Major Classes of Bug Drugs

Question 1

Natural Penicillins MOA, Use, Examples, & SEs

Answer 1

• 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

Question 2

Amino-penicillins MOA, Examples, Use & SEs

Answer 2

• 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

Question 3

Anti-Staphylococcal Penicillins MOA, Use, Examples, & SEs

Answer 3

• 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

Question 4

Extended Spectrum Penicillins MOA, Use, Examples, & SEs

Answer 4

• 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

Question 5

Beta-lactamase Inhibitors MOA, Examples, & SEs

Answer 5

• MOA: Competitively and irreversibily inhibits some beta-lactamases
• Examples: (CaST)
  
  • Clavulanic acid
  • Sulbactam
  • Tazobactam
• SEs: diarrhea

Question 6

Cephalosporins

Answer 6

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

Question 7

1st Generation Cephalosporins (give examples)

Answer 7

Cefazolin

Cephalexin

Question 8

2nd Generation Cephalosporins (give example)

Answer 8

Cefuroxime

Question 9

3rd Generation Cephalosporins (give example)

Answer 9

Ceftriaxone

Question 10

4th Generation Cephalosporins (give example)

Answer 10

Cefepime

Question 11

Carbapenems

Question 12

Aztreonam

Answer 12

• 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

Question 13

Aminoglycosides MOA, Examples, & SEs

Answer 13

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

Question 14

Macrolides MOA, Examples & SEs

Answer 14

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

Question 15

Tetracyclines MOA, Examples, & SEs

Answer 15

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

Question 16

Chloramphenicol MOA & SEs

Answer 16

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

Question 17

Clindamycin

Answer 17

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.”

Question 18

Sulfonamides MOA & Examples & AEs

Answer 18

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)

Question 19

Trimethoprim

Answer 19

Inhibits bacterial dihydrofolate reductase

Bacteriostatic

• Side effects:
  
  • Megaloblastic anemia, leukopenia, granulocytopenia. (May alleviate with supplemental folinic acid/leucovorin)

Question 20

Fluoroquinolones

Answer 20

Blocks DNA gyrase (topoisomerase II) and topoisomerase IV

Bactericidal

• Examples:
  
  • Ciprofloxacin
  • Levofloxacin
  • Moxifloxacin
  • Gemifloxacin
• Side effects:
  
  • Nausea, vomiting, diarrhea
  • Cartilage damage
  • Prolonged QT interval

Question 21

Metronidazole

Answer 21

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

Question 22

Nitazoxanide MOA, Use, & SEs:

Answer 22

• 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

Question 23

Praziquantel

Answer 23

• 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

Question 24

Mefloquine

Answer 24

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)

Question 25

Vancomycin

Answer 25

• Class: glycopeptide antibiotic
• MOA: inhibits bacterial cell wall synthesis by blocking glycopeptide polymerization thru binding tightly to D-alanyl-D-alanine portion of cell wall precursor
• Side effects: red man syndrome (flushing and hypotension), fever, fatigue, diarrhea