Special population reactions

Therapeutic use (Phase III/IV) Refine understanding of benefit/risk relationship in general or special populations and/or environment Identity less common adverse reactions Refine dosing recommendation Comparative effectiveness studies Studies of mortality/morbidity outcomes Studies of additional endpoints Large simple trials Pharmacoeconomic studies... 

Special populations - In elderly, debilitated, or malnourished patients, or patients with renal, hepatic, or adrenal insufficiency, the initial dosing, dose increments, and maintenance dosage of rosiglitazone/glimepiride should be conservative to avoid hypoglycemic reactions. 

Special populations - Consider a slower rate of dose titration and a lower target dose in the elderly, patients with hepatic impairment, debilitated patients, or those who have a predisposition to hypotensive reactions. Perform dose escalation with caution. 

Special populations Use a starting dose of 6 mg/25 mg for patients with a predisposition to hypotensive reactions, patients with hepatic impairment, or patients who exhibit a combination of factors that may slow the metabolism of olanzapine/fluoxetine (eg, female gender, elderly, nonsmoking status). When indicated, perform dose escalation with caution in these patients. Olanzapine/fluoxetine has not been systemically studied in patients older than 65 years of age or in patients younger than 18 years of age. 

However, the effect of a drug on the general population is only part of the story. The acceptability of a drug for market, particularly an OTC drug without a clinician intermediary, is often determined by its effect on special populations, including those patients who are particularly sensitive to its effects. Care should be taken to examine atypical patients in a study population, as well as individual adverse reaction reports. Precautions may be required in the labeling for populations at particular risk. 

Starting doses of ACE inhibitors should be low, with even lower doses started in patients at risk for orthostatic hypotension. Acute hypotension may occur at the onset on ACE inhibitor therapy. Patients who are sodium- or volume-depleted, in heart failure exacerbation, very elderly, or on concurrent vasodilators or diuretics are at high risk for this effect (see the Hypertension in Older People and Patients at Risk for Orthostatic Hypotension sections under Special Populations ). It is important to start with half the normal dose of an ACE inhibitor for all patients with these risk factors and to use slow dose titration. The risk of serious adverse reactions overah can be decreased approximately 50% by using a 6-week time interval between dose increases versus a 2-week interval. ... 

There is one special class of reaction systems in which a simplification occurs. If collisional energy redistribution of some reactant occurs by collisions with an excess of heat bath atoms or molecules that are considered kinetically structureless, and if fiirthennore the reaction is either unimolecular or occurs again with a reaction partner M having an excess concentration, dien one will have generalized first-order kinetics for populations Pj of the energy levels of the reactant, i.e. with... 

After five cycles of selection and ampHfication, a population of single-stranded DNAs was enriched that catalyzed the Pb +-dependent cleavage at the ribose residue. This intramolecular cleavage activity was transformed into an inter-molecular reaction by separating the 38-nucleotide long catalytic domain from the 21-mer substrate which was cleaved specifically and with high turnover rates. Remarkably, the deoxyribozyme can perform well only with the special DNA/RNA chimeric oHgonucleotide substrate and cannot cleave a pure RNA substrate of the same sequence. 

Overdose relative to a particular patient. Adverse reactions may be explained by the way drugs are metabolised in phenotypically different sub-sets the population. There are, for example, differences in the way that some drugs are metabolised by the liver microsomal enzymes (dealt with elsewhere), which alter the kinetics of the drug and its metabolites. Special care must be taken with such drugs and interactions with other drugs. 

Erard et al.25a,43 believe that the psychosis Is a special form of an acute schizophrenic episode activated by the drug In some susceptible persons. Luisada estimated that 1-5% of the population may be susceptible (Luisada, P.V. personal comunicatlon). Although the Army volunteers were psychologically screened, preschizophrenic test subjects may have been Included. As noted, the psychotic reactions associated with SNA typically occur Immediately or soon after consumption of the drug. If serious mental consequences were not observed during the Immediate followup period or during the later Army tour of duty, It seems unlikely that a delayed SNA psychosis occurred. 

The reason why the boundaries in physical problems are often natural becomes obvious by looking at the simple example of radioactive decay in IV.6. The probability for an emission to take place is proportional to the number n of radioactive nuclei, and therefore automatically vanishes at n = 0. The same consideration applies when n is the number of molecules of a certain species in a chemical reaction, or the number of individuals in a population. Whenever by its nature n cannot be negative any reasonable master equation should have r(0) = 0. However, this does not exclude the possibility that something special happens at low n by which the analytic character of r(n) is broken, as in the example of diffusion-controlled reactions. A boundary that is not natural will be called artificial in section 7. 

Since his arrival at McMaster in 1988, Randall Dumont has focused on statistical theories and their origin in quantum and classical mechanics. His interests include the development of Monte Carlo implementations of statistical theory wherein dynamical processes are simulated by random walks on potential energy surfaces. The breakdown of statistical theory and the appearance of nonexponential population decay are also topics of his ongoing investigations. Other questions of interest are the incorporation of quantum effects into statistical theory and the effects of collisions on reaction processes. He has a special interest in argon cluster evaporation in vacuum197 and in the description of simple isomerization reactions.198 His other interests include the semiclassical description of classically unallowed processes such as tunneling.199... 

It is convenient to represent the ratio k/x by the symbol m. It is then found necessary to consider two separate cases, namely, the general case for which m p 0, and the special case for which m = 0. The former corresponds to a reaction system in which radicals can be lost from reaction loci by first-order processes the latter effectively corresponds to a reaction system in which radicals cannot be lost from reaction loci by first-order processes, although theoretically the case m = 0 also includes reaction systems for which % is truly infinite (and therefore k. is truly infinite) and k may or may not be zero. For the case m 0, the behaviour of the reaction system during the decay period is characterised by the locus-population generating function... 

The second major section will focus on those special centers of minerals thought to be of importance to their catalytic activity, with an emphasis on the known and possible effects of electronic excitation on the population and mode of action of these centers. Metastable states constitute a hidden variable in defective solids, a non-negligible one for non-stoichiometric ones. With regard to concepts of mineral catalysis, the only systems for which extensive spectroscopic information on mineral catalytic centers has been definitively coupled to the mechanism of a well understood surface chemical reaction is exchange on binary oxides. Existing data for the... 

From its origin over a century ago, organic photochemistry has undergone a transformation from an area of science populated by a few specialized organic and physical chemists to a field that now attracts the interest of members of the broad synthetic organic chemistry community. Along the way, the basic chemical and physical foundations of the science were developed and the full synthetic potential of photochemical reactions of organic substrates has been realized. 

Primary steps of photoinduced electron transfer have been studied in plant reaction centers (PS-I and PS-II), by flash absorption and EPR. In PS-I two questions wereinvestigated i) the properties of the primary radical pair P-700+, A0 (kinetics of decay nature of A0, presumably a specialized chlorophyll a decay by recombination to populate the P-700 triplet state) and ii) the nature of the secondary acceptor A,. Extraction-reconstitution experiments indicate that A, is very probably a molecule of vitamin K,. 

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