Nephrotoxicity hypertension

Cyclosporine demonstrates immunosuppressive activity by inhibiting the first phase of T-cell activation. It also inhibits release of inflammatory mediators from mast cells, basophils, and polymorphonuclear cells. It is used in the treatment of both cutaneous and arthritis manifestations of severe psoriasis. The usual dose is between 2.5 and 5 mg/kg/day given in two divided doses. Adverse effects include nephrotoxicity, hypertension, hypomagnesemia, hyperkalemia, alterations in liver function tests, elevations of serum lipids, GI intolerance, paresthesias, hypertrichosis, and gingival hyperplasia. Cumulative treatment for more than 2 years may increase the risk of malignancy, including skin cancers and lymphoproliferative disorders. 

Compared with previously available therapy, the adverse effects associated with cyclosporine are much less severe but still worthy of concern. Nephrotoxicity, which can occur in up to 75% of patients, ranges from severe tubular necrosis to chronic interstitial nephropathy. This effect is generally reversible with dosage reduction. Vasoconstriction appears to be an important aspect of cyclosporine-induced nephrotoxicity. Hypertension occurs in 25% of the patients and more frequently in patients with some degree of renal dysfunction the concomitant use of antihypertensive drugs may prove useful. Hyperglycemia, hyperlipidemia, transient liver dysfunction, and unwanted hair growth are also observed. 

Adverse effects include nephrotoxicity, hypertension, tremor, seizures, increased incidence of infections, gingival hyperplasia, hirsutism, flushing, paraesthesias, tinnitus, headache, gynaecomastia and conjunctivitis. It has no toxic effects on bone marrow and RE system. 

Toxicities are numerous and include nephrotoxicity, hypertension, hyperglycemia, liver dysfunction, hyperkalemia, altered mental status, seizures, and hirsutism. Cyclosporine causes very little bone marrow toxicity. While an increased incidence of lymphoma and other cancers (Kaposi s sarcoma, skin cancer) have been observed in transplant recipients receiving cyclosporine, other immunosuppressive agents may also predispose recipients to cancer. Some evidence suggests that tumors may arise after cyclosporine treatment because the drug induces TGF-B, which promotes tumor invasion and metastasis. 

Clinical experience following kidney transplantation suggests that primary prophylaxis with tacrolimus results in 1-year graft and patient survival rates that are equivalent to those achieved with Cy A therapy, although with lower rates of acute rejection episodes.Five-year follow-up data suggest improved graft survival with tacrolimus compared with Cy A. Nephrotoxicity, hypertension, and posttransplant diabetes mellitus may occur and v/ere reported commonly in the early studies. ... 

Cyclosporine Tissue transplantation Nephrotoxicity, hypertension, peripheral neuropathy... 

Vancomycin 4-6 h > 80 mg/L Ototoxic and nephrotoxic. Hypertension, skin rash/flushing ( red-man syndrome ) associated with IV administration. 

Cyclosporine is a cyclic polypeptide immunosuppressant typically used to prevent organ rejection in transplant patients. Its use is restricted to patients with fulminant or refractory symptoms in patients with active IBD. Significant toxicides associated with cyclosporine are nephrotoxicity, risk of infection, seizures, hypertension, and liver function test abnormalities.1,13,14... 

Determine if drug therapy may be contributing to ARF. Consider not only drugs that can directly cause ARF (e.g., aminoglycosides, amphotericin B, NSAIDs, cyclosporine, tacrolimus, ACE inhibitors, and ARBs), but also drugs that can predispose a patient to nephrotoxicity or prerenal ARF (i.e., diuretics and anti hypertensive agents). 

Methotrexate has been used successfully with cyclosporine, either concurrently34 or in rotation. Rotational therapy is particularly effective since it minimizes the serious adverse effects of both agents hepatotoxidty from methotrexate and hypertension and nephrotoxicity from cyclosporine. Having an overlapping treatment period may not be necessary and patients have been successfully switched after a 1-week washout period.21,35 This is a very useful combination of systemic agents in the longterm management of this chronic disease. 

Cyclosporine -immunosuppressant -nephrotoxicity -hirsutism -hepatotoxicity -tremor -anxiety -hypertension... 

Cyclosporine reduces production of cytokines involved in T-cell activation and has direct effects on B cells, macrophages, bone, and cartilage cells. Its onset appears to be 1 to 3 months. Important toxicities at doses of 1 to 10 mg/kg/day include hypertension, hyperglycemia, nephrotoxicity, tremor, GI intolerance, hirsutism, and gingival hyperplasia. Cyclosporine should be reserved for patients refractory to or intolerant of other DMARDs. It should be avoided in patients with current or past malignancy, uncontrolled hypertension, renal dysfunction, immunodeficiency, low white blood cell or platelet counts, or elevated Ever function tests. 

Nephropathy has been associated with chronic lead poisoning. " A study of two large cohorts of heavily exposed lead workers followed through 1980 demonstrated a nearly threefold excess of deaths attributed to chronic nephritis or other hypertensive disease, primarily kidney disease. Most of the excess deaths occurred before 1970, among men who began work before 1946, suggesting that current lower levels of exposure may reduce the risk. Experimental animal studies suggest there may be a threshold for lead nephrotoxicity, and in workers, nephropathy occurred only in those with blood levels over 62p,g/dl for up to 12 years."... 

Cyclosporine has no myelotoxicity but the drug is nephrotoxic. It is because of this nephrotoxicity that cyclosporine has a narrow therapeutic index that makes blood level monitoring necessary. Other toxicities include hypertension, hepatotoxicity, neurotoxicity, hirsutism, gingival hyperplasia and gastrointestinal disturbances. 

The introduction of cyclosporin, a peptide derived from a fungus, revolutionised immunosuppressive therapy, and was one of the major influences in the improvement of early graft survival in transplant surgery when introduced in the 1980s. The main action is a relatively selective inhibition of IL-2 production and consequently a decreased proliferation of T cells. A major advantage of cyclosporin is that it does not cause myelosuppression in therapeutic doses. The major side effect is nephrotoxicity, which occurs in about 20% of patients, and about 50% of patients develop moderate hypertension. The other major side effect is hepatotoxicity with cholestasis and hyperbilirubinaemia. 

Cyclosporine has significant nephrotoxicity, and its toxicity can be increased by drug interactions with diltiazem, potassium-sparing diuretics, and other drugs inhibiting CYP3A. Serum creatinine should be closely monitored. Other toxicities include hypertension, hyperkalemia, hepatotoxicity, gingival hyperplasia, and hirsutism. 

Tacrolimus can be administered orally or intravenously. The half-life of the intravenous form is approximately 9-12 hours. Like cyclosporine, tacrolimus is metabolized primarily by P450 enzymes in the liver, and there is potential for drug interactions. The dosage is determined by trough blood level at steady state. Its toxic effects are similar to those of cyclosporine and include nephrotoxicity, neurotoxicity, hyperglycemia, hypertension, hyperkalemia, and gastrointestinal complaints. 

Adverse Effects. The primary problem associated with cyclosporine is nephrotoxicity, which can range from mild, asymptomatic cases to severe kidney dysfunction, which requires discontinuation of the drug.33,46 Hypertension is also a common adverse effect, especially when cyclosporine is used for prolonged periods.58 Other problems include neurotoxicity, gingival hyperplasia, hair growth (hirsutism), and increased infections. These problems, however, tend to... 

Hypertension is associated with increased TXA2 and decreased PGE2 and PGI2 synthesis in some animal models, eg, the Goldblatt kidney model. It is not known whether these changes are primary contributing factors or secondary responses. Similarly, increased TXA2 formation has been reported in cyclosporine-induced nephrotoxicity, but no causal relationship has been established. 

Other Depression, retinal detachment, hypertension, nephrotoxicity, impaired fertility, fever... 

Patients with liver impairment, such as cirrhosis with portal hypertension (particularly alcoholic cirrhosis/hepatitis) or acute liver failure, are more susceptible to renal impairment than those without liver impairment. Care should be taken with any drug that is potentially nephrotoxic or could contribute to renal dysfunction in these types of patients. 

Cyclosporine A Cyclosporine was used for the first time by G. Routhier et al. (1980) and by G.J. M. Alexander et al. (1984) with encouraging results, yet with nephrotoxic side effects. In subsequent studies, the clinical picture and laboratory parameters as well as histological findings also showed significant improvement. However, an imptairment of renal function and the occurrence of hypertension have to be anticipated. (180, 189, 288)... 

The safety and efficacy of ABCD have been stndied in 220 bone marrow transplant recipients enrolled in the same five phase I or phase II stndies (23). The median dose in this population was 4 (range 0.4—8.0) mg/kg, and the median duration of treatment was 16 (range 1-409) days. Overall, 37 (19%) of the patients had nephrotoxicity, defined as a doubling of serum creatinine from baseline, an increase of 88 pmol/l from baseline, or at least a 50% fall in calculated creatinine clearance. There were no significant changes in hepatic transaminases, alkaline phosphatase, or total bilirubin. Fever and chills were reported by 12 and 11% of patients respectively. Other acute, severe, infusion-related adverse events were hypoxia (4.1%), hypertension (2.7%), and hypotension (2.7%). 

Calcium channel blockers are given to transplant patients for their protective effect against cidosporin-induced nephrotoxicity and to optimize ciclosporin immunosuppression in order to reduce early rejection of renal grafts. Nifedipine has been used to treat cidosporin-induced hypertension, although amlodipine may be just as effective (185). 

The pathophysiology of ciclosporin-induced hypertension is complex and not yet fully elucidated. Increased systemic vascular resistance subsequent to altered vascular endothelium function, renal vasoconstriction with reduced glomerular filtration and sodium-water retention, and/or increased activity of the sympathetic nervous system were suggested, while only a minor role or none was attributed to the renin-angiotensin system (10). However, hypertension often occurs before changes in renal function or sodium balance can be demonstrated, and ciclosporin nephrotoxicity alone does not explain ciclosporin-associated hypertension (8,11). 

Many factors have been postulated as being relevant to ciclosporin nephrotoxicity. Whereas in several studies initial high doses of ciclosporin increased the risk of chronic nephrotoxicity (115,121), others suggested that patients maintained on relatively high ciclosporin concentrations had no more chance than others of developing toxic nephropathy (116). Neither the daily dose nor the duration of ciclosporin treatment reasonably predicts the risk of chronic renal insufficiency. Chronic renal dysfunction can be observed, despite the maintenance of ciclosporin blood concentrations below 400 ng/ml. However, age, sustained hypertension, hypertriglyceridemia, low HDL cholesterol concentrations, and recurrent episodes of severe acute nephrotoxicity increase susceptibility to chronic ciclosporin nephrotoxicity (122,142). 

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