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)

Fifty healthy mothers, with normal placental function, were anaesthetised with ketamine for Caesarean section. Anaesthesia was maintained with nitrous oxide, oxygen, muscle relaxants and controlled ventilation. Surgery was conducted in the lateral tilt position. Arterial blood samples were drawn from the mothers, and from the vessels of a double clamped section of umbilical cord, for blood-gas analysis. Results obtained were compared with those of a previous series anaesthetised with thiopentone, nitrous oxide, oxygen and muscle relaxants. Eight infants were clinically depressed, judged on the basis of their modified Apgar score 2 minutes after delivery. The average time to sustained respiration (TSR) was 58.1 seconds. The mean maternal pH and base excess values in the ketamine group were significantly greather than those reported after thiopentone anaesthesia. Mean Uv and Ua pH levels were also significantly higher after ketamine; in contrast, the average fetal base excess values did not differ from those obtained previously with thiopentone. The mean (Ma-Uv) and (Ma-Ua), pH gradients were 0.019 and 0.025 pH units greater respectively in the ketamine group compared to the thiopentone (P less than 0.005). The average (Uv-Ua) PO2 gradient was 3.4 mmHg less after ketamine anaesthesia (P less than 0.005). A significant inverse correlation was observed relating the I-D interval to the Ma and Ua pH values. Maternal arterial base deficit values appeared to increase with delay in delivering the fetus. Prolongation of the uterine incision to delivery (U-D) interval was associated with a decrease in Ua pH and base excess values. (Ma-Ua) pH and base excess gradients increased with lengthening of the U-D interval. No convincing evidence of awareness during anaesthesia was found during the study. Five patients, appeared to be hallucinated in the immediate post-anaesthetic period. Unpleasant dreams were reported in 5 instances. In this study ketamine appeared to be unassociated with significant biochemical asphyxia, but may have been responsible for some element of drug induced neonatal depression. In view of our own experience and that of other workers, it is suggested that ketamine induction for Caesarean section should be re-evaluated using a lower dose of the drug.
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PMID:Anaesthesia for Caesarean section with ketamine. 0 39

Their frequency is estimated with difficulty, although on autopsy pulmonary edema is found almost routinely. It is a major complication of overdoses (48 p. 100 of severe intoxications). Their formation can be suspected, when after the first phase of respiratory depressions, with coma, myosis, and a variable latent period, a second attack of respiratory insufficiency occurs with tachypnea, and cyanosis. The chest X-ray shows diffuse alveolar infiltration, sparing the apices. The heart being generally of normal size. Rapid disappearance of this infiltrate (24 to 48 hours) enables the elimination of two diagnoses: pneumonia due to inhalation of gastric fluid, an infectious pneumonia. Their pathogenesis remains very debatable: - in the majority of cases abrupt L.V.F. can be eliminated: -on the other hand it could be an allergic accident of the anaphylactic type, or local liberation of histamine, or a local toxic action on the pulmonary capillaries; - hypoxia, secondary to respiratory depression, could lead to pulmonary edema, by the same mechanism as at altitude; - finally, owing to the central neurological disorders a neurogenic theory can be put forward. Their treatment is essentially a combination of Nalorphine with oxygen therapy (by mask, or if necessary by assisted, controlled ventilation) with prevention of inhalation of gastric fluid (gastric emptying) or curative treatment of possible aspiration by antibiotics, and cortico-steroids. Diuretics can be useful, as well as cardiotonics.
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PMID:[Pulmonary edemas due to acute heroin poisoning]. 0 75

The activity of serotonergic (5HT) neurons in the dorsal raphe nucleus was inhibited by the i.v. administration of certain antipsychotic drugs (methiothepin, clozapine and thioridazine). However, other antipsychotic agents (chlorpromazine, haloperidol and pimozide) did not inhibit raphe cell firing. The inhibitory potency of these drugs on raphe activity correlates with reported central noradrenergic blocking efficacy. An alpha-adrenergic blocking agent, piperoxane, but not the beta-blocking agents, propranolol and MJ 1999, inhibited raphe activity when administered systemically. All of these drugs appear to act indirectly since they (and NE) have relatively weak or variable effects when applied microiontophoretically to raphe neurons. The depressant effects of certain antipsychotic drugs and piperoxane on 5HT neurons appears to be mediated by a cnetral adrenergic system since (1) the depression could be reversed by the catecholamine releasing agents 1- and d-amphetamine; (2) the depression could be abolished by destruction of adrenergic pathways in the CNS by chemical, mechanical, or electrothermic lesions. While a precise localization has not yet been obtained, the data suggest that these drug effects may be mediated by an adrenergic pathway ascending from the lower brainstem.
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PMID:Effect of antipsychotic drugs on the firing of dorsal raphe cells. I. Role of adrenergic system. 1 Jan 73

Dibenamine (DB) produced contraction due to influx and release of Ca in normal medium, whereas it produced relaxation of the K-induced contraction due to depression of the activity of the muscle cell membrane. DB inhibited active influx, passive influx and release of Ca induced by ACh in this order as the concentrations were increased and also inhibited the contraction by histamine selectively as compared with the contractions by ACh, K and Ba, the inhibition of the ACh-, K- and Ba-contractions being almost to the same degree. In addition, DB inhibited to much the same degree the phasic contraction(PC) and tonic contraction(TC) by histamine, whereas it inhibited TC in preference to PC induced by ACh, K and Ba. Irreversible inhibition by DB of ACh-, K- and Ba-induced contractions were protected by Ca, whereas those of histamine-induced contraction were selectively protected by histamine and antihistamine, but not by Ca. These results indicate that the antagonism of DB and its irreversibility against histamine may be due to blockade of the histaminergic receptor, whereas those against ACh, K and Ba may be due to inhibition of the Ca-site. Evidence has been obtained suggesting that the irreversible parallel shift to the right of the log concentration-action curve of histamine after washout of DB may be due to spare receptors, whereas that of ACh, K or Ba may be due to inhibition of the Ca-site.
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PMID:[Action mechanism of dibenamine on the tonus and inhibition of drug-induced contraction of the isolated guinea pig ileum, with special reference to its relationship to Ca]. 1 Feb 36

It was discovered that the product of a mix containing the enzyme creatine phosphokinase (CPK) and either glutathione (GSH) or cysteine caused platelets to adhere together in vitro. This platelet adhesive factor (PAF) was formed as CPK enzyme activity declined. An alternative method for the destruction of enzyme activity--heat at 56 degrees C--also resulted in the formation of an in-vitro active PAF which was both less stable and active than its chemically produced counterpart. Assay of the platelet adhesive potency of the CPK-GSH mix, using human platelets, revealed a wide variation in the response of different individuals' platelets to standard quantities of PAF. The nature of this preparation of PAF was investigated by both biochemical and biophysical means, including ion exchange chromatography, electrophoresis, amino acid analysis and analytical ultracentrifuge studies. Evidence is presented that PAF is the product of the disruption of the dimeric structure of the CPK molecule. PAF was found to adhere to paper, under the conditions of electrophoresis imposed, and also to cause sephadex beads to bind together, characteristics which suggested that the platelet adhesion reaction was probably a biophysical process. Red and white cells were not similarly affected. The feasibility of this novel concept for the initiation of platelet adhesion, as a naturally occurring process, was supported by the results of animal experiments in which a statistically depression of platelets in the systemic circulation followed the intravascular administration of PAF. The possible relevance to man of this basic mechanism in relation to exercise and disease processes, including ideopathic and post-traumatic thrombosis, atherogenesis, and dysbaric aseptic necrosis of bone, is discussed.
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PMID:The formation of a platelet adhesive factor by disruption of the creatine phosphokinase molecule. 1 Mar 63

In isolated papillary muscles of cats the changes in Ca inward current and isometric contractile force following a decrease of extracellular pH from 7.4 to 5.5 were studied. The Ca current was analyzed (a) by measuring the upstroke velocity of Ca-mediated action potentials and (b) in voltage clamp experiments using the double sucrose gap technique. 1. At a pH of 5.5 the upstroke velocity of the Ca-mediated action potential decreased to 65% of the control, while overshoot and action potential duration remained almost unchanged. Furthermore, the relative refractory period was prolonged and in some cases, a "Wenckebach-like" phenomenon occurred. In voltage clamp experiments, the slow inward current was found to be diminished to 50-60% of the initial control value and over a broad voltage range the current voltage relationship curve was shifted to weaker currents. Acidosis did not influence the steady state inactivation but altered the kinetics of inactivation of the slow inward current and induced an increase of tauinactivation and taurecovery. This indicates that acidosis exerts a complex effect on the slow membrane channel. 2. The normal response of the Ca current towards variations of the extracellular Ca concentration (0.5-4 mM) or towards the addition of the beta-stimulating compound isoproterenol (2 mg/l) was not altered by the lowered extracellular pH. 3. In the acid medium, isometric contractile force declined to 40% of the control value within 25 min and, thus, reacted stronger than the Ca current. This indicates that those forms of acidosis used in the present experiments caused their negative inotropic effect not exclusively via a depression of the Ca current. Rather an additional intracellular effect has to be assumed which finally leads to a reduced activity of the contractile system. 4. At pH 5.5 excess Ca (4 mM) induced the same quantitative response of the contractile system as obtained at normal pH. In contrast, the positive-inotropic effect of 2 mg/l isoproterenol was more pronounced, whilst the sensitivity of the Ca inward current towards this beta-stimulating compound remained unchanged.
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PMID:Influence of low extracellular pH upon the Ca inward current and isometric contractile force in mammalian ventricular myocardium. 1 May 49

Following an initial dose response study, metoprolol, a selective beta1-receptor blocking agent, was compared with equipotent dosages of propanolol in a double blind cross-over study, including exercise tolerance tests, on fourteen patients with angina pectoris. Long term therapy with metoprolol then followed until the seventy-second week. Patients performed 8% more total work on metoprolol with 15% more work recorded up to the onset of S-T depression, in comparison with propranolol. In the long term, ther was no significant difference in work performed when the daily dosage of metoprolol was changed from a q.i.d. to a b.d. regime. Metoprolol was shown to be an effective anti-anginal compound with good tolerance and safety, with gradual improvement in underlying myocardial ischaemia during long term treatment.
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PMID:An eighteen months' study of the clinical response to metoprolol, a selective beta1-receptor blocking agent, in patients with angina pectoris. 1 May 64

A series of studies on the pharmacokinetic and pharmacodynamic properties of some tricyclic antidepressants is reviewed. During treatment with the same oral dose of these drugs, patients develop widely differing plasma levels. The importance of this variability for the clinical effects has been studied in detail for the monomethylated compound, nortriptyline. There is an association between side-effects and high plasma levels of this drug. In endogenously depressed patients, the relationship between plasma level and effect appears to be curvilinear. The tricyclic antidepressants differ in their capacity to inhibit transmitter uptake into noradrenaline- and serotonin neurons respectively. Nortriptyline is a preferential noradrenaline uptake inhibitor, while the dimethylated compound, chlorimipramine also has a profound influence on serotonin neurons. These differential effects are also reflected in changes in the levels of the transmitter metabolites in cerebrospinal fluid (CSF). The CSF studies have also supported the hypothesis of a biochemical heterogeneity of the depressive syndrome. The levels of the serotonin metabolite, 5-HIAA were bimodally distributed in CSF. In patients with a low level of 5-HIAA there was a significant correlation between the CSF metabolite level and the severity of the depression, and these patients also appeared to be more suicide-prone than those with higher 5-HIAA levels. These patients seemed to be less amenable to treatment with nortriptyline. The effect of chlorimipramine treatment in this subgroup of depressives is presently being explored.
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PMID:Treatment of depression with tricyclic drugs--pharmacokinetic and pharmacodynamic aspects. 1 May 83

A relationship between brain monamines and endogenous depression is suggested by observations on the mode of action of drugs producing or alleviating depressive symptoms. For example, reserpine is capable of faithfully mimicking the clinical picture of endogenous depression, which may be related to monoamine depletion. On the other hand, antidepressant drugs, e.g. the monoamine oxidase inhibitors, the tricyclic antidepressants and the monoamine precursors appear to increase the availability of monoamines at postsynaptic receptor sites. The different classes of antidepressant agents in general appear to potentiate each other's actions, according to animal data and clinical observations. Studies on the mode of action of tricyclic antidepressants with different profiles and on monoamine precursors suggest that 5-hydroxytryptamine is primarily involved in the control of mood, and noradrenaline in psychomotor activity. Clincial investigations initiated by the drug studies have demonstrated changes in monoamine metabolism in endogenous depression. The available evidence thus suggests a causal relationship between disturbances in monoamine metabolism and depression.
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PMID:The contribution of drug research to investigating the nature of endogenous depression. 1 May 84

Tardive dyskinesia has been regarded as a long-term complication of neuroleptic administration to patients with the diagnosis of schizophrenia. However, nine of the first fourteen patients evaluated for an investigation of tardive dyskinesia met diagnostic criteria for depression. Neuroleptics produce blockade of post-synaptic dopaminergic receptors. Tardive dyskinesia occurs when neuroleptics are discontinued, and is regarded as a manifestation of super-sensitive post-synaptic dopaminergic receptors. Tardive dyskinesia occurs when neuroleptics are discontinued, and is regarded as a manifestation of super-sensitive post-synaptic dopaminergic receptors. Chronically decreased neurotransmission in the synapse of a patient with depression may contribute to the development of a super-sensitive receptor and could explain the high proportion of patients with depression seen in this sample of patients with tardive dyskinesia.
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PMID:Tardive dyskinesia and depressive illness. 1 Jun 3


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