The most likely diagnosis in this patient is primary hyperaldosteronism buy cheap sumatriptan 25mg online, also known as Conn’s syndrome generic 25mg sumatriptan with amex. The patient has no physical features that suggest con- genital adrenal hyperplasia or Cushing’s syndrome purchase sumatriptan 25 mg. In addition generic 50mg sumatriptan fast delivery, there is no glucose intol- erance as is commonly seen in Cushing’s syndrome discount sumatriptan 50mg with visa. The lack of episodic symptoms and the labile hypertension make pheochromocytoma unlikely. The ﬁndings of hypokalemia and metabolic alkalosis in the presence of difﬁcult to control hypertension yield the likely diagnosis of Conn’s syndrome. Diagnosis of the disease can be difﬁcult, but the preferred test is the plasma aldosterone/renin ratio. Selective adrenal vein renin sampling may be performed after the diagnosis to help determine if the process is unilat- eral or bilateral. Although ﬁbromuscular dysplasia is a common secondary cause of hy- pertension in young females, the presence of hypokalemia and metabolic alkalosis should suggest Conn’s syndrome. Thus, magnetic resonance imaging of the renal arteries is un- necessary in this case. Measurement of 24-h urine collection for potassium wasting and aldosterone secretion can be useful in the diagnosis of Conn’s syndrome. These patients often have a variety of su- praventricular and ventricular arrhythmias and are at risk for sudden death due to the in- trinsic cardiomyopathy as well as the low ejection fraction. Implantable cardioverter deﬁbrillators should be considered in the appropriate patient. Global left ventricular dys- function is a common ﬁnding in dilated cardiomyopathies, whereas focal wall motion abnormalities and angina are more common if there is ischemic myocardium. This pa- tient is at risk for venous thromboembolism; however, chronic thromboembolism would V. Amyotrophic lateral sclerosis is a disease of motor neurons and does not involve the heart. An advanced atrial septal defect would present with cyanosis and heart failure (Eisen- menger’s physiology). During inspiration, it is normal to hear the closing of the aortic valve (A2) before the closing of the pulmonic valve (P2). A ﬁxed split of the second heart sound occurs in the setting of an atrial septal defect. With this congenital heart defect, the volume of blood that is shunted from the left atrium to the right atrium results in a stable right-ventricular stroke volume. Thus, there is no difference between inspiration and expiration, resulting in a ﬁxed split of the second heart sound. Thickened myocardium increases back pressure in the coronary circulation thereby reducing coronary perfusion, leading to ischemia. In addition, diastolic pressures are lower when there is severe aortic regurgitation, which further decreases coronary perfu- sion. Myocardial oxygen consumption increases when there is ventricular hypertrophy as a result of increased mass and contractility. In chronic aortic regurgitation, the equilibration of end-diastolic left-ventricular and aortic pressures exacerbates left-ventricular remodeling and will cause premature closure of the mitral valve or functional mitral regurgitation. Diagnosing paroxys- mal atrial ﬁbrillation with a 24-h monitor is an option if there is no evidence of pulmonary hypertension. There is no evidence that percutaneous or surgical repair of mitral stenosis is beneﬁcial for slight or no functional impairment. Insulin resistance is thought to be a mediator of many of the other as- pects of the metabolic syndrome, including hypertension and hyperglycemia. Increases in visceral obesity are thought to be more harmful than subcutaneous stores because of the direct effect of free fatty acids on the liver from the visceral stores. The inﬂammatory milieu of the metabolic syndrome is enhanced by the overproduction of the proinﬂammatory cytokines by the expanded adi- pose tissue. Treating hypertension, hyperglycemia, dyslipidemia, and the oxidative stress of the proinﬂammatory state is important when treating metabolic syndrome. However, adi- pose tissue loss is the primary approach to treating the underlying cause of the disorder. Commonly used physiologic maneuvers include change with respiration, Valsalva maneuver, position, and exercise. In hypertrophic cardiomyopathy, there is asymmetric hypertrophy of the interventricular septum, which creates a dynamic outﬂow obstruction. Maneuvers that decrease left-ventricular ﬁlling will cause an in- crease in the intensity of the murmur, whereas those that increase left-ventricular ﬁlling will cause a decrease in the murmur.
Peak and trough concentrations did not appear to be influenced by the septic state buy generic sumatriptan 50mg on line. These observations with ciprofloxacin were confirmed in patients with intraabdominal infection (37) buy 50mg sumatriptan with amex. Studies with levofloxacin in patients with critical illness (39) and with ventilator- associated pneumonia (40) have similarly demonstrated no adverse changes in pharmacoki- netic profiles order 25 mg sumatriptan. The observation that the quinolone group of antibiotics have very large Vd that exceeds total body water means that increases in extracellular water volume have little impact sumatriptan 50mg otc. This potentially constitutes an advantage for this group of antibiotics in the febrile sumatriptan 25 mg overnight delivery, critically ill patient, and perhaps in the trauma patient as well. This has led to considerable interest in the identification of alternative antibiotic treatment for both community-associated and hospital-acquired staph- ylococcal infections. The combined observations of the quinolones and linezolid suggest that antibiotics with Vd that exceed total body water are less likely to be adversely affected by physiologic changes of injury, critical illness, and sepsis. Traditional pharmacokinetic dosing could be employed, where peak and trough measurements permit the clinician to adjust the total dose, the dosing interval, or both. This becomes a biological titration where doses are empirically modified and remeasurement is undertaken to assess favorable changes in subsequent peak/trough concentrations. This has been a traditional way of managing aminoglycosides and in some cases vancomycin use. Most clinical pharmacokinetic dosing has been geared to avoid toxicity and only secondarily to the maintenance of therapeutic concentrations. Measurement of these nontoxic agents will be an expense that most will not be willing to accept. Increase the Dose/Frequency of the Drug One strategy to overcome the reduction in antibiotic concentrations in the febrile, trauma patient is to either increase the dose or shorten the dosing interval. It does give a high peak concentration, which may be of value for antibiotics like the aminoglycosides that are concentration-dependent and have a sustained post-antibiotic effect (47). For example, a q6h drug might be shortened to give the same dose to q4h to reduce the interval of subtherapeutic concentration. Increasing the dose or shortening the dosing interval can only be entertained when the antibiotic being used has a favorable therapeutic ratio. The rate of clearance of the drug and the Vd are dynamic processes, and very high concentrations of the antibiotic can be the result when dosing is increased in a patient with rapidly resolving pathophysiological hemody- namics of the systemic inflammatory response. Continuous Antibiotic Infusion Antibiotic infusions are commonly given as 30 to 60 minute infusions. This results in the rapid spike in antibiotic concentration in serum that is identified in Figure 1. A very large amount of Antibiotic Kinetics in the Multiple-System Trauma Patient 531 Figure 3 Illustrates the enhanced serum concentration of antibiotics that are achieved when the dose is doubled of a hypothetical drug with a normal dosing interval of six hours and a T1/2 of 1. Figure 4 Illustrates the effects of con- tinuous infusion and prolonged infusion upon the serum concentrations of the theoretical antibiotic model. Continuous infusion is begun after the initial inter- mittent full dose has been administered. The pro- longed infusion results in an area under the curve that is similar to the same dose given normally, but the slower increase in the peak concentration results in slower total drug elimination. If the antibiotic is given by a continuous infusion, it is possible to sustain the antibiotic concentration above the desired concentration target, but without the peaks and troughs that characterize the normal rapid administration. The strategy has been to give a standard dose of the antibiotic and then begin the infusion of the drug at an hourly rate that approximates the ordinary total 24-hour administration under conventional delivery methods (Fig. Some trials have indicated that distributing the infusion rate over 24 hours permits maintenance of antibiotic concentrations at target levels, but with a reduction in overall total drug that is given. Clinical trials that have compared continuous infusion to conventional drug adminis- tration are summarized in Table 3. These are time-dependent agents without an appreciable post-antibiotic effect, which makes a sustained antibiotic concentration that is above the target threshold a treatment goal (60). Reviews and meta-analysis of continuous infusion have extolled the 532 Fry Table 3 Selection of Studies where Continuous Infusion of Antibiotics Was Compared with Intermittent Infusion Patients continuous/ Authors Antibiotic(s) Type of infection intermittent Adembri et al. A prospective, randomized trial with a large population of well-stratified patients is needed to answer the question of continuous infusion of antibiotics as a superior treatment strategy. Studies have suffered from small number of patients and an absence of consistent severity in the study populations. Because the continuous infusion technique adds an additional therapeutic imposition at the bedside in the intensive care unit, additional evidence is necessary to validate the utility of this method. Prolonged Antibiotic Infusion A compromise position between conventional intermittent and continuous infusion is the concept of prolonged or extended infusion of antibiotics.
Airlines have a duty of care to other passengers w ho m ay be inconvenienced by em ergency diversions cheap sumatriptan 50 mg overnight delivery, unscheduled stops and delays in the event of a m edical em ergency buy sumatriptan 50 mg without prescription. Recertification of drivers and pilots follow ing m yocardial infarction depends upon their subsequent risk of incapacitation w hilst at the controls buy sumatriptan 25mg without prescription. All pilots and all professional drivers have a duty to inform the relevant licencing authority as soon as possible follow ing m yocardial infarction buy 50mg sumatriptan visa. There are no international regulations governing the prospective passenger w ho has recently suffered a m yocardial infarction and no statutory duty to inform the airline concerned buy 50 mg sumatriptan free shipping. M ost w ill be guided in the decision w hether to fly or not by their cardiologist or fam ily doctor. M odern passenger aircraft have a cabin atm ospheric pressure equivalent to 5–8,000 feet, and alveolar oxygen tension falls by around 30%. This m ay exacerbate sym ptom s in any patient w ho experiences angina or shortness of breath w hilst w alking 50 m etres or clim bing 10 stairs. The enforced im m obility of the passenger on a long flight, airport transfers and the crossing of tim e zones should be considered. If few er than 10 days have elapsed since m yocardial infarction, or if there is significant cardiac failure, angina or arrhythm ia the patient m ay require oxygen or suitable accom panim ent. Private pilots are subject to the sam e regulations but m ay fly w ith a suitably qualified safety pilot in a dual control aircraft w ithout undergoing angiography. Sym ptom atic or treated angina, arrhythm ia or cardiac failure disqualifies any pilot from flying. Professional drivers m ay be relicenced 3 m onths after m yocardial infarction provided that there is no angina, peripheral vascular disease or heart failure. Arrhythm ia, if present, m ust not have caused sym ptom s w ithin the last 2 years. Treatm ent is allow ed provided that it causes no sym ptom s likely to im pair perform ance. Private drivers need not inform the licencing authority after m yocardial infarction, but should not drive for one m onth. If arrhythm ia causes sym ptom s likely to affect perform ance, or if angina occurs w hilst driving, the licencing authority m ust be inform ed, and driving m ust cease until sym ptom s are adequately controlled. How should such patients be m anaged to im prove outcom e and what are the results? Prithwish Banerjee and Michael S Norrell The advent of the throm bolytic era has not altered the incidence or m ortality rate for cardiogenic shock com plicating m yocardial infarction (M I). It still represents alm ost 10% of patients w ith M I, w ith alm ost 90% dying w ithin 30 days. Recently, a few random ised trials have attem pted to com pare such early (w ithin 48 hours) revascularisation w ith a strategy of initial m edical stabilisation. Thirty day m ortality w as reduced in the early intervention group (46% vs 56% ) w ith this benefit extending out to 6 m onths and particularly apparent in the younger (<75 years) age group. The low m ortality in the control group is striking, and explains the lack of a large difference betw een the tw o groups. Nevertheless, it suggests benefit even w ith a relatively aggressive conservative policy in these patients. Because of trial recruitm ent difficulties it is unlikely that further random ised data w ill em erge in the foreseeable future. M ean tim e to revascularisation w as under 1 hour in the trial, and quite how m uch later such benefit m ight extend is unclear. Em ergency cardiac procedures in patients in cardiogenic shock due to com plications of coronary artery disease. Early revascularisation in acute m yocardial infarction com plicated by cardiogenic shock. The figures given should ideally be those currently being achieved by the team to w hom the patient is referred. In general term s, registry data are m ore representative than published series, w hich inevitably include bias tow ards m ore successful figures. The data should be adjusted up or dow n to m atch the circum stances of the individual patient, w ho is helped tow ards a rational decision based on the anticipated risks and benefits. It therefore applies to the typical patients – m ale, elective, aged 60–70, w ith an adequate left ventricle. Patients w ith one or m ore risk factors for perioperative death, w hich are older age, fem ale sex, obesity, w orse ventricular function, diabetes, very unstable or em ergency status, or significant co-m orbidity of any type, should have the stated risk appropriately increased. The United Kingdom Heart Valve Registry provides very reliable thirty day m ortality figures w hich for the three years 1994–1996 inclusive w ere 5% for aortic valve replacem ent and 6% for m itral valve replacem ent. Lethal brain damage and permanently disabling hemiplegia are rare w ith a com bined risk of about 0. If every focal deficit discovered on brain im aging, or every transient neurological 100 Questions in Cardiology 71 sign is included the incidence w ould probably be nearer 5%. Air, left atrial throm bus and calcific valve debris are additional risk in valve surgery.
Terbutaline 25 mg sumatriptan mastercard, a b2-agonist buy 25mg sumatriptan with visa, is used to suppress premature labor because of its ability to stop uterine contractions cheap sumatriptan 50mg overnight delivery. Drug abuse can be observed in patients using centrally acting adrenoreceptor agonists such as amphetamine sumatriptan 25 mg online. They reduce sympathetic activity and heart contractility order sumatriptan 25 mg without prescription, thereby reducing the oxygen demand. The b-blocker propranolol is a good choice for an antihypertensive medica- tion; however, it is also successfully used for other indications, such as prophylaxis of migraine headaches, situational anxiety, and hyperthyroidism-induced palpitations. The other choices are all acceptable antihypertensive medications, but from this list, only propranolol is used for migraine prophylaxis. Metoprolol is more selective at b1-adrenoceptors, which are more abundant in the heart than in the lungs. Prazosin is the only drug listed that blocks postjunctional a1-adrenoceptors and inhibits epinephrine-mediated vasoconstriction. Edrophonium, which will increase muscle strength in untreated myasthenic patients, is the preferred acetylcholinesterase inhibitor (Tensilon test) because it has a short du- ration of action. Plasma cholinesterase is responsible for the rapid inactivation of succinylcholine. In patients with malignant hyperthermia, a rare hereditary disorder, an impaired sarcoplasmic reticulum is unable to sequester calcium. The sudden release of calcium results in extensive muscle contraction that can be reduced with dantrolene. Clonidine acts at prejunctional a2-adrenoceptors and is used to treat hyper- tension. Dopa- mine activates both pre-junctional and postjunctional dopamine receptors and also b1-adrenoceptor. In the absence of a nicotinic receptor antagonist, norepinephrine may result in a reflex baroreceptor-mediated increase in vagal activity. The presence of such an agent unmasks the direct stimulant effect of norepinephrine on heart rate. Atropine blocks the effects of increased acetylcholine resulting from cholines- terase inhibition. Physostigmine indirectly activates cholinoceptors; bethanechol and pilocar- pine directly activate cholinoceptors. Dobutamine, a relatively selective b1-adrenoceptor agonist, increases cardiac output and lowers peripheral resistance. Metaproterenol has a relatively more selective action on the respiratory system than the cardiovascular system. Atropine produces both mydriasis and cycloplegia (the inability to accommo- date for near vision). Acetylcholine accumulation due to neostigmine inhibition of cholinesterase will reverse the action of the competitive neuromuscular blocking agents. The b1-adrenoceptor antagonist metoprolol blocks the b1-adrenoceptor activ- ity of dobutamine. Most agents affect water balance indirectly by altering electrolyte reabsorption or secretion. Natriuretic diuretics produce diuresis, associated with increased sodium (Na+) excre- tion, which results in a concomitant loss of water and a reduction of extracellular volume. Diuretics can cause electrolyte imbalances such as hypokalemia, hyponatremia, and hypochloremia and disturbances in acid–base balance. They are secreted into the lumen of the proximal tubule via an or- ganic acid carrier. However, unlike thiazides, these agents may be effective in the presence of some renal impairment. Indapamide has proven especially useful in diabetic patients with hyperten- sion, where it reduces the risk of cardiovascular disease. Thiazide diuretics are the preferred class of diuretic for treatment of hypertension when re- nal function is normal; they are often used in combination with other antihypertensive agents to enhance their blood pressure-lowering effects. These agents reduce the formation of new calcium stones in idiopathic hypercalciuria. Site 2 is the ascending limb of the loop of Henle, site of action of the loop diuretics. These agents are often used in combination with a potassium-sparing diuretic to manage mild cardiac edema, cirrhotic or nephrotic edema, and edema produced by hormone imbal- ances. Thiazide diuretics should be used cautiously in the presence of renal or hepatic diseases such as cirrhosis, and they should be used only as an an- cillary treatment in nephrotic syndrome. Thiazide diuretics produce electrolyte imbalances such as hypokalemia, hyponatremia, and hypochloremic alkalosis.