Arthritis Australia

By D. Rufus. New England Conservatory of Music.

A change in pharmacodynamics may affect the level (position) or width of the therapeutic window (Figure 1 cheap plavix 75 mg free shipping; see also Annex 1) quality 75 mg plavix. The therapeutic window reflects the sensitivity of the patient to the action of the drug. Changes in the therapeutic window are sometimes expressed as the patient being ‘resistant’ or ‘hyper-sensitive’. The only way to determine the therapeutic window in the individual patient is by trial, careful monitoring and logical thinking. In Patient 17 (diabetes) it is important to note that β-blockers counteract the effect of insulin. This means that higher concentrations of insulin are needed for the same effect: the therapeutic window for insulin shifts upwards. The plasma curve no longer matches the window, and the daily dose of insulin must be raised. For these two reasons you may decide to change to another drug group that does not affect glucose tolerance, e. Patient 18 (lung cancer) has probably become tolerant to morphine, as he responded well to the drug before. The therapeutic window is shifted upwards and the dose has to be raised, for example to 15 mg twice daily. In terminal patients drug absorption and metabolism may be so disturbed that even larger dosages (e. Changes in plasma concentration-time curve The plasma concentration-time curve may be lowered or raised, or the concentration may fluctuate outside the therapeutic window. In Patient 19 (pain at night) the plasma concentration of Figure 2: Slow fall in plasma concentration late at night indometacin probably falls below the therapeutic window in patient 19 early in the morning (see Figure 2). Any change in medication should therefore aim at increasing the plasma level in that period. You could advise her to take the evening dose later, or to set the alarm in the night to take an extra tablet. You could also increase the strength of the evening suppository to 100 mg, while decreasing her first morning tablet to 25 mg. He has probably been overdosed, patient 18 because his metabolism is impaired by the terminal cancer, decreasing the elimination of the drug and therefore lengthening its half-life. In addition, the distribution volume of his body is reduced because of emaciation. The curve therefore probably lies above the window, implying that the daily dose should be reduced. Remember that it takes about four half-lives to lower the plasma concentration to a new steady state. If you want to speed up this process you can stop the morphine for one day, after which you can start with the new dose. Metabolism is high Excretion is high How can you define the position of the plasma curve in an individual patient? The plasma concentration can be Plasma concentration curve measured by laboratory investigations, but in many will rise if: settings this is not possible and it may be expensive. More Absorption is high Distribution is low important, each measurement represents only one point Metabolism is low of the curve and is difficult to interpret without special Excretion is low training and experience. More measurements are expensive and may be stressful to the patient, especially in an outpatient setting. Figure 4: Downward shifted window and upward shifted curve Changes in window and curve in patient 20 Changes in both window and curve are also possible, as illustrated in Patient 20 (depression) (see Figure 4). Dosage schedules for antidepressant drugs in the elderly usually recommend that the dose be reduced to half the adult dose, for two reasons. First, in the elderly the therapeutic window of antidepressant drugs shifts downwards (a lower plasma concentration will suffice). At a full adult dose the plasma curve may rise above the therapeutic window, leading to side effects, especially 58 Chapter 8 Step 3: Verify the suitability of your P-drug anticholinergic and cardiac effects. Secondly, metabolism and renal clearance of the drug and its active metabolites may be reduced in the elderly, also increasing the plasma curve. Thus, in prescribing the normal adult dosage your patient will be exposed to unnecessary and possibly harmful side effects. For example, two tablets once daily are much more convenient than half a tablet four times daily. Complex dosage schedules decrease patient adherence to treatment, especially when more than one drug is used, and thus decrease effectiveness. If you had not adapted the schedule, the P-drug treatment would have been less effective, or unsafe. You can prevent this by carefully checking the suitability of the standard dosage schedule before writing the prescription. How to adapt a dosage schedule Figure 5: Relation between There are three ways to restore the mismatch between frequency and fluctuations curve and window: change the dose, change the in plasma concentration frequency of administration, or both. The daily dose determines the mean plasma concentration, while the frequency of administration defines the fluctuations in the plasma curve.

Final Report Page 7 Access to medicines for multiple sclerosis February 2014 Charles River Associates 1 cheap plavix 75 mg overnight delivery. It affects three times as many women as men plavix 75mg for sale, with the diagnosis typically occurring in patients aged in their 20s or 30s and is more prevalent in Northern Europe (as well as North America, Australia and New Zealand). The symptoms appear periodically – relapses – which may last for a few hours, or many months. In terms of explanation, they found that the large variations in patients with access to innovative drugs could be explained by economic differences among European economies. However, they found that price levels do not reflect the affordability levels in different markets. They also identified differences in medical practice, the ease of access to care and availability of care. This has shown that access continued to vary dramatically across Europe countries. Final Report Page 8 Access to medicines for multiple sclerosis February 2014 Charles River Associates and look more closely at the reason for variation in access and the corresponding policy implications. Meeting the Employment and Career Aspirations of People with Multiple Sclerosis”, The Work Foundation. Also excluded were the symptomatic treatments which do not contribute directly to the calculation of additional patient numbers (Fampridine and Nabiximols). However, it does allow us to make cross- country comparisons and compare to the earlier studies. However, compared to the situation in 2008, the availability and quality of data has significantly improved. Secondly, to ensure that we had a range of different country circumstances we supplemented this with alternative data sources. The countries that passed the first steps are represented in dark green in Figure 3. Despite a covering a variety of countries in Northern, Southern, and Western Europe, there is no coverage of Eastern Europe. Norway was also selected due to information available on the level of access from Farmastat. Final Report Page 14 Access to medicines for multiple sclerosis February 2014 Charles River Associates 2. Over the last five years, there has been a substantial change in the availability of data, the differences in diagnosis criteria and the availability of new treatments on the market. Update on prevalence The Kobelt report discusses the different diagnosis criteria that affect the estimated prevalence. The Poser criteria typically require at least one or two attacks, defined as the occurrence of symptoms of neurological dysfunction lasting more than 24 hours, and clinical evidence of one or two lesions as demonstrated by neurological examination. In 14 out of the 15 countries that we looked at use the McDonald criteria for diagnosis. Polman et al (2011), “Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria”, Annals of Neurology 69. Final Report Page 16 Access to medicines for multiple sclerosis February 2014 Charles River Associates Romania, Slovenia, Spain, Sweden, and the United Kingdom. Given the differences in the diagnosis criteria, any comparison over time is problematic. Prevalence depends on the survey instrument used; the inclusion of benign or early cases (which varies between countries) and diagnosis differences between countries as explained in the diagnostic criteria section. We undertook a literature review to identify all studies conducted from 2005 (the year of the prevalence data used in the Kobelt report). They observed that prevalence and incidence estimates tended to be higher in the more recent studies and were higher in the Nordic countries and in northern regions of the British Isles. This was an improved version of the initial questionnaire from 2008, 31 Hurwitz, B. Kobelt used local studies to develop prevalence for similar ethnic/geographic groups and derived an average prevalence rate per specific age group and then applied this to the population in each country. We therefore focus primarily on differences in access between countries rather than comparisons over time. Firstly, Kingwell et al stated that the more recent studies used in their literature review were generally of higher quality and used the more recent diagnostic criteria. Secondly, they concluded that any comparison over time is likely to be problematic although it is reasonable to conclude that more recent studies tended to show a higher prevalence than the older studies. Final Report Page 20 Access to medicines for multiple sclerosis February 2014 Charles River Associates 2. This has a number of assumptions: • We assumed that every patient is on the treatment for the full year. As we did not have data in every country at the pack level, when calculating patient number for drugs that are known to have multiple pack types, we used the pack that had the highest proportion of sales. The 2013 number of patients receiving treatment in each of the selected countries is listed in table 4.