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)

Serum angiotensin I converting enzyme, identical with kininase II, was measured fluorometrically in patients with acute viral hepatitis (n=18), liver cirrhosis without (n=44) and with (n=19) ascites. In all groups of patients the enzyme was significantly elevated as compared to 44 healthy controls (p less than 0.001). No correlation could be found between angiotensin I converting enzyme activity and liver function tests (serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, total protein, albumin, bilirubin) or other parameters (serum potassium, serum sodium). High serum converting enzyme activity in chronic liver diseases might originate primarily from an altered pulmonary circulation and indicates higher conversion rate of angiotensin I by passage through the lungs as well as increased bradykinin degradation. The reason for the enzyme liberation in acute viral hepatitis is as yet uncertain.
 ...
PMID:Changes of serum angiotensin I converting enzyme in patients with viral hepatitis and liver cirrhosis. 22 16

The bindings of perindopril and of its active metabolite perindoprilat to human serum, isolated proteins and to erythrocytes were studied by equilibrium dialysis. Within the therapeutic concentrations range, perindopril was 74% bound to serum involving a non-saturable process, NKa = 2.87. The main binders are serum albumin and alpha 1-acid glycoprotein. The serum binding of perindoprilat involved two successive steps. First, a saturable high-affinity binding (Ka: 2.8 x 10(9) M-1) occurred, involving probably the angiotensin converting enzyme (ACE). The second binding step was non-saturable with a very weak binding capacity, NKa = 0.15, quite superimposable to the HSA bound perindoprilat. Free fatty acids (FFA) did not alter the binding to HSA. The binding of both compounds to erythrocytes was low especially with perindopril, when measured in the presence of plasma. A significant correlation showed that the overall serum binding percentage of both drugs was essentially determined by HSA concentration. Serum binding was decreased in renal failure or cirrhosis, this result was principally linked to the hypoalbuminemia. Interactions with other drugs were limited to the binding of salicylate, tolbutamide and digitoxin to HSA.
 ...
PMID:Specific and high affinity binding of perindoprilat, but not of perindopril to blood ACE. 133 Sep 41

Diuretics have long been used to lower blood pressure in hypertensive patients or to control body fluid and electrolyte homeostasis in diseases such as congestive heart failure, chronic renal failure or cirrhosis. The initial response to diuretics is a negative sodium and fluid balance. The diuretic-induced loss of salt and water activates several hormonal systems such as vasopressin, the renin-angiotensin-aldosterone system or the sympathetic nervous system which tend to compensate for the changes in sodium and water balance. This neurohormonal response may have important clinical implications. Thus, the activation of the renin-angiotensin-aldosterone cascade appears to be partially responsible for the flat dose-blood pressure response curve of thiazides in hypertensive patients. It may also be responsible for the difference between responders and non-responders to diuretic therapy and for the development of side-effects such as hypokalaemia, metabolic alkalosis or hyponatraemia. There are several ways to prevent the undesirable consequences of the neurohormonal responses to diuretics. The first is to use low doses of these agents. It is also possible to combine them with agents that block the activity of the renin-angiotensin-aldosterone system such as ACE inhibitors or in combination with drugs that reduce aldosterone secretion such as calcium antagonists. The development of drugs able to enhance urinary sodium excretion and to reduce simultaneously the activity of the renin-angiotensin-aldosterone system may offer a new interesting alternative. This might perhaps be achieved in the future with the administration of neutral endopeptidase inhibitors which interfere with the enzymatic degradation of atrial natriuretic peptide.
 ...
PMID:Neurohormonal consequences of diuretics in different cardiovascular syndromes. 136 43

Perindopril is a non-sulphydryl angiotensin converting enzyme (ACE) inhibitor which requires hydrolysis to its active metabolite, perindoprilat, to produce its effects. Ten cirrhotic patients with mild to severe disease were studied after oral administration of a single 8 mg dose of perindopril as its tert-butylamine salt. Compared with a historical control group of young healthy volunteers receiving the same single oral dose of perindopril, mean AUC values of the prodrug perindopril were double in patients with liver cirrhosis (602 +/- 294 s.d. ng ml-1 h vs 266 +/- 70 s.d. ng ml-1 h) whereas the mean AUC of perindoprilat was found to be similar (134 +/- 139 ng ml-1 h vs 120 +/- 29 ng ml-1 h). The partial metabolic clearance of perindopril to perindoprilat was much lower in the cirrhotics (26 +/- 12 ml min-1 vs 58 +/- 22 ml min-1). The maximum inhibition of plasma ACE activity measured in the cirrhotic patients (87.5 +/- 5.1%) was comparable with that previously reported with perindopril in patients with mild hepatic impairment as well as in patients with essential hypertension. We suggest that liver cirrhosis may be associated with imparied deesterification of perindopril to its active metabolite perindoprilat but that no dosage adjustment of perindopril is required in cirrhotic patients.
 ...
PMID:The pharmacokinetics of perindopril in patients with liver cirrhosis. 157 57

The RAS is part of an extremely powerful feedback system for long-term control of blood pressure and volume homeostasis. Disturbances that tend to lower blood pressure, such as heart failure, cirrhosis, and peripheral vasodilation, cause sodium and water retention until blood pressure returns to normal due, in large part, to the combined actions of ANGII and reduced arterial pressure. In response to increased sodium intake, decreased ANGII formation greatly amplifies the effectiveness of pressure natriuresis, thereby preventing large increases in body fluid volumes and blood pressure. In circumstances in which the RAS is inappropriately activated, the sodium retaining effects of ANGII necessitate increased blood pressure to maintain sodium balance via pressure natriuresis. Because the RAS is so powerful in regulating blood pressure, blockade of the system with ACE inhibitors offers a powerful therapeutic tool in diseases such as hypertension and congestive heart failure. The control of sodium excretion and blood pressure by ANGII is exerted through multiple intrarenal as well as extrarenal effects, including stimulation of aldosterone secretion, which can influence renal excretion. Current evidence suggests that the intrarenal effects of ANGII are quantitatively more important than those mediated by aldosterone in controlling blood pressure and renal excretion. The most important intrarenal effects of ANGII include efferent arteriolar constriction as well as direct effects on sodium transport. The constrictor effect on efferent arterioles also is important in preventing reductions in GFR in circumstances associated with impaired renal perfusion. Therefore blockade of ANGII formation in circumstances such as renal artery stenosis may caused marked reductions in GFR. However, in many patients efferent arteriolar vasodilation caused by ANGII blockade may not lower GFR markedly because of other autoregulatory mechanisms that compensate by causing parallel reductions in afferent arteriolar resistance. In these individuals, chronic ACE inhibition may prove to be beneficial in slowing the progression of renal disease because a reduction in glomerular hydrostatic pressure may help to prevent glomerular damage.
 ...
PMID:The renin-angiotensin system: renal actions and blood pressure regulation. 187 29

The possibility of an impaired hepatic de-esterification of enalapril to enalaprilat due to hepatic dysfunction was assessed in seven patients with compensated liver cirrhosis and 10 normal control subjects. The peak serum concentration and time to the peak serum concentration of enalaprilat, as well as the suppression of serum angiotensin converting enzyme activity, following a single oral dose of enalapril maleate (10 mg) were not different in the two groups. The elimination half-life of enalaprilat was related to renal function. The results suggest that hepatic biotransformation of the drug may not be disturbed in a clinically significant manner in patients with moderate hepatic dysfunction due to compensated liver cirrhosis.
 ...
PMID:The pharmacokinetics of enalapril in patients with compensated liver cirrhosis. 216 99

The influence of hepatic disease on the pharmacokinetics of the new ACE inhibitor, benazepril hydrochloride, was evaluated in 12 male patients suffering from liver cirrhosis. The patients received a single oral 20 mg dose. The plasma concentrations and urinary excretion of unchanged benazepril and its active metabolite benazeprilat were determined. Compared with a historical control group of healthy volunteers treated with the same benazepril. HC1 dose, the plasma concentrations of benazepril were doubled in the cirrhotic patients. However, the time to reach maximum concentration (0.5 h) was not affected. The plasma kinetics and the urinary excretion of the metabolite benazeprilat were not significantly altered: Area under the curve and maximum concentration as well as time to maximum concentration (1.5 h) were comparable with those in the healthy subjects. There was also no significant difference between the two populations for the total urinary excretion and the renal clearance of benazeprilat. Both benazepril and benazeprilat were highly bound to serum proteins (96 and 94 per cent, respectively). In conclusion, the rate and the amount of bioactivation of the inactive prodrug benazepril to the active benazeprilat were virtually unaffected by hepatic cirrhosis. Thus, there seems to be no need for dosage adjustment of benazepril hydrochloride in patients suffering from cirrhosis of the liver.
 ...
PMID:The influence of hepatic cirrhosis on the pharmacokinetics of benazepril hydrochloride. 227 51

Perindopril has been studied in groups of normal young and elderly subjects, in patients with hepatic cirrhosis and in hypertensive patients. Plasma concentrations of perindoprilat are increased and renal clearance reduced in elderly subjects, resulting in an increase in the acute pharmacodynamic effect of perindopril. Compensated hepatic cirrhosis does not have any independent effect on the pharmacokinetics of perindopril. After intravenous administration, perindoprilat concentrations show multiexponential decay with a terminal half life of over 30 hours associated with sustained inhibition of ACE. During repeated dosing there is little accumulation of drug, and no evidence of increased haemodynamic effect after chronic treatment in hypertensives. The therapeutic consequences of these findings are: binding of perindoprilat to ACE prolongs the haemodynamic effect, giving the option of once daily administration; despite the long terminal elimination half life of the drug, significant accumulation is not a problem during chronic treatment; increased plasma concentrations of active metabolite in the elderly and reduced renal elimination may require reduced doses to be used; further dose adjustment in compensated hepatic cirrhosis is not routinely necessary.
 ...
PMID:Pharmacokinetics of perindopril: therapeutic consequences. 250 11

1. Perindopril, a new ACE inhibitor, is a prodrug requiring conversion into its active form perindoprilat by hydrolysis in the liver. 2. The pharmacodynamics and pharmacokinetics of perindopril (8 mg oral) and perindoprilat (2 mg intravenously) were studied in a double-blind randomised crossover study in a group of patients with compensated biopsy-proven hepatic cirrhosis. 3. Blood pressure and heart rate responses were similar after the two routes of administration as were plasma renin activity and aldosterone levels following dosing. 4. The AUC of perindoprilat after oral administration of perindopril represented 46 +/- 4% of the total AUC of perindopril and its metabolite when expressed in molar terms. Comparison with the AUC of perindoprilat after its intravenous administration suggested that 30 +/- 6% of the oral dose of perindopril was converted to its active metabolite. 5. The findings are comparable with those in healthy subjects. It appears that the presence of relatively mild hepatic cirrhosis does not significantly alter the pharmacokinetics of perindopril.
 ...
PMID:The pharmacokinetics and pharmacodynamics of perindopril in patients with hepatic cirrhosis. 255 45

Perindopril has been studied in groups of normal young and elderly subjects, in patients with hepatic cirrhosis and in hypertensive patients. Plasma concentrations of perindoprilat are increased and renal clearance reduced in elderly subjects, resulting in an increase in the acute pharmacodynamic effect of perindopril. Compensated hepatic cirrhosis does not have any independent effect on the pharmacokinetics of perindopril. After intravenous administration, perindoprilat concentrations show multiexponential decay with a terminal half-life of over 30 hours, associated with sustained inhibition of ACE. During repeated dosing, there is little accumulation of the drug and no evidence of increased hemodynamic effect after chronic treatment in hypertensives. The therapeutic consequences of these findings are: (1) Binding of perindoprilat to ACE prolongs the hemodynamic effect, giving the option of once daily administration. (2) Despite the long terminal elimination half-life of the drug, significant accumulation is not a problem during chronic treatment. (3) Increased plasma concentrations of active metabolite in the elderly and reduced renal elimination may require reduced doses to be used. (4) Further dose adjustment in compensated hepatic cirrhosis is not routinely necessary.
 ...
PMID:Pharmacokinetics of perindopril: therapeutic consequences. 260 99


1 2 3 4 5 6 Next >>