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)

Topically administered beta blockers are the preferred medical therapy for glaucoma. These agents reduce intraocular pressure (IOP), thereby preventing damage to the optic nerve and the subsequent loss of vision. Timolol, betaxolol, levobunolol, metipranolol, and carteolol are the topical beta blockers available in the U.S. They have similar IOP-lowering efficacy, but differ in other pharmacological properties. Topically administered beta blockers are generally well tolerated. They undergo systemic absorption, however, and can adversely affect cardiovascular and bronchopulmonary function in patients with existing diseases such as heart failure, sinus bradycardia, chronic obstructive airways disease, or asthma. Betaxolol, which is beta 1-selective, and carteolol, which has intrinsic sympathomimetic activity (ISA), may have systemic tolerability profiles superior to the traditional nonselective, non-ISA beta blockers. These hypotheses require confirmation in controlled clinical trials. Local adverse effects associated with beta blockers include stinging, burning, red eye, itching, tearing and loss of corneal sensitivity. Stinging upon instillation is a particularly frequent finding with betaxolol (up to 30% to 40% of patients). Preliminary evidence suggests that carteolol has the best local tolerability profile of these drugs.
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PMID:Topical ophthalmic beta blockers: a comparative review. 790 96

All eye drops raise problems of local tolerance, but with variable frequencies. They can induce pain on instillation, allergic reactions, delayed healing, punctate keratitis, disturbances of lacrimal secretion, disturbances of accommodation (especially the parasympathomimetics) and local pigmentation after prolonged use. Corticosteroids are associated with 2 major risks: chronic glaucoma and cataract, initially reversible if treatment is stopped. There is still a major risk of corneal herpes with corticosteroids. It is important to be aware of these local problems as they are responsible for poor patient compliance. The systemic effects essentially concern the agonists and antagonists of the autonomic nervous system. beta-Blocker eye drops can cause bronchospasm, heart failure, syncope and psychiatric disorders, especially at high doses and with nonselective beta-blockers. These consequences are usually related to failure to comply with the prescribing precautions. alpha-Adrenergic agonists, which exert dose-dependent effects, can induce hypertensive crises or angina attacks. Apart from patients at risk (children under the age of 30 months and the elderly), parasympathomimetics cause few systemic adverse effects; anticholinesterases, which have curare-like properties, are contraindicated for 6 weeks before general anesthesia. In the very young and the very old, atropinic eye drops carry a risk of cardiovascular collapse and neuropsychiatric disturbances. Problems may also occur with other classes of drugs such as anti-infectives, antispectics, anti-inflammatories and contact lens products. Nevertheless, it is clear that this form of treatment is generally very well tolerated in relation to the volume of eye drops prescribed by ophthalmologists each day.
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PMID:Systemic and local tolerability of ophthalmic drug formulations. An update. 809 91

A 73-year-old woman with cardiac dysfunction had several episodes of severe bradycardia and pulmonary oedema when waiting for peripheral vascular surgery. She used timolol eye drops for primary open-angle glaucoma. The first episode of pulmonary oedema occurred two weeks prior to and the second on the day before the planned surgery. There were another two episodes of pulmonary oedema before she was transferred to the Department of Internal Medicine where she had a further two episodes of cardiac failure. After changing timolol to pilocarpine eye drops, the patient's condition was stabilized, and two weeks later surgery and postoperative recovery were uneventful.
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PMID:Cardiac failure aggravated by timolol eye drops: preoperative improvement by changing to pilocarpine. 872 73

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

Dexanabinol is a non-psychotropic cannabinoid NMDA receptor antagonist under development by Pharmos Corp for the potential treatment of cerebral ischemia, glaucoma, Alzheimer's disease, cardiac failure, head injury and multiple sclerosis (MS) [311522]; it is in phase III trials for traumatic brain injury (TBI) [388709]. Dexanabinol was licensed to Pharmos for development from its originator, the Hebrew University of Jerusalem [180441]. Pharmos is seeking to enter into a strategic agreement with another company to develop and commercialize dexanabinol [317369]. Unlike its enantiomer, HU-210 (Yissum Research Development Co), dexanabinol does not interact with cannabinoid receptors [223330]. It has also exhibited more effective antioxidant and anti-inflammatory properties than MK-801 (dizocilpine; Merck & Co Inc) [167980], [168212]. In addition, dexanabinol is generally well tolerated and appears toxicologically safe [170116]. Pharmos has been awarded a Small Business Innovation Research grant from the National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke, Division of Stroke and Trauma. The grant covers the development of new prodrugs and novel formulations of dexanabinol and will support additional study of dexanabinol compounds for various indications. The prodrugs being studied are part of the group of compounds that include dexanabinol [247958]. A Notice of Allowance was received in March 1999 on a patent covering the use of the drug in the treatment of MS [324163]. The use of dexanabinol and its derivatives to treat MS is described in US-05932610 [358503]. An oral formulation of dexanabinol is claimed in US-05891468. Dexanabinol analogs with special utility in acute and chronic pain are claimed in US-04876276, while dexanabinol analogs for neuroprotection are claimed in US-06096740. Pharmos estimates that the worldwide market for dexanabinol in the treatment of severe head trauma may reach $1 billion per year [319244].
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PMID:Dexanabinol Pharmos. 1124 4

Initially it was considered that moxonidine, like clonidine, acted at central (2)-adrenoceptors to reduce blood pressure. With the characterisation of imidazoline binding sites distinct from (2)-adrenoceptors, the consensus became that moxonidine was acting predominantly at imidazoline I(1) receptors in the rostral ventrolateral medulla to lower blood pressure. Moxonidine acts at prejunctional (2)-adrenoceptors on sympathetic nerve endings to decrease noradrenaline release and this may contribute to its ability to lower blood pressure. The predominant site of action of moxonidine may also depend on route of administration, with imidazoline I(1) receptors being predominant after central, and (2)-adrenoceptors predominant after systemic administration. The controversy over the mechanism and site of action with moxonidine is ongoing. In animal models, moxonidine lowers blood pressure, reduces cardiac hypertrophy and remodelling, reduces cardiac arrhythmias and increases blood flow in cerebral ischaemia. Moxonidine also has beneficial effects in animal models of diabetes and kidney disease. Moxonidine increases sodium and water excretion in rats, but not humans. Animal studies indicate that moxonidine may be useful in the treatment of glaucoma by reducing intra-ocular pressure. Animal studies show that moxonidine may also be effective in pain and in ethanol withdrawal. In humans, the pharmacokinetics of moxonidine are of the one-compartment model with first-order absorption. Renal elimination is the major route of elimination and individual titration of moxonidine is needed in patients with renal impairment. There is overwhelming evidence that moxonidine is a safe and effective antihypertensive. A large clinical trial of moxonidine in heart failure, MOXCON, was stopped because of excessive deaths in the moxonidine group. Moxonidine should not be used in patients with heart failure, but there are no obvious reasons to stop its use as an antihypertensive, or its development for other clinical uses.
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PMID:Moxonidine: some controversy. 1133 90

The aquaporins are a family of small, integral membrane proteins that function as plasma membrane transporters of water and in some cases small polar solutes such as glycerol. There are at least 10 distinct aquaporins in mammals with specific patterns of expression in epithelial, endothelial and other tissues. Recent studies in aquaporin-null mice have indicated key roles for certain aquaporins in the urinary concentrating mechanism, fluid secretion by glands, brain swelling, skin moisture, hearing and vision, and gastrointestinal absorption. The only known inhibitors of some aquaporins are mercurial sulfhydryl-reactive compounds, which are too toxic and nonspecific for use in vivo. Small-molecule or peptide aquaporin blockers have potential applications in the treatment of disorders of fluid/pressure homeostasis such as heart failure, hypertension, brain swelling and glaucoma.
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PMID:Applications of aquaporin inhibitors. 1281 84

beta-Adrenoceptor blocking agents (beta-blockers) have been established as therapeutics for treatment of patients with hypertension, ischemic heart diseases, chronic heart failure, arrhythmias, and glaucoma. However, their clinical use is limited because some patients are adversely affected by their side effects. The discovery of cardioselective (beta(1)-selective) blockers has overcome some of the problems. Current retrospective studies have revealed that vasodilating beta-blockers (so-called beta-blockers of the third generation) have advantages over the conventional type of beta-blockers in terms of minimizing the adverse effects and improving the disease-derived dysfunction, thus enhancing the quality of life variables. Some of the possible advantages include improvement of insulin resistance, decrease in low-density lipoprotein cholesterol in association with increase in high-density lipoprotein cholesterol, attenuation of bronchial asthma attack and respiratory dysfunction, alleviation of coronary vasospasm provocation, peripheral circulatory disturbances, and erectile dysfunction, and better patient compliance. Release of nitric oxide, antioxidant action, beta(2)-adrenoceptor activation, Ca(2+) entry blockade, and other mechanisms underlying the vasodilating action may be responsible for the beneficial therapeutic effects of these agents.
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PMID:Vasodilating beta-adrenoceptor blockers as cardiovascular therapeutics. 1465 11

Mitochondriopathies (MCPs) are either due to sporadic or inherited mutations in nuclear or mitochondrial DNA located genes (primary MCPs), or due to exogenous factors (secondary MCPs). MCPs usually show a chronic, slowly progressive course and present with multiorgan involvement with varying onset between birth and late adulthood. Although several proteins with signalling, assembling, transport, enzymatic function can be impaired in MCP, most frequently the activity of the respiratory chain (RC) protein complexes is primarily or secondarily affected, leading to impaired oxygen utilization and reduced energy production. MCPs represent a diagnostic challenge because of their wide variation in presentation and course. Systems frequently affected in MCP are the peripheral nervous system (myopathy, polyneuropathy, lactacidosis), brain (leucencephalopathy, calcifications, stroke-like episodes, atrophy with dementia, epilepsy, upper motor neuron signs, ataxia, extrapyramidal manifestations, fatigue), endocrinium (short stature, hyperhidrosis, diabetes, hyperlipidaemia, hypogonadism, amenorrhoea, delayed puberty), heart (impulse generation or conduction defects, cardiomyopathy, left ventricular non-compaction heart failure), eyes (cataract, glaucoma, pigmentary retinopathy, optic atrophy), ears (deafness, tinnitus, peripheral vertigo), guts (dysphagia, vomiting, diarrhoea, hepatopathy, pseudo-obstruction, pancreatitis, pancreas insufficiency), kidney (renal failure, cysts) and bone marrow (sideroblastic anaemia). Apart from well-recognized syndromes, MCP should be considered in any patient with unexplained progressive multisystem disorder. Although there is actually no specific therapy and cure for MCP, many secondary problems require specific treatment. The rapidly increasing understanding of the pathophysiological background of MCPs may further facilitate the diagnostic approach and open perspectives to future, possibly causative therapies.
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PMID:Mitochondriopathies. 1500 63

The differentiation of haemangiomas and vascular malformations is histological, clinical and prognostic. Although the majority of haemangiomas evolve towards spontaneous resolution, as many as 10% of cases can develop complications with ulceration, pain and haemorrhaging. Besides, the localisation of haemangiomas in the head and neck, next to vital structures, can compromise their functions. Hence, compression of the airway might be a vital emergency. Periorbital haemangiomas can give rise to amblyopia due to sensory deprivation or due to a restrictive strabismus. Lumbosacral haemangiomas must be studied with Nuclear Magnetic Resonance because of their frequent association with alterations in the midline at the level of the spine, anus, genitals or kidneys. Amongst visceral haemangiomas, hepatic haemangiomas are the most serious due to their association with congestive cardiac insufficiency. The association of extensive facial haemangiomas with anomalies of the central nervous system, vascular, cardiac, ocular and sternal anomalies, is denominated PHACE syndrome and is frequently complicated by mental deficiency, convulsions or ictus. Vascular malformations of trigeminal localisation are associated in up to 15% of cases with glaucoma or choroidal or leptomeningeal haemangiomas (Sturge-Weber syndrome). Combined vascular malformations localised in the extremities can become complicated with thrombophlebitis, regional osteolysis and even distant thromboembolisms (Klippel-Treneaunay Syndrome). On the other hand, there is a coagulopathy due to consumption (Kassabach-Merrit Syndrome) that can complicate some vascular tumours such as the Kaposiform haemangioendothelioma and the tufted angioma. Finally, the complications of the treatments employed are reviewed.
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PMID:[Complications in the evolution of haemangiomas and vascular malformations]. 1514 12


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