Medical Instructor, University of Iowa Roy J. and Lucille A. Carver College of Medicine
Carfilzomib Carfilzomib [Kyprolis] works similarly to bortezomib by binding to the active sites of the core particle within the 26S proteasome gastritis diet óëûáêà purchase pariet 20 mg without a prescription. It is approved for treatment of patients with multiple myeloma who have received at least two prior therapies gastritis nerviosa cheap pariet 20 mg amex. Other infusion reactions have also occurred gastritis znacenje purchase 20 mg pariet mastercard, including shortness of breath, chest tightness, fever, and chills. Dexamethasone can be administered before treatment in an attempt to reduce infusion-associated incidences. The most common adverse effects are fatigue, diarrhea, nausea, altered taste, anorexia, weight loss, thrombocytopenia, and anemia. Severe thrombocytopenia has also occurred when vorinostat is combined with valproic acid. The most common are nausea, vomiting, fatigue, anorexia, taste disturbance, and hematologic deficits: anemia, leukopenia, and thrombocytopenia. Romidepsin can harm the developing fetus and hence should not be used during pregnancy. In contrast to vorinostat, romidepsin has not been associated with pulmonary embolism. Romidepsin binds with receptors for estrogen and can thereby reduce the effects of estrogen-containing contraceptives. Ipilimumab Ipilimumab [Yervoy] is indicated for unresectable or metastatic melanoma. By promoting T-cell activation and proliferation, ipilimumab can cause severe or fatal immune-mediated effects. Among these are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathies (both motor and sensory), and endocrinopathies (e. If a severe immune-mediated reaction is diagnosed, ipilimumab should be immediately and permanently discontinued, and patients should be treated with high-dose systemic glucocorticoids. Interferon Alfa-2b Interferons are naturally occurring proteins with complex antiviral, anticancer, and immunomodulatory actions. Release of endogenous interferons is triggered by viral infections and other stimuli. Interferons are active against a variety of solid tumors and hematologic malignancies. Discussion here is limited to two interferons: interferon alfa-2b [Intron A] and peginterferon alfa-2b [Sylatron]. Anticancer effects of interferon alfa-2b are thought to result from two basic processes: (1) enhancement of host immune responses and (2) direct antiproliferative effects on cancer cells. Both processes are mediated by binding of interferon alfa-2b to cell-surface receptors, with resultant increased expression of certain genes and reduced expression of others. In addition, it can cause0 proliferating cells to differentiate into nonproliferative mature forms. The most common is a flu- like syndrome characterized by fever, fatigue, myalgia, headache, and chills. Other common effects include anorexia, weight loss, diarrhea, abdominal pain, dizziness, and cough. Prolonged or high-dose therapy can cause fatigue, cardiotoxicity, thyroid dysfunction, and bone marrow suppression, manifesting as neutropenia and thrombocytopenia.
H e has experienced angina-like chest pressure with strenuous exertion and near-syncope while climbing a flight of stairs gastritis symptoms bloating buy pariet once a day, and now he has symptoms of heart fail- ure (H F) such as orthopnea and paroxysmal nocturnal dyspnea gastritis diet àáâ order pariet 20mg online. H eart failure is also suggested by physical signs of volume overload (pedal edema gastritis and diarrhea cheap pariet 20 mg, elevated jugular venous pressure, and crackles suggesting pulmonary edema). The cause of his heart failure may be aortic valvular stenosis, given the late systolic murmur radiating to his carotid, the paradoxical splitting of his second heart sound, and the diminished carotid upstrokes. Diagnostic test: Echocardiogram to assess the aortic valve area as well as the left vent ricular syst olic funct ion. Know the causes of chronic heart failure (eg, ischemia, hypertension, valvular disease, alcohol abuse, cocaine, and thyrotoxicosis). Be familiar with the evaluation of aortic stenosis and the indications for valve replacement. Co n s i d e r a t i o n s T his is an elderly patient with symptoms and signs of aortic stenosis. The valvular disorder has progressed from previous angina and presyncopal symptoms to heart failure, reflect ing worsening severit y of the st enosis and worsening prognosis for sur vival. T his pat ient should undergo urgent evaluat ion of h is aort ic valve surface area and coronary artery st atus to assess the need for valve replacement. A ser ies of neurohumoral responses develop, includ- ing act ivat ion of t he renin-angiotensin-aldosterone axis and increased sympat het ic act ivit y, which init ially may be compensat ory but ult imat ely cause furt her cardiac decompensation. Symptoms may be a result of forward failure (low cardiac output or systolic dysfunction), including fatigue, lethargy, and even hypotension, or back- ward failure ( in cr eased fillin g p r essu r es o r d iast olic d ysfu n ct io n ), in clu d in g dyspnea, peripheral edema, and ascites. Some pat ient s have isolat ed right -sided heart failure (wit h elevat ed jugular ven o u s p r essu r e, h ep at ic co n gest io n, p er ip h er al ed em a b u t n o p u lm o n a r y ed em a), but more commonly patients have left ventricular failure (with low cardiac output and pulmonary edema) t hat progresses to bivent ricular failure. Auscultatory find- ings may include an S (atrial gallop) or an S (ventricular gallop), low-pitched heart 4 3 sounds that are heard best with the bell of the stethoscope. For example, h eart failure related to t achycardia, alcohol consumpt ion, or viral myocarditis may be reversible with removal of the incit ing factor. In patient s with underlying multivessel ath- erosclerot ic coronary disease and a low eject ion fract ion, revascularizat ion wit h coron ar y ar t er y bypass gr aft ing improves cardiac fun ct ion an d prolongs sur vival. For pat ient s wit h h eart failure, appropriat e invest igat ion is guided by the h ist or y but may include echocardiography to assess ejection fraction and valvular function, cardiac st ress t est ing, or coron ar y angiogr aph y as in dicat ed, an d, in some cases, endomyocardial biopsy. The three major treatment goals for patients with chronic heart failure are relief of symptoms, preventing disease progression, and a reduction in mortality risk. T h e heart failure symptoms, which are mainly caused by low cardiac output and fluid overload, usually are relieved with dietary sodium restriction and loop diuret- ics. Because heart failure has such a subst ant ial mort alit y, however, measures in an attempt to halt or reverse disease progression are necessary. Digoxin can be added to these regimens for persistent symptoms, but it provides no survival benefit. Nitrates and nitrites: (not as common ly used) Reduce preload and clear pulmonar y congest ion. Some devices may also be useful in reducing symptoms and mortality in patients with heart failure. In patients with acute decompensated heart failure, the in it ial t reat ment goals are to stabilize the patient’s hemodynamic derangements and to identify and treat revers- ible factors that may have precipitated the decompensation, such as arrhythmias or myocardial ischemia.
Chylomicrons Hypertriglyceridemia is a risk factor for pancreatitis gastritis diet options trusted pariet 20mg, but its Chylomicrons are involved primarily in the transport of role in the development of atherosclerosis and heart disease dietary lipids from the gut to the adipose tissue and liver gastritis diet 9 month purchase on line pariet. Clinical trials of drugs that reduce serum When cholesterol and triglycerides are ingested gastritis diet 5 bites purchase pariet with american express, they are triglycerides have not consistently reduced cardiovascular emulsifed in the intestines by the bile acids and other bile events and have not reduced mortality. After chylo- of premature death in industrialized countries, it is impor- microns are secreted into the circulation, they deliver tant to detect and eliminate modifable risk factors asso- triglycerides to adipose tissue via the action of a lipoprotein ciated with it. In addition to hyperlipidemia, these risk lipase located in the vascular endothelial cells. By this factors include hypertension, cigarette smoking, and a low process, chylomicrons are converted to a cholesterol-rich 144 Chapter 15 y Drugs for Hyperlipidemia 145 chylomicron remnant, which transports cholesterol to Normal arterial wall Tunica the liver. In atheromas, cholesterol is Macrophage phagocytosed by macrophages, which are transformed into foam cells as they become flled with oxidized cholesterol. Steps in the pathogenesis of atherosclerosis are as follows: (1) Damage to the endothelium is followed by invasion of macrophages. Ezetimibe inhibits the absorption of dietary and biliary cholesterol from the intestines. Table 15-1 provides whose physiologic function is unknown and whose occur- information about the characteristics and types of rence is genetically determined. These factors include biochemical defects in defciency that prevents delivery of triglycerides to adipose lipoprotein metabolism, excessive dietary intake of lipids, tissue. Chapter 15 y Drugs for Hyperlipidemia 149 from fat should be limited to 25% to 35% of total calories, extensive frst-pass metabolism. Lovastatin and simvastatin with saturated fat limited to less than 7% of total calories. Statins with shorter half-lives are taken in the evening or Dietary modulations are particularly useful in persons at bedtime to ensure inhibition of nocturnal cholesterol bio- with multiple risk factors or angiographic evidence of coro- synthesis. Lovastatin should saturated and trans fatty acids and high in linoleic acid and be taken with the evening meal to facilitate its absorption, omega-3 fatty acids (linolenic acid and those in fsh oils) whereas the other drugs can be taken without regard to food. These diets may Lovastatin and simvastatin cross the blood-brain barrier also reverse the angiographic evidence of coronary athero- and can cause sleep disturbances in some patients. The omega-3 fatty acids contain a acid and is the rate-limiting enzyme in cholesterol biosyn- double bond between the third and fourth carbon from the thesis (see Figs. The statins also reduce serum triglycerides but are with the effects and properties of other drugs discussed in usually not a suffcient treatment for hypertriglyceridemia by this chapter. Atorvastatin and rosuvastatin also have the greatest effect on triglyceride levels and can be Chemistry and Pharmacokinetics useful in treating patients with mixed hyperlipidemia. The most myocardial infarction, stroke, and revascularization pro- frequent adverse effects are gastrointestinal problems, cedures. Some of the benefts produced by statins may result including abdominal cramps, constipation, diarrhea, and from their ability to improve vascular endothelial function heartburn. Clinical trials also indicate that elevate serum levels of hepatic enzymes (see Table 15-5). Increase inhibitors and myalgia, rhabdomyolysis, and other myopathies risk of myopathies when taken with erythromycin, gemfbrozil, or niacin. For example, they increase warfarin levels is reversible on statin withdrawal and resolves in 2 to 3 slightly by inhibiting warfarin metabolism. Myalgia can be followed by myositis or muscle statins and fbric acid derivatives may cause myopathies, the infammation accompanied by muscle pain, leakage of combined use of drugs should be avoided or used with great muscle creatine kinase into the plasma, and elevated creatine caution. Myositis can eventually lead to rhabdomyoly- sis in which muscle cells disintegrate, thereby releasing myo- Bile Acid–Binding Resins globin into the circulation.
Syndromes
Heart attack or stroke
Wear rubber gloves when handling or cleaning fish tanks.
Pain when sitting or putting pressure on the tailbone
Do not eat or drink anything after midnight unless told otherwise by your doctor.
Loss of body fluids from the bloodstream into the tissues due to conditions such as severe infections (sepsis) or burns, or heart, liver, or kidney failure
Various caulking compounds
Aspiration (food and fluids get into the lungs, causing pneumonia)
Diabetes
Naphthylamine
Mouth sores (oral lesions)
Although hyperkalemia is most likely when spironolactone is used alone gastritis medication order pariet 20mg visa, it can also develop when spironolactone is used in conjunction with potassium-wasting agents (thiazides and loop diuretics) chronic gastritis leads to cheap 20 mg pariet mastercard. Endocrine Effects Spironolactone is a steroid derivative with a structure similar to that of steroid hormones (e gastritis znacenje buy discount pariet 20mg line. As a result, spironolactone can cause a variety of endocrine effects, including gynecomastia, menstrual irregularities, impotence, hirsutism, and deepening of the voice. Benign and Malignant Tumors When given long term to rats in doses 25 to 250 times those used in humans, spironolactone has caused benign adenomas of the thyroid and testes, malignant mammary tumors, and proliferative changes in the liver. Drug Interactions Thiazide and Loop Diuretics Spironolactone is frequently combined with thiazide and loop diuretics. The goal is to counteract the potassium-wasting effects of the more powerful diuretic. Agents That Raise Potassium Levels Because of the risk for hyperkalemia, caution must be employed when combining spironolactone with potassium supplements, salt substitutes (which contain potassium chloride), or another potassium-sparing diuretic. Triamterene Mechanism of Action Like spironolactone, triamterene [Dyrenium] disrupts sodium-potassium exchange in the distal nephron. However, in contrast to spironolactone, which reduces ion transport indirectly through blockade of aldosterone, triamterene is a direct inhibitor of the exchange mechanism itself. The net effect of inhibition is a decrease in sodium reabsorption and a reduction in potassium secretion. Because it inhibits ion transport directly, triamterene acts much more quickly than spironolactone. Therapeutic Uses Triamterene can be used alone or in combination with other diuretics to treat hypertension and edema. Adverse Effects Hyperkalemia Excessive potassium accumulation is the most significant adverse effect. Hyperkalemia is most likely when triamterene is used alone but can also occur when the drug is combined with thiazides or loop diuretics. Caution should be employed when triamterene is used in conjunction with another potassium- sparing diuretic or with potassium supplements or salt substitutes. B l a c k B o x Wa r n i n g : Tr i a m t e re n e a n d A m i l o r i d e Triamterene and amiloride carry a risk for hyperkalemia that is potentially fatal if uncorrected. Monitor potassium levels at treatment start, at dose change, and during illness affecting renal function. Other Adverse Effects Relatively common side effects include nausea, vomiting, leg cramps, and dizziness. Amiloride Pharmacologic Properties Amiloride has actions similar to those of triamterene. Both drugs inhibit potassium loss by direct blockade of sodium-potassium exchange in the distal nephron. Although it can be employed alone as a diuretic, amiloride is used primarily to counteract potassium loss caused by more powerful diuretics (thiazides, loop diuretics). Accordingly, concurrent use of other potassium- sparing diuretics or potassium supplements must be monitored closely. C H A P T E R 3 6 Drugs Acting on the Renin- Angiotensin-Aldosterone System Laura D. The aldosterone antagonist eplerenone has only two indications: hypertension and heart failure; spironolactone is also used to prevent diuretic-induced hypokalemia and treat hyperaldosteronism.
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