Antimicrobials in the forms of antibacterials, antifungals, and antivirals have added significantly to the clinical care of infected patients since the introduction of penicillin in the 1940s. The development of drug-resistant strains of these pathogens has greatly expanded the number of antimicrobials necessary, and this has increased the overall potential for toxicity after use. Fortunately, toxicity due to acute overdose and even chronic therapeutic doses does not preclude their appropriate use in the majority of patients.
The majority of the adverse effects related to antimicrobials occur as a result of iatrogenic complications rather than intentional overdose. The diverse origins of these complications include dosing, route and decision errors, allergic reactions, adverse drug effects, and drug-drug interactions. Prevention in the form of process improvements and information regarding populations at risk for adverse drug effects is required to minimize these untoward events. Dosing errors are common in neonates and infants, necessitating careful and constant diligence on the part of all healthcare providers.
Antimicrobials are more commonly associated with anaphylactic reactions than are other xenobiotics. The reason for this is unclear, but it may be a result of their high frequency of use, repeated interrupted exposures caused by intermittent prescriptive use, or environmental contamination. A complete and clear allergy history is essential to minimize these adverse events in patients being considered for antimicrobial therapy.
Many adverse effects attributed to antimicrobials are difficult to predict even when given patient- and population-specific parameters. In some cases, a diluent or an excipient is responsible for the adverse effect, as recognized with the use of procaine penicillin G in patients with procaine allergy. Antimicrobials are involved in many of the common and severe drug interactions, primarily through the inhibition of metabolic enzymes. Patients being considered for antimicrobial therapy should be carefully assessed for the use of concomitant drug therapy that may be pharmacokinetically or pharmacodynamically affected by the chosen antimicrobial.
Antimicrobial pharmacology is aimed at the destruction of microorganisms through the inhibition of cell-cycle reproduction or the altering of a critical function within a microorganism. Table 56–1 lists antimicrobials and their associated mechanisms of activity. Often the mechanisms for toxicologic effects following acute overdose differ from the therapeutic mechanisms. Table 56–1 also lists the toxicologic effects and related mechanisms. Table 56–2 lists the pharmacokinetics of each class of drugs.
Table 56–1. Antimicrobial Pharmacology and Adverse Effects |Favorite Table|Download (.pdf)
Table 56–1. Antimicrobial Pharmacology and Adverse Effects
|Antimicrobial||Antimicrobial Mechanism of Action||Acute Overdose||Chronic Administration|
|Aminoglycosides||Inhibits 30s ribosomal subunit||Neuromuscular blockade—inhibits the release of acetylcholine from presynaptic nerve terminals and acts as an antagonist at acetylcholine receptors||Nephrotoxicity/ototoxicity—forms an iron complex that inhibits mitochondrial respiration and causes lipid peroxidation|
|Penicillins, cephalosporins, and other β-lactams||Inhibits cell wall mucopeptide synthesis||Seizures—agonist at picrotoxin binding site causing GABA antagonism|
|Chloramphenicol||Inhibits 50s ribosomal subunit ...|
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