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The principal effects of cardiac glycosides probably can be classified as parasympathomimetic or sympathomimetic. Data from animals and from man suggest that polar cardiac glycosides, such as ouabain and digoxin, possess greater parasympathomimetic (vagal) cardiac effect for a given amount of sympathomimetic (positive inotropic) cardiac effect than do less polar cardiac glycosides, such as digitoxin. Polar glycosides therefore offer some advantage in uncomplicated paroxysmal atrial tachycardia and in uncomplicated atrial flutter and atrial fibrillation when the principal desired effect is reduction in the number of atrial impulses reaching the ventricles or conversion to normal sinus rhythm. Non-polar glycosides offer an advantage when positive inotropicity is desired but when there is some degree of atrioventricular block or when inappropriate sinus bradycardia or anorexia, nausea, or vomiting are present. Ecotopic impulse formation when due to cardiac glycosides is a toxic manifestation of excessive sympathomimetic effect, but is aggravated by vagal-induced sinus bradycardia, so that both parasympathomimetic and sympathomimetic capability of cardiac glycosides must be considered when dealing with myocardial electrical instability.
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PMID:Clinical implications of differences in pharmacodynamic action of polar and nonpolar cardiac glycosides. 83 69

A 46-year-old man, presenting with headache, nausea, and lassitude, was diagnosed as having diabetes mellitus and hyponatremia, and admitted to Tohoku University Hospital. Insulin treatment improved the hyperglycemia but aggravated hyponatremia, which was proved to be elicited by the inappropriate secretion of antidiuretic hormone (SIADH). An acute water load failed to suppress ADH release in the supine posture but slightly increased plasma atrial natriuretic peptide (ANP). On the other hand, plasma ADH markedly increased in response to an upright posture, accompanied by a fall in blood pressure and a rise in heart rate. After treatment with droxidopa "a sympathomimetic drug", ambulatory blood pressure gradually increased and hyponatremia disappeared. However, blood pressure and ADH responses to upright posture were not improved by treatment with the drug. Moreover, plasma ADH was still not sufficiently suppressed by acute water loading in the supine position, but plasma ANP markedly increased, thereby resulting in urinary dilution and natriuresis. These results suggest that exaggerated ADH release (SIADH) was brought about by the baroreceptor reflex stimulated by the postural hypotension, and also by the impaired osmoregulation associated with diabetic neuropathy, and that droxidopa improved cardiovascular function and increased ANP release with resultant urinary dilution and natriuresis in spite of slightly increased ADH release.
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PMID:A case of syndrome of inappropriate secretion of antidiuretic hormone associated with diabetes mellitus. 179 39

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of ipratropium bromide are reviewed. Ipratropium bromide, a synthetic quaternary isopropyl derivative of atropine, interrupts vagally mediated bronchoconstriction by inhibiting the cyclic guanosine 3',5'-monophosphate system at parasympathetic nerve endings. Ipratropium bromide is poorly absorbed after oral and inhaled administration but diffuses rapidly into tissue after i.v. or i.m. administration. The elimination half-life is 3.2-3.8 hours. After inhalation, the drug is eliminated in the urine and feces. The bronchodilatory effect of ipratropium bromide in stable chronic obstructive pulmonary disease appears to be comparable, and may be superior, to that of the beta-sympathomimetic agents. In acute exacerbations, ipratropium bromide is useful but may not be the preferred agent because of a delayed onset of action (within 15 minutes; mean dose-dependent duration of effect, three to five hours). Combination therapy with other bronchodilating drugs has proved useful. Ipratropium bromide may be a useful adjunctive agent in the treatment of asthma. Since the onset of action is delayed, ipratropium bromide should not be used as single-drug therapy in an acute asthmatic exacerbation. Reported adverse effects, including cough, nausea, palpitations, dry mouth, nervousness, gastrointestinal distress, and dizziness, have been mild. The usual dosage is two inhalations (36 micrograms) four times daily, and the maximum number of doses per day should not exceed 12. Although ipratropium bromide is currently indicated only for maintenance therapy in stable chronic bronchitis and emphysema, it may be useful as adjunctive therapy in asthma and in the management of acute exacerbations of chronic bronchitis and asthma. Additional experience in a variety of chronic obstructive pulmonary disorders will help to clarify the role of ipratropium bromide in the treatment of obstructive pulmonary disease.
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PMID:Use of ipratropium bromide in obstructive lung disease. 297 9

A case of intracerebral hemorrhage and characteristic angiographic changes associated with methamphetamine is reported. A 23-year-old woman suddenly complained of headache, nausea, vomiting and gait disturbance several minutes after intravenous injection of 30 mg of methamphetamine. She was admitted with consciousness disturbance, aphasia and right hemiparesis 26 hours after the onset. CT scan revealed subcortical hemorrhage in the left fronto-parietal region. Left carotid angiogram showed irregular segmental arterial narrowing, "beading" of the anterior and middle cerebral arteries. Emergency craniotomy was performed and a left fronto-parietal hematoma was removed totally. Histologically, the surgical specimen showed many vessels in which included thrombi with perivascular hemorrhage. Post-operative course was uneventful. Repeat carotid angiogram 4 months after the operation revealed normal anterior and middle cerebral arteries. We discussed about associations between the abuse of methamphetamine and the occurrence of intracranial hemorrhage and characteristic angiographic changes. As far as we know, there were 23 reports in an extensive review of the literature on intracranial hemorrhage associated with methamphetamine abuse. In the present case "beading" of the intracranial vessels may be related to angiitis induced by methamphetamine. Both the presence of arterial inflammation and increased blood pressure caused by sympathomimetic action of methamphetamine are probably the important factors in the occurrence of intracranial hemorrhage associated with methamphetamine.
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PMID:[Intracerebral hemorrhage and characteristic angiographic changes associated with methamphetamine--a case report]. 379 Mar 61

In 70-80% of asthmatic patients, an attack of asthma will follow 6-10 min of strenuous exercise. The increase in airway resistance is accompanied by hyperinflation and arterial hypoxemia and makes it difficult to continue or resume exercise. The past 10 yr have seen major advances in the prevention and treatment of exercise-induced asthma (EIA). The beta-sympathomimetic drugs, when administered as aerosols, have been shown to be most effective in reversing the airway obstruction, hyperinflation, and exercise-induced hypoxemia in patients with asthma. When administered as aerosols prior to exercise, the increase in airways resistance, hyperinflation, and hypoxemia are blocked in about 90% of patients. In addition to the sympathomimetic agents, sodium cromoglycate will also ameliorate or prevent EIA in 60-70% of patients. Oral administration of beta-sympathomimetics or methylxanthines is less efficacious in the prevention or treatment of EIA. Delay in absorption from the gastrointestinal tract requires at least 1-2 h before a significant response is observed. Prevention of EIA requires an adequate blood level, possibly because a high concentration of the drug does not reach the airway when the drug is given by the oral route. More importantly, aerosol administration prevents EIA at a fraction of the dose required orally. The side effects, such as nausea, tachycardia, and skeletal muscle tremor commonly observed following oral bronchodilator administration are rare with aerosol therapy.
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PMID:Drugs affecting the respiratory system with particular reference to asthma. 611 44

There is an increasing use and variety of beta-adrenoceptor blocking agents (beta-blockers) available for the treatment of hyperthyroidism. Recent comparative studies suggest that atenolol (200mg daily), metoprolol (200mg daily); acebutolol (400mg daily), oxprenolol ( 160mg daily), nadolol ( 80mg daily) and timolol (20mg daily) produce a beneficial clinical response equal to that seen with propranolol ( 160mg daily). Most beta-blockers reduce resting heart rate by approximately 25 to 30 beats/min, although a lesser reduction is seen with those possessing intrinsic sympathomimetic activity such as oxprenolol and pindolol. While earlier studies employing large doses of intravenous propranolol concluded that beta-blockade reduced myocardial contractility, more recent non-invasive studies suggest that the predominant cardiac effect is on heart rate. In patients with cardiac failure, beta-blockers may, however, produce a profound fall in cardiac output. Nevertheless, in combination with digoxin they may be useful in controlling the atrial fibrillation of thyrocardiac disease. beta-Blockers improve nervousness and tremor (although to a lesser extent with cardioselective agents) and severe myopathy, and they also reduce the frequency of paralysis in patients with thyrotoxic periodic paralysis. There is often subjective improvement in sweating but usually no major effect on eye signs. Recent studies show a 10% reduction in oxygen consumption/basal metabolic rate with long term oral use of selective or nonselective beta-blockers. In addition, many agents (propranolol, metoprolol, nadolol and sotalol but not acebutolol, atenolol or oxprenolol) reduce circulating tri-iodothyronine (T3) concentration by between 10 and 40%, although the clinical significance of this effect (if any) is not established. beta-Blockers may also have endocrinological effects on gastrin, cyclic AMP, catecholamines and other hormone levels. Given in adequate dosage, propranolol has been shown to control thyrotoxic hypercalcaemia. Minor side effects (nausea, headaches, tiredness, etc.) are quite common but overall beta-blockers are well tolerated by the thyrotoxic patient. The major use of these drugs is in symptomatic control while awaiting definitive diagnosis or treatment. As an adjunct to antithyroid drugs or radioactive iodine, beta-blockers will produce a satisfactory clinical response in the weeks to months before these forms of therapy produce a euthyroid state. beta-Blockers are more convenient than antithyroid drugs in the control of patients receiving therapeutic radioiodine, in that continuous therapy and assessment of biochemical response is possible.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Use of beta-adrenoceptor blocking drugs in hyperthyroidism. 614 1

Tertatolol is a noncardioselective beta-blocker without intrinsic sympathomimetic activity. In a preliminary 3-month open study, it was shown that T was devoid of any atherogenic effect since HDL-cholesterol (HDL-C) and apoprotein levels did not change for 3 months of therapy. To investigate the long-term effects of tertatolol on the lipid profile and its safety in hypertensive patients with peripheral arterial disease (PAD), a 9-month, randomized, double-blind, parallel group study was carried out in 40 patients. Tertatolol 5 mg once daily was compared with metoprolol 200 mg once daily. If BP was not controlled after 2 months, a vasodilatator agent, dihydralazine, was added at the lowest dose required to control BP (diastolic BP < 90 mm Hg). Lipoprotein fractions and apoproteins were assayed before (M0) and after 2, 6 and 9 months of therapy. At the same occasions, peripheral arterial disease (PAD) was evaluated on exercise tests carried out on a treadmill and on the regional blood flow measured in the ankle arteries by the Doppler technique. Four patients were not eligible for analysis. In the tertatolol group, 1 patient with a normal BP, and 2 patients who dropped out, 1 because of persistent nausea and 1 because of personal reasons. In the metoprolol group, 1 patient refused to take dihydralazine. In the 35 fully documented patients, BP control was achieved in both groups. The mean reductions in supine systolic/diastolic BP were 31.4/14.6 and 34.7/17.1 mm Hg in the tertatolol and metoprolol groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of tertatolol on lipid profile. 790 13

Local anesthetics are frequently administered in dentistry and thus can be expected to be a major source of drug-related complications in the dental office. Additionally, the dentist will more often be confronted with the treatment of risk patients; thus, the incidence of side effects can be expected to rise. In this study, 2731 patients receiving dental anesthesia were evaluated by questionnaire for risk factors, type and dosage of local anesthetic applied, type and duration of treatment, and complications associated with the administration of the local anesthetic. Of all patients, 45.9% had at least one risk factor in their medical histories, with cardiovascular diseases and allergies being the most frequent. The overall incidence of complications was 4.5%. It was significantly higher in risk patients (5.7%) than in nonrisk patients (3.5%). The most frequently observed complications (dizziness, tachycardia, agitation, nausea, tremor) were transient in nature and did not require treatment. Severe complications (seizure, bronchospasm) occurred in only two cases (0.07%). Articaine was found to be administered in over 90% of all dental anesthesias in Germany despite the great variety of local anesthetics available. Articaine 1:100,000 caused more sympathomimetic side effects than did articaine 1:200,000. Additionally, doses of local anesthetics proved not to be strictly determined according to body weight, especially for patients weighing less than 50 kg. In summary, it can be stated that dental local anesthesia can be considered safe. Nevertheless, the incidence of complications due to dental anesthesia can be expected to be further reduced if (a) patients are routinely evaluated for risk factors with an adequate medical history prior to dental treatment, (b) doses of local anesthetics are strictly determined according to body weight, (c) anesthetics with low concentrations of epinephrine are used, and (d) the concept of a differentiated dental anesthesia is applied.
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PMID:The incidence of complications associated with local anesthesia in dentistry. 948 57

Blockers of adrenergic beta-receptors (beta-blockers) are commonly administered in cardiology for coronary heart disease, arrhythmias, hypertension and some cardiopathic treatment. They have been also approved as a therapy of chronic heart failure recently. From pharmacological point of view, cardioselective and non selective beta-blockers (with or without intrinsic sympathomimetic activity) are distinguished. New drugs like celiprolol, carvedilol or sotalol have been developed and so the range of the group still continues to widen out. In toxicological routine practice we meet beta-blockers either in acute intoxication cases or in a control of patient's adherence to prescribed therapy. Dizziness, nausea, weakness, vasoconstriction and bradycardia are their usual undesirable effects, whilst in grave cases of a drug overdose bronchoconstriction, coronary spasms, hypotension and even cardiac insufficiency may occur. The article deals with the possibility of detection and identification of beta-blockers and their metabolites in urine by thin layer chromatography.
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PMID:[Identification of blockers of adrenergic beta-receptors by thin layer chromatography]. 1650 5

dl-threo-Methylphenidate is a highly efficacious drug for treating attention-deficit hyperactivity disorder (ADHD) that is currently administered as immediate- or controlled-release and osmotically controlled-released formulations. The drug exists as two enantiomers, d-threo-methylphenidate and l-threo-methylphenidate, with the former having been developed as a medication to treat ADHD in its own right. dl-threo-Methylphenidate undergoes enantioselective metabolism in the liver, which results in marked differences in the plasma concentrations of its isomers, depending on the route of administration and formulation. When dl-threo-methylphenidate is orally administered, the plasma concentrations of d-threo-methylphenidate are higher than those of l-threo-methylphenidate. However, with the recently developed methylphenidate transdermal system (MTS), 'first-pass' metabolism is circumvented and, as a consequence, plasma concentrations of d-threo-methylphenidate are consistent with those produced by oral formulations, but the relative concentrations of l-threo-methylphenidate are much higher, i.e. 50-60% of those of d-threo-methylphenidate. In this article, we review the pharmacokinetics and pharmacology of dl-threo-methylphenidate and its isomers to assess the extent to which their mechanism of action as noradrenaline (norepinephrine) and dopamine reuptake inhibitors is responsible for their efficacy and commonly occurring adverse effects. The major findings are that d-threo-methylphenidate and l-threo-methylphenidate share the same pharmacological profile as the parent racemate, i.e. catecholamine-selective reuptake inhibition with higher potency against dopamine versus noradrenaline reuptake in vivo. However, d-threo-methylphenidate is approximately 10-fold more potent than the l-isomer in this regard. For these drugs, their abilities not only to ameliorate the behavioural and cognitive dysfunctions in ADHD, but also to induce the common adverse effects of reduced appetite, nausea/vomiting and stomach ache, are almost certainly due to their ability to potentiate noradrenergic and/or dopaminergic function in the central and peripheral nervous systems. The sympathomimetic actions of ADHD drugs on cardiovascular function are currently an issue of concern. Since noradrenaline reuptake inhibition is the likely mediator for the effects of dl-threo-methylphenidate on blood pressure and heart rate, the more potent d-isomer will therefore be predominantly responsible. Motor and vocal tics are the other important adverse event to be considered in the treatment of ADHD. It is now accepted that tics are a frequently occurring behavioural manifestation of ADHD itself and the evidence for or against their exacerbation by treatment with dl-threo-methylphenidate or other stimulants remains highly contradictory. Focusing on the enantiomers of dl-threo-methylphenidate, it can be concluded that d-threo-methylphenidate, which is the more potent and abundant of the two isomers, is the major contributor of both efficacy and adverse effects, irrespective of the formulation or route of administration of the racemate. Moreover, for the oral, extended-release formulations of dl-threo-methylphenidate, the d-isomer represents the only pharmacologically active moiety when these medications are used in the clinic. With the MTS, plasma concentrations of l-threo-methylphenidate are higher than are achieved using oral formulations, but even in this case, it is likely that the contribution of this enantiomer to the efficacy and adverse effects of the racemate is no greater than 5-10% of the total.
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PMID:Methylphenidate and its isomers: their role in the treatment of attention-deficit hyperactivity disorder using a transdermal delivery system. 1695 48


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