By T. Umbrak. The Scripps Research Institute. 2018.

    For a given drug: if log P=0 buy indocin 50mg mastercard, there is equal distribution of the drug in both phases if log P>0 buy cheap indocin 75 mg on line, the drug is lipid soluble if log P<0 trusted 75mg indocin, the drug is water soluble 19 Table 1. Thus in general, the higher the log P, the higher is the affinity for lipid membranes and thus the more rapidly the drug passes through the membrane via passive diffusion. Values of log P that are too high (>6) or too low (<3) may be associated with poor transport characteristics. Drugs with very high log P values have poor aqueous solubility, which is partly the reason for their poor absorption properties, as some degree of aqueous solubility is required for drug absorption (see Section 1. Furthermore, if a drug is too lipophilic, it will remain in the lipidic membrane and never partition out again into the underlying aqueous environment. Very polar compounds (with very low log P values) are not sufficiently lipophilic to be able to pass through lipid membrane barriers. If a drug molecule forms hydrogen bonds with water, desolvation and breaking of the hydrogen bonds is required, prior to partitioning into the apical membrane of the epithelial cell. If the number of hydrogen bonds between the drug and water is > 10, too much energy is required and there will be minimal drug transport across the membrane. The number of hydrogen bonds a drug forms with water can be estimated by inspection of the drug structure (Table 1. The lipid solubility of a drug molecule can be increased by blocking the hydrogen bonding capacity of the drug. This may be achieved by, for example, substitution, esterification or alkylation of existing groups 20 on the molecules and will decrease the drug’s aqueous solubility, favoring partitioning of the drug into the lipid membrane. The development of clindamycin, which differs from lincomycin by the single substitution of a chloride for a hydroxyl group, is such an example. Alternatively, the drug may be covalently bound to a lipid carrier, such as long-chain fatty acids. Altering the structure of the drug carries the concomitant risks of: • compromising the activity of the drug; • increasing the toxicity of the drug; • increasing the molecular weight to such an extent that the molecule will be too large to cross the membrane barrier (see Section 1. An alternative strategy, which overcomes these limitations, is to use the prodrug approach (Figure 1. This involves the chemical transformation of the active drug substance to an inactive derivative (prodrug), which is subsequently converted to the parent compound in vivo by an enzymatic or non-enzymatic process. Thus a prodrug of a drug, because of its increased lipid solubility, may demonstrate enhanced membrane permeability in comparison to the parent drug. Enzymatic or chemical transformation converts the inactive prodrug to the pharmacologically active drug, after absorption has taken place. A further important point, discussed in detail in the next section, is that lipid solubility must be considered in the context of the degree of ionization of the drug. Therefore the pH of the solution will affect the overall partition coefficient of an ionizable substance. For ionizable drugs log P is pH dependent and hence log D, the log distribution coefficient of the drug at different pHs, is usually employed instead of log P, as an estimation and/or prediction of absorptive potential. The pH at which the log D is measured should be reported but values normally correspond to determinations carried out at a physiological pH of 7. Log D is effectively the log partition coefficient of the unionized form of the drug at a given pH. The relationship between the observed overall partition coefficient and the distribution coefficient is given by the equation: where α is the degree of ionization of drug. The interrelationship between the dissociation constant and lipid solubility of a drug, as well as the pH at the absorption site, is known as the pH-partition theory of drug absorption.

    Wireless clinical alerts for critical medication purchase indocin 50mg without a prescription, laboratory and physiologic data indocin 50mg. Primary care physicians’ use of an electronic medical record system: a cognitive task analysis order 50mg indocin amex. Review of the evidence of the impact of computerized physician order entry system on medication errors. The development of a computerised equipment and drug calculator for use in resuscitation. HandiStroke: A handheld tool for the emergent evaluation of acute stroke patients. Understanding the impact on intensive care staff workflow due to the introduction of a critical care information system: a mixed methods research methodology. A Meta-analysis of 16 randomized controlled trials to evaluate computer-based clinical reminder systems for preventive care in the ambulatory setting. Past, present, and future of insulin pump therapy: A better shot at diabetes control. Comparison of the applicability of rule-based and self- organizing fuzzy logic controllers for sedation control of intracranial pressure pattern in a neurosurgical intensive care unit. Towards effective implementation of a pediatric asthma guideline: integration of decision support and clinical workflow support. Proceedings - the Annual Symposium on Computer Applications in Medical Care 1994;797-801. Computer-based guideline implementation systems: A systematic review of functionality and effectiveness. Analysis of medication administration time and the effects of an automated distribution system. Exclude - Not a Primary Study Shklovskiy-Kordi N, Zingerman B, Rivkind N and others. The effects of on-screen, point of care computer reminders on processes and outcomes of care. Effect of point-of-care computer reminders on physician behaviour: A systematic review. Construction and evaluation of new anti-cancer drug prescription support system to promote proper use of anticancer drugs. Gan to Kagaku Ryoho [Japanese Journal of Cancer & Chemotherapy] 2008;35(10):1717-20. Comparison of supplementary prescribers’ and doctors’ compliance with guidelines for drug dosing in haemofiltration on an intensive care unit. Tight glycaemic control: A prospective observational study of a computerised decision-supported intensive insulin therapy protocol. Analysis of physicians’, pharmacists’, and nurses’ attitudes toward the use of computers to access drug information. Computer-generated medication profile review as replacement for automatic stop orders. Automating drug distribution to save cognitive services at an academic medical center. Evaluation of a computerized drug review system: impact, attitudes, and interactions. A usability inspection of medication management in three personal health applications. A usability inspection of medication management in three personal health applications. Symptom management for cancer patients: A trial comparing two multimodal interventions.

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