Anti-infective agent Antibacterial drug

Stockley IH. Antibacterial and anti-infective agent drug interactions. In Stockley IH, ed. Stockley s drug interactions. 6th ed. London Pharmaceutical Press 2002. p. 128-232. 

Sulfonamides are antibacterial agents, meaning they are active against bacteria Another term that may be used to describe the general action of these drugs is anti-infective because they are used to treat infections caused by certain bacteria Sulfadiazine, sulfisoxazole, and sulfamethizole are examples of sulfonamide preparations. 

Bacterial membranes have a much more complex construction than mammalian membranes. This enables bacteria to survive in the various environments of host organisms. Knowledge of the composition and functioning of bacterial membranes is therefore essential to the development of anti-infective drugs. In order to be effective, antibacterial agents not only have to have optimal pharmacokinetic properties such as uptake and distribution in the patient, but they must also be able to cross an additional barrier, the cell wall of the bacteria, so that they can reach the target site. This additional barrier is remarkable on account of its rigidity and permeability. The construction and structural uniqueness of this barrier is briefly described below. 

Derivatives of all three heterocyclic systems have been widely investigated for use in synthetic drugs (see also above) amongst the most commonly used compounds are the antibacterial Trimethoprim, the antimalarial Pyrimethamine and the anti-hypertensive agent Hydralazine (containing a phthalazine nucleus). Piperazine (hexahydropyrazine) is used in the treatment of intestinal nematode (worm) infections. 

Figure 1.1. Opposite) Sulpha drugs and their mode of action. The first sulpha drug to be used medically was the red dye prontosil rubrum (a). In the early 1930s, experiments illustrated that the administration of this dye to mice infected with haemolytic streptococci prevented the death of the mice. This drug, while effective in vivo, was devoid of in vitro antibacterial activity. It was first used clinically in 1935 under the name Streptozon. It was subsequently shown that prontosil rubrum was enzymatically reduced by the liver, forming sulphanilamide, the actual active antimicrobial agent (b). Sulphanilamide induces its effect by acting as an anti-metabolite with respect to /iflra-aminobenzoic acid (PABA) (c). PABA is an essential component of tetrahydrofolic acid (THF) (d). THF serves as an essential co-factor for several cellular enzymes. Sulphanilamide (at sufficiently high concentrations) inhibits manufacture of THF by competing with PABA. This effectively inhibits essential THF-dependent enzyme reactions within the cell. Unlike humans, who can derive folates from their diets, most bacteria must synthesize it de novo, as they cannot absorb it intact from their surroundings...

Consider the following well-known example for the design of a urinary tract anti-effective. The site of infection is the urinary tract. The example selected is the pro-drug, methenamine. In acidic pH, methenamine is converted to formaldehyde, which acts as an antibacterial agent (Fig. 9.39). Tablets of methenamine often are enteric coated to prevent conversion to formaldehyde in the stomach. Methenamine is cleared intact from the kidney into the urine, where it is hydrolyzed to formaldehyde if the pH is less than 6.5. The rate of hydrolysis is controlled by the urinary pH. 

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