Adrienne D. Briggs MD
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The effects of colloids on intravascular volume are a consequence of their relatively large molecular size (greater than 30 kDa) cholesterol levels diabetes purchase 60 pills abana mastercard, limiting their passage across the capillary membrane in large amounts. Alternately stated, colloids can be conceptualized as "sponges" drawing fluid into the intravascular space from the interstitial space. In the case of isosmotic colloids (5% albumin, 6% hetastarch, and dextran products), initial expansion of the intravascular space is essentially 65% to 75% of the volume of colloid administered, accounting for some "leakage" of the colloid from the intravascular space. In the case of hyperoncotic solutions such as 25% albumin, fluid is pulled from the interstitial space into the vasculature, resulting in an increase in the intravascular volume that is much greater than the original volume of the 25% albumin that was administered. Although theoretically attractive, hyperoncotic solutions should not be used for hypovolemic shock because the expansion of the intravascular space is at the expense of depletion of the interstitial space. Hetastarch and pentastarch are semisynthetic hydroxyethyl starches derived from amylopectin. The dextran products are semisynthetic glucose polymers that vary in terms of the average molecular weight of the polymers. Superiority of one colloid solution over another in terms of efficacy has not been clearly established. Generally, the major adverse effects associated with colloids are fluid overload, dilutional coagulopathy, and anaphylactoid/anaphylactic reactions. More importantly, hetastarch has been associated with an increased risk of acute kidney injury in several recent clinical trials. This, in fact, is the only setting in which freshly procured whole blood is administered. However, for critically ill patients who have received appropriate fluid resuscitation and have no signs of ongoing bleeding, a more restrictive transfusion threshold of 7 g/dL (70 g/L or 4. Recent large studies have also shown that transfusions are associated with increased infection and higher mortality, possibly because of adverse immune and inflammatory effects. Although replenishment of intravascular volume is undoubtedly the cornerstone of hypovolemic shock therapy, use of vasopressors may be warranted as a temporary measure in patients with profound hypotension or evidence of organ dysfunction in the early stages of shock. Monitoring of end-organ function such as adequate urine output should also be used to monitor therapy. A recent study of tranexamic acid in trauma patients with or at risk of significant bleeding demonstrated a decrease in mortality compared with placebo. Lactic acidosis, which typically accompanies hypovolemic shock as a consequence of tissue hypoxia, is best treated by reversal of the underlying cause. Administration of alkalizing agents such as sodium bicarbonate has not been demonstrated to have any beneficial effects and may actually worsen intracellular acidosis. The most common agents used for stress ulcer prophylaxis are the histamine2receptor antagonists and proton pump inhibitors.
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Patients should eat a balanced diet and consider a multivitamin with minerals cholesterol levels in fertilized eggs generic abana 60pills otc, but supplementation with specific vitamins is generally unceccesary. The treatment of nonmotor symptoms, such as psychological conditions, sleep disorders, and autonomic dysfunction, should include both pharmacologic and nonpharmacologic approaches. Autonomic and Other Problems Drooling may be accompanied by speech problems and dysphagia. Patients with urinary frequency may find a bedside urinal and a decrease in evening fluid intake helpful. When psychological changes are suspected, potential causes to rule out include infections, metabolic changes, electrolyte disturbances, or toxic exposures. Constipation can be improved by increased fluid intake, a fiber-rich diet, probiotics, and physical activity. Stool softeners, osmotic or bulk-forming laxatives, glycerin suppositories, or enemas may help, while cathartic laxatives should be avoided. At her last visit 3 months ago, ropinirole was removed, and her daily Sinemet dose was increased to cover the afternoon off period that had previously been treated with ropinirole. Since then she reports a similar level of functioning with minimal off time and no dyskinesias. Were therapeutic goals achieved in this patient after discontinuation of her dopamine agonist and adjustment of her carbidopa/levodopa If a patient was unable to speak due to disease progression, what would be the advantages and disadvantages of having a significant other communicate for the patient Treatment of Response Fluctuations As the disease progresses, most patients develop response fluctuations. Use various dosage plans to minimize suboptimal or delayed peak levodopa Patient Encounter, Part 3: First Follow-up Visit 3 Months Later the patient returns for a follow-up visit 3 months after adjustments were made to her therapy. Since then, she reports improvement in her ability to cook and can go for longer walks. She feels that she has less tremor and stiffness throughout the day with no off periods. However, about an hour after she takes her morning dose of carbidopa/levodopa with ropinirole, her husband describes movements consistent with chorea. Additionally, her husband reports that she sometimes sees faces in the shadows at night. She also reports feeling dizzy and lightheaded when standing quickly from sitting in a chair and has fallen. She is taking polyethylene glycol one time per week with five to seven bowel movements per week.
The tumor infiltrates extensively along the hepatic sinusoids cholesterol medication zocor side effects abana 60 pills without prescription, causing gradual atrophy and effacement of the liver trabecula. Well-differentiated tumors may often show only plump, mildly atypical endothelial cells that line cords of hepatocytes or resemble cavernous hemangiomas. Epithelioid angiosarcoma may show sheets of tumor cells with eosinophilic cytoplasm and mildly pleomorphic nuclei. When present, Thorotrast can be recognized as granular, gray, refractile, nonbirefringent, extracellular material within histiocytes. Angiosarcoma, similar to other vascular tumors, demonstrates evidence of endothelial differentiation by immunohistochemistry and electron microscopy. Differential Diagnosis Imaging studies are invaluable in making the diagnosis preoperatively, because biopsies may result in major bleeding. Metastatic angiosarcoma is morphologically indistinguishable from primary hepatic angiosarcoma. Well-differentiated angiosarcoma may only show subtle endothelial cell atypia and may be mistaken for hepatocellular carcinoma if the tumor cells infiltrate or line thickened hepatocyte cords. Solid spindle cell areas may resemble sarcomatoid carcinoma or other rare sarcomas, such as fibrosarcoma or leiomyosarcoma. Treatment and Prognosis Angiosarcoma is a highly aggressive tumor with no genuinely effective therapy, and most patients die within 6 months of diagnosis. Usually incidental finding or presents as abdominal discomfort in middle-aged women. Multiple tumor nodules composed of spindle cells with slit-like spaces resembling capillary hemangioma; extravasated erythrocytes; lesions predominantly centered on portal tracts, spreading into the adjacent parenchyma along sinusoidal spaces. With careful examination, three components can be identified: smooth muscle, fat, and vessels. Markedly thickened and often hyalinized vessels with narrow lumen and abnormal hyperplastic elastic layers. Hepatic failure and intraabdominal bleeding account for deaths in a large percentage of cases. It has been suggested that lymphangiomatosis represents a generalized congenital malformation of the lymphatic system. Incidence and Demographics Hepatic involvement by lymphangioma is rarely isolated, occurring most often as part of lymphangiomatosis of the spleen, bone, and other organs. Clinical Manifestations Lymphangioma in the liver may be asymptomatic or may manifest as hepatomegaly. In the latter, depending on the organs involved, symptoms and signs at presentation may include fractures, splenomegaly, pleural effusion, or ascites.
Bradykinesia is defined as hesitancy in movement initiation cholesterol rates buy 60 pills abana with amex, slowness in movement performance, or rapid fatiguing during movement. Patients may have a decrease in automatic movements, such as eye blinking, hypomimia, or a decrease in arm swing while walking. Postural instability results from the loss of reflexes necessary to maintain balance when ambulating. Gait abnormalities may include slow shuffling, leg dragging, festination, propulsion, retropulsion, or freezing. Rigidity and bradykinesia may make handwriting difficult as evidenced by micrographia. Dementia and depression occur frequently with the latter likely due to abnormalities in dopamine and serotonin activity. Often comorbid with depression, anxiety has been noted in up to 66% of patients with motor fluctuations. Motor complications include delayed peak response, early and unpredictable "wearing off," freezing, and dyskinesias. Risk factors for developing motor complications include younger age at diagnosis, high dosage of levodopa, and longer duration and severity of disease. Wearing off can be conceptualized as the therapeutic window of levodopa narrowing over time. This clinician and patient rated scale has four parts that can be used individually or in combination. It takes about 30 minutes to complete, so it may not be collected in its entirety at each visit. These commonly include sleep disturbances, autonomic impairment, psychological disturbances, and others such as anosmia or sensory disturbances. Visual problems such as difficulty reading, double vision, decreased blinking, and burning or itchy eyes are the result of impairment of the ocular mucles. Orthostatic hypotension may cause dizziness, lightheadedness, fainting upon standing, or fall-related injuries. Sexual dysfunction manifests as decreased libido or inability to achieve orgasm in both sexes and erectile or ejaculatory dysfunction in men. The most common interventions include maintaining good nutrition, physical condition, and social interactions. Coordinated care with an optometrist/ophthalmologist, dentist, dietician, physical therapists, speech therapist, and social worker is needed to maximize patient outcomes. This procedure electrically stimulates the subthalamic nucleus or globus pallidus interna. Describe nonpharmacologic and pharmacologic treatments that are available for the patient.
Once target levels are achieved cholesterol from eating eggs buy 60pills abana overnight delivery, monitor serum calcium and phosphorus levels every 1 to 3 months. Reductions in the number of functioning nephrons decrease glomerular filtration regulation of electrolytes and acid secretion. Thus, urine becomes fixed at an osmolality close to that of the plasma, approximately 300 mOsm/kg (300 mmol/kg), and presents as nocturia. Hydrogen ions are excreted at the same rate of production by the kidney via buffers in the urine created by ammonia generation and phosphate excretion to maintain the pH of body fluids within a very narrow range. As kidney function declines, bicarbonate reabsorption is maintained, but hydrogen excretion is decreased because the ability of the kidney to generate ammonia is impaired. Metabolic acidosis can directly cause bone disease, particularly in children, and contribute significantly to the bone disease induced by secondary hyperparathyroidism, as discussed previously. Metabolic acidosis also decreases hepatic albumin synthesis, which contributes to hypoalbuminemia and muscle wasting. Mild hyperkalemia and metabolic acidosis are generally not associated with overt symptoms. Symptoms of chronic metabolic acidosis present as bone abnormalities and growth retardation in children. Genitourinary: Sodium abnormalities result in change in urine volume and consistency. Laboratory Tests Sodium: Increased blood pressure; sodium levels remain within the normal range; urine osmolality is generally fixed at 300 mOsm/kg (300 mmol/kg). Electrolyte disorders resulting from an acute increase in intake can be more severe and prolonged. Patients should be advised to refrain from adding salt to their diet but should not restrict sodium intake. Changes in sodium intake should occur slowly over a period of several days to allow adequate time for the kidney to adjust urinary sodium content. Sodium restriction produces a negative sodium balance, which causes fluid excretion to restore sodium balance. Fluid restriction is generally unnecessary as long as sodium intake is controlled. Fluid intake should be maintained at the rate of urine output to replace urine losses, usually fixed at approximately 2 L/day as urine concentrating ability is lost.
The frequency of dosing and drug cost should be taken into consideration when choosing a particular drug cholesterol medication fenofibrate purchase 60 pills abana otc. The long-term effects of -blockers on morbidity and mortality in patients with chronic stable angina are largely unknown. Relative contraindications include asthma, bronchospastic disease, and severe depression. However, selectivity is dose dependent, and 1-selective agents may induce bronchospasm in higher doses. There are several precautions to consider with the use of -blockers in patients with diabetes or heart failure. All -blockers may mask the tachycardia and tremor (but not sweating) that commonly accompany episodes of hypoglycemia in diabetes. In addition, nonselective -blockers may alter glucose metabolism and slow recovery from hypoglycemia in insulin-dependent diabetes. However, -blockers are negative inotropes (ie, they decrease cardiac contractility). Therefore, -blockers may worsen symptoms of heart failure in patients with left ventricular dysfunction (ie, ejection fraction less than 40% [0. Other potential adverse effects from -blockers include fatigue, sleep disturbances, malaise, depression, and sexual dysfunction. If the decision is made to stop -blocker therapy, the dose should be tapered over several days to weeks to avoid exacerbating angina. Inhibition of calcium entry into the vascular smooth muscle cells leads to systemic vasodilation and reductions in afterload. Inhibition of calcium entry into the cardiac cells leads to reductions in cardiac contractility. Verapamil and diltiazem are contraindicated in patients with bradycardia and preexisting conduction disease in the absence of a pacemaker. Long-Acting Nitrates Nitrate products are available in both oral and transdermal formulations for chronic use.
Syndromes
On the other hand cholesterol ratio risk factor buy abana 60 pills free shipping, chronic rejection is not primarily a cellular process but an ischemic/fibrotic event manifested by progressive bile duct loss (ductopenic chronic rejection) and/or arterial damage and obstruction (arteriopathic chronic rejection). Therefore, acute or late cellular rejection can be treated using immunosuppressive drugs that abrogate the cellular immune response, whereas chronic rejection is not affected by these immunosuppressive drugs. However, newer therapeutic agents may attempt to "rescue" chronic rejection, especially when it is still evolving and is in the early stages. Thus, currently, immunosuppression may be attempted in both cellular as well as early chronic rejection, the latter with variable results. Although distinctive processes, cellular rejection and chronic rejection represent a continuum of immunologic damage; chronic rejection usually follows repeated, severe, or refractory cellular rejection. Thus, cellular rejection and chronic rejection are not mutually exclusive, and features of both may be present simultaneously in a biopsy. Less severe cases of humoral rejection that do not cause precipitous graft failure may clinically resemble acute cellular rejection. Mild degrees of ductular reaction and small aggregates of neutrophils are common findings in time zero or reperfusion biopsies; the latter are not significant unless accompanied by hepatocyte necrosis. Steatotic livers are more sensitive to reperfusion damage, which results in release of fat from damaged hepatocytes into the extracellular space; these extracellular and perisinusoidal fat globules compress the sinusoids and obstruct blood flow, leading to variable degrees of ischemic necrosis. Histologically, large fat droplets are seen that appear to be in sinusoids on a hematoxylin and eosin stain but are mostly in the Disse space on a trichrome stain. As the lesion evolves, the fat droplets are surrounded by macrophages and mobilized from the lobule to the portal tracts, clearing within 4 weeks. Clinical Manifestations Humoral rejection may manifest either within a few hours or a few days of transplantation as hyperacute or acute humoral rejection, respectively. Vascularization of the newly implanted allograft results in normal bile production initially but also introduces preformed antibodies into the graft. Signs of microvascular injury on liver biopsy in addition to other characteristics commonly associated with rejection are noted. There is progressive worsening of liver tests and eventually liver allograft failure ensues. Acute cellular rejection occurs mostly, but not exclusively, between 5 and 30 days of transplantation. Many episodes of mild rejection are subclinical and detected by abnormal liver tests in asymptomatic patients. The biochemical profile of acute cellular rejection is characterized by elevations of alkaline phosphatase, bilirubin, and gamma glutamyltransferase, with minor elevation of transaminases.
Most common side effects are headache cholesterol medication natural generic abana 60pills without a prescription, usually occurring in the first week of therapy with improvement thereafter, and fever, dryness of the skin and mucous membranes, skin rash, peripheral edema, mucositis, pruritus, and conjunctivitis. Characterized by fever, leukocytosis, dyspnea, weight gain, diffuse pulmonary infiltrates on chest X-ray, and pleural and/or pericardial effusions. Usually observed during the first month of therapy but may follow the initial drug dose. Benign intracranial hypertension with papilledema, headache, nausea and vomiting, and visual disturbances. Following oral administration, parent vandetanib and metabolites, including N-oxide vandetanib and N-desmethyl vandetanib, are detected in plasma, urine, and feces. Use with caution in patients with moderate or severe (CrCl < 30 mL/min) renal impairment. Patients with recent history of hemoptysis of 1/2 teaspoon of red blood should not receive vandetanib. Rare cases of severe skin reactions (including Stevens-Johnson syndrome) resulting in deaths have been reported. Elimination is hepatic, with excretion in feces (~94%), with renal elimination accounting for approximately 1% of the administered dose. Monitor for severe dermatologic reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis. Monitor patients for eye reactions, including uveitis, iritis, and retinal vein occlusion. No dose adjustment is needed for patients with mild or moderate hepatic and/or renal dysfunction. Cutaneous squamous cell cancers and keratoacanthomas occur in up to 25% of patients. Ophthalmologic side effects, including uveitis, iritis, photophobia, and retinal vein occlusion. On day 4, use 400 mg in combination with azacitidine or decitabine and 600 mg in combination with low-dose cytarabine. Drugs such as amiodarone, azithromycin, captopril, carvedilol, cyclosporine, felodipine, quinidine, ranolazine, and ticagrelor, which are P-glycoprotein inhibitors, may decrease the rate of metabolism of venetoclax, resulting in increased drug levels and potentially increased toxicity. The dose of venetoclax should be reduced by at least 50% if a P-glycoprotein inhibitor is used. Dose of warfarin may require careful adjustment in the presence of venetoclax therapy. No dose reduction is recommended for patients with mild or moderate renal dysfunction.
At first lowering cholesterol tlc diet purchase 60 pills abana mastercard, tacrolimus was used primarily as a rescue agent in patients with refractory rejection under cyclosporine. Recent data support the use of tacrolimus monotherapy with low rejection rates in liver transplantation. Many centers augment this with an antiproliferative agent and/or steroids for some time. Studies suggest a lower incidence of rejection with tacrolimus when compared with cyclosporine, and tacrolimus has become the calcineurin inhibitor of choice at most centers. The variety of available immunosuppressants now affords the clinician a choice of medications that can be tailored to each recipient. Sirolimus/Everolimus Sirolimus (Rapamycin) is the product of the bacterium Streptomyces hygroscopicus originally found in a soil sample from Easter Island, also known as "Rapa Nui. The chief advantage sirolimus has over calcineurin inhibitors is that it is less toxic to kidneys. Transplant patients maintained on calcineurin inhibitors long term tend to develop impaired kidney function or even chronic renal failure. Sirolimus can be used alone, in conjunction with calcineurin inhibitors, or with mycophenolate mofetil, so as to provide steroid-free immunosuppression regimes. A well-known side effect of sirolimus, impaired wound healing, may limit use of this agent in the immediate postoperative period. The antiproliferative effect of sirolimus has also been used in conjunction with coronary stents to prevent restenosis in coronary arteries following balloon angioplasty. These antiproliferative actions have also led to the study of this drug for its antitumor properties. Mycophenolate Mofetil Mycophenolate mofetil (Cellcept) is frequently given as part of a double or triple drug regimen. It is used interchangeably with azathioprine and has a similar side effect profile. The primary benefit of an antiproliferative agent in conjunction with a calcineurin inhibitor is an increase in the overall level of immunosuppression. Use of these agents may allow lower dosing of the calcineurin inhibitors, thus minimizing nephrotoxicity and preserving long-term renal function. The primary side effects of mycophenolate mofetil include gastrointestinal distress that can manifest as nausea or loose stools and bone marrow suppression resulting in neutropenia and anemia. This drug is one of the oldest known 624 immunosuppressive agents and acts by inhibiting the proliferation of leukocytes (as well as all fast-growing cells). Azathioprine was used in conjunction with steroids as the immunosuppressive regimen first used in kidney and liver transplantation. This dual therapy was the standard in antirejection therapy until the introduction of calcineurin inhibitors in the late 1970s. This agent is generally well tolerated with its primary side effect being bone marrow suppression. Many centers use either azathioprine or mycophenolate mofetil in liver transplant patients to permit a lower dosing of the nephrotoxic calcineurin inhibitors.
Although children have more renal reserve and tolerate the nephrotoxicity of the calcineurin inhibitors better than adults cholesterol hazards 60 pills abana with amex, they still have a high rate of chronic renal dysfunction. Children have a much better healing capacity than adults so that wound and postoperative infections are rare. These patients are at higher risk for opportunistic infections when compared with nonimmunosuppressed children, but the rates are still lower than those seen in adults. This disease is manifest by lymphadenopathy or the presence of any mass lesion after transplant. Workup starts with liver Doppler ultrasound to evaluate the vascular flow to the graft. If this study 622 Immunosuppression Agents Cyclosporine Cyclosporine (Sandimmune, Neoral) came into accepted clinical use in 1979 and quickly revolutionized immunosuppression therapy. Cyclosporine A is a product of a fungus and inhibits cell-mediated immunity through suppression of T-cell function. This agent does not impede phagocytosis or hematopoiesis but does have numerous negative side effects including renal impairment, hypertension, gingival hyperplasia, and hirsutism. Cyclosporine was first used in combination with corticosteroids at the time of its introduction, and was subsequently combined with both azathioprine and corticosteroids, depending upon the clinical situation. These regimens resulted in dramatically improved graft and patient survival rates. In recent years, tacrolimus has become the preferred calcineurin inhibitor, but cyclosporine remains clinically available and is often used interchangeably with tacrolimus depending upon the desired side effect profile for a particular patient. Its mechanism of action is similar to that for cyclosporine and it is also derived from a fungus. Although tacrolimus is nephrotoxic, among the advantages of tacrolimus over cyclosporine are less gingival hyperplasia and hirsutism, better oral absorption, and higher potency. Other side effects reported for tacrolimus include posttransplant diabetes, hypertension, hair loss, hyperkalemia, hypertriglyceridemia, 623 Practical Hepatic Pathology: A Diagnostic Approach tremor, headaches, and a lowered seizure threshold. Tacrolimus has also been linked to an increased prevalence of cardiomyopathy, particularly in pediatric patients, which is not reported with cyclosporine use. Prednisone Prednisone is a synthetic corticosteroid that results in a broad suppression of the immune response and is used in the treatment of a wide variety of disease processes. Prednisone has been an important component of immunosuppression in organ transplantation since its inception. Prednisone taken orally is converted in the liver to prednisolone, an active steroid. This drug suppresses the adrenal glands and results in a variety of side effects including high blood glucose levels, weight gain, poor tissue healing, osteoporosis, glaucoma, and Cushing syndrome. Induction Therapy the use of induction therapy with antilymphocyte monoclonal or polyclonal antibody preparations is now a frequent practice at many liver transplant centers.
Finley, 27 years: Either photophobia or phonophobia (not both) Duration: 30 minutes to 7 days Criteria for diagnosis: 10 or more attacks fulfilling above criteria occurring on average less than 1 day per month are necessary Patient Encounter, Part 1 A 34-year-old woman complains of "almost monthly" headaches around the time of menstruation. Thus, if a hypoalbuminemic patient has a low total phenytoin level and the phenytoin dose is increased, the free phenytoin concentration may rise to a toxic level. Women of reproductive age must have two negative pregnancy tests before starting therapy: one should be 10 to 14 days before therapy is begun, and the second should be 24 hours before therapy. Rare adverse effects include hydralazine-induced lupus-like syndrome and hypertrichosis from minoxidil.
Amul, 59 years: B, Extensive perivenular coagulative necrosis involving zones 2 and 3 around the central veins. It is important to realize that in hospitalized patients, multiple other forms of fluid loss must be considered. Such calculators may omit certain risk indicators that can be important in individual patients, provide only an approximate risk estimate and require clinical judgment for interpretation. An official American Thoracic Society clinical practice guideline: Exerciseinduced bronchoconstriction.
Mezir, 38 years: Monitor for infusion-related reactions, and interrupt the infusion for any grade reaction and treat accordingly. Rituximab and hyaluronidase is not indicated for the treatment of non-cancer conditions. Hepatitis E may be misdiagnosed as rejection or drug-induced liver injury on a liver biopsy. Patients should also be questioned about diet to establish any symptom relationship to meals or specifically after consumption of certain foods.
Sulfock, 48 years: Elimination is mainly in feces (95%), predominantly as metabolites (91%) and only 4% of unchanged midostaurin. Chemicals in tobacco smoke induce theophylline metabolism and increase its clearance. Patients who decide to discontinue medication before pregnancy should taper medication slowly. Table 23 Factors Influencing Medication Nonadherence Three or more chronic medical conditions Five or more chronic medications Three times or more per day dosing or 12 or more medication doses per day Four or more medication changes in past 12 months Three or more prescribers Significant cognitive or physical impairments Recent hospital discharge Caregiver reliance Low health literacy Medication cost History of medication nonadherence Living alone in the community cost of medications.
Ortega, 47 years: Secretory diarrhea results from increased movement (secretion) of ions into the intestinal lumen, leading to increased intraluminal fluid. The prominence of mood symptoms and the history of mood episodes distinguish bipolar disorder and schizophrenia. Evaluation of atropine 1% ophthalmic solution administered sublingually for the management of terminal respiratory secretions. Given that the serum calcium has significant protein binding, the serum calcium measurement must be corrected in patients who have low albumin concentrations (the major serum protein).
Faesul, 25 years: Rehabilitation programs may be conducted in the inpatient, outpatient (most common), or home setting. Nearly 81% of drug is recovered in feces and only 3% in urine, with the majority of eliminated drug being in metabolite form. Parent compound and its metabolites are excreted mainly through the hepatobiliary system into feces. Concentration-related adverse effects happen with increasing frequency and severity as the dose or serum concentration of a drug is increased.
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