Major Classes of Bug Drugs Flashcards
Natural Penicillins MOA, Use, Examples, & SEs
- MOA:
- Bind penicillin-binding proteins (transpeptidases) → Block transpeptidase cross-linking of peptidoglycan → prevention of cell wall synthesis
- Activate autolytic enzymes
- Use: gram ⊕, N. meningitidis, T. pallidum
- Bactericidal for gram-positive cocci, gram-positive rods, gram-negative cocci, and spirochetes
- Penicillinase sensitive
- Examples:
- Penicillin G - IV or IM
- Penicillin V - oral
- Side effects:
- Hypersensitivity reactions
- Hemolytic anemia
Amino-penicillins MOA, Examples, Use & SEs
- MOA:
- Bind penicillin-binding proteins (transpeptidases) → Block transpeptidase cross-linking of peptidoglycan
- Activate autolytic enzymes
- Examples:
- Ampicillin
- Amoxicillin
- Use: Gram ⊕ and Extended-spectrum into these gram ⊖
- Haemophilus influenzae
- E. coli
- Listeria monocytogenes
- Proteus mirabilis
- Salmonella
- Shigella
- Enterococci
- Side effects:
- Hypersensitivity reactions
- Rash
- Pseudomembranous colitis
Anti-Staphylococcal Penicillins MOA, Use, Examples, & SEs
- MOA:
- Bind penicillin-binding proteins (transpeptidases) → Block transpeptidase cross-linking of peptidoglycan
- Activate autolytic enzymes
- Penicillinase resistant b/c of bulky R group that blocks beta-lactamase access to beta-lactam ring
- Use: S. aureus (except MRSA)
- Examples:
- Nafcillin
- Oxacillin
- Dicloxacillin
- SEs:
- Hypersensitivity reactions
- Intestinal nephritis
Extended Spectrum Penicillins MOA, Use, Examples, & SEs
- MOA: Same as penicillin, but extended spectrum.
- Penicillinase-susceptible, must use w/ Beta-lactamase inhibitors
- Use: gram ⊕, gram ⊖, including Pseudomonas
- Examples:
- Piperacillin
- Ticarcillin
- SEs: hypersensitivity reactions
Beta-lactamase Inhibitors MOA, Examples, & SEs
- MOA: Competitively and irreversibily inhibits some beta-lactamases
- Examples: (CaST)
- Clavulanic acid
- Sulbactam
- Tazobactam
- SEs: diarrhea
Cephalosporins
β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases
Bactericidal
- Side effects:
- Hypersensitivity reactions
- Vitamin K deficiency
- Low cross-reactivity with penicillins
- ⇡ nephrotoxicity of aminoglycosides
1st Generation Cephalosporins (give examples)
Cefazolin
Cephalexin
2nd Generation Cephalosporins (give example)
Cefuroxime
3rd Generation Cephalosporins (give example)
Ceftriaxone
4th Generation Cephalosporins (give example)
Cefepime
Carbapenems
Aztreonam
- Class: Monobactam
- MOA: Prevents peptidoglycan cross-linking by binding to penicillin-binding protein 3
- resistant to β-lactamases
- Synergistic with aminoglycosides.
- No cross-allergenicity with penicillins
- Use: gram ⊖ rods only
- For penicillin-allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides
- Side effects: GI upset
Aminoglycosides MOA, Examples, & SEs
Bind the 30S ribosomal subunit. Inhibit formation of initiation complex and cause misreading of mRNA. Also block translocation. All → inhibition of protein synthesis
Bactericidal
- Examples:
- Neomycin
- Gentamicin
- Tobramycin
- Streptomycin
- Side effects:
- Nephrotoxicity
- Ototoxicity
Macrolides MOA, Examples & SEs
Bind irreversibly to the 50S ribosomal subunit of the bacterial ribosome → inhibits elongation step → inhibits bacterial protein synthesis
Bacteriostatic
- Examples:
- Azithromycin
- Clarithromycin
- Erythromycin
- Side efects: (are MACRO)
- Motility → nausea/vomiting/diarrhea
- Arrythmia due to prolonged QT
- Cholestatis hepatitis
- Rash
- eOsinophilia
Tetracyclines MOA, Examples, & SEs
Binds to the 30S ribosomal subunit → blocks binding of aminoacyl tRNA to mRNA → inhibition of bacterial protein synthesis
Bacteriostatic
- Examples:
- Tetracycline
- Doxycycline
- Minocycline
- SEs:
- GI distress
- Discolor teeth in children
- Inhibit bone growth in children
- Photosensitivity
Chloramphenicol MOA & SEs
Blocks peptidyltransferase at 50S ribosomal subunit
** Bacteriostatic**
- Sides effects:
- Reversible bone marrow suppression
- Aplastic anemia
- Limited use owing to toxicities but often still used in developing countries because of low cost
Clindamycin
Blocks peptide transfer (translocation) at 50S ribosomal subunit
Bacteriostatic
- USE: anaerobic infections above the diaphragm
- Side effects:
- Pseudomembranous colitis (C. difficile overgrowth)
- Fever
- Diarrhea
- “Avoid using it. Its binding site overlaps w/ macrolides, so use them.”
Sulfonamides MOA & Examples & AEs
Inhibit folic acid synthesis. Para-aminobenzoic acid (PABA) antimetabolites inhibit **dihydropteroate synthase **
Bacteriostatic
- Examples:
- Sulfamethoxazole (SMX)
- Sulfadiazine
- Side effects:
- Hypersensitivity reactions
- hemolysis if G6PD deficient
- nephrotoxicity
- photosensitivity
- kernicterus in infants
- displace other drugs from albumin (e.g., warfarin)
Trimethoprim
Inhibits bacterial dihydrofolate reductase
Bacteriostatic
- Side effects:
- Megaloblastic anemia, leukopenia, granulocytopenia. (May alleviate with supplemental folinic acid/leucovorin)
Fluoroquinolones
Blocks DNA gyrase (topoisomerase II) and topoisomerase IV
Bactericidal
- Examples:
- Ciprofloxacin
- Levofloxacin
- Moxifloxacin
- Gemifloxacin
- Side effects:
- Nausea, vomiting, diarrhea
- Cartilage damage
- Prolonged QT interval
Metronidazole
Metronidazole is reduced by PFOR (normally converts pyruvate → acetyl CoA + CO2 in anaerobic fermentation), which causes fermentation to stop and reduced metronidazole is a toxic radical that damages DNA, lipids, and proteins.
Bactericidal, antiprotozoal
- USE: anaerobic infections below the diaphragm
- Side effects:
- Unpleasant metallic taste
- N/V/D w/ alcohol use (should be avoided)
- Disulfiram-like reaction (severe flushing, tachycardia, hypotension) with alcohol
- Headache
Nitazoxanide MOA, Use, & SEs:
- Antiprotozoal
- MOA:
- Nitazoxanide is rapidly metabolized to the active metabolite tizoxanide in vivo.
- Activity may be due to interference with the pyruvate:ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer reaction which is essential to anaerobic metabolism.
- This is because nitazoxanide is a structural analogue of thiamine pyrophosphate, so it can inhibit the PFOR that converts pyruvate to acetyl CoA
- Use: Cryptosporidium parvum, Giardia lamblia
- Side effects: headache; abdominal pain, diarrhea, nausea, vomiting; urine discoloration
Praziquantel
- Class: antihelminthic
- Use: broad spectrum against trematodes and cestodes
- MOA: Praziquantal acts as a calcium agonist that is rapidly taken up by susceptible helminths → ⇡calcium levels → tetanic muscular contraction and destruction of the helminth tegument → exposure of antigens to which host antibodies can bind → complement and eosinophil recruitment
- AEs: GI disturbances, headache, fever, urticaria
Mefloquine
Its exact mechanism of action unknown; but, like quinine, it can apparently damage the parasite’s membrane. It is also believed to share a similar MOA to chloroquine, which is the inhibition of heme polymerase leading to a buildup of heme causing membrane damage and subsequent cell lysis. Another proposed MOA is that it produces swelling of the P falciparum food vacuole.
- Prophylactic use in malaria
- Side effects: neuropsychiatric adverse events (Black box warning)
