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  • Title: [Pharmacokinetic and pharmacodynamic characteristics of antihypertensive drugs in the treatment of hypertensive patients with chronic diseases of the liver].
    Author: Mikheeva OM, Drozdov VN, Komisarenko IA.
    Journal: Ter Arkh; 2011; 83(12):49-55. PubMed ID: 22416445.
    Abstract:
    AIM: To determine optimal treatment of arterial hypertension (AH) in patients with hepatic cirrhosis (HC) basing on pharmacokinetic and pharmacodynamic characteristics of angiotensin-converting enzyme (ACE) inhibitors and beta-adrenoblockers (BAB). MATERIAL AND METHODS: A total of 360 patients with AH of the second degree, steatosis and alcoholic HC of class A according to Child-Pue participated in the study. The control group consisted of 120 patients with peptic ulcer in remission and normal function of the liver. The patients' treatment with enalapril (pharmacologically inactive prodrug), lisinopril (biologically active substance), atenolol (hydrophilic drug) and metoprolol (lipophylic drug) was analysed. RESULTS: Lisinopril showed a better hypotensive effect than enalapril in AH patients with HC. BAB decreased blood pressure in all hypertensive patients. Atenolol and metoprolol effectively reduced blood pressure in 88.89% patients with AH and HC. Bradycardia episodes in atenolol treatment were observed in 14.4% patients while in metoprolol treatment--in 22.2% patients, this evidencing for pronounced shifts in pharmacokinetic parameters of metoprolol exposed to hepatic metabolism. CONCLUSION: Biological activity is an essential criterion of choice of ACE inhibitor in patients with hepatic pathology. Enalapril, for example, as a pharmacological inactive prodrug, is metabolized in the liver to acquire activity, whereas lisinopril has a direct biological activity and has, therefore, a stronger hypotensive action in AH patients with HC. BAB should be selected by the ability to effectively control blood pressure and heart rate without inducing bradycardia the appearance of which necessitates correction of dose regimen with reduction of day dose.
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