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.
T are useful indicators of those patients at high risk for • Burning polyurethane (foam stuffing in furniture and mattresses) evolving myocardial infarction indocin 25mg otc. They convert hemo- several days previously globin to methemoglobin order indocin 50mg fast delivery, which binds cyanide in the blood before reaching the tissues buy indocin 50 mg cheap. Carbon Monoxide Carbon monoxide binds to cytochrome al a3 but less tightly than cyanide. Depending genin), which allows energy loss as heat to maintain a basal temperature around the kidneys, on the degree of salicylate neck, breastplate, and scapulae in newborns. These react rapidly with lipids to cause peroxidation, with proteins, and with other substrates, resulting in denaturation and precipitation in tissues. These small quantities are normally destroyed by protective enzymes such as catalase. In the special case of erythrocytes, large amounts of superoxide are generated by the spontaneous dissociation of the oxygen from hemoglobin (occurrence is 0. The processes that adequately detoxify the superoxide require a variety of enzymes and compounds, including superoxide dismutase, catalase, as well as glutathione peroxidase, vitamin E in membranes, and vitamin C in the cytoplasm. Mutations in these genes affect highly aerobic tissues (nerves, muscle), and the diseases exhibit characteristic mitochondrial pedigrees (maternal inheritance). Because the daily amount of creatinine in urine is constant per unit muscle mass, the amount of urinary creatinine can be used as a normalizing factor for other materials that are excreted. However, increases in creatinine levels in the bloodstream are indicative of renal problems. Diagnosis of Myocardial Infarctions with Creatine Kinase Isoforms A 62-year-old man was shoveling snow after a recent snowstorm. Shortly thereafter, he began to complain of chest pain, dizziness, and shortened breath. In myocardial infarctions, there is a blockage of blood flow to the heart, resulting in lysis of cardiac cells. Also, elevated serum levels of cardiac-specific troponins are most often used for rapid diagnosis of myocardial infarction (see Bridge to Pathology on page 184). During a myocardial infarction, the oxygen supply to an area of the heart is dramatically reduced, forcing the cardiac myocytes to switch to anaerobic metabolism. Which of the following enzymes is affected most directly by the active metabolite of this drug? When nitroprusside is given in higher than usual doses, it may be accompanied by the administration of thiosulfate to reduce potential toxic side effects. Which complex asso- ciated with electron transport or oxidative phosphorylation is most sensitive to the toxic byproduct that may accumulate with high doses of nitroprusside? A patient has been exposed to a toxic compound that increases the permeability of mito- chondrial membranes for protons. Oxaloacetate, produced from pyruvate, exits the mitochondrion after conver- sion to malate. Glycogen synthesis and degradation occur primarily in liver and skeletal muscle, although other tissues, including cardiac muscle and the kidney, store smaller quantities. Glycogen is stored in the cytoplasm as either single granules (skeletal muscle) or as clusters of granules (liver). The granule has a central protein core with polyglucose chains radiating out- ward to form a sphere (Figure 1-14-1). Glycogen granules composed entirely of linear chains have the highest density of glucose near the core. If the chains are branched, the glucose density is highest at the periphery of the granule, allowing more rapid release of glucose on demand. A Glycogen Granule Glycogen stored in the liver is a source of glucose mobilized during hypoglycemia. In white (fast-twitch) muscle fibers, the glucose is converted primarily to lactate, whereas in red (slow-twitch) muscle fibers, the glucose is completely oxidized. Glycogen Metabolism Glycogen Synthase Glycogen synthase forms the a1,4 glycosidic bond found in the linear glucose chains of the granule.
What is the most likely interpretation of the nontreponemal tests become seronegative order indocin 75 mg with visa. D A positive reaction with nontreponemal antigen and a negative reaction with a treponemal antigen is C purchase indocin 25mg with visa. Syphilis that has been successfully treated most likely caused by a biological false-positive D purchase indocin 75 mg with mastercard. Immunology/Correlate laboratory data with physiological processes/Syphilis/Testing/2 9. A This patient may be in the secondary stage of syphilis Immunology/Correlate laboratory data with and is producing large amounts of antibody to physiological processes/Syphilis/Testing/1 T. Impossible to interpret; testing error Immunology/Correlate laboratory data with physiological processes/Syphilis/Testing/2 90 Chapter 3 | Immunology 11. Cross reaction; biological false-positive result making enough antibodies to be detected by D. Clinical signs may be misinterpreted (helper T cells) and various categories of clinical Immunology/Correlate laboratory data with symptoms. Presence or absence of lymphadenopathy The M group is further divided into 9 subgroups, D. Human trials cannot be performed (helper T) cell count of less than 200/μL or 14% in the C. B Improper washing may not remove unbound enzyme conjugated anti-human globulin, and every 25. Positive results for hepatitis markers consider clinical signs as well as laboratory tests that D. Is not spread through blood or sexual contact has a shorter incubation period (2–7 weeks) than Immunology/Apply knowledge of fundamental hepatitis B virus (1–6 months). Epidemics of hepatitis biological characteristics/Hepatitis/1 A virus can occur, especially when food and water become contaminated with raw sewage. All of the following hepatitis viruses are spread virus is also spread via the oral–fecal route and, like through blood or blood products except: hepatitis A virus, has a short incubation period. Hepatitis D Immunology/Apply knowledge of fundamental biological characteristics/Hepatitis/1 3. Which hepatitis B marker is the best indicator of Answers to Questions 28–33 early acute infection? Which is the ﬁrst antibody detected in serum is the ﬁrst detectable hepatitis B antibody. What is the most likely explanation when a of hepatitis B infection when both the surface antigen patient has clinical signs of viral hepatitis but tests and surface antibody are undetectable. The IgM negative for hepatitis A IgM, hepatitis B surface anti-hepatitis B core and the anti-hepatitis B core total antigen, and hepatitis C Ab? Tests were performed improperly markers in the serum of a patient in the core window B. Which hepatitis antibody confers immunity against reinfection with hepatitis B virus? Given a heterophile antibody titer of 224, which consistently elevated in viral hepatitis? No titer reduction No titer reduction Immunology/Correlate laboratory data with C. Five-tube titer reduction Five-tube titer reduction physiological processes/Hepatitis/Testing/1 D.
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