INDEX pharmacologic

The therapeutic efficacy of a dmg is generally measured in terms of ED q or ID q which represent the concentration of dmg which produces 50% of the maximum effect or 50% of maximum inhibition. LD q represents the concentration of dmg that produces 50% fataUties in test animals. The therapeutic index is the ratio of the ED q versus LD q. Detailed descriptions of the terminology and fundamental principles of pharmacology are available (32) (see Pharmacodynamics). 

The applicant should provide justification for using the racemate. Where the interconversion of the enantiomers in vivo is more rapid than the distribution and elimination rates, then use of the racemate is justified. In cases where there is no such interconversion or it is slow, then differential pharmacological effects and fate of the enantiomers may be apparent. Use of the racemate may also be justified if any toxicity is associated with the pharmacological action and the therapeutic index is the same for both isomers. For preclinical assessment, pharmacodynamic, pharmacokinetic (using enantiospecific analytical methods) and appropriate toxicological studies of the individual enantiomers and the racemate will be needed. Clinical studies on human pharmacodynamics and tolerance, human pharmacokinetics and pharma-cotherapeutics will be required for the racemate and for the enantiomers as appropriate. 

Figure 4.4 The general protocol for information extraction from an herbal text (A-E) is paired with case examples from our work with the Ambonese Herbal by Rumphius. (A) Text is digitized. (B) Through either manual reading or automated extraction the plant name(s), plant part(s), and symptoms or disorders are identified. (C) These extracted data are then updated (as necessary) to reflect current names of the plants, using the International Plant Names Index (IPNI), and the pharmacological function(s) of the described medicinal plants are extrapolated from the mentioned symptoms and disorders. (D) The current botanical names are queried against a natural products database such as the NAPRALERT database to determine whether the plant has been previously examined. (E) Differential tables are generated that separate the plants examined in the literature from plants that may warrant further examination for bioactivity. (Adapted from Trends in Pharmacological Sciences, with permission.) See color plate.

We have developed a system based on SNOW-MED to extract medical information from herbal texts. SNOW-MED is a semantic index that recognizes relationships between groups of words [26], For example, the semantic map for thrush is related to yeast, infection, and microbe. Although this system may eventually allow a potential pharmacological function to be extrapolated, we are currently using the system to simply extract disorders from the text. We have used the Mayo Vocabulary Server to perform this data mining [34, 35]. 

An alternative method for assessing cell layer integrity is through the use of hydrophilic paracellular transport markers (e.g., radiolabeled D-mannitol or fluorescein-Na+), which passively traverse cells by the paracellular route. Small amounts of compound required for in vitro conjunctival cell culture transport experiments make this approach well suited for screening purposes. Relative absorption index of a series of pharmacologically active molecules can be ranked against known markers for the identification of candidates with potential absorption problems, which is a reliable tool to select drug candidates with optimal characteristics. 

Direct isolation of sufficient quantities of each metabolite for structural characterization, assay validation and pharmacological or toxicological testing from in vivo studies using biological specimens is, therefore, often impossible, particularly from dmgs with a low therapeutic index. Furthermore, many metabolites have structural modifications which are difficult to replicate by traditional chemical methods. A number of synthetic steps may be required to prepare such metabolites from the API, or, in the worst case, a completely new synthetic route may need to be developed. 

Even unifying information about a very specific field such as the pharmacology of discrete drugs is a monumental task. The primary reason for this difficulty is the disparity of purpose between various information sources. Consider how different the purposes are ofWDI (World Drug Index) [20], PDR (Physician s Desk Reference) [21], MSDS (Material Safety Data Sheets) [22] and REG (Chemical Abstracts Registry) [23], each of which has a different natural data model. 

Shulgin, Alexander, Utopian Pharmacology, Erowid. Available online. URL http //www.mdma.net/index.html. Downloaded on September 5,... 

L14. Lorber, A., Atkins, C. J., Chang, C. C., and Starrs, J., Serum gold levels a pharmacological index for improved chrysotherapy. Arthritis Rheum. 12, 677-678... 

Thioxanthenes differ structurally from phenothiazine in that the nitrogen atom of the central ring of the tricyclic system is replaced by carbon, which is joined to a side chain with a double bond. Their pharmacological action is similar to the corresponding phenothiazine analogues. They have the exact mechanism of action and an analogons effect on the CNS. Drugs of this series differ from one another by quantitative indexes. 

If pharmacological promiscuity is strongly reduced and only very few activities remain, a risk assessment has to be performed based on the therapeutic index. 

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