Antibacterial drugs

Question 1

describe penicillins pharmacokinetics

Answer 1

• stability in acid varies
• lipid insoluble
  o do not enter mammalian cells
  o cross the blood–brain barrier only if the meninges are inflamed
• most penicillins are eliminated via the renal route (90% by tubular secretion) rapidly

Question 2

describe penicillin mechanism of action

Answer 2

Beta-lactam ring causes peptidase activity during cell wall synthesis in bacteria

Question 3

describe penicillin adverse effects

Answer 3

• opening of b-lactam ring → benzylpenicilloyl (major determinant, 95%)
• hypersensitivity reactions
  o Type I - symptoms appear (~ an hour) in the skin, e.g., itch, urticaria; anaphylaxis in up to 0.04%
  of patients
  o Type IV - T-cell mediated

Question 4

describe penicillin and cephalosporins mechanisms of drug resistance

Answer 4

1. Produce alterations in PBPs → decreased drug binding and subsequent ↓ antibacterial activity
2. Prevent β-lactams from accessing and traversing pore channels and reaching PBPs in the cell
   membrane of gram-negative bacteria

3.Produce β-lactamase to inactivate β-lactams

Question 5

describe cephalosporins in terms of pharmacokinetics

Answer 5

• acid stable
• most are administered parenterally; a few can be administered orally
• distribution - extracellular fluid ; some can cross blood-brain barrier to treat meningitis
• excretion is mostly by renal tubular secretion

Question 6

describe cephalosporins mechanism of action

Answer 6

Beta-lactam ring

Question 7

describe cephalosporins adverse effects

Answer 7

Cephalosporin-related adverse drug reaction
* similar to penicillins
* cross-reactivity between penicillins and cephalosporins
o similarity of side chain between penicillins and cephalosporins
(1st and 2nd gen.)

Question 8

explain the use of Augmentin to overcome penicillin resistance

Answer 8

combined drug therapy of amoxicillin and clavulanic acid.

Clavulanic acid inhibits B-lactamase properties of bacterias allowing amoxicillin to act

Question 9

describe aminoglycosides of bacterial protein synthesis in terms of pharmacokinetics

Answer 9

Pharmacokinetics
* administered intramuscularly or intravenously (not
absorbed from the GI tract)
* elimination by glomerular filtration

Question 10

describe aminoglycosides of bacterial protein synthesis in terms of mechanism of action

Answer 10

[30S]
- inhibit codon-anticodon interaction, causing mRNA misreading
- bactericidal

Question 11

describe aminoglycosides of bacterial protein synthesis in terms adverse effects

Answer 11

ototoxicity
* hearing loss and impaired vestibular functions
nephrotoxicity
* accumulation in proximal tubular epithelial cells

Question 12

describe aminoglycosides of bacterial protein synthesis in terms of mechanisms of drug resistance

Answer 12

(g) drug modification

Question 13

describe tetracyclines bacterial protein synthesis inhibition in terms of pharmacokinetics

Answer 13

Pharmacokinetics
* administered generally orally but can also be
administered parenterally

Question 14

describe tetracyclines bacterial protein synthesis inhibition in terms of mechanism of action

Answer 14

inhibit aa-tRNA binding to the A site

Question 15

describe tetracycline bacterial protein synthesis inhibition in terms adverse effects

Answer 15

Gastrointestinal disturbance
* direct irritation and modification of gut flora following prolonged use

Calcium chelation
* tetracycline accumulation in teeth and growing bones
o staining and bone deformities - avoid in
children and pregnant women (category D)

Question 16

describe tetracycline bacterial protein synthesis inhibition in terms of mechanisms of drug resistance

Answer 16

(b) active efflux of the drug from the cell; (g) drug modification

Question 17

describe chloramphenicol bacterial protein synthesis inhibition in terms of pharmacokinetics

Answer 17

• rapid absorption following oral administration
• hepatically cleared (UGT2B7; 10% excreted unchanged in the urine)

Question 18

describe chloramphenicol bacterial protein synthesis inhibition in terms of mechanism of action

Answer 18

inhibit peptide bond formation

Question 19

describe chloramphenicol bacterial protein synthesis inhibition in terms adverse effects

Answer 19

Bone marrow suppression
* idiosyncratic; pancytopenia - ↓ in all blood cell elements

Grey baby syndrome
* insufficient hepatic glucuronidation and excretion in newborns

Question 20

describe chloramphenicol bacterial protein synthesis inhibition in terms of mechanisms of drug resistance

Answer 20

(d) target modification (ribosomal RNA or proteins)

Question 21

describe antibacterial macrolides bacterial protein synthesis inhibition in terms of pharmacokinetics

Answer 21

• oral (common) or IV administration
• substrates for and inhibitors of CYP3A4 - drug-drug interactions

Question 22

describe antibacterial macrolides bacterial protein synthesis inhibition in terms of mechanism of action

Answer 22

prevent transfer of tRNA with the growing peptide from A site to P site

Question 23

describe antibacterial macrolides bacterial protein synthesis inhibition in terms adverse effects

Answer 23

Gastrointestinal disturbance

Question 24

describe antibacterial macrolides bacterial protein synthesis inhibition in terms of mechanisms of drug resistance

Answer 24

(d) target modification (ribosomal RNA or proteins); (h) drug degradation (by esterases)