Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Irbesartan inhibits the activity of angiotensin II (AII) via specific, selective noncompetitive antagonism of the AII receptor subtype 1 (AT1) which mediates most of the known physiological activities of AII. In patients with mild to moderate hypertension, once daily administration of irbesartan 150 or 300 mg, with or without adjunctive antihypertensive agents, provides effective 24-hour BP control. Irbesartan reduced BP to a similar extent to enalapril and atenolol and to a significantly greater extent than losartan. The combination of irbesartan and hydrochlorothiazide resulted in additive antihypertensive effects. The drug is effective in the elderly and dosage adjustment is not required in these patients or in those with renal or hepatic failure. Preliminary studies evaluating the efficacy of irbesartan in patients with heart failure have produced encouraging results. Irbesartan is very well tolerated and neither the frequency nor the pattern of adverse events differed from those seen in placebo recipients, although headache was significantly more frequent with the latter. Similarly, the incidence of adverse events did not differ significantly between irbesartan and enalapril in patients who received either drug as monotherapy. Headache, upper-respiratory tract infection and musculoskeletal pain were the most common complaints. Thus, irbesartan is an effective therapy for patients with mild to moderate hypertension and had an adverse event profile similar to that of placebo in clinical trials. On this basis it would appear to be an effective therapeutic option in this indication.
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PMID:Irbesartan. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in the management of hypertension. 942 95

Nitrates, which have been used for more than a century, are the second oldest drug (after digitalis alkaloids) in the cardiological pharmacological arsenal. However, several facets of their mode of use still remain controversial. Their vasodilator and arteriolodilator action (especially in coronary vessels) and their platelet aggregation inhibitory effect make them useful drugs, particularly in all clinical forms of ischaemic heart disease (unstable or stable angina and acute myocardial infarction), for the prevention or treatment of ischaemic episodes (silent or not) and also in heart failure where nitrates are useful not only as symptomatic treatment (alone or associated with diuretics), but also in view of their positive effect on survival (associated with hydralazine: V-Heft I trial). At the present time, nitrates can be administered via the sublingual, oral, intravenous of transdermal routes in the form of nitroglycerin and isosorbide dinitrate or mononitrate (short-acting and sustained-effect forms). Their rare contraindications concern patients suffering from severe hypotension (< 70 mmHg), severe anaemia, glaucoma or intracranial hypertension. The most serious adverse effects are pulsatile headache (which usually disappear after several days), postural hypotension (possibly causing fainting), facial erythema, vertigo, palpitations or nausea and vomiting. Most of these adverse effects can be controlled by dosage adaptation and it is rarely necessary to stop treatment. However, the major problem raised by the use of nitrates concerns the development of a tolerance. The pathophysiology of this multifactorial phenomenon is still unclear. The protagonist role played by loss of SH groups or activation of humoral feedback mechanisms, with an increase of circulating catecholamine levels, activation of the R-A-A system and increased plasma volume, has been postulated. This complication can be avoided by prescribing intermittent treatment, with a drug-free interval of 10-12 hours per day. A single dose of a sustained-release preparation (60 mg of isosorbide dinitrate or 40 to 60 mg of isosorbide mononitrate), or 2 or 3 doses of a short-acting preparation (20-40 mg of isosorbide mononitrate) can be prescribed via the oral route. When the transdermal route is used, the patch should be left in place for 12 hours. Treatment should be started at low doses, which are then gradually increased. The free period is usually at night, which can be covered, when necessary, by other antiischaemic drugs (for example, beta-blockers and/or calcium channel blockers), already usually used in combination with nitrates. This interruption is not accompanied by a rebound phenomenon. It must be remembered that nitrates potentiate the action of other vasodilators and calcium channel blockers and that, in some patients, intravenous nitroglycerin reduces the anticoagulant effect of heparin, while indomethacin can inhibit their vasodilator effect. Nitrates are therefore in very good health despite their advanced age and, when used correctly, they continue to be very useful in the pharmacological treatment of cardiovascular diseases.
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PMID:[Principles and rules of the use of nitrates]. 945 73

Calcium antagonists are potent vasodilators and are widely used in the treatment of hypertension and angina pectoris. The currently available compounds belong to three classes: (1) dihydropyridines (e.g. nifedipine, amlodipine and felodipine), (2) phenylalkylamines (e.g. verapamil) and (3) benzothiazepines (e.g. diltiazem). The three classes differ in their pharmacological profile and safety. For example, verapamil and diltiazem lower heart rate, while dihydropyridines increase it or leave it unchanged. With most of the latter compounds, a marked activation of the sympathetic nervous system has been noted. Most compounds exhibit negative inotropic effects, particularly the first-generation molecules, which is disadvantageous in patients with impaired left-ventricular function. The most common side effects of these drugs are flushing, headache and edema. With verapamil, constipation may represent a problem in certain patients. Hence, in spite of a large number of calcium antagonists available, there remains a need for new compounds with enhanced efficacy and improved tolerability. A new compound should lack any negative inotropism, avoid any increase in sympathetic outflow or heart rate and exhibit a high degree of vascular selectivity. Furthermore, a low incidence of side effects, particularly ankle edema and optimal pharmacokinetics allowing once-daily dosing would be desirable. Mibefradil is a new calcium antagonist with promising pharmacological and clinical properties. The compound has a high bioavailability, lacks negative inotropic effects at therapeutic concentrations, does not exhibit reflex tachycardia during vasodilation and actually slightly decreases heart rate. It is a potent direct vasodilator efficacious in hypertension and chronic angina pectoris, elicits endothelium-dependent relaxations and facilitates the effects of nitric oxide in vascular smooth muscle. The drug is a particularly efficacious vasodilator in intramyocardial coronary arteries which may be important for its anti-ischemic effects and the lack of steal in the coronary circulation. Furthermore, mibefradil has antiproliferative properties in human vascular smooth muscle cells in culture. As a unique property, mibefradil blocks T-type calcium channels and hence represents a new class of calcium channel blockers. In patients with hypertension, mibefradil has a high efficacy in controlling blood pressure. The drug does not cause constipation and has a low incidence of ankle edema. A large trial is under way to further delineate the properties of this new calcium antagonist in patients with heart failure.
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PMID:Comparative pharmacological properties among calcium channel blockers: T-channel versus L-channel blockade. 957 Apr 24

All consecutive cases of chronic renal failure (CRF) seen over a twelve-month period (January-December 1992) were evaluated. Those that fulfilled strict diagnostic criteria for hypertension induced CRF (HICRF) were further studied to determine peculiarities of its clinico-pathological features that may render this possibly preventable condition readily identifiable. Twenty one (23.1%) of the 91 cases of CRF satisfied these criteria. There was a male preponderance (M.F.4.3:1). Nocturia was a prominent symptom predating other symptoms of CRF in all. Throbbing frontal headache necessitating significant consumption of analgesic was found in 13(61.9%). Hypertension had been diagnosed in the patients for periods ranging from 2-15 years and compliance to therapy was adjudged poor. Ten smoked cigarette in significant quantities. Hypertension occurred in 8 of the families of the patients. Hypertension was severe in all, with evidence of accelerated phase in 19(90.5%). A majority (71.4%) presented with severe uraemia (serum creatinine > or = 100 umol/l). Target organ damage, evident in cardiomegaly with heart failure occurred in 15, while ultrasonographic features of bilateral shrunken kidneys was seen in all. Blood pressure control was largely inadequate with a combination of 3 drugs. Mortality rate was 51% in the first year. Renal histopathological findings of glomerular sclerosis, malignant arteriolar changes with absence of glomerular cellular proliferation were observed in renal biopsies and 6 autopsy tissues. It is concluded that HICRF is a major cause of mortality; renal failure is often advanced at presentation, and blood pressure is usually in the accelerated phase. Significant cigarette smoking, severe headache necessitating consumption of significant quantity of analgesics, and a family history of hypertension are striking features.
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PMID:Hypertension induced chronic renal failure: clinical features, management and prognosis. 971 16

103 patients from a group of 115 patients with catecholamine secreting tumours were reinvestigated 7.0 +/- 4.9 years following surgery. Throughout the follow-up period 15 patients had died. In four of them death was definitively, in seven subjects possibly associated to the primary endocrine disorder. Following surgery improvement of general well-being was documented in 85% of the patients. Hypertension was corrected in 61 %, but 26% of the patients remained hypertensive and symptoms of hypotension like orthostasis developed in 24%. A significant increase in weight (> 5 kg) was observed in 26% of the subjects throughout the follow-up period, but did not result in a higher prevalence of diabetes mellitus which had to be treated in 16% of the patients before and only 14% following surgery. However, palpitations, increased sweating and headache persisted in 16%, 17% and 12% of the patients, respectively. Symptoms of cardiac insufficiency developed in 32%. Persistent discomfort related to the scar was reported by 55% of the patients following lumbar surgery and by 30% of the subjects that were operated on via a transabdominal approach. Hence we conclude that surgery of catecholamine-secreting tumours results in an improvement of health and well-being in most subjects according to objective criteria as well as to the judgement of the patients themselves.
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PMID:Follow-up in 103 patients with catecholamine-secreting tumours. 973 87

Sildenafil is the first orally administered available treatment for erectile dysfunction. It produces a selective vasodilatation of corpus carvernosum, mediated by the inhibition of phosphodiesterase 5, an enzyme that degrades GMPc. Its therapeutic efficacy has been demonstrated in organic as well as psychogenic or mixed erectile dysfunction. Most of its adverse effects, such as headache, flushing, gastroesophageal reflux and color vision disturbances, are related to the mechanism of action. Its interactions with other medications, can have severe adverse consequences. The concomitant use of sildenafil with drugs that release nitric oxide in their molecule, can produce severe hypotension. In patients with coronary heart disease or cardiac failure, this interaction can cause death. Sildenafil is metabolized in the liver through cytochrome P-450. This enzymatic system can be inhibited by cimetidine, ketoconazole or erythromycin. These drugs can increase plasma concentrations of sildenafil. We must identify the groups of patients that will have a better response to the drug and those in whom the drug will be useless. We must also know more about the security profile of the drug. With time, we will know the real role of sildenafil in the treatment of erectile dysfunction.
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PMID:[Sildenafil (viagra) at the time of warnings]. 1034 69

Angiotensin II receptor blockers (ARBs) represent a new class of effective and well tolerated orally active antihypertensive agents. Recent clinical trials have shown the added benefits of ARBs in hypertensive patients (reduction in left ventricular hypertrophy, improvement in diastolic function, decrease in ventricular arrhythmias, reduction in microalbuminuria, and improvement in renal function), and cardioprotective effect in patients with heart failure. Several large long-term studies are in progress to assess the beneficial effects of ARBs on cardiac hypertrophy, renal function, and cardiovascular and cerebrovascular morbidity and mortality in hypertensive patients with or without diabetes mellitus, and the value of these drugs in patients with heart disease and diabetic nephropathy. The ARBs specifically block the interaction of angiotensin II at the AT1 receptor, thereby relaxing smooth muscle, increasing salt and water excretion, reducing plasma volume, and decreasing cellular hypertrophy. These agents exert their blood pressure-lowering effect mainly by reducing peripheral vascular resistance usually without a rise in heart rate. Most of the commercially available ARBs control blood pressure for 24 h after once daily dosing. Sustained efficacy of blood pressure control, without any evidence of tachyphylaxis, has been demonstrated after long-term administration (3 years) of some of the ARBs. The efficacy of ARBs is similar to that of thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors or calcium channel blockers in patients with similar degree of hypertension. Higher daily doses, dietary salt restriction, and concomitant diuretic or ACE inhibitor administration amplify the antihypertensive effect of ARBs. The ARBs have a low incidence of adverse effects (headache, upper respiratory infection, back pain, muscle cramps, fatigue and dizziness), even in the elderly patients. After the approval of losartan, five other ARBs (candesartan cilexetil, eprosartan, irbesartan, telmisartan, and valsartan) and three combinations with hydrochlorothiazide (irbesartan, losartan and valsartan) have been approved as antihypertensive agents, and some 28 compounds are in various stages of development. The ARBs are non-peptide compounds with varied structures; some (candesartan, losartan, irbesartan, and valsartan) have a common tetrazolo-biphenyl structure. Except for irbesartan, all active ARBs have a carboxylic acid group. Candesartan cilexetil is a prodrug, while losartan has a metabolite (EXP3174) which is more active than the parent drug. No other metabolites of ARBs contribute significantly to the antihypertensive effect. The variation in the molecular structure of the ARBs results in differences in the binding affinity to the receptor and pharmacokinetic profiles. The differences observed in lipid solubility, absorption/distribution, plasma protein binding, bioavailability, biotransformation, plasma half-life, and systemic elimination influence the time of onset, duration of action, and efficacy of the ARBs. On the basis of the daily mg dose, the antihypertensive potency of the ARBs follows the sequence: candesartan cilexetil > telmisartan approximately = losartan > irbesartan approximately = valsartan > eprosartan. After oral administration, the ARBs are rapidly absorbed (time for peak plasma levels = 0.5-4 h) but they have a wide range of bioavailability (from a low of 13% for eprosartan to a high of 60-80% for irbesartan); food does not influence the bioavailability, except for valsartan (a reduction of 40-50%) and eprosartan (increase). A limited dose-peak plasma levels/areas under the plasma level-time curve proportionality is observed for some of the ARBs. Most of these drugs have high plasma protein binding (95-100%); irbesartan has the lowest binding among the group (90%). The steady-state volumes of distribution vary from a low of 9 L (candesartan) to a high of 500 L (telmisartan). (ABSTRACT TRUNCATE
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PMID:Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. 1085 85

A case with systemic non-Hodgkin lymphoma involving the sella turcica and kidney is reported. A 69-year-old man presented with a progressive two month history of visual disturbance and headache. Neurological examination revealed bilateral visual disturbance and right optic atrophy. MRI showed a contrast-enhancing mass in the sella turcica. The tumor extended to the right optic nerve. Without extensive studies for systemic disease, the patient immediately underwent transsphenoidal surgery. The slightly firm, fibrous and vascular-rich tumor was subtotally removed. The histopathological examination revealed a malignant lymphoma, diffuse-large-cell type with B-cell phenotype. The postoperative course was uneventful and the patient's symptoms subsided gradually. The patient received radiation therapy and the tumor disappeared. Postoperative CT examinations of the abdomen and pelvis revealed a large mass at the upper portion of the left kidney. Ga-scan also suggested the mass to be consistent with the abdominal CT. However, the patient suddenly died of acute heart failure with unknown cause just before starting chemotherapy for systemic lymphoma. Patients presenting primary central nervous system lymphoma (PCNSL) may have systemic non-Hodgkin lymphoma. To exclude systemic non-Hodgkin lymphoma, systemic investigation is essential for the initial management of patients presenting PCNSL.
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PMID:[Systemic non-Hodgkin lymphoma initially presented with visual disturbance due to intrasellar lymphoma--a case report]. 1121 68

Biogenic amines are formed in foods as a result of amino acid decarboxylation catalyzed by bacterial enzymes. When consumed in sufficient quantities, these compounds will cause headache, hypertension, fever, and heart failure. Technologies such as vacuum packaging and carbon dioxide-modified atmosphere packaging (CO2-MAP), when combined with low-temperature storage (-1.5 degrees C), allow fresh pork to have a storage life long enough for export to overseas markets. During low-temperature storage of pork in these packaging systems, the lactic acid bacteria (LAB), which possess the enzymes for biogenic amine formation, dominate the microflora. The objectives of this study were to determine the quantities of biogenic amines in packaged fresh pork, to monitor LAB growth, and to determine the storage life by sensory evaluation. Vacuum-packaged and CO2-MAP pork were stored at -1.5+/-0.5 degrees C for 9 and 13 weeks, respectively. Phenylethylamine, putrescine, cadaverine, histamine, tyramine, spermidine, and spermine concentrations were determined weekly by high-performance liquid chromatography and capillary gel electrophoresis. LAB and carnobacteria were enumerated weekly. Samples were evaluated for odor and appearance. The CO2-MAP was successful in delaying bacterial growth and the development of unacceptable off-odors compared with the vacuum packaging. The storage lives of the vacuum-packaged and CO2-MAP pork were 5 and 13 weeks, respectively. High-performance liquid chromatography was the superior method for biogenic amine quantification. Tyramine and phenylethylamine in pork of both packaging treatments approached levels considered to be potentially toxic. Given Canada's increasing role in the export of fresh meat to foreign markets, it is recommended that the formation of biogenic amines in vacuum-packaged and CO2-MAP pork be further investigated.
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PMID:Biogenic amines in vacuum-packaged and carbon dioxide-controlled atmosphere-packaged fresh pork stored at -1.50 degrees C. 1127 71

The authors present an unusual complication of a recurrent chiasmal/hypothalamic pilocytic astrocytoma. From his second year of life onwards, the patient was repeatedly operated on and also underwent external radiation therapy (54 Gy total dose) 1 month after the first subtotal tumor resection. Nine years after irradiation, the patient was referred to our center with a sudden onset of severe headache, vomiting and neck stiffness. Computed tomography, magnetic resonance imaging, and cerebral angiography demonstrated an intratumoral, intraventricular, and subarachnoidal hemorrhage from an anterior communicating artery aneurysm encased in the pilocytic astrocytoma. The aneurysm was clipped and the patient recovered nicely from the hemorrhage. Three years later, the patient suddenly died of cardiac failure. Autopsy disclosed vessel wall changes compatible with radiation-induced vasculopathy. In light of this finding, the importance of radiation therapy and intracranial neoplasms for aneurysm formation is discussed.
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PMID:Intracranial hemorrhage from an aneurysm encased in a pilocytic astrocytoma--case report and review of the literature. 1130 72


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