Penicillins therapeutic index

The therapeutic index is determined by measuring the frequency of desired response and toxic response at various doses of drug. For example, Figure 2.9 shows the response to warfarin (see p. 199), an oral anticoagulant with a narrow therapeutic index, and penicillin (see p. 297), an antimicrobial drug with a large therapeutic index. 

Penicillin (example of a drug with a large therapeutic index) For... 

Penicillin is an effective antibiotic that has a high therapeutic index because it interferes with cell wall synthesis—and bacterial cells have walls, but human cells do not. What else is characteristic about cell walls that could lead to the design of an antibiotic We know that enzymes and other proteins are polymers of L-amino acids. Cell walls, however, contain both L-amino acids and D-amino acids. Therefore, if the racemization of naturally occurring L-amino acids to mixtures of l- and o-amino acids could be prevented, o-amino acids would not be available for incorporation into cell walls, and bacterial cell wall synthesis could be stopped. 

Don t harm innocent bystanders The primary goal of antimicrobial therapy is to kill bacteria without harming tissues of the host (Fig. 7.1). Drugs like penicillin, which are effective against certain bacteria, but cause few side effects, have high selective toxicity (i.e., good therapeutic index). In contrast, drugs like amphotericin, which are toxic to human cells at therapeutic doses, have poor selective toxicity. 

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