Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With the failure of the heart as a pump, there ensues a series of neurohumoral compensations that defend organ perfusion at the expense of alterations in cardiac filling pressures and the distribution of blood flow to various regional circulations. Activation of the sympathetic nervous system and the renin-angiotensin II-aldosterone system and increases in circulating arginine vasopressin maintain arterial blood pressure by producing systemic arteriolar vasoconstriction and the renal retention of salt and water. Constriction of the efferent arterioles in the kidney by angiotensin II and norepinephrine promotes reabsorption of glomerular filtrate in the peritubular capillaries and maintains glomerular filtration in the face of declines in glomerular plasma flow and the glomerular permeability-surface area ultrafiltration coefficient. In resting, sodium-replete, conscious animals and humans, pharmacologic inhibition of renal cyclo-oxygenase by nonsteroidal anti-inflammatory drugs has little or no effect on renal hemodynamics. However, electrical or reflex stimulation of the renal nerves, intrarenal infusion of angiotensin II, or infusion of arginine vasopressin stimulates the release of vasodilator prostaglandins from the kidneys. In sodium-depleted animals or humans, and when cardiac output decreases, there is an increase in total peripheral vascular resistance but little change in renal vascular resistance. Increased renal synthesis of vasodilator prostaglandins (presumably by the blood vessels) maintains renal blood flow despite increased release of renin and norepinephrine from the kidneys. In these situations, pharmacologic inhibition of renal cyclo-oxygenase is accompanied by marked reductions in renal blood flow and glomerular filtration rate. When this occurs in patients with advanced heart failure, reversible oliguric renal failure may result. In this setting, cyclo-oxygenase inhibition may also increase arterial pressure and induce additional depression of cardiac function. Recent data indicate that blood vessels have the capacity to synthesize the sulfidopeptide leukotrienes C4, D4, and E4, which can constrict peripheral and renal blood vessels and alter vascular permeability. The vascular cell types responsible for leukotriene C4 synthesis and the potential roles of these vasoactive eicosanoids in kidney and other regional circulations are currently under study.
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PMID:Prostaglandins in congestive heart failure and the effects of nonsteroidal anti-inflammatory drugs. 309 62

Intake of the anticonvulsant drug valproic acid, or its sodium salt, has been associated with occasional instances of severe and sometimes fatal hepatotoxicity. Probably at least 80 cases have occurred worldwide. The syndrome affects perhaps 1 in 10,000 persons taking the drug, and usually develops in the early weeks or months of therapy. Most instances have involved children, usually those receiving more than 1 anticonvulsant. Multiple cases have occurred in 2 families. The typical presentation is of worsening epilepsy, increasing depression of consciousness, and progressive clinical and biochemical evidence of liver failure. The liver has sometimes shown hepatocyte necrosis, and on other occasions widespread microvesicular steatosis, while cholestatic changes have also occurred. The appearances are interpreted as consistent with a drug toxicity reaction. During the hepatotoxicity increased amounts of unsaturated metabolites of valproate, notably 4-en-valproate, have been found in blood and urine. In 4 cases there has been evidence of impaired beta-oxidation of valproate with, in 1 case, accumulation of isomers of valproate glucuronide caused by intramolecular rearrangement of the conjugate. There are molecular structural similarities between 4-en-valproate and 2 known hepatotoxins (4-en-pentanoate and methylenecyclopropylacetic acid, the latter being responsible for hypoglycin poisoning). There are also clinical and histopathological similarities between valproate hepatotoxicity and both hypoglycin poisoning and certain spontaneous disorders of isoleucine metabolism (one pathway of valproate metabolism is analogous to oxidative degradation of isoleucine). Unsaturated metabolites of valproate, in particular 4-en-valproate, may contribute to the hepatotoxicity of the drug. However, since the hepatotoxicity appears to involve an element of idiosyncrasy, the primary defect in some cases may be an inherited or acquired deficiency in the drug's beta-oxidation. This defect may divert valproate metabolism towards omega-oxidation, with increased formation of the toxin 4-en-valproate, but may also allow increased formation of a toxic metabolite derived from isoleucine, since beta-oxidation of isoleucine derivatives will also be impaired.
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PMID:Valproate-associated hepatotoxicity and its biochemical mechanisms. 313 28

Lithium salts, in particular the carbonate and citrate, were formerly in widespread use, forming part of alkaline salt mixtures which were used for treatment of the many disorders belonging to the uric acid diathesis. Among these disorders were mania, depression, acute mania, acute melancholia and periodic depression. Satisfactory prophylactic effects on periodic depression were directly claimed. Daily doses of 3 to 26 mmol of lithium were recommended as standards. Only slight or moderate symptoms of poisoning were reported in a very few cases during the period in question (1860 to 1930), when the popularity of these lithium-containing prophylactic drugs with a favourable therapeutic index was at its peak. Lithium intoxication was not a serious clinical problem until 1949 when Cade introduced his fortuitously effective, but nevertheless high, dosage regimen which was continued until signs of recovery from mania appeared. For the maintenance dose, Cade in principle recommended, but seldom adhered to, 17 mmol/day. Chronic lithium intoxication starts insidiously with silent affliction of the kidneys followed by 'prodromal' symptoms, and when moderate severity has been reached, an accelerating renal vicious circle with decreasing kidney function is imminent. After this point the chronic intoxication resembles acute intoxication. Active detoxification at this, or an earlier stage, leaves the patient with a good chance of recovery. At a later stage, with the occurrence of oliguria, semi-coma or coma, and latent convulsive movement, recovery is less certain. There is no specific antidote for the toxic effects of lithium. Haemodialysis is the most effective treatment for acute lithium poisoning. For patients with impaired, or potentially impaired renal function, peritoneal dialysis may be an alternative, but less effective, treatment. Forced diuresis demands unimpaired renal function, and is little more effective than withdrawal of treatment, supplemented with correction of water and electrolyte balance. Sodium overloading is not recommended. Patients on lithium prophylaxis are treated on an outpatient basis. Prevention of intoxication depends on cooperation between patient and clinician, and possibly on the use of smaller, low risk dosages in most patients.
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PMID:Clinical features and management of lithium poisoning. 328 25

Experimental and clinical experience with compounds containing antimony have shown that the trivalent compounds are generally more toxic than the pentavalent ones. APT can cause severe pain and tissue necrosis and is therefore not given by intramuscular or subcutaneous injection. APT has the actions and uses of AST, but it is less soluble and more irritating than the sodium salt which is therefore more suitable for intravenous use. Trivalent antimony compounds are toxic when used topically. Adverse effects are similar for all trivalent compounds, and include nausea, vomiting, weakness and myalgia, abdominal colic, diarrhoea, and skin rashes, including pustular eruptions. Hypersensitivity reactions also occur. Respiratory symptoms include cough, dyspnoea, and chronic lung changes. Cardiotoxicity is the most important and may produce arrhythmias, myocardial depression and damage, Stokes-Adams attacks, heart failure, and cardiac arrest. Hepatic damage and necrosis, as well as blood dyscrasias, may occur. Toxic effects on the kidney may follow chronic use. Continuous treatment with small doses of antimony may give rise to symptoms of subacute poisoning, similar to those of chronic arsenic poisoning, due to accumulation of antimony in the body, especially if trivalent compounds are used, because of their long biological half-lives. Reproductive disorders and chromosome damage have been reported; antimony compounds are, therefore, potentially toxic to reproduction and have mutagenic, and oncogenic potential. Antimony compounds should, therefore, not be used during pregnancy or in the presence of hepatic, renal, or heart disease. Pentavalent antimony preparations especially the organic compounds, together with non-metallic synthetic preparations, such as the diamidines, have now replaced APT for use in leishmaniasis. Because of the toxicity of antimony compounds, investigations have been undertaken to reduce their adverse effects by combining them with chelating agents. These preparations appear to have reduced the toxic effects of antimony without affecting the efficacy of the preparations. Liposome-encapsulated antimony products have, more recently, been shown to be much less toxic because of the reduced dose of the antimony compound required for effective therapy. The historical uses of antimony were based on the belief that the topical and systemic adverse effects, for example, skin eruptions and diarrhoea and vomiting, were signs that the condition being treated was responding by being brought to the surface to relieve congestion at the diseased area. There is no evidence in topical use, but there is evidence that such use can cause severe reactions.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Toxicity of antimony and its compounds. 330 36

The metabolite S-adenosyl-L-methionine (SAMe), when prepared as the stable p-toluene-sulfonate complex of its sulfate salt and given parenterally in high doses, appears to have mood-elevating effects in depressed adults. The material is remarkably well tolerated when given by injection or intravenous infusion for this purpose, even in elderly or demented patients. Assuming that the toluene sulfonate component is inert, SAMe appears to have central neuropharmacologic effects after systemic injection in high doses. Nevertheless, the functional consequences of these remain unclear and, indeed, the ability of exogenous SAMe to reach the brain, and especially neuronal cytoplasm, is limited. SAMe has small effects on monoamine metabolism and, after injection, appears to have effects on the microviscosity of cell membranes that may be related to stimulation of phospholipid synthesis. The recent introduction of an orally administered form of SAMe for use in the treatment of osteoarthritis promises to stimulate further study of SAMe in disease-associated depression, major depressive disorder, and other neuropsychiatric conditions.
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PMID:Neuropharmacology of S-adenosyl-L-methionine. 331 48

Serotonin content and accumulation in platelets and its release from them, as well as changes in thrombus formation in mesenteric arterioles and venules of the small intestine have been investigated in control rats and rats with spontaneous hypertension (SHR). Serotonin accumulation in platelets was determined upon its incubation with platelets. Disodium ADP salt was used as an inductor of release. Laser-induced thrombosis was caused by microvessels exposure to impulse laser irradiation. The control animals revealed a significant difference between the initial serotonin platelet level and serotonin level upon incubation and release; in values, the values of basic thrombus-forming parameters were higher than in arterioles. In SHR there is a decrease in biogenic amine content in platelets, a depression in its accumulation and release, an increase in the time of thrombus growth, its size up to the separation of the first embolus and its length along the vascular wall. It is concluded that spontaneous hypertension is characterized by decreased functional activity of platelets and depressed resistance of arterioles and venules to thrombus formation.
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PMID:[Serotonin metabolism in thrombocytes and microvascular hemostasis in spontaneous arterial hypertension]. 334 66

Thirty-one female inpatient depressives underwent a systematic open trial with rubidium chloride, 180 to 720 mg/day. By week 2, at least two-thirds had improved significantly (p less than 0.01) as measured by standard rating instruments such as the Brief Psychiatric Rating Scale and the Hamilton Depression Scale. Regression analysis suggested that the retarded endogenous pattern was most predictive of positive response. Treatment-emergent symptomatology, such as diarrhea, polyuria, and excitement, was generally mild and rarely necessitated interruption of the trial. The authors conclude that this salt has shown sufficient clinical promise to warrant more extensive trials under double-blind conditions.
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PMID:Exploration of the clinical profile of rubidium chloride in depression: a systematic open trial. 337 41

Urinary excretions of arginine vasopressin (AVP), sodium, potassium, osmoles and creatinine were measured in three in-patients with bipolar manic-depressive psychosis on at least eight 24-hour periods in each affective phase. Mood and body weight were recorded twice daily. The excretion by each patient of sodium, water and osmoles was greater in mania than during depression. Comparison of electrolytes and osmoles suggested that the increase was due to increased intake of salt and water rather than of total diet. There was a fall of mean AVP excretion during mania, the magnitude of the fall being related to the increase of water throughput. Compared with controls, AVP excretion was high and variable. It did not show the normal relationship to urine osmolality. Days with very high AVP were not associated with any characteristic feature of the other measurements; nor were they confined to any one point in the manic-depressive cycle. AVP does not appear to play a major role in the salt and water changes characteristic of manic-depressive psychosis and we have no evidence of its having any direct relationship to mood changes. We suggest that the observed abnormalities of AVP excretion are another manifestation of the central defect of this disease.
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PMID:Arginine vasopressin in manic-depressive psychosis. 343 61

The relaxation effects of endothelium-dependent (acetylcholine, histamine) and endothelium-independent (nitroprusside, nitrite) relaxing substances were comparatively examined on contracted thoracic aortic rings from normotensive and experimental renal and desoxycorticosterone acetate (DOCA)-salt hypertensive Wistar rats. On the aorta preparations from hypertensive animals a highly significant depression of the maximal relaxation effect of histamine and acetylcholine was observed. This was not seen with nitroprusside and nitrite. By use of a bioassay technique it was demonstrated that the depression of the endothelium-mediated response is not due to a diminished release of endothelium-derived relaxing factor. Impaired coupling between the endothelium and the smooth muscle cells is suggested to be responsible for that depression.
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PMID:Endothelium-dependent and independent relaxation of aortic rings from hypertensive rats. 345 79

The depressant action of antidromic volleys of impulses on gustatory nerve signals from the tongues of bullfrogs was studied. Electrical stimulation of the glossopharyngeal nerve at a rate of 100 Hz for 10 s and at supramaximal intensity slightly depressed the integrated glossopharyngeal nerve responses to quinine and to mechanical taps to the tongue. The same antidromic stimuli resulted in a 30-40% reduction in the responses to salt, acid, water, and warmed saline, but depressed greater than 80% of the afferent impulses firing spontaneously. The magnitude of responses to quinine and NaCl and the number of spontaneous discharges decreased gradually with an increase in either the frequency or the duration of antidromic stimuli. Similar results were obtained with intensities above the threshold for exciting gustatory and slowly adapting mechanosensitive fibers. The time required to recover from termination of the antidromic stimuli to two-thirds of the maximal amount of depression ranged between 6 and 7 min, with no significant differences among the depressions. The possible mechanisms involved in the antidromic depression of gustatory nerve signals are discussed.
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PMID:Selective depressant action of antidromic impulses on gustatory nerve signals. 348 68


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