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)

Selected cardiovascular and renal functions were measured for 5 hours in conscious, chair-restrained, female rhesus macaques (Macaca mulatta) after IV (0.05 and 1.0 mg/kg) or oral (1.0 mg/kg) administration of staphylococcal enterotoxin B (SEB). Cardiovascular functions, renal hemodynamics, and renal metabolism were also studied between 6 and 11 hours after IV SEB inoculation. Oral SEB produced few changes in cardiorenal functions. In contrast, IV SEB produced hypotension, tachycardia, increased total peripheral and renal vascular resistance, and decreased cardiac and renal functions. The early significant (P less than 0.05) renal depression was not associated with hypotension (mean arterial blood pressure greater than 100 mm of Hg). However, all measured renal functions except extraction ratio of PAH were positively correlated with decreased blood pressure (r = 0.52 - 0.71) in the later phase of SEB toxemia. It is concluded that the kidney is one of the organs affected by IV SEB. Renal impairment may partially contribute to death during SEB enterotoxemia in macaques.
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PMID:Effect of staphylococcal enterotoxin B on cardiorenal functions in rhesus macaques. 41 47

Chronic renal insufficiency was produced surgically in Fischer 344 rats in order to evaluate the effects of enflurane anesthesia in animals with impaired renal function. Three groups of rats were anesthetized with enflurane: a control group without impairment of renal function (n = 7); a group with minimal impairment of renal function (n = 6); and a group with moderately severe renal impairment (n = 9). Another group of rats with moderately severe renal impairment (n = 8) was anesthetized with halothane. Two hours of anesthesia resulted only in mild transient depression of urea clearance in all groups. Six hours of anesthesia resulted in a 5 to 10 ml/day increase of urinary output in all groups and small increases in urea nitrogen levels in both groups with moderately severe renal impairment. Deterioration of the model was noted late in the experiment; at sacrifice, animals that had been anesthetized with enflurance and four with halothane had terminal renal failure. The morphological lesion in both groups was similar, resembling glomerulonephritis. Thus, there was no difference in the renal response to enflurane or halothane anesthesia among rats with chronic renal insufficiency.
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PMID:Renal effects of enflurane anesthesia in Fischer 344 rats with pre-existing renal insufficiency. 49 Mar 24

Because of the multiplicity of disease conditions and diminished tolerance for drugs in the aged, it is necessary to know concomitant pathologic conditions to determine which antihypertensive drug to use. In the Philadelphia Geriatric Center, there are about 1,000 residents, between 70 and 100 years of age. About 40% have hypertension; almost 50% have or once had depression; there are many cases of hiatal hernia and/or peptic ulcer; in one subdivision of residents, almost 40% have renal disease with BUN above 30 mg/100 ml. In antihypertensive treatment, some individuals respond fairly well to reassurance and weight reduction, when obese, even without drugs. All are given a low-salt diet. A diuretic is first used--thiazide in cases of good renal function, furosemide with impaired renal function. Liquid potassium supplements are given. If there is but little reduction in blood pressure in several weeks, methyldopa is added in ascending doses, in cases with or without renal impairment. In hypertension with impaired renal function, furosemide and/or methyldopa were especially valuable. Furosemide as an antihypertensive drug was also noted to delay the onset of congestive heart failure. Since reserpine can aggravate peptic ulcer and can precipitate or aggravate depression, it should seldom be used to treat hypertension in the aged. Guanethidine is rarely used, since it can cause cerebrovascular insufficiency and marked weakness. High blood pressure should be reduced slowly in the aged, to avoid untoward effects.
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PMID:An approach to the treatment of hypertension in the aged. 105 27

Thirty-three cases of infective endocarditis presenting during a 6.5 year period to a district general hospital were analysed retrospectively. The annual incidence was 22 cases per million population. Twenty-two cases had pre-existing cardiac disease, mainly valvular disease-usually rheumatic (nine cases) and prosthetic valves (10 cases). Recognizable precipitants such as recent surgery were uncommon. Two cases presented after deliberate drug overdose possibly due to depression exacerbated by systemic disease. Symptoms were usually non-specific. All but two cases had murmurs and most were pyrexial. Splinter haemorrhages and clubbing were seen in about 20% of cases. Viridans-type streptococci were the commonest infecting organisms (14 cases). Staphylococcal infection (six cases) was confined to intravenous drug abusers and patients with prosthetic valves. Five cases were culture negative. Cardiac failure was present in 13 cases at presentation and developed in seven others during treatment. Acute valve replacement was necessary in eight cases, and late replacement in three. Renal impairment (plasma urea > 8 mmol/l and/or plasma creatinine > 120 mumol/l) occurred in 19 cases during the course of their illness. Embolic phenomena occurred in 12 patients and mostly involved the central nervous system. In the 8 fatal cases, the cause of death was cardiac failure in six, cerebrovascular accident in one, and myocardial infarction in one. Four of the six patients who subsequently died of cardiac failure had been referred for surgery. Both those who were not referred had coexisting medical problems. Factors associated with increased mortality were age, male sex, cardiac failure (P < 0.01), renal impairment (P < 0.05), and embolic phenomena (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Infective endocarditis in a district general hospital. 143 86

The calcium antagonists are a heterogeneous class of drugs which block the inward movement of calcium into cells through 'slow channels' from extracellular sites. By inhibiting phase 0 depolarisation in cardiac pacemaker cells and phase 2 plateau in myocardium, and by depressing calcium ion flux in smooth muscle cells of blood vessels, these agents may exert profound effects on the cardiovascular system, particularly in susceptible individuals or in overdose. Sinus node depression, impaired atrioventricular (AV) conduction, depressed myocardial contractility, and peripheral vasodilatation may result. Pharmacokinetic features of calcium antagonists include rapid and complete absorption from the gastrointestinal tract, with extensive first-pass hepatic metabolism yielding generally low bioavailability. The volume of distribution is generally large and protein binding is high. Elimination is almost entirely by the liver. Impaired renal function does not affect pharmacokinetics. Verapamil is the most potent inhibitor of cardiac conduction and contractility, with diltiazem also showing such effects. Nifedipine is the most potent vasodilator, but only occasionally impairs the sinus node or AV conduction. Significant pharmacodynamic effects are common during combination therapy with calcium antagonists, especially verapamil and beta-blockers. Verapamil may significantly elevate serum digoxin concentrations and may exert additive negative effects on chronotropism and dromotropism when this combination is used. Overdoses of calcium entry blockers are becoming more frequent and reflect an extension of the known pharmacodynamic profile of these agents. Typical features include confusion or lethargy, hypotension, sinus node depression and cardiac conduction defects. Onset of symptoms may be delayed if a sustained release preparation is ingested. Management of calcium antagonist overdose includes gut decontamination with lavage and activated charcoal. All symptomatic patients and patients with a history of ingesting a sustained release preparation should be admitted for ECG monitoring. If bradycardia and/or conduction defects contribute to hypotension, atropine or isoprenaline (isoproterenol) may accelerate the ventricular rate. Transvenous pacing may be required. Depressed myocardial contractility usually responds well to calcium chloride or calcium gluconate administration, but further inotropic support may be required. Peripheral vasodilation should be managed with intravenous fluids and a pressor agent such as dopamine or norepinephrine (noradrenaline).
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PMID:Poisoning due to calcium antagonists. Experience with verapamil, diltiazem and nifedipine. 179 22

Sertraline is slowly absorbed after oral administration, with peak plasma concentrations at 6-8 h. Plasma concentrations are linearly related to dose. The elimination half-life is about 32 h; metabolism is by demethylation to an inactive metabolite. Once-daily dosing is recommended, with steady state being reached after about 7 days. The kinetics of sertraline in the elderly and in patients with renal impairment are similar to those in young healthy female volunteers. In young male volunteers, peak plasma concentrations were lower, and elimination half-life shorter, than in elderly men or both groups of women. Nevertheless, no reduction in dosage is recommended for these groups. Sertraline is highly active in animal models of depression, and administration of the drug to healthy human beings causes a selective, dose-related inhibition of 5-hydroxytryptamine (5-HT) uptake into blood platelets. Single doses of sertraline in volunteers caused changes in the quantitative pharmaco-electroencephalogram suggesting antidepressant and anxiolytic actions, with sedative potential evident only at doses of 200 mg or more. Sertraline does not impair psychomotor performance, including simulated car driving, and overall seems neither stimulating nor sedating: an increase in critical flicker fusion threshold suggests a slight alerting effect, whereas subjective tests indicate an increase in perceived sedation at doses of 100 mg or more. No potentiation of the effects of ethanol has been noted in either young or elderly subjects. No adverse effects on the electrocardiogram, blood pressure, or systolic time intervals have been detected, and sertraline lacks anticholinergic action. These studies imply a low probability of adverse central nervous and cardiovascular effects. Sertraline is probably a weak inducer of hepatic microsomal enzyme activity. Sertraline does not affect the clearance of lithium but there may be a pharmacodynamic interaction which leads to increased tremor when the drugs are given together. No clinically relevant effects were noted in the interaction studies with digoxin, atenolol and diazepam. The pharmacokinetics and pharmacodynamics of sertraline are generally favourable. However, caution is needed when sertraline is given to patients receiving lithium or drugs with a low therapeutic ratio, such as corticosteroids, oral hypoglycaemic agents, and warfarin.
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PMID:Clinical implications of the pharmacology of sertraline. 180 26

A porcine strain of Pasteurella multocida (serotype D:3) produced a toxin causing turbinate atrophy (TA) in pigs. The toxin (TAT), processed on a high performance liquid chromatography size exclusion column, eluted as a single peak (molecular weight of about 160,000) containing trace amounts of endotoxin (lipopolysaccharide, LPS; protein:LPS, 85:1). The eluted fraction migrated on sodium dodecyl sulfate polyacrylamide gels as a single band. It could be prevented from dissociating into two prominent polypeptides by addition of a protease inhibitor. A single dose (2.0 to 79.0 micrograms/kg) of TAT given to pigs intravenously was lethal. Doses from 0.02 to 1.0 microgram/kg caused transient clinical signs of porcine systemic toxicosis with reduced appetite, generalized weakness, depression, lethargy, weight loss, and in some instances, death. Intradermal doses of TAT (greater than or equal to 0.1 microgram/site) produced hemorrhagic areas within four hours. Systemically, TAT causes bilateral TA, lymphopenia, liver dysfunctions, and possible renal impairment. Affinity of TAT for cells of epithelial origin was demonstrated in mice given 125I-TAT. In vitro, TAT stimulated DNA and protein syntheses of peripheral blood lymphocytes and suppressed syntheses in turbinate and kidney cell cultures without being cytolytic. Biological effects of TAT were eliminated by exposure to either heat, trypsin or anti-TAT antibody.
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PMID:Host response to Pasteurella multocida turbinate atrophy toxin in swine. 230 67

The elderly represent a special challenge to the physician in providing effective cancer chemotherapy. Though they represent the majority of the patients who eventually will need such therapy, until recently little information was available on its use in this population. There are variable age changes in pharmacokinetics, particularly in renal elimination of drug and metabolites, which may necessitate dosage amendment. Concomitant renal impairment or hepatic disease may further alter drug disposition. Other common pre-existing conditions in the elderly also may increase susceptibility to adverse drug effects. For example, the risk of toxicity from doxorubicin and vincristine can be increased in the presence of pre-existing cardiac disease or peripheral neuropathy, respectively. Because of the variability of the ageing process and the effects of concomitant disease, each patient must be assessed on an individual basis. Furthermore, in treatment planning, not only age and health status but also the patient's attitude and the tumour type are important considerations. Chemotherapy for most malignancies appears beneficial and well tolerated in the elderly, and there is little evidence that age per se is a determinant of chemotherapy regimen selection and dosing. The exceptions may be the curable haematological malignancies for which chemotherapy seems less efficacious and more toxic in geriatric than younger patients. The complications of chemotherapy such as vomiting, mucositis and bone marrow depression must be anticipated, diagnosed early and managed aggressively in aged patients. Guidelines are provided to help manage these problems. Chemotherapy in the elderly is still at a relatively early stage of development. Further research is required to establish optimal regimens for use in this population, in particular for curable haematological neoplasms.
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PMID:Problems in the use of anticancer drugs in the elderly. 266 Nov 98

Life-threatening increased intracranial pressure can be reversed by a variety of drugs. These compounds all have some disadvantages, producing rebound effects, severe coma or cardiovascular depression and electrolyte imbalance. However, reduction of intracranial pressure is a prerequisite for recovery and the benefits of treatment outweigh the risks. Dexamethasone is rapidly eliminated, the short half-life (about 3 hours) indicating that dosage intervals should be kept small. As yet, however, its therapeutic efficacy has not been clearly demonstrated. Therefore, an association between pharmacokinetics and pharmacodynamics cannot be established. Osmotic diuretics are the most widely used agents for reduction of intracranial pressure. Pharmacokinetics show a very close relationship to changes in serum osmolality, but there are large variations in the clearance. For the use of osmotics, the blood-brain barrier must be intact. Osmotic diuretics may lead to intracerebral oedema or to acute renal failure as serum osmolality increases. Considering the pharmacokinetics of each drug, and the dynamics of intracerebral pressure and osmolality, an intermittent, individually titrated dosage should be administered, with simultaneous monitoring of intracranial pressure. Frusemide (furosemide) can be used as an adjunct, to enhance the effect of osmotic diuretics. Its pharmacokinetics are limited by renal function, depending on age as well as on the extent of renal impairment. Altered renal elimination of concomitantly administered drugs, and electrolyte imbalances should be anticipated when diuretics are used. Barbiturates are certain to decrease intracranial pressure in humans by an as yet unknown mechanism. Their administration is recommended for patients that do not respond to conventional therapy. As barbiturates can result in deep coma, knowledge of their pharmacokinetics is of great importance for recovery. Following single doses, pentobarbitone has a relatively long elimination half-life (about 22 hours). However, after repeated administration for several days, its elimination may be enhanced due to autoinduction. Thiopentone kinetics are characterised by distribution and redistribution into deep peripheral compartments. Administration of high and frequent doses leads to considerably delayed recovery. This is not true for methohexitone, which shows comparable pharmacokinetics after single and multiple dose administration. Elimination depends on liver blood flow. Thus, recovery from methohexitone-coma is rapid. Rapid elimination is also an important characteristic of etomidate and alphaxalone/alphadolone, two non-barbiturate hypnotics.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical pharmacokinetic considerations in the treatment of increased intracranial pressure. 330 68

Cardiovascular status and reactivity have been investigated in spontaneously hypertensive rats (SHR) with glycerol-induced acute renal failure. SHR with acute renal failure had significantly lower mean arterial blood pressures and heart rates. The pressor responses to noradrenaline and the chronotropic responses to right cervical sympathetic and vagal nerve stimulation were diminished in uraemic SHR compared to control SHR. The cardiovascular depression observed in SHR with acute renal failure was similar to that previously noted in normotensive rats with acute renal impairment.
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PMID:Cardiovascular responses in spontaneously hypertensive rats with acute renal failure. 614 56


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