Abstract
Medical therapy in patients with more than one pathology means using more pharmaceuticals, which results in a higher risk of drug interactions which are modifications in the action of one drug when it is administered in the presence of another. The consequences can be diminished therapeutic effect or increased adverse reactions. The pharmacological interactions can be either physico-chemical, pharmacokinetic or pharmacodynamic, on the basis of their mechanisms. Pharmacokinetic interactions are the most important and can emerge during various phases of absorption, distribution, metabolism and drug elimination. The absorption of many antimicrobial agents can be modified through various mechanisms. Some drugs (for example the anticholinergics and opiates) or food can slow gastric motility, slowing the absorption and reducing maximum concentrations of the antibiotic. Variations in gastric pH can alter the solubility or chemical stability of molecules such as the beta-lactams, the natural macrolides and some azoles. The bioavailability of these drugs can be reduced due to molecules used to raise gastric pH. Antibiotics such as tetracycline or the fluoroquinolones have reduced bioavailability due to chelation from bi- and trivalent cations. The primary number of clinically relevant pharmacological interactions is correlated with modifications of biotransformation of drugs due to Cytochrome P450 (CYP) hepatic enzymes which are involved in oxidative drug processes, including lipophilic antimicrobial drugs such as the macrolides, the fluoroquinolones (to be considered amphoteric) and the antifungal azole derivatives. CYP3A is probably one of the most important isoenzymes since it contributes to at least the partial transformation of 60% of drugs that undergo oxidation: erythromycin and clarithromycin are CYP3A4 substrates. Many isoenzymes can also be inhibited by antimicrobial drugs, including both antibacterials and antifungals (for example the macrolides, fluoroquinolones, metronidazole, sulfonamides and azole derivatives) with a consequent reduction in the metabolism of other drugs, thus increasing their blood concentrations and possible correlated adverse reactions. On the other hand, rifampicin, rifabutin and some anticonvulsants can induce enzymatic metabolism, causing reduced blood concentrations and lower AUC of itraconazole and voriconazole with possibly lower therapeutic efficacy. This brief review of pharmacological interactions among certain chemotherapeutic agents leads us to believe that this problem is destined to occur with more frequency in daily clinical practice. What is needed is basic knowledge of drug interactions on the part of all physicians who work in the fields of clinical therapeutics with the goal of reducing the high number of medical errors.
Similar content being viewed by others
References
Bulfoni A, Concia E, Costantino S, Giusti M, Iori I, Mazzei T, Nardi R, Salsi A, Schito GC (2007) Orientamenti terapeutici per il trattamento delle infezioni batteriche nel paziente anziano in Medicina Interna. Italian J Med 1(2) Suppl. III-IV:1–101
De Bac C, Novelli A (2005) Interazioni tra farmaci. Clinica delle reazioni avverse, EDIMES, Pavia
Granowitz EV, Brown RB (2008) Antibiotic adverse reactions and drug interactions. Crit Care Clin 24:421–442
Novelli A, Mini E, Mazzei T (2004) Pharmacological interactions between antibiotics and other drugs in the treatment of lower respiratory tract infections. Eur Respir Mon 9(28):229–254
Zhang Y, Benet LZ (2001) The gut as a barrier to drug absorption: combined role of cytochrome P450 3A and P-glycoprotein. Clin Pharmacokinet 40:159–168
Gregg CR (1999) Drug interactions and anti-infective therapies. Am J Med 106:227–237
Narasimhulu S (2010) New cytochrome P450 mechanisms: implications for understanding molecular basis for drug toxicity at the level of the cytochrome. Expert Opin Drug Metab Toxicol 6(1):1–15
Polk R, Qaqish RB (2003) Drug interactions involving antimicrobial agents. In: Finch RG, Greenwood D, Norrby SR, Whithley RJ (eds) Antibiotic and chemotherapy. Anti-infective agents and their use in therapy, 8th edn. Churchill Livingstone, Edimburg, pp 67–100
Sousa M, Pozniak A, Boffito M (2008) Pharmacokinetics and pharmacodynamics of drug interactions involving rifampicin, rifabutin and antimalarial drugs. J Antimicrob Chemother 62:872–878
Gubbins PO, Heldenbrand S (2009) Clinically relevant drug interactions of current antifungal agents. Mycoses 53:95–113
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mazzei, T. The difficulties of Polytherapy: examples from antimicrobial chemotherapy. Intern Emerg Med 6 (Suppl 1), 103 (2011). https://doi.org/10.1007/s11739-011-0680-x
Published:
DOI: https://doi.org/10.1007/s11739-011-0680-x