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

Classifications of antiarrhythmic drugs have developed because of a need to organize the large number of agents available according to pharmacological properties of clinical relevance. The current classification is a hybrid of classification systems developed in the early 1970s. It subdivides drugs according to 4 major pharmacological actions: (a) depression of phase 0 sodium current; (b) antagonism of adrenergic effects on the heart; (c) prolongation of of action potential duration; and (d) calcium channel blockade. Further subdivision of sodium channel blockers is based on the kinetics of sodium channel blockade and drug effects on action potential duration. A critical analysis of selected aspects of the clinical actions of antiarrhythmic drugs indicates the value of the current classification, as well as some limitations in its ability to separate drugs into distinct groups with characteristic clinical properties. The strengths of the current classification are due to the clinical importance of the pharmacological properties on which it is based. These results in electrophysiological actions, indications, and adverse effects that are typical for each group of drugs. The limitations of the current system relate to the propensity of individual drugs to have actions of more than one class simultaneously, the way that the various actions of a given drug are dependent on concentration, rate, and tissue type, and to problems in subclass definition. Some of these shortcomings could be alleviated by returning to the concept, originally put forward by Singh and Vaughan Williams, of classes of drug action rather than classes of drug per se. This approach would be pharmacologically more realistic than trying to assign each antiarrhythmic agent to a single unique class, would be better able to incorporate the complexities of drug action, and would potentially be more flexible. The wide use of antiarrhythmic drug classifications attests to their value, and suggests that they are likely to continue to be important in the future.
 ...
PMID:Antiarrhythmic drug classifications. A critical appraisal of their history, present status, and clinical relevance. 171 4

The effects of L-type calcium channel blockers and stimulants on naloxone-precipitated withdrawal in mice acutely dependent on morphine were evaluated. Verapamil (10-80 mg/kg), diltiazem (20-120 mg/kg) and nicardipine (20-160 mg/kg), when administered subcutaneously, produced a dose-dependent reduction in forepaw tremor and weight loss during the abstinence reaction; jumping was also reduced by all three drugs, although the effect was not statistically significant in the case of nicardipine. By contrast, the calcium agonist Bay K 8644 (0.5-2 mg/kg, SC) increased forepaw tremor and weight loss, although this latter effect did not reach statistical significance. The effects of the calcium channel active drugs on the rotarod test were also explored, no correlation appearing with the results observed in abstinence (except for the jumping response), which suggests that the withdrawal results are not influenced by motor incoordination or unspecific CNS depression. These findings suggest that L-type calcium channels probably play an important role in withdrawal after acute morphine dependence. Taken together with other observations in chronic models, these results show that calcium channels are similarly involved in morphine abstinence after acute and chronic dependence, in contrast to the differences in the content and uptake of neuronal calcium induced by morphine under both conditions.
 ...
PMID:Differential effects of L-type calcium channel blockers and stimulants on naloxone-precipitated withdrawal in mice acutely dependent on morphine. 171 13

We screened the antiischemic, hemodynamic, and inotropic effects of different dosages of the new calcium channel blocker Ro 40-5967 in 65 patients with stable effort-induced angina pectoris. In a double-blind way, patients were randomized to recieve a single oral dose of 50, 100, or 200 mg Ro 40-5967 or placebo, given as a drinking solution. Left ventricular ejection fraction (LVEF), blood pressure (BP), and heart rate (HR) were measured at rest and during a supine bicycle exercise test on day 0 (baseline) and 2 h after drug intake on day 1. Twenty-four hours later, the bicycle exercise test was repeated. Ro 40-5967 improved exercise duration and resting LVEF. After 200 mg, exercise time increased significantly from 8.4 +/- 0.8 min (mean +/- SEM) to 9.6 +/- 0.7 min (p = 0.018), and LVEF at rest increased from 54.5 +/- 2.2 to 58.1 +/- 2.6% (p = 0.045). Time to 0.1 mV ST-segment depression increased significantly from 4.3 +/- 0.8 to 5.5 +/- 0.9 min in the 100-mg group (p = 0.013) and from 4.3 +/- 1.3 to 5.4 +/- 1.5 min in the 200-mg group (p = 0.027). Maximum ST-segment depression decreased significantly at all dose levels (p = 0.01), with the maximum decrease noted in the 200-mg group (from 0.21 +/- 0.03 to 0.15 +/- 0.02 mV, p = 0.004). BP, HR, and rate-pressure product did not change significantly at rest or at maximum exercise. A single dose of Ro 40-5967 has antiischemic properties in patients with stable angina pectoris, with maximum effects obtained after 200 mg. No signs of negative inotropy were noted, and the drug was well tolerated.
 ...
PMID:Lack of negative inotropic effects of the new calcium antagonist Ro 40-5967 in patients with stable angina pectoris. 172 72

Direct cardiac effects of KT-362 (5-[3 [[-2-(3,4-dimethoxyphenyl)-ethyl]amino]-1-oxopropyl]-2,3,4,5- tetrahydro-1,5-benzothiazepine fumarate), a drug that may inhibit intracellular calcium mobilization as well as extracellular calcium influx was compared to verapamil. Guinea pig hearts (n = 19) were used to examine the changes in atrial rate, atrioventricular conduction time (AVCT), coronary flow, myocardial oxygen consumption (MVO2), and isovolumetric left ventricular pressure (LVP). Both drugs concentration-dependently and reversibly decreased atrial rate, contractility, and MVO2; AVCT increased during spontaneous rhythm. The increases in AVCT and the incidence of AV dissociation were accentuated during cardiac pacing. Verapamil significantly increased coronary flow, while KT-362 did not. Median effective concentration (EC50) was about 25 times lower for verapamil in depressing LVP and about three times lower in depressing atrial rate and AV conduction. The changes in calcium channel current in voltage-clamped single canine Purkinje cells (n = 6) were also examined. Verapamil (0.3 microM) and KT-362 (7 microM) decreased peak Ca2+ channel current at maximum activation (+10 mV) by 38.1 +/- 8% and 28.6 +/- 6%, respectively, without shifting the current-voltage relationship. This study indicates that verapamil is more potent than KT-362 in depressing contractile function, heart rate, and AV conduction in isolated hearts and calcium current in isolated cardiac Purkinje cells. Moreover, there was a much greater difference between the EC50 for verapamil and that for KT-362 for the depression of indices of contractility (23-30-fold) than for the depression of sinoatrial and atrioventricular nodal function (2.5-4-fold).
 ...
PMID:Comparative cardiac effects of KT-362 and verapamil in isolated heart--correlation to calcium channel current depression. 172 38

Experimental studies have shown that calcium channel blockade has a protective effect on the ischemic myocardium. Although these agents may act by decreasing intracellular Ca2+ accumulation during reperfusion or to reduce oxygen requirements by decreasing myocardial work load, recent evidence suggests that calcium blockers may also favorably alter energy substrate metabolism in ischemic and reperfused myocardium. In this study, TA-3090, a new calcium channel blocker with minimal effect on myocardial work load, was used to study the effect of calcium channel blockade on both myocardial substrate utilization and reperfusion recovery of ischemic hearts. Isolated working rat hearts were perfused at an 11.5 mm Hg preload and an 80 mm Hg afterload with Krebs-Henseleit buffer containing 11 mM glucose, 1.2 mM palmitate, and 500 microunits/ml insulin. In aerobically perfused spontaneously beating hearts, a 0.5 microM dose of TA-3090 had a mild depressant effect on heart rate but no effect on peak systolic pressure development. In paced hearts (250 beats/min), 0.5 microM TA-3090 had no effect on either peak systolic pressure development or contractility. Fatty acid and glucose oxidation was determined by measuring 14CO2 production in hearts perfused with either [14C]palmitate or [14C]glucose, respectively, whereas glycolysis was determined by measuring 3H2O production from [3H]glucose. Under aerobic conditions, fatty acid oxidation was not altered by TA-3090, but a significant decrease in glucose oxidation and glycolytic rates was observed. If hearts were subjected to a 30-minute period of no-flow ischemia, the addition of 0.5 microM TA-3090 to the perfusate before ischemia significantly improved reperfusion recovery of mechanical function. The protective effects of TA-3090 were not observed if TA-3090 was added at the time of reperfusion and were not related to a depression of function before ischemia. TA-3090, added before ischemia, significantly reduced glycogen and ATP depletion during no-flow ischemia and also significantly decreased glycolytic rates in hearts subjected to low-flow ischemia (coronary flow = 0.5 ml/min). Combined, our data suggest that the beneficial effects of calcium channel blockade on the ischemic myocardium are not related solely to a decrease in myocardial work load or metabolic demand before ischemia, but rather may in part be related to a decrease in myocardial energy demand during ischemia itself, resulting in preservation of ATP and a decrease in glycolysis. The decrease in glycolytic rates during ischemia may also result in a reduction of glycolytic product accumulation during ischemia.
 ...
PMID:Effects of TA-3090, a new calcium channel blocker, on myocardial substrate utilization in ischemic and nonischemic isolated working fatty acid-perfused rat hearts. 174 68

Poisoning is a significant problem in the elderly. The majority of poisonings in older people are unintentional and may result from dementia and confusion, improper use of the product, improper storage or mistaken identities. Depression is also common in the elderly and suicide attempts are more likely to be successful in this age group. The elderly patient's recuperative abilities may be inadequate as a result of numerous factors including impaired hepatic or renal function as well as chronic disease processes. General management of poisoning in the elderly parallels management of younger adults, but it is especially important to ascertain underlying medical conditions and concurrent medications. In most poisonings, activated charcoal and cathartic are sufficient. Haemodialysis or haemoperfusion may be required at lower plasma drug concentrations in elderly patients. While the specific indications for antidotes are the same for all age groups, dosage alterations and precautions may need to be considered in the elderly. Drugs most often implicated in poisonings in the elderly include psychotherapeutic drugs, cardiovascular drugs, analgesics and anti-inflammatory drugs, oral hypoglycaemics and theophylline. Cardiovascular and neurological toxicities occur with overdoses of neuroleptic drugs and, more frequently and severely, with cyclic antidepressants. Patients with pre-existing cardiovascular disease are at particular risk of worsening ischaemic heart disease and congestive heart failure. Benzodiazepines only appear to produce significant toxicity during long term administration or in combination with other CNS depressants. Digoxin can cause both chronic and acute intoxication, most seriously cardiac toxicity including severe ventricular arrhythmias, second or third degree heart block or severe refractory hyperkalaemia. Immune Fab antibody is indicated for the management of digoxin toxicity, although patients dependent on the inotropic effect of digoxin may develop heart failure after digoxin Fab antibody administration. Nitrates can cause toxicity including headache, vomiting, hypotension and tachycardia from excessive sublingual, transdermal or intravenous doses. Conduction disturbances and hypotension occur with overdoses of antihypertensive drugs; these effects are mild with angiotensin converting enzyme (ACE) inhibitors, occasionally severe with beta-blockers and of significant concern with calcium channel antagonists. The elderly commonly use aspirin and other salicylates, are more likely to develop chronic intoxications to these agents, and are more susceptible to severe complications such as pulmonary oedema. Salicylate poisoning, recognition of which is often delayed, should be considered in elderly patients with neurological abnormalities or breathing difficulties, especially in the setting of acid-base abnormalities. The clinical effects of NSAID overdose are mild and usually involve the central nervous system and gastrointestinal tract.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Poisoning in the elderly. Epidemiological, clinical and management considerations. 179 7

Isradipine is a potent dihydropyridine calcium channel blocker. It is highly selective for vascular smooth muscle, with very few negative inotropic or chronotropic effects. It may have minor depressant effects on the sinoatrial node, hence reducing the incidence of reflex tachycardia. The drug is extensively metabolized in the liver, with several pharmacologically inactive metabolites. As the elimination half-life is about 9 h the drug is usually given twice daily, but a once-daily modified release form is under investigation. Isradipine is effective monotherapy in essential hypertension, and has been successfully combined with pindolol and captopril. On the basis of more limited evidence it also appears to be beneficial in stable angina and in congestive cardiac failure. A trial is also under way to assess its antiatherogenic properties. Adverse effects are those predicted for a vasodilator calcium antagonist, and may be less frequent than for equivalent doses of nifedipine. This needs to be confirmed by more extensive clinical experience. Overall, isradipine can be considered favourably in essential hypertensives where a calcium channel blocker is indicated, particularly if it is desirable to avoid myocardial depression or to minimize reflex tachycardia. Its role in other cardiovascular disease awaits further evaluation.
 ...
PMID:Isradipine. 183 Mar 20

We evaluated whether cromakalim (BRL 34915), a vasorelaxant agent which acts by opening potassium channels, could affect the systemic effects of endothelin, a newly discovered vasoconstrictive peptide. Intravenous administration of endothelin alone (400 pmol/kg) to anesthetized dogs produced blood pressure elevation, which was associated with an increase in cardiac output in the early phase, and was associated with an increase in total peripheral resistance in the late phase. Electrocardiogram showed significant ST-elevation in II, III, and aVF, and ST-depression in aVR and aVL. The same dose of endothelin given to dogs pretreated with cromakalim did not induce these hemodynamic and electrocardiographic changes. Thus, cromakalim, a potassium activator, inhibited the hemodynamic and electrocardiographic actions of endothelin, suggesting that hyperpolarization due to potassium channel activation inhibited the voltage-dependent calcium channel, which is thought to be a major mechanism for the pressor action of endothelin.
 ...
PMID:Effect of cromakalim (BRL 34915) on hemodynamic and electrocardiographic changes induced by endothelin in dogs. 185 May 97

The effects of removing extracellular Ca++ ions or of adding the organic calcium channel antagonist, nitrendipine, were tested on twitches and tetani (100 Hz for 2 sec) in frog toe muscles. Under conditions that did not reduce or that potentiated twitches, both procedures reduced the size of the tetanic responses. This depression was seen as an inability to maintain the maximum tetanic tension for more than 0.5 sec. Intracellular microelectrode recordings showed that the muscle fibers were depolarized (mean about 23 mV) during the stimulus train and the fiber only slowly repolarized after the train. The latter effect is the "late negative afterpotential" and it is produced by the accumulation of K+ ions in the t-tubules during the action potential train. Neither the depolarization nor the late negative afterpotentials were decreased in amplitude by nitrendipine. These results indicate that the voltage-sensitive, slow Ca++ channels are opened by the accumulation of K+ ions in the t-tubules during the tetanus and that the Ca++ ions entering via these channels are required to maintain the full strength of the tetanic contraction. It is suggested that this is a function of these Ca++ channels concentrated in the t-tubules of skeletal muscle fibers.
 ...
PMID:Decrease in the size of tetanic responses produced by nitrendipine or by extracellular calcium ion removal without blocking twitches or action potentials in skeletal muscle. 190 44

The effects of antihypertensive drugs, such as nifedipine, chlorpromazine, reserpine and thiopental on mean arterial blood pressure (ABP), mean intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were studied in 43 patients with systemic hypertension and intracranial hypertension due to hemorrhagic cerebrovascular diseases and other causes. These drugs are commonly used in neurosurgical practice for the treatment of systemic hypertension. Nifedipine, chlorpromazine and reserpine reduced the mean ABP, raised the mean ICP and decreased the CPP. The effects of these drugs on mean ICP and CPP were more pronounced in patients with severely increased ICP (more than 40 mmHg) than in patients with moderately increased ICP (20-40 mmHg). Thiopental reduced both mean ABP and ICP, whereas the CPP was unchanged from the preadministration level. During thiopental administration, however, respiratory depression was observed, and hence, intubation and ventilation were required. We suggest that, in the treatment of systemic hypertension in patients with increased ICP, barbiturates are more desirable than agents with calcium channel or alpha-adrenergic blocking actions, despite the problem of respiratory control.
 ...
PMID:Effects of antihypertensive drugs on intracranial hypertension. 195 Feb 24


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>