Pharmacological effective dose

It relates the pharmacologically effective dose to the toxic or lethal dose (Fig. 2.8). The therapeutic index gives some indication of the safety of the compound in use, as the larger the ratio, the greater the relative safety. However, as already indicated, simple comparison of parameters derived from the dose-response curve such as the LD50 and TD50 may be... 

The Phase I study was designed as a randomized, double-blind, placebo-controlled, single ascending dose study to evaluate the pharmacokinetics and pharmacodynamics of the new ERA. Cohorts of nine subjects with baseline hemoglobin levels less than 14.5 g/dl were randomized to receive ERA treatment (N= 6) or matched placebo (N= 3) at each dose level. The various dose levels considered in this study were lx, 3x, lOx, 30x, lOOx, and 300x. The objective of the study was to identify the pharmacological effective dose (PED), defined as the dose level where four or more treated subjects achieved more than 1 g/dl increase from baseline in hemoglobin within 28 days. 

Fig. 1.3 Probability of achieving the pharmacological effective dose as a function of dose. The shaded area represents the uncertainty in the probability of achieving the pharmacological effective dose. Vertical dotted lines represent the dose range where more than 95% of the replicate cohorts have four or more subjects with hemoglobin increases of more than 1 g/dl within 4 weeks. The vertical bold line represents the observed pharmacological effective dose.

The margin of safety of a tested chemical is sometimes estimated by considering the ratio of the lethal dose to the pharmacologically effective dose (the dose at which some detectable biologic effect occurs). On the basis of animal data on the psychochemicals tested, the margin of safety for short-term effects is large for acute intravenous, intragastric, intraperitoneal, and subcutaneous administration and somewhat smaller for inhalation of th% aerosolized form. 

Kawashima Y, Serigano T, Hino T, Yamamoto H, Takeuchi H. Surface-modified antiasthmatic dry powder aerosols inhaled intratracheally reduce the pharmacologically effective dose. Pharm Res 1998 15 1753-1759. 

Zipeprol [34758-83-3] (58) is another European antitussive with a wide range of pharmacological effects, including antispasmodic, antihistaminic, and local anesthetic activities (85,86). It has been reported that zipeprol has been abused in Italy because high doses cause hallucinations (87). Spontaneous withdrawal symptoms similar to those of opiates have been observed withdrawal symptoms can also be precipitated by naloxone. Zipeprol can be... 

The pharmacological activities of the isomers should be compared in vitro and in vivo in both animals and humans. Separate toxicological evaluation of the enantiomers would not usually be required when the profile of the racemate was relatively benign but unexpected effects - especially if unusual or near-effective doses in animals or near planned human exposure - would warrant further studies with the individual isomers. 

Concentration-response curve, a more specific (and technically correct) term for a dose-response curve done in vitro. This curve defines the relationship between the concentrations of a given molecule and the observed pharmacological effect. 

Potential undesirable pharmacologic effects when given in usual doses by any route... 

Epinephrine has a narrow benefit-to-risk ratio. Along with its therapeutic effects, when administered in recommended doses by any route, it potentially causes transient anxiety, fear, restlessness, palpitations, pallor, tremor, and headache. Although usually perceived as adverse effects, such symptoms indicate that a pharmacologically active dose of the medication has been absorbed. The desirable pharmacologic effects of epinephrine cannot be separated from the undesirable pharmacologic effects [10]. 

Additional in vivo studies on the biological activity of proanthocyani-dins investigating a series of behavioral activities (motihty, body weight gain, body temperature, motoric coordination, anticonvulsant effects and central analgesic activities) showed no or only moderate pharmacological effects [53]. On the other hand, dietary supplementation with cocoa pro-cyanidin supplements can dose-dependently prevent the development of hyperglycemia in diabetic obese mice [54]. 

Because p-blockers decrease blood pressure and heart rate, they should be started at low doses to increase tolerability. Propranolol is hepatically metabolized, and its half-life and pharmacologic effects are prolonged in portal hypertension. A reasonable starting dose of propranolol is 10 mg two to three times daily. 

Otherwise, if benzodiazepines are combined with disulfiram the pharmacologic effect may be greater than expected, and the dose of benzodiazepine may need to be lowered. 

Develop a plan to assess effectiveness of pharmacologic therapy after 4 weeks of being on a clinically effective dose. 

Caffeine is also effective in the antagonism of peripheral adenosine (type I) receptors, which are known to inhibit lipolysis by subduing adenylate cyclase activity.28 The appeal of this mechanism of action is that the majority of the pharmacological effects of adenosine on the central nervous system can be inhibited by doses of caffeine that are well within physiologically non-toxic levels comparable to only a couple of cups of coffee.5... 

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