Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antidiabetic drug metformin (MF) typically achieves only micromolar levels in plasma with normal therapeutic use. However, it is also known to accumulate in various tissues up to several times higher after standard oral dosing and we now have evidence from both in vivo and in vitro experiments with spontaneously hypertensive rats (SHR) that millimolar levels stimulate release of norepinephrine (NE) from vascular sympathetic nerve endings (SNEs). As shown in the present work with SHR tail arterial tissue (rich in SNEs), the known vasodilator effect of millimolar levels of MF on the smooth muscle (even if contracted with a nonadrenergic agonist), is attenuated by the presence of the SNEs unless phentolamine (an alpha receptor blocker) is present. We reasoned that the mechanism for this apparent NE-releasing action of MF is not exocytotic release as that would require depolarization of the neuronal cell membranes in SNEs, and MF at millimolar levels is known to repolarize (not depolarize) membranes of other cells. Thus, we tested the possibility that MF releases NE by an indirect sympathomimetic-like action. Such an action should be amplified by monoamine oxidase inhibitors (e.g. iproniazid) and blocked by NE-carrier inhibitors (e.g. desipramine). Accordingly, we found that the abovementioned attenuating effect of intact SNEs on MF's relaxation of SHR tail arterial tissue (compared to tissues in which SNEs were experimentally removed with 6-hydroxydopamine) was amplified nearly 3-fold by iproniazid (p<0.05) and blocked by desipramine (p<0.05). These results support an indirect sympathomimetic action of MF and raise the question whether commonly used antidepressants with properties similar to iproniazid and desipramine might alter MF's beneficial vasodilatory (and thus antihypertensive) effectiveness in diabetic patients with hypertension.
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PMID:A possible indirect sympathomimetic action of metformin in the arterial vessel wall of spontanously hypertensive rats. 1150 51

The Seville orange extract Citrus aurantium contains m-synephrine (phenylephrine) and octopamine; it causes cardiac disturbances in animals and is used by humans for weight loss. Juice from the orange (Seville orange juice [SOJ]) is used to "knock out" intestinal cytochrome P450 (CYP) 3A4 in bioavailability studies. The purpose of this study was to determine synephrine and octopamine concentrations in SOJ and SOJ's cardiovascular effects in normotensive humans. Subjects consumed 8 ounces of SOJ and water in crossover fashion followed by a repeat ingestion 8 hours later. Hemodynamic (heart rate; systolic, diastolic, and mean arterial pressure) measurements followed. Synephrine and octopamine were determined by high-performance liquid chromatography. Hemodynamics did not differ significantly between water and SOJ groups. Mean synephrine concentration of SOJ samples was 56.9 +/- 0.52 microg/ml; octopamine was not detected. SOJ ingestion by normotensive subjects is expected to be safe. Individuals with severe hypertension, tachyarrhythmias, and narrow-angle glaucoma and monoamine oxidase inhibitor recipients should avoid SOJ consumption. Persons taking decongestant-containing cold preparations should also refrain from SOJ intake.
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PMID:Seville (sour) orange juice: synephrine content and cardiovascular effects in normotensive adults. 1158 73

Local anesthesia is without doubt the most frequently used drug in dentistry and in medicine. In spite of records of safety set by using these drugs, there is evidence to adverse reactions ranging from 2.5%-11%. Most of the reactions originate from the autonomic system. A recent, well-planned study indicates that adverse reactions are highly correlated to the medical status of the patient: the higher the medical risk, the greater the chance to experience an adverse reaction. This study also found that adverse reactions highly correlated to the concentration of adrenalin. Another recent study found a direct relationship between adverse reactions and the level of anxiety experienced by the patient and to the dental procedure. Most of the reactions in this study occurred either immediately at injection time and within 2 hours following the injection. Since the beginning of last century, vasoconstrictors have been added to local anesthesia solutions in order to reduce toxicity and prologue activity of the LA. However, today it is commonly agreed that this addition to local anesthesia should not be administered to cardiac patients especially those suffering from refractory dysrhythmias, angina pectoris, post myocardial infarction (6 months) and uncontrolled hypertension. Other contraindications to vasoconstrictors are endocrine disorders such as hyperthyroidism, hyperfunction of the medullary adrenal (pheochromocytoma) and uncontrolled diabetes mellitus. Cross reactivity of local anesthetic solutions can occur with MAO inhibitors, non specific beta adrenergic blockers, tricyclic antidepressants, phenothiazides and cocaine abusers. Noradrenaline added to local anesthetics as a vasoconstrictor has been described as a trigger to a great increase in blood pressure and therefore has been forbidden for use in many countries. This paper describes 4 cases of severe complications following the injections of local anesthesia of which three ended in fatality.
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PMID:[Emergencies evolving from local anesthesia]. 1185 46

Excess secretion of any of the adrenal cortical or medullary hormones contributes to a number of well-known clinical syndromes.. They may result from benign or malignant adrenal tumours, adrenal hyperplasia or, least frequently, from extra-adrenal disease. Differentiation among these possibilities is often impossible on clinical or biochemical grounds alone. Location of the site(s) of excess hormone production in the past depended on relatively insensitive or invasive radiological methods. The non-invasive evaluation began with X-ray computed tomography but the functional significance of anatomical abnormalities cannot be determined from CT scan. Incorporation of specific radiopharmaceuticals into the abnormal tissues allows scintigraphic localization of functional abnormalities with a high degree of efficacy. The combination of adrenal scintigraphy and kompjuterizovanom tomografijom CT or magnetskom rezonancijom MRI should in most cases obviatc the need for more invasive procedures. Phaeochromocytoma is rare in hypertensive population, affecting only an estimated of 0.1%. However, a high index of suspicion is essential, since these tumours have potentially life-threatening cardiovascular effects and their successful resection is curative. Important clinical clues include the presence of orthostatic hypotension in an untreated hypertensive, resistance of hypertension to standard therapy (including possible exacerbation by (beta-blockers). In most cases, the diagnosis can be established by demonstrating high levels of free catecholamines and their metabolites (metanephrines and Vanillylmandelic acid). Clonidine test may be important in some cases. The purpose of this study is to point that metaiodobenzylguanidine (mlBG) has proved to be a safe, sensitive and highly specific agent for the location of phaeochromocytoma. The first successful schinigraphic demonstration of phaeochromocytomas in man was reported in 1981, using a new radiopharmaceutical, 131l-metaiodobenzylguanidinc (mlBG). mlBG is an aralkyl-guanidine which structurally resembles noradrenaline sufficiently to be recognized and be stored in the catecholamine storage vesicles. Whereas unstored noradrenaline is rapidly degraded, the halogenated benzyl ring of mlBG conlers resistance to catechol-o-methyltransferase (COMT) while its guanidino side-chain is resistant to monoamine oxidase (MAO). Uptake of mIBG is inhibited by some inhibitors (reserpine, tricyclic antidepressants, cocaine, labetalol, calcium-chanel blockers...). 131I-mlBG is normally taken up by liver, spleen, myocardium and salivary glands. Thyroid uptake ol liberated radioiodide will also occur unless the thyroid is blocked with stable iodide. The normal adrenal glands are usually not seen but faint uptake may be visible 48-72 h after injection in up to 16% of cases. Hepatic uptake is maximal at 24 h, declining to very low levels by 72 h (even more rapid in patients with phaeochromocytoma. Dosimetric corlsiderations limit the amount of 131l-mlBG that is administered for diagnostic studies. This, coupled with the low detection efficiency of gamma cameras for the 364 keV photon of 131l, led to the introduction of 131l-mlBG as an adrenomedullary scintigraphic agent of choice. In our department we started with mIBG scintigraphy in 1985 and we treated near 1000 patients. In this study we are talking about 180 patients from the beginning of 1996 to the end of 2001 all treated with 131l-mlBG. Like the other worldwide experience with this agent our sensitivity was 88.58% and specificity of 98.46%. Positive predictive value was 88.5% and negative predictive value was 93.46%. False negative results were 6.52% and there were no false positive results. After all we can say that mlBG has proved to be a safe, sensitive and highly specific agent for the location of phaeochromocytoma and neuroblastoma. Other radiolabelled aralkylamines have been examined as potential adrenal medullary scintigraphic agents. None has demonstrated superiority over mlBG in animal or limited human studies. 131l-mlBG should always be considered the radiopharmaceutical of choice for imaging purposes if it is available. 131l-mlBG in high doses is successfully used in therapy of malignant phaeochromocytoma and especially in nuroblastoma.
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PMID:[Nuclear medicine diagnosis of pheochromocytoma with metaiodobenzylguanidine]. 1258 93

Between 20 and 35% of all dementias are vascular in origin, their etiology is due to cerebrovascular disease and the risk factors are known (e.g. hypertension, diabetes, smoking, or hyperlipidemia). Primary and secondary preventions are the basis of therapeutics. Symptomatic treatment is emerging, notably in the field of cognitive disorders. In that respect, monoamine oxidase inhibitors, and more recently acetylcholinesterase inhibitors, are in the process of being recognized as first-line treatments of established vascular dementia.
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PMID:Drugs and vascular dementia. 1271 93

Clinical trials have shown that linezolid (600 mg twice daily in adults) is safe and generally well tolerated for up to 28 days. Drug-related adverse events, which are typically mild to moderate in intensity and of limited duration, include diarrhoea, nausea and headache in adults, and diarrhoea, loose stools and vomiting in children. Clostridium difficile-related complications with linezolid are uncommon. Linezolid is a weak, reversible monoamine oxidase inhibitor: foods containing high concentrations of tyramine should be avoided, and linezolid should be used with caution in patients taking adrenergic or serotonergic agents or in those with uncontrolled hypertension. In the majority of patients, linezolid has minimal adverse effects on blood chemistry or haematology. There have been case reports of reversible thrombocytopenia, anaemia and neutropenia associated with linezolid therapy. In Phase III studies, 2.4% of patients treated with linezolid and 1.5% of patients treated with comparator drugs developed reversible thrombocytopenia (P = 0.066), but there was no evidence of an increased risk of agranulocytosis, aplastic anaemia or other irreversible blood dyscrasias. Reduced platelet counts were associated with linezolid treatment for >/=2 weeks; complete blood counts should be monitored weekly in patients receiving linezolid for more than 14 days and treatment should be discontinued if there is evidence of myelosuppression.
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PMID:Safety and tolerability of linezolid. 1273 Jan 42

Development of the MAO-inhibitors has been an important advance in the treatment of tuberculosis, mental depression, several of the collagen diseases, hypertension and angina pectoris. Treatment must be carefully controlled and individualized. A sufficient number of MAO-inhibitors is available at present to afford ready and correct selection of the proper one for a given patient and disease. Provided such care is observed, treatment is most successful and side effects are few and, as a rule, readily corrected.
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PMID:The aminase oxidase inhibitors. Their current place in clinical medicine. 1373 Jan 83

In the Netherlands monoamine oxidase (MAO) inhibitors are not registered for the treatment of patients with depression. The classical, nonselective MAO inhibitors--phenelzine and tranylcypromine--are effective but their use is associated with interactions (with tyramine in food, sympathicomimetics and serotonine re-uptake inhibitors) and side-effects (hypertension, hypotension, headache, sleep disturbances and neuromuscular symptoms in particular). Therefore, the classical MAO inhibitors are indicated only in depressive disorders that are unresponsive to the first stages of treatment. Taking this selection into account, treatment should be long-term to avoid relapse.
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PMID:[Classical monoamine oxidase inhibitor: not registered for, but still a place in the treatment of depression]. 1457 73

Although systemic hypertension is a common clinical disorder, hypertensive emergencies are unusual in clinical practice. Situations that qualify as hypertensive emergencies include accelerated or malignant hypertension, hypertensive encephalopathy, acute left ventricular failure, acute aortic dissection, pheochromocytoma crisis, interaction between tyramine-containing foods or drugs and monoamine oxidase inhibitors, eclampsia, drug-induced hypertension and possibly intracranial hemorrhage. It is important to recognize these conditions since immediate lowering of systemic blood pressure is indicated. The diagnosis of hypertensive emergencies depends on the clinical manifestations rather than on the absolute level of the blood pressure. Depending on the target organ that is affected, the manifestations of hypertensive emergencies can be quite expressive, yet variable. Thus, the physician has to make the clinical diagnosis urgently in order to render appropriate therapy. Several parenteral drugs can quickly and effectively lower the blood pressure in hypertensive emergencies. Intravenous fenoldopam, a selective dopamine (DA1) receptor agonist, offers the advantage of improving renal blood flow and causing natriuresis. Intravenous nicardipine may be beneficial in reserving tissue perfusion in patients with ischemic disorders. Whereas trimethaphan camsilate is the drug of choice for managing acute aortic dissection, hydralazine remains the drug of choice for the treatment of eclampsia. The alpha-adrenoceptor, phentolamine, is useful in patients with pheochromocytoma crisis. Enalaprilat is the only ACE inhibitor available for parenteral use and may be particularly useful in treating hypertensive emergencies in patients with heart failure. However, ACE inhibitors may cause a precipitous fall in blood pressure in patients who are hypovolemic. Although useful as adjunctive therapy in hypertensive crises, diuretics should be used with caution in these patients because prior volume depletion may be present in some conditions such as malignant hypertension. The treating physician should be familiar with the pharmacological and clinical actions of drugs which are indicated for and useful in the treatment of hypertensive emergencies. Once the patient's situation has stabilized, the patient may be switched to an oral medication and the physician should discuss long term follow up plans. With appropriate clinical diagnosis, hypertensive emergencies can be successfully treated and the complications can be prevented with timely intervention.
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PMID:Hypertensive emergencies. Etiology and management. 1472 43

The goal of the German drug safety program in psychiatry AMSP (Arzneimittelsicherheit in der Psychiatrie) is the assessment of severe or new adverse drug reactions (ADRs). Here we report on 53,042 of 122,562 patients treated with antidepressants who were monitored from 1993 to 2000 in 35 psychiatric hospitals in German-speaking countries. The overall incidence of severe ADRs of antidepressants was 1.4 % of exposed patients; when only ADRs rated as probable or definite were considered, a rate of 0.9 % in patients treated with antidepressants was observed. ADR rates were higher for TCAs (imputed in 1.0 % of patients overall, respectively in 0.6 % of patients when only ADs were imputed) and lower for MAO inhibitors and SSRIs (0.7 % for both, respectively 0.3 % and 0.4 %). Within the TCA group there was a difference among clomipramine (2.1 %, respectively 1.0 %), amitriptyline (1.0 %, respectively 0.6 %), and doxepin or trimipramine (both 0.6 %, respectively 0.3 %). With regard to single SSRI, similar rates were observed for paroxetine (0.8 %, respectively 0.5 %) and for citalopram (0.7 %, respectively 0.4 %). Of the new dual-acting antidepressants, venlafaxine ranged at 0.9 %, (respectively 0.5 %) and mirtazapine at 0.6 % (respectively 0.5 %). In particular, TCAs were associated with known risks, such as toxic delirium, grand mal seizures, and hepatic (i. e., increased liver enzymes), urologic (i. e., urinary retention), allergic (i. e., exanthema), or cardiovascular (i. e., mainly orthostatic collapse) reactions. In SSRI-treated patients (non-delirious) psychic and neurological ADRs were most prominent, followed by gastrointestinal, dermatologic, and endocrinological/electrolyte reactions, with agitation, hyponatremia (probably as part of the SIADH syndrome and associated with severe neurologic or psychiatric symptoms in 64 % of all cases), increased liver enzymes, nausea, and the serotonin syndrome as leading unwanted symptoms. Venlafaxine (in the immediate-release formulation) was associated with adverse CNS and somatic symptoms such as severe agitation, diarrhea, increased liver enzymes, hypertension, and hyponatremia. Mirtazapine was mostly connected with increased liver enzymes, cutaneous edema, and collapse, but with no case of significant hyponatremia. For drugs that potently inhibit serotonin uptake, serum sodium concentration should be controlled when applied in high-dose therapy or in vulnerable patients.
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PMID:Severe adverse drug reactions of antidepressants: results of the German multicenter drug surveillance program AMSP. 1505 13


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