N-ephrotoxicity O-totoxicity Tthrombophlebitis Diffuse flushing
How can one prevent red man syndrome?
Red man syndrome - associated w/ vancomycin toxicity.
- mediated by histamine
Vancomycin Resistance
Occurs with amino acid change of D-ala D-ala to D-ala D-lac.
Protein synthesis inhibitors target which bacterial ribosome?
70S (made up of 50S and 30S subunits), which leave 80S ribosome (human ribosome) unaffected
Aminoglycosides
Gentamicin, Neomycin, *Amikacin, Tobramycin, Streptomycin
Macrolide: Clinical Use
Atypical pneumonias (Mycoplasma, Chlamydia, Legionella)
STDs (for Chlamydia)
Gram-positive cocci (Streptococcal infections in patients allergic to penicillin
Macrolides: Toxicity
MACRO: Motility issues, Arrhythmia caused by prolonged QT, acute Cholestatic hepatitis, Rash, eOsinophilia. Increases serum concentration of theophyllines, oral anticoagulants
Macrolide Resistance
Methylation of 23S rRNA binding site
30 S inhibitors
“AT” 30
Aminoglycosides
Tetracyclines
50S inhibitors
CCEL at 50
Chloramphenicol, Clindamycin
Erythromycin (macrolides)
Linezolid
Aminoglycoside: Mechanism
Bacteriocidal
- bind to 30S ribosomal subunit unit to inhibit formation of initiation complex and cause misreading of mRNA
- blocks translocation
- Requires oxygen for uptake thus inaffective against anaerobes
Aminoglycoside: Clinical USe
Severe gram-negative rod infections
Syngergistic with B-lactam antibiotics
Neomycin for bowel surgery
Amingoglycoside Toxiciity
Nephrotoxicity (esp. when used with cephalosporins)
Neuromusclar blockade
Ototoxicity (esp. when used with loop diuretics - furosemide)
Teratogen
Aminoglycoside resistance
Transferase enzymes that inactivate trug by acetylation, phosphorylation or adenylation
Tetracycline
Tetracycline, Doxycycline, Demeclocycline
Demeclocycline
- ADH antagonist
- acts as diuretic in SIADH. Rarely used as an antiobiotic
Tetracycline mechanism
Bacterostatic:
bind to 30S and prevent attachment of aminoacyl-tRNA
limited CNS prenetration