Amphotericin hypokalemia with

Amphotericin is highly effective in the treatment of visceral leishmaniasis (18). In a prospective study of 938 patients from Bihar, India, who received the drug in a dosage of 1 mg/kg/day infused over 2 hours for 20 days, serum creatinine values over 177 pmol/l were noted in 6.3%, and acute renal insufficiency developed in three patients. Two patients died, possibly related to amphotericin, one with renal insufficiency and one with hypokalemia and cardiac arrest. Infnsion-related chills occurred in 92% and fever in 40% of patients. The parasitological cure rate (no relapse within 6 months) exceeded 99%. 

When amphotericin B or diuretics are administered with ACTH, the potential for hypokalemia is increased. There may be an increased need for insulin or oral antidiabetic drag s in the patient with diabetes who is taking ACTH. There is a decreased effect of ACTH when the agent is administered with the barbiturates. Profound muscular depression is possible when ACTH is administered with the anticholinesterase drugp. Live virus vaccines taken while taking ACTH may potentiate virus replication, increase vaccine adverse reaction, and decrease the patient s antibody response to the vaccine... 

L A. Nephrotoxicity is the most common and most serious toxicity associated with amphotericin B administration. This is manifested by azotemia (elevated serum blood urea nitrogen and creatinine), and by renal tubular acidosis, which results in the wasting of potassium and magnesium in the urine (leading to hypokalemia and hypomagnesemia, requiring oral or intravenous replacement therapy). Normochromic normocytic anemia is also seen with long-term amphotericin B administration. Elevation of hver enzymes is not associated with the use of amphotericin B. 

One compound that has been associated with distal tubular injury is amphotericin B, a polyene antifungal agent used in the treatment of systemic mycoses caused by opportunistic fungi. Clinical utility of amphotericin B is limited by its nephrotoxicity, characterized functionally by polyuria resistant to antidiuretic hormone administration, hyposthenuria, hypokalemia, and mild renal tubular acidosis. 

Because amisulpride may dose-dependently prolong QTc interval, use with caution in patients who have hypokalemia and/or hypomagnesemia or who are taking drugs that can induce hypokalemia and/or magnesemia (e.g., diuretics, stimulant laxatives. Intravenous amphotericin B, glucocorticoids, tetracosactide)... 

ADRs can also be classified as mild/ moderate/ or severe. Mild reactions/ such as dysgeusia associated with clarithromycin/ are bothersome but may not require a change in therapy. Moderate reactions/ such as amphotericin B-induced hypokalemia/ often require a change in therapy/ additional treatment/ or continued hospitalization. Reactions that are disabling or life-threatening/ or those that considerably prolong hospitalization/ are classified as severe (18). 

The safety and efficacy of ABLC 5 mg/kg/day in patients with neutropenia and intolerance or refractoriness to amphotericin deoxycholate have been reported in two smaller series of 25 treatment courses from the UK. In one, the mean serum creatinine at the start of therapy was 139 pmol/l and at the end of therapy 132 pmol/l there were no infusion-related adverse events (27). There was an increase in alanine transaminase activity in 12 of the 22 analysed treatment courses. In the other, there was an increase in serum creatinine in 5 of 18 courses (28%), and hypokalemia (less than 2.5 mmol/1) in two courses (11%) premedication for infusion-associated reactions was required in three courses (17%) (28). There were modest increases in serum alanine transaminase activities in five patients (30%). 

Amphotericin deoxycholate in glucose versus amphotericin in nutritional fat emulsion The safety of DAMB prepared in nutritional fat emulsion (a non-approved mode of amphotericin administration) has been reviewed (SEDA-21, 282) (SEDA-22, 285). It is not clear whether it has a better therapeutic index than other formulations, and methods of preparing it have not been standardized. The adverse effects of amphotericin prepared in nutritional fat emulsion have been compared with those of amphotericin prepared in 5% dextrose in two studies. While one of the studies showed a significantly lower frequency of infusion-related reactions and hypokalemia in patients receiving the fat emulsion (49), there were no differences in safety and tolerance between the two formulations in the other study (50). The safety of amphotericin prepared in nutritional fat emulsions has been reviewed (SEDA-21, 282) (SEDA-22, 285). Because of stability concerns and lack of systematic safety data, this form of amphotericin cannot be recommended. 

Continuous infusion of amphotericin has been assessed in an open study in six lung transplant recipients with invasive or semi-invasive bronchopulmonary azole-resistant candidal infections who were treated for 40 (17-73) days by 24-hour continuous infusions of amphotericin 1 mg/kg (113). They received at least 1000 ml/day of 0.9% saline intravenously. Apart from ciclosporin, five patients received aminoglycosides for at least 2 weeks, and four received ganciclovir. Calculated creatinine clearance fell from 57 (43-73) ml/minute to a nadir of 35 (28-39) and recovered to 52 (33-60) after the end of therapy. One patient needed temporary hemofiltration for 7 days. Besides three episodes of mild hypokalemia there were no adverse effects attributable to amphotericin. Asymptomatic colonization with Candida persisted for 10 months in one case, but the other five patients were cured. 

The safety and efficacy of liposomal amphotericin in 40 preterm and 4 full-term neonates with invasive yeast infections have been studied retrospectively (134). The initial dosage was 1 mg/kg/day, and was increased stepwise by 1 mg/kg to a maximum of 5 mg/kg, depending on the clinical condition. There were no infusion-associated reactions. Blood pressure, hepatic, renal, and hematological indices were not altered. Hypokalemia was noted in 16 infants but was always transient and responsive to potassium supplementation. Treatment with liposomal amphotericin was successful in 72% of the children. However, 12 of the 40 preterm infants succumbed to the fungal infection all had a birth weight of less than 1.5 kg. 

Major functions of the distal nephron include the regeneration of bicarbonate, the excretion of acid (hydrogen ion), the secretion of potassium, and the reabsorption of water. Damage to this portion of the nephron may present as significant acidemia and either hypo-or hyperkalemia, depending on the mechanism of injury. For example, amphotericin B produces small pores in the luminal membrane of distal tubular cells. These pores allow small molecules such as potassium to leak out the molecules are then wasted in the urine. Consequently, amphotericin B nephrotoxicity is characterized by hypokalemia secondary to renal potassium wasting. ATN is associated with urinary sediment characterized by the presence of tubular cells, coarse granular casts, and rarely, RBC casts. 

Hypomagnesemia has been associated with more than 50 drugs, especially those that are nephrotoxic, including cisplatin, aminoglycoside antibiotics, cyclosporine, and amphotericin B. Secondary hypocalcemia and hypokalemia may result with myasthenia and tetany (Swaminathan 2003). 

Renal toxicity is dose-limiting with amphotericin B. Azotemia is commonplace and sometimes is severe enough to warrant dialysis. Decreases in glomerular filtration rate may be reversible, but irreversible damage can occur, presenting as renal tubular acidosis with hypokalemia and hypomagnesemia. The answer is (C). 

Prolonged therapy with amphotericin B may lead to kidney damage, which may be irreversible [429]. Nephrotoxicity and hypokalemia are the major... 

Observational studies Adverse reactions to amphotericin B deoxycholate have been studied in a retrospective analysis of 39 courses of treatments in 33 Chilean patients 1% On average, therapy lasted 12 (range 2-39) days and the cumulative dose was 600 (100-1950) mg. In 63% of cases 24-hour infusions were used and 36% received a 4-to 6-hour infusion. In addition, 37% received daily an infusion of saline before amphotericin. There were adverse reactions in 40% of treatments fever was the most common (25%). Nephrotoxicity was relatively infrequent (9.4%), and it affected only patients without previous renal disease and not requiring dialysis. Hypokalemia developed in 22% of treatments. In a multivariate analysis, age over 60 years was an independent factor for infusion-related adverse reactions and a Sequential Organ Failure Assessment (SOFA) score over 3 and glucocorticoid administration at the same time as amphotericin were independently associated with fatal outcomes. 

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