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The ence silent ischemia that may delay them from seeking pro- Canadian Cardiovascular Society classifies clients with angina fessional help purchase protonix 40mg with amex. Individuals with diabetes mellitus may present 774 CHAPTER 53 ANTIANGINAL DRUGS 775 BOX 53–1 TYPES OF ANGINA PECTORIS Classic causes platelets to aggregate at the site of injury cheap protonix 20mg with amex, form a throm- Classic angina (also called stable order 40 mg protonix with amex, typical buy cheap protonix 20 mg, or exertional angina) bus, and release chemical mediators that cause vasoconstriction occurs when atherosclerotic plaque obstructs coronary arteries and (eg, thromboxane, serotonin, platelet-derived growth factor). The the heart requires more oxygenated blood than the blocked arter- disrupted plaque, thrombus, and vasoconstriction combine to ies can deliver. Chest pain is usually precipitated by situations that obstruct blood flow further in the affected coronary artery. When increase the workload of the heart, such as physical exertion, ex- the plaque injury is mild, blockage of the coronary artery may be posure to cold, and emotional upset. Recurrent episodes of classic intermittent and cause silent myocardial ischemia or episodes of angina usually have the same pattern of onset, duration, and in- anginal pain at rest. Pain is usually relieved by rest, a fast-acting may progress until the coronary artery is completely occluded, preparation of nitroglycerin, or both. The spasms occur most often in practice guidelines for the management of angina, defines unstable coronary arteries that are already partly blocked by atherosclerotic angina as meeting one or more of the following criteria: plaque. Variant angina usually occurs during rest or with minimal • Anginal pain at rest that usually lasts longer than 20 minutes exercise and often occurs at night. It often occurs at the same time • Recent onset (<2 months) of exertional angina of at least each day. Long-term Canadian Cardiovascular Society Classification (CCSC) management includes avoidance of conditions that precipitate va- class III severity sospasm, when possible (eg, exposure to cold, smoking, and emo- • Recent (<2 months) increase in severity as indicated by pro- tional stress), as well as antianginal drugs. Unstable However, myocardial ischemia may also be painless or silent Unstable angina (also called rest, preinfarction, and crescendo in a substantial number of clients. Overall, the diagnosis is usu- angina) is a type of myocardial ischemia that falls between classic ally based on chest pain history, electrocardiographic evidence of angina and myocardial infarction. It usually occurs in clients with ischemia, and other signs of impaired cardiac function (eg, heart advanced coronary atherosclerosis and produces increased fre- failure). It often leads to Because unstable angina often occurs hours or days before myocardial infarction. The resulting injury to the endothelium farction, heart failure, or sudden cardiac death. The American Heart Association has released osclerotic plaque, develop in response to elevated blood cho- guidelines for the management of angina. Initially, white blood cells (monocytes) become Numerous overlapping factors contribute to the develop- attached to the endothelium and move through the endothelial ment and progression of CAD. To aid understanding of drug layer into subendothelial spaces, where they ingest lipid and therapy for angina, these factors are described in the following become foam cells. Advanced lesions also contain hemor- rhages, ulcerations, and scar tissue. Factors contributing Coronary Atherosclerosis to plaque development and growth include endothelial in- jury, lipid infiltration (ie, cholesterol), recruitment of in- Atherosclerosis (see Chap. Endothelial injury may BOX 53–2 CANADIAN CARDIOVASCULAR SOCIETY CLASSIFICATION OF PATIENTS WITH ANGINA PECTORIS Class I: Ordinary physical activity (eg, walking, climbing stairs at a normal pace and in normal conditions can elicit stairs) does not cause angina. Angina oc- Angina occurs on walking one or two blocks on the level and curs on walking or climbing stairs rapidly, walking uphill, climbing one flight of stairs in normal conditions and at a nor- walking or stair climbing after meals, or in cold, in wind, mal pace. Walking more than two blocks Class IV: Inability to carry on any physical activity without on the level and climbing more than one flight of ordinary discomfort—anginal symptoms may be present at rest. When coronary arteries are partly blocked by ponents to come in contact with and stimulate abnormal atherosclerotic plaque, vasospasm, or thrombi, blood growth of smooth muscle cells and connective tissue in the flow may not be able to increase sufficiently. The endothelium of normal coronary arteries synthe- Atherosclerosis commonly develops in the coronary ar- sizes numerous substances (see Chap. As the plaque lesions develop over time, they become against vasoconstriction and vasospasm, bleeding and larger and extend farther into the lumen of the artery. Im- sions may develop for decades before they produce symp- paired endothelium (eg, by rupture of atherosclerotic toms of reduced blood flow. Eventually, such events as plaque or the shear force of hypertension) leads to plaque rupture, mural hemorrhage, formation of a thrombus vasoconstriction, vasospasm, clot formation, formation that partly or completely occludes an artery, and vasocon- of atherosclerotic plaque, and growth of smooth mus- striction precipitate myocardial ischemia. NO, which is synthesized from 80% of the artery, blood flow cannot increase in response to the amino acid arginine, is released by shear stress on the increased need; if stenosis blocks 90% or more of the artery, endothelium, sympathetic stimulation of exercise, and blood flow is impaired when the client is at rest. When the endothelium is that connect the coronary arteries and allow perfusion of an damaged, these vasodilating and antithrombotic effects area by more than one artery.

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Dosage of quinupristin/dalfopristin and linezolid Dosage of chloramphenicol must be reduced in premature does not need to be reduced in clients with renal failure buy generic protonix 40 mg on line. Clindamycin should be given to neonates Use in Hepatic Impairment and infants only if clearly indicated order 20 mg protonix, and then liver and kidney function must be monitored order protonix 20mg on line. Diarrhea and pseudomembra- Erythromycin should be used cautiously 40mg protonix, if at all, in clients nous colitis may occur with topical clindamycin for treatment with hepatic impairment. The safety and efficacy of metronidazole have been active metabolite that is excreted in the bile. Avoiding the established in children only for the treatment of amebiasis. It has comycin is often used in children, including preterm and full- also been associated with cholestatic hepatitis, most often term neonates, for the same indications as in adults. Azithromycin is mainly eliminated unchanged in bile and could accumulate with impaired liver function. Use in Older Adults Clarithromycin is metabolized in the liver to an active metabo- lite that is then excreted through the kidneys. Because it is me- is not recommended for clients with hepatic impairment and tabolized in the liver and excreted in bile, it may be useful in normal renal function but is required with severe renal im- clients with impaired renal function. Dirithromycin is not indicated with azithromycin and dirithromycin, but may metabolized in the liver to an active metabolite that is then be needed if clarithromycin is given to older adults with se- excreted in bile and feces. Because effects in justed for impaired renal function in older adults as in other moderate to severe hepatic impairment have not been stud- age groups. Quinupristin/dalfopristin and linezolid do not require Clindamycin, chloramphenicol, and metronidazole should dosage adjustment in older adults. The miscellaneous drugs be used cautiously, if at all, in the presence of liver disease. Be- are used in older adults for the same indications as in younger cause these drugs are eliminated through the liver, they may adults. With quinupristin/dalfopristin and Use in Renal Impairment linezolid, there are currently no recommendations to alter dosage in hepatic impairment. With the macrolides, dosage of erythromycin does not need reduction because it is excreted mainly by the liver. With the newer drugs, there are no data about azithromycin dosage Use in Critical Illness in renal impairment and no dosage reduction is recom- mended for dirithromycin. However, clarithromycin dosage Erythromycin is seldom used in critical care settings, partly be- should be halved or the dosing interval doubled in clients cause broader spectrum bactericidal drugs are usually needed with severe renal impairment (creatinine clearance [CrCl] in critically ill clients, and partly because it inhibits liver me- <30 mL/minute). In addition, the combination of clarithro- tabolism and slows elimination of several other drugs. For a mycin and ranitidine bismuth citrate therapy (Tritec; used to critically ill client who needs a macrolide antibiotic, one of the treat peptic ulcers associated with H. Dosage of clindamycin does not need reduction in renal im- Clindamycin should be used only when necessary (ie, for pairment because it is excreted primarily by the liver. Dosage serious infections caused by susceptible anaerobes) because CHAPTER 37 MACROLIDES AND MISCELLANEOUS ANTIBACTERIALS 555 critically ill clients may develop hepatic impairment and and linezolid are often used in critically ill clients because pseudomembranous colitis (also called antibiotic-associated infections with resistant pathogens commonly occur in this colitis). Metronidazole is often used in critically ill clients with mixed infections. These clients are at risk for drug tox- Most of the macrolides and miscellaneous drugs may be icity from accumulation of active metabolites. The role of the home care nurse is penetrates tissues well in critically ill clients and achieves generally the same as with other antibiotic therapy; that is, the therapeutic levels well above the minimum inhibitory con- nurse may need to teach clients or caregivers about drug ad- centration for most staphylococci and enterococci. For clients taking oral drug levels and renal function should be monitored. Although metronidazole or vancomycin for pseudomembranous coli- usually given by IV infusion, vancomycin is given orally to tis, stool specimens may need to be collected and tested in the treat pseudomembranous colitis. NURSING Macrolides and Miscellaneous Antibacterials ACTIONS NURSING ACTIONS RATIONALE/EXPLANATION 1. Adequate water aids absorption; regular intervals help to maintain therapeutic blood levels.

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UK Department of Health directly purchase protonix 20mg with visa, government • Development and acquisition of relapse pre- research agencies or large UK research charities 40mg protonix mastercard. The main developmental roots for CBT have been • Schema focused therapy order protonix 40 mg on-line. This began over 20 years ago but more recently the approach has TREATMENT DEVELOPMENT been applied to people with schizophrenia discount protonix 40mg visa. This later development produced changes in the way New treatments usually evolve through a number the intervention is presented, although the under- of stages. Initially the problem is identified and lying model of change may be similar to that suggestions, involving theoretical and pragmatic adopted for the other disorders. The main aim of elements in varying degrees, are advanced for its the intervention is to reduce distress, disability solution. The next stage consists therapies are active and structured therapeutic of uncontrolled and small exploratory controlled methods and should be distinguished from psy- trials. These are often innovative but methodolog- choeducation which tends to be simple, didactic ically weak. Brief educational packages have tion, the large randomised controlled trial (RCT), been shown to be ineffective either with families4 is carried out if the new treatment is showing suf- or with individual patients. RCTs are increasingly large and Although there are specific components of methodologically rigorous and therefore more CBT that would be accepted by all its proponents, expensive, often now involving numerous sites these ingredients may be given in different and large numbers of patients. A further theme COGNITIVE BEHAVIOUR THERAPY 275 is that of identifying what is responsible for the not random. Tri- ment included individual and group treatment als that identify the key components responsible of patients and families while assessments were for the changes are essential to the further devel- neither independent nor blind. However, three opment of treatment and to the dissemination medium size methodologically robust trials of of the treatment package into the wider health CBT variants have been carried out with chronic service. However, this lack of an accepted the- schizophrenic patients,14–16 and one large multi- oretical base does not (and should not) prevent site trial with recent onset acute patients (the a number of different and successful treatment SoCRATES Trial17). It is therefore appropriate to innovations from being introduced into health review not only these trials but also the changes services. Pragmatic trials, which address the issue in clinical trial methods in this field in order to of whether or not a new treatment works within begin to define the most optimal strategy for the a routine service setting, are usually large, simple future evaluation of this and other psychologi- and multi-centred and evaluate a small number of cal therapies. But this under- WHY CARRY OUT CLINICAL TRIALS standing is essential because the costs of care OF PSYCHOLOGICAL TREATMENTS? These treat- There are a number of different beneficiaries ment extensions, although important, rarely get from clinical trials. From the health services adequate funding following the initial innova- perspective there is an increase in knowledge tive RCTs. In addition, for clinical of other treatments in mental health and has academics there may be elements of the design of followed a characteristic path. Numerous case a trial that will allow certain models of aetiology studies were published, some as far back as or treatment efficacy to be tested which can the 1950s. Beck initially inform theories of the disorder as well as leading worked with psychotic patients and published to improvements in treatment. For therapists a case study of the cognitive treatment of a the trial may produce clinical improvements patient suffering from delusional disorder6 before that mean that the participants can make health moving to start his seminal work on depres- gains and for the patients the treatments may sion. Other case studies were published in the provide them with changes that are valued, such 1970s and 1980s (see Tarrier7,8 and Haddock as increased social inclusion. Small trials with methodological weak- change the type of trial performed, particularly in nesses were initially published. It cannot be ments were not blind and group allocation was assumed that all groups will value all outcomes 276 TEXTBOOK OF CLINICAL TRIALS to the same extent, or that the same outcome at the Institute of Psychiatry in London. The would be measured in the same way from the involvement of service users in clinical trials in different viewpoints. For instance, symptoms can the UK is now defined in guidelines provided be measured as a simple change over treatment, by the Consumers in Research Unit within the by a threshold amount or by the effects on the Department of Health. This new undertaking does emotional life of the patient, for example the not seem to be prevalent in other countries. The difficulty for research into psychological Possible outcomes of treatment: treatments is that studies are usually funded from public resources even at the early stages.

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