INDEX drug interactions

Theophylline is also considered an alternative to inhaled corticosteroids for the treatment of mild persistent asthma however, limited efficacy compared to inhaled corticosteroids, a narrow therapeutic index with life-threatening toxicity, and multiple clinically important drug interactions have severely limited its use. Theophylline causes bronchodilation through inhibition of phosphodiesterase and antagonism of adenosine and appears to have anti-inflammatory and immunomodulatory properties as well.36... 

Theophylline is a non-specific phosphodiesterase inhibitor that increases intracellular cAMP within airway smooth muscle resulting in bronchodilation. It has a modest bronchodila-tor effect in patients with COPD, and its use is limited due to a narrow therapeutic index, multiple drug interactions, and adverse effects. Theophylline should be reserved for patients who cannot use inhaled medications or who remain symptomatic despite appropriate use of inhaled bronchodilators. 

A good look at the index of this book indicates the items commonly encountered in examinations. The index is an exhaustive one and is divided into proprietary names, generic names, subject areas and conditions. A self-assessment exercise is to check that you have adequate knowledge of examples of the topics listed above and then attempt the tests. A review of the drugs in the index provides examples of medicines that certainly need attention. You should be familiar with the action, classification, side-effects, clinically significant drug interactions, contraindications and cautions of a number of classes of drugs, such as ... 

Geriatric Considerations - Summary Increased risk of side effects in patients with CVD and hepatic dysfunction. Theophylline has a narrow therapeutic index and is associated with numerous drug interactions. Target serum concentrations are 5-20 mg/L, with adverse effects increasing between 15-20 mg/L. Hepatic metabolism and renal excretion declines with age and the half-life of theophylline increases by 3 to 9 hours in older adults. Smoking induces theophylline metabolism therefore, if a pa-tienf sfops smoking, empiric dosage reduction may be indicated and follow serum concenfrafions closely. 

Members of this class of antidepressants are likely to be involved in pharmacodynamic and CYP-mediated pharmacokinetic drug-drug interactions. The latter are of concern because of the narrow therapeutic index of TCAs. 

Draft guidance for industry drug interaction studies-study design, data analysis, and implications for dosing and labeling http //www.fda.gov/cder/ guidance/index.htm (to be published in 2006). 

Drug Interactions and Side effects Index. (1994) Oradell, NJ Medical Economics Co. Goldstein, A., Aronow, L. and Kalman, S. (1974) Principles of Drug Action The Basis of Pharmacology, 2nd ed. New York John Wiley Sons. 

Precautions The tricyclic antidepressants should be used with caution in manic-depressive patients, since they may unmask manic behavior. The tricyclic antidepressants have a narrow therapeutic index for example, 5 to 6 times the maximal daily dose of imipramine can be lethal. Depressed patients who are suicidal should be given only limited quantities of these drugs and should be monitored closely. Drug interactions with the tricyclic antidepressants are shown in Figure 12.5. 

For transporters, relatively low protein expression level and limited transport capacity makes for nonlinear, enzyme-like transport kinetics that is, the transport rate saturates with increasing substrate concentration. This phenomenon is the basis for the competitive interactions generally found for chemicals that are handled by one or more common transporters this is usually manifest as inhibition of the transport of one chemical by a structural analog. The extent to which these competitive interactions are important depends on the concentrations of the chemicals involved, their relative affinities for the common transporter, and their phar-macological/toxicological profiles (effects, effective concentrations, therapeutic index). Competition for transport is discussed below in the context of drug-drug interactions. 

---