Page 810 - Basic _ Clinical Pharmacology ( PDFDrive )

796 SECTION VIII Chemotherapeutic Drugs

Amidase H H H H S
S CH CH 3
R N C C C 3 R N CH CH C
B A CH 3 Penicillin CH 3
H
C N C C N CH COOH
O COOH
Lactamase O
Substituted 6-aminopenicillanic acid
6-Aminopenicillanic acid
The following structures can each be substituted
O H H H at the R to produce a new penicillin.
S H
R 1 C N C C C R
B A H Cephalosporin
C N C
O C CH 2 R 2 CH 2 Penicillin G
COOH
Substituted 7-aminocephalosporanic acid
OCH 2 Penicillin V
O H H H
R C N C C CH 3
B Monobactam
C N C C Oxacillin
O SO H N C
3
Substituted 3-amino-4-methylmonobactamic acid O CH 3
(aztreonam)
Cl
HO H H C C Dicloxacillin

HC C C N C
B S R Cl O CH 3
H C C N
3
Carbapenem
O COOH OC H
2 5
NH Nafcillin
R: CH 2 CH 2 NH CH
Substituted 3-hydroxyethylcarbapenemic acid
(imipenem)
CH Ampicillin
FIGURE 43–1 Core structures of four β-lactam antibiotic
families. The ring marked B in each structure is the β-lactam ring. NH 2
The penicillins are susceptible to inactivation by amidases and
lactamases at the points shown. Note that the carbapenems have HO CH Amoxicillin
a different stereochemical configuration in the lactam ring that
imparts resistance to most common β-lactamases. Substituents for NH 2
the penicillin and cephalosporin families are shown in Figures 43–2
and 43–6, respectively.
CH
NHCO
2. Antistaphylococcal penicillins (eg, nafcillin)—These Piperacillin
penicillins are resistant to staphylococcal β-lactamases. They N O
are active against staphylococci and streptococci but not against
enterococci, anaerobic bacteria, and Gram-negative cocci and
rods. O
N
3. Extended-spectrum penicillins (aminopenicillins and C H
antipseudomonal penicillins)—These drugs retain the anti- 2 5
bacterial spectrum of penicillin and have improved activity against
Gram-negative rods. Like penicillin, however, they are relatively FIGURE 43–2 Side chains of some penicillins (R groups).
susceptible to hydrolysis by β-lactamases.