Dose-modifying agents

Reactions of the hydrated electron possibly may be somewhat relevant to the action of dose-modifying agents such as 02, NO, C02, and sulfhydryl compounds. It can safely be assumed that these exert their influence at the radiation-chemical level, and it is notable that many of them react rapidly with hydrated electrons. Table II, taken from a paper by Braams (6), compares the rate constant for reaction with the hydrated electron with the concentration at which certain compounds have been used as protective agents. It can be seen that, at the concentrations used in biological systems, those substances which are effective as protectors can compete favorably with oxygen for hydrated electrons. Penicillamine was not a good protector at the concentration used and did not compete as favorably as the other substances for hydrated electrons. Higher concentrations of penicillamine could not be... 

Oxygen may therefore be considered to be the classic dose-modifying agent or sensitizer and must be present during delivery of radiation, at least for all practical purposes, to exert its sensitizing effect. The mechanism is considered to be electron acceptance from target radicals generated by the radiation ... 

Anthracyclines - Adriamycin (ADR 20) has continued to be the dominant force in the expanding use of chemotherapeutic agents. Its wide spectrum of activity coupled with its dose-limiting cardiac toxicity continue to stimulate the search for structurally modified agents with improved biological profiles. Recent reviews on daunomycin (DNR 21),ADR and related antibiotics have appeared that discuss their chemistry and pharmacology. N-Trifluoroacetyladriamycin-14-valerate (AD-32 22), unlike the basic anthracyc lines, ADR and DNR, has been shown not to... 

Dose-response assessment is the process of characterizing the relationship between the dose of an agent administered or received and the incidence of an adverse health effect in e.xposed populations, and estimating the incidence of the effect as a function of e.xposure to the agent. This process considers such important factors as intensity of exposure, age pattern of exposure, and possibly other variables that might affect response, such as sex, lifestyle, and other modifying factors. 

Leukotriene modifiers either inhibit 5-lipoxygenase (zileuton) or competitively antagonize the effects of leukotriene D4 (montelukast and zafirlukast). These agents improve FEV, and decrease asthma symptoms, rescue drug use, and exacerbations due to asthma. Although these agents offer the convenience of oral therapy for asthma, they are significantly less effective than low doses of inhaled corticosteroids.2,33... 

Clarithromycin is a macrolide antibacterial agent that should be used with caution in patients with renal impairment. The dose should be reduced if creatinine clearance is less than 30 mL/minute and the modified-release oral preparation should be avoided in this scenario. 

The effects of ozone appear to be cumulative for initial exposures followed by adaptation. Five of six subjects exposed to 0.5 ppm ozone 2 hours/day for 4 days showed cumulative effects of symptoms and lung function tests for the first 3 days, followed by a return to near control values on day 4." In animals exposure to 0.3-3 ppm for up to 1 hour permits the animals to withstand multilethal doses for months afterwards. However, repeated exposures impart protection from all forms of lung injury (e.g., susceptibility to infectious agents, enzyme activities, inflammation). Initial ozone exposure may act to reduce cell sensitivity and/or increase mucus thickness, factors which may modify the accessibility and action of the gas. It is not known how variations in the length, frequency, or magnitude of exposure modify the time course for tolerance. 

---