Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitrendipine [3-ethyl-5-methyl-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine dicarboxylate] is a calcium antagonist with a dihydropyridine structure that has a great structural resemblance to nifedipine. Instead of a methyl group in position 3, it has an ethyl group and the NO2 group is in the meta instead of in the ortho position. These minor structural differences have a pronounced impact with respect to both the pharmacokinetics and pharmacodynamics of nitrendipine as compared to nifedipine. Based on equimolar plasma concentrations, nitrendipine is on average three times more potent than nifedipine with regard to the reduction of peripheral vascular resistance, arterial blood pressure, and increased leg blood flow. The terminal half-life is on average 8 h, and thus substantially longer than the terminal half-life of 2-3 h for nifedipine. Despite its almost complete absorption, bioavailability is on average 15-25% and shows great interindividual variability ranging from 7 to 40%. The systemic plasma clearance of the drug is on average 18 ml/min/kg and thus approaches the liver blood flow. In patients with liver cirrhosis, the half-life is prolonged to 19.6 h, the total plasma clearance is decreased by 50%, and the bioavailability is more than doubled to 54%. No data are available if liver disease alters the pharmacodynamic response of the drug. Kidney disease has some effect on the disposition of the drug. Systemic clearance is not changed but the terminal elimination half-life is slightly prolonged to 10.5 h. This increase in half-life is due to an increased volume of distribution. Bioavailability, which is 21.2%, is not grossly altered in renal failure.
 ...
PMID:Pharmacokinetics and pharmacodynamics of nitrendipine in healthy subjects and patients with kidney and liver disease. 246 76

The frequency of mesangial IgA deposition was examined in 250 consecutive autopsy cases without known renal disease. Diffuse granular mesangial deposits of IgA were detected in 12 of 250 cases (4.8%). In six patients IgA deposits were associated with liver cirrhosis. Six patients (2.4%) suffered from various other conditions including endocarditis, bronchial asthma, cardiovascular disease, and neoplasia. Two of these patients had completely negative urine analysis on repeated investigations, whereas three patients exhibited microscopic haematuria and/or mild proteinuria. IgA1 was the major constituent in all specimens. C3c deposits in glomeruli were detected in one kidney. Our findings indicate that clinically overt renal disease is present in only a limited proportion of individuals with mesangial IgA deposits. Apparently, it represents the tip of an iceberg.
 ...
PMID:Frequency of mesangial IgA deposits in a non-selected autopsy series. 251 84

Since 1970, the types of glomerulopathy encountered in patients with cirrhosis of the liver have been accurately determined. In alcoholic cirrhosis IgA glomerulonephritis is frequent, usually non-proliferative and latent, sometimes membranoproliferative. Defective elimination of circulating immune complexes made up of bacterial or food antigens and IgA antibodies is thought to play a part in the pathogenesis of this type of glomerulonephritis. Extramembranous or membranoproliferative glomerulonephritis, occasionally containing the viral antigen, may complicate post-hepatitis cirrhosis, in which case an antiviral treatment might be effective against the renal disease.
 ...
PMID:[The glomerulopathies of cirrhosis of the liver]. 252 8

The pharmacokinetics of etodolac, a new nonsteroidal anti-inflammatory drug, were compared in normal subjects, in patients with renal and hepatic disease, and in elderly patients. In 28 normal subjects, orally administered etodolac was rapidly absorbed. By 1.2 hours after ingestion of a 200 mg dose, the maximum serum concentration (Cmax) averaged 15.9 micrograms/ml, with more than 99% of the drug bound to serum protein. Clearance was primarily hepatic. The mean half-life (t1/2) was 6 to 7 hours. There were no apparent differences in Cmax, the time at which Cmax occurred (tmax), area under the serum concentration/time curve (AUC0-24), or t1/2 between groups of young men (n = 20), elderly men (n = 24), and elderly men with osteoarthritis (n = 20), after a single dose of etodolac or after 7 days of subchronic administration. Moreover there was no evidence of accumulation. There also were no differences in Cmax, tmax, AUC0-24 or t1/2 between groups of normal subjects (n = 10) and patients with mild-to-moderate renal impairment (n = 10). Patients with end-stage renal disease who were receiving chronic hemodialysis had the same mean serum concentration of free drug as normal subjects, even though mean serum levels of protein-bound etodolac were slightly lower than those in the normal subjects. The only significant (p less than 0.05) difference between patients with stable hepatic cirrhosis and normal, age-matched subjects was a slightly shorter tmax in the cirrhotic subjects (1.1 vs. 1.4 hours). These findings suggest that no alteration of etodolac dosage would be necessary in these high-risk groups.
 ...
PMID:Profile of etodolac: pharmacokinetic evaluation in special populations. 252 81

During the past two decades, essentiality of zinc for man has been established. Deficiency of zinc in man attributable to nutritional factors and several diseased states has been recognized. High phytate content of cereal proteins decreases availability of zinc; thus the prevalence of zinc deficiency is likely to be high in the population subsisting mainly on cereal proteins. Zinc deficiency has been noted to occur in patients with malabsorption syndrome, chronic renal disease, cirrhosis of the liver, sickle cell disease, AE (acrodermatitis enteropathica), and other chronically debilitating diseases. Growth retardation, male hypogonadism, skin changes, poor appetite, mental lethargy, and delayed wound healing are some of the manifestations of chronically zinc-deficient human subjects. In severely zinc-deficient patients, dermatological manifestations, diarrhea, alopecia, mental disturbances, and intercurrent infections predominate. If untreated, the condition becomes fatal. Zinc deficiency affects testicular functions adversely in man and animals. This effect of zinc is at the end-organ level. It appears that zinc is essential for spermatogenesis. Zinc is involved in many biochemical functions. Several zinc metalloenzymes have been recognized in the past decade. Zinc is required for each step of cell cycle in microorganisms and is essential for DNA synthesis. The effect of zinc on protein synthesis may be attributable to its vital role in nucleic acid metabolism. The activities of many zinc-dependent enzymes have been shown to be affected adversely in zinc-deficient tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Clinical and biochemical manifestations of zinc deficiency in human subjects. 258 Aug 77

A follow-up study of 1939 diabetic patients with a mean observation period of 9.4 years was carried out in Osaka, Japan. The mortality rates per 1000 person-years were 31.35 for males and 21.99 for females, and the ratios of observed to expected number of deaths were 1.69 for males and 1.74 for females, indicating an excess mortality for diabetic patients of both sexes and higher mortality in males than in females in Japan. Factors related to the prognosis of the patients were age, elevated fasting glucose level, lower obesity index, hypertension, diabetic retinopathy, and albuminuria at entry to the study. Insulin treatment was also associated with poor prognosis. Cerebro-cardiovascular and renal disease were the major causes of death in diabetic patients; heart disease killed 19.5%, cerebrovascular disease 16.7% and renal disease 13.1%. The relatively high frequency of renal disease as a cause of death in type 2 diabetes, especially in patients with a lower age of onset, was noteworthy, suggesting some difference in the clinical manifestations of diabetes between Japan and Western countries. Malignant neoplasms accounted for 25% of deaths, and cirrhosis of the liver for 6.4%.
 ...
PMID:Mortality and causes of death in type 2 diabetic patients. A long-term follow-up study in Osaka District, Japan. 275 88

The pharmacokinetic changes that occur not infrequently when a single drug is taken by an elderly individual are usually not clinically important because of the wide therapeutic index between pharmacological and toxic effects. On the other hand, when multiple medications are administered simultaneously, additive effects may be seen. This concept is extended further in the presence of impaired function of an excretory or of a metabolic organ, such as with renal disease or cirrhosis of the liver. Thus when an agent whose pharmacological half-life is prolonged in the elderly is administered to an older person with cirrhosis of the liver and/or renal disease, the dose must be reduced considerably in order to avoid excessively elevated blood levels and the concomitant side effects. In contrast, in the absence of liver and/or renal disease, no toxic side effect might be expected. When multiple drugs are given, which may interact with each other, the potential for drug reaction is greatly increased. The physician's recognition of these basic pharmacological changes in the elderly should greatly reduce such drug reactions.
 ...
PMID:Gastrointestinal drugs in the elderly. 287 51

In a study of 228 consecutive medico-legal autopsies, malignant disease was discovered in 19 cases. The malignant diseases are discussed as to their primary sites and histologic types, age groups in which they occurred, conditions with which they may have been associated, symptoms and signs which in some cases may have warned of malignant disease, and supposed reasons why the malignant diseases were not recognized while the deceased were still alive. It was found that undetected malignant diseases occur mainly in the elderly, that chronic renal disease with scarred kidneys and cirrhosis of the liver may be predisposing conditions in cancer development, and that malignant disease in the aged may be undetected because of confusion with general weakness or because of small size and obviously slow growth of the tumor with lack of symptoms.
 ...
PMID:[Malignant diseases as secondary findings in forensic autopsies]. 291 26

Prostaglandin (PG) synthesis in the kidney is localised to specific sites and is not uniformly present throughout the nephron. It is generally accepted that the regional heterogeneity of PGs, as well as the lack of vascular communications between the medulla and cortex, dictate that PGs [primarily prostacyclin (PGI2)] synthesised in the cortex (glomeruli and vasculature) regulate cortical function, while PGs (primarily PGE2) synthesised in the medulla (collecting tubule and medullary interstitial cells) regulate medullary function. Measurement of urinary unmetabolised PGs, or their stable hydration products, provides the best clinical assessment of the state of renal PG production. Under physiological circumstances, renal function is not critically dependent upon the integrity of PG synthesis, possibly because other regulatory mechanisms can compensate for PG synthesis inhibition. However, when renal PG synthesis is activated in response to altered haemodynamics (e.g. cirrhosis with ascites) or is pathologically reduced (e.g. chronic glomerular disease) then the consequences of pharmacological inhibition can become clinically apparent and measurable. In these circumstances, drugs that inhibit renal cyclo-oxygenase activity can acutely reduce glomerular filtration rate and renal blood flow by 30 to 50%. These functional changes are usually reversible upon discontinuing the drug. The long term consequences of renal PG synthesis inhibition are more difficult to assess. Theoretically, chronic inhibition of renal PG synthesis might be responsible for medullary ischaemia, possibly contributing to the picture of so-called analgesic nephropathy. Selective sparing of renal cyclo-oxygenase activity can be obtained by at least 3 mechanisms: differential 'sensitivity' of the glomerular cyclo-oxygenase; selective intra-renal inactivation of an active metabolite of the drug; differential rate of recovery of glomerular cyclo-oxygenase following irreversible acetylation by aspirin. The recent demonstration of a functional correlate of such biochemical selectivity suggests novel strategies for reducing the chronic renal toxicity of cyclo-oxygenase inhibitors.
 ...
PMID:The role of prostaglandin synthesis inhibition in the renal syndromes associated with non-narcotic analgesics. 310 92

Non-steroidal anti-inflammatory drugs (NSAIDs) may produce acute renal failure, papillary necrosis and interstitial nephritis. These adverse drug reactions are rare but have been reported in patients with congestive heart failure, cirrhosis, renal parenchymal disease, lupus nephritis and hypertension. All these conditions may be associated with hypovolaemia and an activated renin-angiotensin system, when renal blood flow and glomerular filtration depend on local renal prostaglandin biosynthesis. A severe impairment of renal function may occur when this synthesis is inhibited by NSAID treatment. It is possible that 1 in 100 of elderly patients have renal parenchymal disease, 1 in 100 arteriolar nephrosclerosis, 1 in 200 unilateral or bilateral renal artery stenosis and an unknown number suffer from atheroembolic renal disease. Fortunately, only a small proportion of 'at risk' patients given NSAIDs appear to develop renal failure. Perhaps bilateral renal disease or salt depletion are necessary factors? Whatever the explanation, NSAIDs should be used with caution in the elderly.
 ...
PMID:Pharmaco-epidemiological considerations in patients with arthritis and vascular disease of the kidney. 349 36


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>