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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review discusses the use of antihypertensive drugs in acute and long term treatment of hypertensive disorders of pregnancy, including their placental transfer and adverse effects on the fetus. All antihypertensive agents cross the placental barrier and are present in varying concentrations in the fetal circulation, with varying resultant effects on fetal metabolism. Antihypertensive drugs that are lipid soluble will pass through the placental barrier with ease whereas the most polar will not. Placental transfer diminishes under conditions that decrease the surface area or increase the thickness of the placenta. Highly protein-bound drugs form complexes which impair placental transfer while unbound drugs cross the placenta easily. The ionised drug form is highly charged and cannot cross lipid membranes while the un-ionised form can easily cross the placenta. A decrease in placental blood flow can slow down the transfer of lipid soluble drugs to the fetus. Close monitoring of the fetal and maternal condition is necessary for the rest of the pregnancy after antihypertensive therapy is commenced. Methyldopa is the initial drug of choice for long term oral antihypertensive therapy in pregnancy. Neither short term nor long term use of methyldopa is associated with adverse effects. In the short term (<6 weeks) beta-receptor antagonists are effective and well tolerated provided there are no signs of intrauterine growth impairment. ACE (angiotensin converting enzyme) inhibitors are contraindicated in the second and third trimesters of pregnancy because they are teratogenic. Intravenous dihydralazine is widely used for rapid reductions of severely elevated blood pressure. The use of nifedipine concurrently with MgSO4 must be approached with caution because the combination is associated with severe hypotension, neuromuscular blockade and cardiac depression. In the last decade, knowledge of antihypertensive drugs used in pregnancy has improved and new drugs, e.g. calcium antagonists, which have been shown to have great potential for use in pregnancy, have been introduced. Safety for the fetus with newer drugs has not yet been adequately evaluated. Currently, well established and cost effective drugs such as methyldopa (long term use) and intravenous dihydralazine (rapid reduction) are the agents of choice to treat hypertensive disorders of pregnancy.
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PMID:Effects of antihypertensive drugs on the unborn child: what is known, and how should this influence prescribing? 1112 43

The prognosis for patients with congestive heart failure (CHF) has been improved as a result of the use of angiotensin converting enzyme inhibitors and beta-adrenergic receptor blockers. The success of these therapies underscores the pathogenic role of neurohormonal activation in CHF. Clinical and experimental evidence supports a pathophysiologic role for pro-inflammatory cytokines and nitric oxide (NO) in the effects of angiotensin II and norepinephrine in CHF. Potential mechanism(s) responsible for the effects of these immunomodulators can be explained on the basis of established principles of myocardial excitation contraction coupling (E-C). A novel hypothesis is proposed that cytokines and NO-mediated alterations in E-C coupling contribute to the reversible myocardial depression and beta-adrenergic desensitization observed in a diverse group of clinical conditions that activate host inflammatory responses, including CHF. Basic studies into cytokine signaling pathways in cardiac myocytes have the potential to provide important new insights relevant to the design of new management strategies for the treatment of congestive heart failure patients.
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PMID:Interactions between cytokines and neurohormonal systems in the failing heart. 1130 30

Normal physiological changes in the cardiovascular system in pregnancy such as increase in cardiac output, vasodilatation and hypervolemia are of clinical relevance as they are able to aggravate, mask or even imitate cardiovascular diseases. There is an increase of cardiac size and volume during pregnancy; furthermore hormonal changes lead to diaphragmatic elevation and barrel-shaped thorax followed by a rotation of the cardiac axis to the left (15 degrees-30 degrees). Cardiac topography and size, changes in cardiac functioning and physiology as well as hemodynamic changes lead to auscultatory and ECG changes (i.e. S1-Q3-type, ST-depression, T wave flattening). In addition there is a high incidence of functional systolic and diastolic sounds during pregnancy, which are also able to imitate cardiovascular diseases. The physiological changes in pregnancy are similar to those under heavy exercise. This results in continuous cardiac stress during the whole pregnancy. This stress is specifically high from the 28th to the 34th week of pregnancy and in the post-partum period; the maximum of cardiac stress is reached during labor. Important for the specific cardiac risk during pregnancy is not the type of heart disease but cardiac functioning and the severity of complaints before pregnancy. Principally it has to be expected that preexisting heart diseases will experience an aggravation of one grade according to NYHA during pregnancy. In cases of heart diseases with shunt defects, with shunt defect and injured myocardium, with continuous arrhythmia or atrial fibrillation, patients are at extremely high risk of cardiac death. A termination of pregnancy should be considered in all patients with heart diseases grade III or IV according to NYHA, severe pulmonary hypertension, Eisenmenger's syndrome, severe aortic or pulmonary stenosis, Marfan's syndrome, and severe continuous cardiac insufficiency. The drug therapy of cardiac diseases during pregnancy depends on the specific type of heart disease. Prescription of most drugs is principally possible during pregnancy and breast feeding. However, for most drugs there is only very limited therapeutic experience during this period. Definitively contraindicated during pregnancy and breast feeding are ACE inhibitors, angiotensin I and II blocking agents, vasopeptidase inhibitors and molsidomin, a NO-prodrug. In life-threatening conditions, however, sometimes it will be necessary to administer drugs with only poor experiences in pregnancy.
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PMID:[Risks of pharmacotherapy in heart diseases in pregnancy]. 1137 45

Several studies confirm cognitive impairment and dementia to be increased after stroke in the elderly. Although not necessarily involving memory deficits, the frequency of cognitive impairments may occur in up to 30% of stroke survivors at 3 months. This impairment may be confounded by preexisting cognitive decline or dementia. By contrast, cognitive changes and dementia are widely recognized in familial forms of stroke, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Several factors, including type of stroke, recurrent episodes, the site and laterality of the lesion(s), volume of cerebral infarction, medial temporal lobe atrophy, and coexistent neurodegenerative pathology predict the degree of impairment. Aphasia, diabetes mellitus, atrial fibrillation, and depression are listed among other biologic factors that further exacerbate cognition and affect long-term survival. There is no clear consensus whether genetic factors, such as the apolipoprotein E e4 allele or angiotensin converting enzyme gene polymorphisms, modify cognitive changes or stroke outcome. Although several neurotransmitter systems may be affected in post-stroke dementia, the amelioration of cholinergic function is a worthy target.
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PMID:Stroke and cognition. 1138

Alterations of the central nervous system may be important for imbalance of cardiovascular and fluid regulation in heart failure. The central renin-angiotensin and atrial natriuretic peptide (ANP) systems act as mutual antagonists. The effects of angiotensin converting enzyme (ACE) inhibition (quinapril, 6 mg/kg/day) and angiotensin II type 1 (AT1) receptor blockade (losartan, 10 mg/kg/day) on ANP levels in 18 selected, microdissected brain nuclei were determined in sham-operated rats and rats with left ventricular dysfunction 8 weeks after myocardial infarction (MI). Plasma ANP tended to increase in MI rats and was further increased by quinapril. ANP was decreased in 12 brain areas of MI rats. ANP concentration was also significantly decreased by quinapril in six brain nuclei including subfornical organ and organum vasculosum laminae terminalis (areas lacking blood-brain barrier), and by losartan in 16 brain nuclei outside and within the blood-brain barrier in sham operated rats. However, both quinapril and losartan prevented a further reduction of central ANP as a result of myocardial infarction. These data suggest that there are effects on central ANP that result from chronic left ventricular dysfunction as well as an ACE-inhibitor and AT1-antagonist. Mechanisms and consequences of central ANP depression remain unclear. They could, however, support systemic vasoconstriction and sodium and fluid retention.
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PMID:Chronic effects of ACE-inhibition (quinapril) and angiotensin-II-type-1 receptor blockade (losartan) on atrial natriuretic peptide in brain nuclei of rats with experimental myocardial infarction. 1140 19

The purpose of this study was to evaluate the antianginal and antiischemic effects of isosorbide-5-mononitrate (Mono Mack) in patents unresponsive to its therapy. Thirty eight patients aged 38 to 70 years who had coronary heart disease (CHD) were followed up. Estimation of the number of daily anginal episodes, 24-hour monitoring, EchoCG, bicycle ergometry, tetrapolar rheocardiography, and self-assessment were made. Prior to the follow-up all the patients were treated with nitrosorbide (80-100 mg/day), beta-blockers, ACE inhibitors, disaggregants, and a complex of physico- and psychotherapies. CHD progression was an indication for the use Mono Mack. Its dose was 20 mg twice a day. Following 18-20 days, the efficiency of its use was evaluated. The treatment yielded a clinical effect in all the patients. The total daily number of anginal episodes decreased from 3.9 to 1.2 times. 24-hour monitoring showed an average decrease in the duration of ST-segment depression from 554 to 245 min a day. There was a significant increase in the patients' physical fitness and a trend for cardiac contractility to increase. They felt all better. With clinical improvement, 5 patients had no changes, as evidenced by instrumental studies. It is concluded that Mono Mack is highly effective with dinitrate tolerance, 1.8-fold decrease in the dose of nitrates, and good interaction with other drugs.
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PMID:[Evaluation of the efficacy of isosorbide-5-mononitrate in CHF patients unresponsive to isosorbide dinitrate therapy]. 1151 Jan 89

We showed recently that post-frusemide (furosemide) natriuresis was associated with a major depression of medullary circulation. In the present study, prior to administration of frusemide the tubular transport of NaCl was modified by loading the animals with 5% saline to elucidate a possible interrelation between the tubular and vascular effects of the drug. Moreover, a possible involvement of the renin-angiotensin system was examined by pharmacological blockade using captopril, an inhibitor of angiotensin converting enzyme (1 mg x kg(-1), I.V.), or losartan, a selective inhibitor of angiotensin AT1 receptor (10 mg x kg(-1), I.V.). The effects of frusemide (0.25 mg x kg(-1) I.V., then the same dose given over 1 h) on renal medullary and cortical circulation (using laser-Doppler flowmetry) and renal excretion of sodium (U(Na)V), water and total solutes were measured in anaesthetised rats. With no pre-treatment, frusemide decreased the medullary flow (36.6 +/- 6.0%) significantly more than the cortical flow (10.1 +/- 1.0%; P < 0.001). The difference between the medulla and cortex was not significant in rats which showed high U(Na)V after hypertonic saline loading (2.0 +/- 0.4 vs. 0.4 +/- 0.1 micromol x min(-1) in non-loaded rats): 21.1 +/- 3.9% and 15.8 +/- 1.5%, respectively. At very high U(Na)V (9.5 +/- 1.1 micromol x min(-1)) the post-frusemide decrease in blood flow tended to be smaller in the medulla (7.6 +/- 7.7%) than in the cortex (16.2 +/- 2.6%). The fall in medullary blood flow was attenuated by pre-treatment with captopril (22.0 +/- 3.3%) and abolished by pre-treatment with losartan (2.8 +/- 11.8%). The decrease in cortical blood flow was not changed by hypertonic saline or angiotensin II blockers. The abolition of the post-frusemide depression of medullary blood flow by previous salt loading confirms the proposed link between tubular transport status and vasoconstriction. A similar modification of the response by blockade of the renin-angiotensin system suggests that the system is involved in the mechanism of medullary vasoconstriction.
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PMID:Renal vascular effects of frusemide in the rat: influence of salt loading and the role of angiotensin II. 1157 89

The Dex/CRH test is one of the most reliable neuroendocrine function tests for hypothalamic-pituitary-adrenocortical (HPA) system dysregulation in depression. Persistent overdrive of HPA system activity after successful antidepressant treatment predicts an enhanced risk for relapse of a depressive episode. As the renin-angiotensin system has been shown to play a role in HPA system activity, we investigated the impact of the angiotensin converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphism, which determines ACE plasma concentrations, on HPA system dysregulation. We performed repeated combined Dex/CRH tests in 115 patients suffering from major depression. Dex/CRH test results were related to the I/D polymorphism within the ACE gene, which was assessed by PCR. Genotype frequencies were comparable to those in the general population (I/I 16.8%, I/D 59.3%, D/D 23.9%). D/D genotypes showed a higher cortisol stimulation during the first Dex/CRH test after admission than homozygous I-allele carriers (repeated measurement ANOVA: P=0.034). Cortisol area under the curve values were highest in those with the D/D genotype (mean+/-SEM [nmol/l*75 min]: 12700+/-2220), intermediate in those with the I/D genotype (9570+/-1000), and lowest in those with the I/I genotype (5160+/-1000; ANOVA: P=0.04). After successful antidepressive treatment and attenuation of HPA system overdrive these differences were no more detectable. The HPA axis stimulating properties of higher ACE and consecutively higher AT-II and/or lower substance P concentrations may be crucial factors for the HPA system hyperactivity during major depressive episodes.
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PMID:Hypothalamic-pituitary-adrenocortical axis dysregulation in patients with major depression is influenced by the insertion/deletion polymorphism in the angiotensin I-converting enzyme gene. 1214 30

The elderly patient may show normal physiological changes of the cardiovascular and respiratory systems that accompany aging, as well as features of intrinsic cardiac disease. The latter include: a past history of myocardial infarction or ischaemic heart disease; history of congestive cardiac failure; angina; arterial hypertension (BP >140/90mm Hg); and conduction disorders. A key aspect to the safe and effective anaesthetic management of the elderly patient with cardiac disease is a careful preoperative assessment and optimisation of pre-existing drug therapies. All cardiac medications should be continued up to and including the morning of surgery with the exception of anticoagulation involving warfarin, and perhaps large doses of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists in patients with hypertension or heart failure. Anaesthetic techniques used in these patients should avoid episodes of excessive hypotension after induction of anaesthesia or large blood loss, or the combination of hypertension and tachycardia after noxious stimulation. The latter physiological disturbances are pivotal for the development of myocardial ischaemia. Both premedication (if used) and anaesthesia should avoid excessive sedation and respiratory depression. The choice of anaesthetic technique may vary between: a balanced technique involving an opiate and a volatile agent; an intravenous technique utilising infusions of propofol; or regional anaesthesia with or without additional sedation. There are no good data to suggest any one technique is better than the rest. The occurrence of ischaemia in the perioperative period may precede the postoperative development of significant cardiac morbidity and mortality (including myocardial infarction or unstable angina, congestive cardiac failure, cerebrovascular accidents, and severe arrhythmias). A number of strategies have been examined to reduce these adverse outcomes. The effect of acute beta-adrenoceptor blockade in treatment-naive patients is associated with reduction in the haemodynamic response to noxious stimuli and decreased ECG evidence of myocardial ischaemia, as well as a reduction in the number of cardiac adverse events. Other drugs (calcium channel antagonists, alpha(2)-agonists and adenosine modulators) have a less predictable influence on both myocardial ischaemia and hard cardiac outcomes. There is inadequate evidence at present to define the optimal time course for acute beta-blockade, or the groups of patients in whom preoperative beta-blockade should be initiated in the absence of contraindications. Nevertheless, addition of beta-blockers to the preoperative regimen should be considered in patients with evidence of or at risk for coronary disease undergoing major surgery. There is also evidence that long-term beta-adrenoceptor or calcium channel blockade or nitrate therapy for the high-risk cardiac patient offers little protection against silent myocardial ischaemia, nonfatal infarction, cardiac failure and cardiac death.
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PMID:Issues in the perioperative management of the elderly patient with cardiovascular disease. 1214 50

Reduction of excessive neurohumoral activation in chronic heart failure (CHF) improves the prognoses. In addition to reduction of angiotensin production or angiotensin II action and the influence of the sympathoadrenal system also blocking of aldosterone effects becomes part of the therapeutic procedure in patients with CHF. Excessive systemic and probably also local aldosterone production promotes undesirable fluid retention, hypokalaemia and hypomagnesaemia, induction of hypertrophy and fibrosis of the heart muscle and blood vessels and the development of endothelial dysfunction, peripheral vasoconstriction and depression of the baroreflex. In addition to classical effects also the existence of a rapid, so-called non-genomic effect of aldosterone is assumed. Adding a blocker of aldosterone receptors to ACE inhibition was not recommended due to possibility development of hyperkalaemia. Later it was revealed that ACE inhibitors are unable to block sufficiently the action of aldosterone and that addition of spironolactone in small amounts to ACE inhibition and diuretics does not cause in patients with CHF a major increase of the potassium level. In the RALES study (Randomized Aldacton Evaluation Study) comprising 1663 patients with serious heart failure (NYHA III, IV) addition of 25 mg spironolactone to standard treatment with ACE inhibitor, diuretic and as rule also digoxin reduced the mortality by another 30% as compared with the addition of placebo. Undesirable effects were minimal. As to potential protective mechanisms of spironolactone the greatest importance is ascribed to the reduction of excessive fibrosis of the heart muscle. Spironolactone reduces the level of the circulating N-terminal aminopeptide procollagen type III the high level of which is associated with deterioration of the prognosis.
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PMID:[The significance of aldosterone in chronic heart failure: the RALES study]. 1242 9


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