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The prevalence of hypertension in adult Nigerians is about 20% and hypertension remains a significant risk factor in cardiovascular morbidity and mortality. In Africans, hypertension carries a dismal prognosis, has a late clinical presentation and certain antihypertensives may be less effective. We therefore conducted a therapeutic audit in order to assess the initial cardiovascular risk profile of Nigerian patients as well as the safety and efficacy of different antihypertensive agents. A cross-sectional survey of 367 patients (M:F:2:1) modal age 25-44 years, mostly WHO II, enrolled in our clinic was undertaken. 56% had been on treatment for up to one year and 2% for longer than ten years. 12.5% had concomitant diabetes mellitus. Statistical analyses of drug efficacy were done by Spearman correlation and Analysis of Variance (ANOVA). The rank order of hypertensive efficacy was as follows: Thiazides (T) (r = 0.57, P less than 0.05), T + Methyldopa (M) (r = 0.91, P less than 0.001) T + M + Hydralazine (r = 0.92, P less than 0.001). Neither propranolol, nor frusemide showed significant overall efficacy. However, propranolol appeared efficacious in hypertensives with renal impairment. Postural dizziness was occasionally reported. Total mortality was 6% occurring mostly in the modal age group. Diabetic hypertensives had a 5 fold enhanced risk of a fatal outcome (X2 P less than 0.001). Our findings support a rational stepped care approach to pharmacotherapy of hypertension in black Africans, a cost-effectiveness analysis of common antihypertensives; it elucidates the associated adverse effects to patients, and draws attention to the lethality of concomitant hypertension and diabetes. Prospective large scale studies of the treatment of hypertension in Africans are required.
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PMID:A therapeutic audit in the management of hypertension in Nigerians. 260 27

The hemodynamic benefits and safety of combined therapy with captopril and hydralazine were studied during invasive hemodynamic monitoring in 14 patients with severe heart failure. In eight patients, the individual effects of both drugs were evaluated before the administration of combined therapy, whereas hydralazine was added to maintenance captopril therapy in the other six patients. In the first group, captopril alone produced a marked decrease in pulmonary wedge pressure (28 +/- 4 to 18 +/- 5 mm Hg) and mean arterial pressure (85 +/- 20 to 69 +/- 13 mm Hg) (both p less than 0.001) without a significant increase in cardiac index. Hydralazine alone produced a marked increase in cardiac index (1.6 +/- 0.4 to 2.7 +/- 0.5 liters/min per m2) (p less than 0.001), but with a minimal decrease in pulmonary wedge pressure (28 +/- 4 to 23 +/- 4 mm Hg) (p less than 0.05) and without a significant change in mean arterial pressure. The combination of captopril and hydralazine produced an increase in cardiac index similar to that of hydralazine alone and decreases in pulmonary wedge pressure and mean arterial pressure similar to those with captopril alone. Most important, when hydralazine was added to captopril in the entire group of 14 patients, cardiac index increased markedly with little additional decrease in mean arterial pressure and no significant increase in heart rate. The one patient who experienced symptomatic hypotension with combination therapy also had dizziness with captopril alone. Seven of the nine patients maintained on long-term treatment experienced symptomatic improvement. Thus, in patients with severe chronic heart failure, the combined use of captopril and hydralazine is feasible and produces acute hemodynamic improvement superior to that from either drug alone.
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PMID:Hemodynamic responses to combined therapy with captopril and hydralazine in patients with severe heart failure. 634 33

Hydralazine was one of the first orally active antihypertensive drugs developed. Currently, it is used principally to treat pregnancy-associated hypertension. Hydralazine causes two types of side effects. The first type is an extension of the pharmacologic effect of the drug and includes headache, nausea, flushing, hypotension, palpitation, tachycardia, dizziness, and salt retention. The second type of side effects is caused by immunologic reactions, of which the drug-induced lupus-like syndrome is the most common, and provides clues to underscoring hydralazine's DNA demethylating property in connection with studies demonstrating the participation of DNA methylation disorders in immune diseases. Abnormalities in DNA methylation have long been associated with cancer. Despite the fact that malignant tumors show global DNA hypomethylation, regional hypermethylation as a means to silence tumor suppressor gene expression has attracted the greatest attention. Reversibility of methylation-induced gene silencing by pharmacologic means, which in turns leads to antitumor effects in experimental and clinical scenarios, has directed efforts toward developing clinically useful demethylating agents. Among these, the most widely used comprise the nucleosides 5-azacytidine and 2'deoxy-5-azacytidine; however, these agents, like current cytotoxic chemotherapy, causes myelosuppression among other side effects that could limit exploitation of their demethylating properties. Among non-nucleoside DNA demethylating drugs currently under development, the oral drug hydralazine possess the ability to reactivate tumor suppressor gene expression, which is silenced by promoter hypermethylation in vitro and in vivo. Decades of extensive hydralazine use for hypertensive disorders that demonstrated hydralazine's clinical safety and tolerability supported its testing in a phase I trial in patients with cancer, confirming its DNA demethylating activity. Hydralazine is currently being evaluated, along with histone deacetylase inhibitors either alone or as adjuncts to chemotherapy and radiation, for hematologic and solid tumors in phase II studies.
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PMID:Hydralazine target: from blood vessels to the epigenome. 1650

BACKGROUND Hydralazine is an effective antihypertensive agent but may rarely have devastating hepatotoxic effects that are extremely variable, thus making the diagnosis difficult. CASE REPORT We report the case of a 74-year-old male patient who had transaminitis after being started on hydralazine by his cardiologist for poorly controlled hypertension. He had extreme dizziness, nausea, and weakness, which all resolved after discontinuation of hydralazine, and liver function test results also dramatically improved. CONCLUSIONS It is imperative that clinicians be aware of the possible hepatotoxicity of hydralazine and its clinical features so that the medication can be promptly discontinued to help promote liver recovery. This case report will add to the current literature about such infrequent cases of hydralazine-induced hepatotoxicity.
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PMID:A Suspected Case of Hydralazine-Induced Hepatotoxicity: A Case Report and Review of Literature. 2998 Jun 61