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

The calcium antagonists diltiazem, nifedipine and verapamil are widely used in the treatment of coronary heart disease, arterial hypertension, certain supraventricular tachyarrhythmias and obstructive hypertrophic cardiomyopathy. During recent years their pharmacokinetic properties and metabolism have been studied in more detail. Although these 3 calcium antagonists exhibit great diversity in chemical structure, they exhibit common pharmacokinetic properties. These drugs are extensively metabolised and only traces of unchanged drugs are eliminated in urine. Their systemic plasma clearances are high and dependent on liver blood flow. Therefore, their bioavailabilities (diltiazem 40 to 50%; nifedipine 40 to 50%; verapamil 10 to 30%) are low despite almost complete absorption following oral administration. During long term treatment, oral clearance decreases and bioavailability increases due to saturation of hepatic first-pass metabolism. Pronounced intra- and inter-individual variations in clearance and bioavailability are observed. In patients with liver cirrhosis the various pharmacokinetic parameters are grossly altered. Clearance decreases, elimination half-life is substantially prolonged, and bioavailability more than doubles. In addition, the volume of distribution increases. Whereas renal disease has no impact on the pharmacokinetics of diltiazem and verapamil, elimination half-life of nifedipine increases in relation to the degree of renal impairment due to an increase in volume of distribution. Systemic clearance, however, remains unchanged. The data so far available indicate that the plasma concentrations of these drugs correlate with both their electrophysiological and haemodynamic effects. However, no effective therapeutic plasma concentration range has been firmly established. As reliable clinical end-points are available for dose titration of calcium antagonists, it is doubtful whether therapeutic drug monitoring will be of great value. Calcium antagonists are often administered in combination with a variety of other drugs. Thus, the potential for both pharmacodynamic and pharmacokinetic drug interaction exists. The interaction between digoxin and these drugs is of clinical importance. Verapamil and diltiazem cause a significant increase in plasma digoxin concentrations. In contrast, nifedipine does not lead to a significant increase in the plasma digoxin concentration. The mechanism responsible for this interaction is inhibition of both renal and non-renal digoxin clearance.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical pharmacokinetics of verapamil, nifedipine and diltiazem. 354 36

The availability of specific chemical assays and the development of appropriate biological models have made it feasible to study the relationship between the pharmacokinetics and the pharmacodynamics of nifedipine, a relationship that is presumed to be sigmoidal for most effects. In healthy volunteers the haemodynamic effects of a single dose of nifedipine are markedly influenced by the pharmaceutical preparation and the rate of drug input. When the plasma concentration of nifedipine increases rapidly, such as after an intravenous bolus injection or rapidly disintegrating capsules, there is a marked increase in heart rate and little or even no effect on blood pressure. On the other hand, when the drug is given as a slow intravenous infusion or as a sustained release tablet and when the capsules are taken together with food, the decrease in blood pressure is accompanied by few or no changes in heart rate. Furthermore, it has been shown that not only haemodynamic effects of nifedipine, but also oesophageal motor function may be used as a quantifiable pharmacological effect. For patients with angina pectoris, a plasma concentration range that is associated with optimal treatment has not been defined, since large inter-individual variations in the nifedipine plasma concentration were observed in effectively treated patients. For patients with hypertension, significant sigmoidally shaped correlations between blood pressure reduction and nifedipine plasma concentrations following single or multiple doses have been demonstrated. The concentration-effect parameters were very similar to those found for normotensive subjects. After 6 weeks of treatment the potency of the drug had decreased, which might indicate the development of some tolerance. In patients with severe renal impairment, the maximal effect of nifedipine on diastolic blood pressure was more than doubled, which cannot be explained by differences in pharmacokinetics; therefore these patients appear to be more sensitive at the pharmacodynamic level. In patients with liver cirrhosis, the pharmacokinetics of nifedipine were quite different due to reduced protein binding and reduced enzyme activity; in patients with a portacaval shunt, considerable increased bypassing of the liver during the first pass after oral administration was observed. When corrected for free drug concentrations, the concentration-effect relationship for these patients is essentially the same as that found for healthy subjects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Nifedipine. Relationship between pharmacokinetics and pharmacodynamics. 354 14

This paper reviews the potential health risks for persons who consume the newly available "non-alcoholic" or "de-alcoholized" beverages which may contain trace amounts of ethanol (less than 0.5% by volume). The discussion includes relative risk rates for chemical dependency, fetal alcohol syndrome, chemical and natural hypersensitivity, cancer, cardiomyopathy, hypertension and cirrhosis for those who drink standard alcoholic drinks and "non-alcoholic" drinks. It is concluded that non-alcoholic drinks pose little risk for developing alcohol related problems based on our current physiological and psychocultural knowledge.
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PMID:On the potential health effects of consuming "non-alcoholic" or "de-alcoholized" beverages. 358 Jan 38

The relation between education, prevalence of 17 chronic diseases or groups of diseases, and pattern of health care utilisation was evaluated from data from the 1983 Italian National Health Survey, based on 58 462 individuals aged 25 or over randomly selected within strata of geographical area, size of place of residence, and size of household, in order to be representative of the whole Italian population. Most of the diseases considered, including diabetes, hypertension, myocardial infarction and other heart disease, haemorrhoids or varices, chronic respiratory disease, anaemias, gastroduodenal ulcer, cholelithiasis and liver cirrhosis, kidney and urological diseases, arthritis, and psychiatric and neurological disturbances, were consistently less prevalent among more educated individuals. The age and sex adjusted risk estimates for individuals educated in high school or university compared with those with only a primary school education or less ranged between 0.21 for liver cirrhosis and 0.80 for anaemias. The sole exception was allergy, which was more prevalent among the more educated individuals (relative risk = 1.42). General practitioner visits and hospital admissions were reported less frequently by the more educated individuals, but specialist consultations of potential preventive value were less frequent among the less well educated. The results were similar when occupation was utilised as an indicator of social class. Thus, the findings of this national survey provide confirmation and quantitative assessment of considerable differences in health and health service utilisation according to indicators of social class.
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PMID:Education, prevalence of disease, and frequency of health care utilisation. The 1983 Italian National Health Survey. 365 37

Cirrhotic dogs without intrahepatic hypertension (IHH) never retain sodium or expand plasma volume. To test the hypothesis that IHH may cause urinary sodium retention early in cirrhosis, we prepared cirrhotic dogs (chronic biliary obstruction) who underwent simultaneous hepatic denervation with end-side portacaval anastomoses. Such animals, along with appropriate controls and unanesthetized were studied by balance techniques. In the experimental group, plasma volume never increased, and sodium retention did not occur until 2 days prior to the appearance of detectable ascites. In a sham-denervated group, plasma volume increased by 10% and sodium retention occurred on the average 8.4 days prior to ascites. When the portal veins were left intact, the sham-denervated group showed the usual magnitude of plasma volume expansion observed in cirrhotic dogs (18.3%) with a 7-day delay between sodium retention and ascites appearance. Those dogs with hepatic denervation demonstrated a 9.2-day delay with 12.6% expansion of plasma volume. When ascites was mobilized with a peritoneovenous valve, and dogs were subjected to a high salt diet (130 meq/day), denervated dogs excreted the load normally, whereas sham-denervated dogs retained sodium and developed anasarca. We conclude that in cirrhotic dogs with IHH, liver denervation prevents early non-volume-related sodium retention.
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PMID:Hepatic denervation alters first-phase urinary sodium excretion in dogs with cirrhosis. 366 18

Patients with portal hypertension of varying etiology may develop pulmonary artery hypertension. In the present autopsy study, pulmonary and hepatic tissue was studied in 12 patients in whom pulmonary and portal hypertension coexisted. Plexogenic pulmonary arteriopathy was present in 10 patients, 7 of whom had coexistent thromboembolic lesions. One patient had isolated medial hypertrophy, which may be an early stage in the plexogenic category, whereas isolated thromboembolic pulmonary vascular disease was observed in one subject. Hepatic disease was consistent with alcoholic cirrhosis in seven patients, cryptogenic cirrhosis in four and extrahepatic portal hypertension without cirrhosis in one. Thrombocytopenia was present in all 10 patients whose platelet count was determined. This study suggests that pulmonary hypertension associated with portal hypertension commonly has a plexogenic appearance on histologic examination. However, thrombosis (whether embolic or in situ) may also contribute to vascular obstruction.
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PMID:Coexistent pulmonary and portal hypertension: morphologic and clinical features. 368 Jul 90

Necropsy findings of hepatobiliary system from 78 patients with end-stage renal disease maintained on hemodialysis are reported. Ninety percent of the patients exhibited some abnormalities. Multiple abnormalities often coexisted in each patient. Hepatomegaly was found in 50% of the patients and could be attributed to a discernible cause in all but two of the affected patients who had isolated hepatomegaly. Hepatic congestion was also prevalent and was complicated by fibrosis, cardiac cirrhosis, and centrilobular necrosis and hemorrhage in some patients. This was associated with chronic fluid overload, hypertension, and/or cardiovascular disease in the affected patients indicating the importance of adequate control of these factors. Mild periportal hepatic fibrosis, fatty metamorphosis, triaditis, hemosiderosis, and cystic changes were also seen with some frequency--the latter were associated with polycystic kidney disease and were complicated by massive intracystic hemorrhage and abscess formation, each in one patient. Chronic active hepatitis was found in three patients and was associated with chronic HBs antigenemia in one patient and presumed non-A, non-B infection in two. Nearly 22% of the patients showed either cholelithiasis at autopsy or before cholecystectomy due to complications. Significant negative findings included lack of acute viral hepatitis, silicone hepatosis, and recently described focal anoxic lesions associated with erythrocyte sludging. In conclusion, the present study has demonstrated the spectrum of hepatobiliary pathology in a large group of patients with end-stage renal disease maintained on hemodialysis.
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PMID:Hepatobiliary pathology in hemodialysis patients: an autopsy study of 78 cases. 375 41

High-resolution real-time ultrasound (6 MHz) demonstrated vascular dilatation in the adventitial layer of the gallbladder in 7 patients with portal hypertension. The hypertension was due to long-standing cirrhosis in 4 patients; the other 3 patients had prehepatic hypertension due to thrombosis involving the portal vein in 1 and the splenoportal confluence in 2. In one of the cirrhotic patients, postmortem correlation of sonographic, angiographic, and pathological findings showed that the dilated vessels seen on sonography were cystic veins draining normally into the portal vein rather than portosystemic anastomoses. This indicates that varicosity of the cystic vein can be associated with portal hypertension, taking the form of either passive dilatation or hepatopetal portal collateral circulation.
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PMID:Dilatation of the cystic veins in portal hypertension: sonographic demonstration. 388 Jun 3

The portal venous system was studied by ultrasonography (US) in 18 patients with cirrhosis of the liver who had previous bleeding from large esophageal varices. Portal-tract pressure for ten of these patients also was measured by hepatic vein catheterization. After 21 days of treatment with atenolol, the calibers of their splanchnic veins decreased during expiration, while a response to breathing maneuvers was restored. The decrease in the caliber of the splenic and superior mesenteric veins seen by US appeared to correlate significantly with the decrease in portal pressure (P less than .05). Nonresponse to treatment also was detected by US. Real-time US may be routinely carried out as a noninvasive, easy-to-repeat technique for the study of portal system hypertension in patients with cirrhosis undergoing therapy with beta-adrenergic blocking agents.
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PMID:Portal pressure changes induced by medical treatment: US detection. 389 6

Eighteen patients with protal hypertension were studied. Portal hypertension was due to schistosomiasis (N = 9), cirrhosis (N = 7) and congenital hepatic fibrosis (N = 2) diagnosed by surgical biopsy during the decompressive surgery (selective splenorenal shunt). All the patients have had at least one episode of digestive hemorrhage due to rupture of esophageal varices and received blood transfusion before or during surgery. The incidence of post-transfusion hepatitis was 44% (eight cases). The short and medium-term follow-up was good regardless the etiology of portal hypertension. The authors attributed these results mainly to good hepatic function at the time of surgery, younger patient population and good surgical technical conditions.
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PMID:[Selective splenorenal shunt and post-transfusional hepatitis. Short and medium-term follow-up]. 393 82


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