Importance of Membrane Stabilizing Effect in Massive Overdose of Propranolol: Plasma Level Study in a Fatal Case

Hong, Chuang‐Ye; Yang, Wen‐Hsien; Chiang, Benjamin N.

doi:10.1177/096032718300200307

Cited by 21 publications

(6 citation statements)

References 18 publications

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“…Rezaei et al have shown that the cell membrane-stabilizing drugs such as cromolyn sodium and ketotifen, similar to propranolol, are able to inhibit T. gondii penetration into nucleated cells at appropriate concentrations in vitro and in vivo (17). Similarly, our data demonstrated that membrane-stabilizing action of beta-blocking agents such as propranolol (2 or 3 mg/kg/day) (26,27) alone and combined with pyrimethamine in tissues of BALB/c mice in both pre-and posttreatment groups reduced the burden of parasites. Previous studies have shown that treatment with cytochalasins impairs entry of T. gondii and Plasmodium falciparum into their respective host cells.…”

Section: Discussionsupporting

confidence: 81%

Evaluation of Propranolol Effect on Experimental Acute and Chronic Toxoplasmosis Using Quantitative PCR

Montazeri

Ebrahimzadeh

Ahmadpour

et al. 2016

Antimicrob Agents Chemother

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dCurrent therapies against toxoplasmosis are limited, and drugs have significant side effects and low efficacies. We evaluated the potential anti-Toxoplasma activity of propranolol at a dose of 2 or 3 mg/kg of body weight/day in vivo in the acute and chronic phases. Propranolol as a cell membrane-stabilizing agent is a suitable drug for inhibiting the entrance of Toxoplasma gondii tachyzoites into cells. The acute-phase assay was performed using propranolol, pyrimethamine, and propranolol plus pyrimethamine before (pretreatment) and after (posttreatment) intraperitoneal challenge with 1 ؋ 10 3 tachyzoites of the virulent T. gondii strain RH in BALB/c mice. Also, in the chronic phase, treatment was performed 12 h before intraperitoneal challenge with 1 ؋ 10 6 tachyzoites of the virulent strain RH of T. gondii in rats. One week (in the acute phase) and 2 months (in the chronic phase) after postinfection, tissues were isolated and DNA was extracted. Subsequently, parasite load was calculated using quantitative PCR (qPCR). In the acute phase, in both groups, significant anti-Toxoplasma activity was observed using propranolol (P < 0.001). Propranolol in the pretreatment group showed higher anti-Toxoplasma activity than propranolol in posttreatment in brain tissues, displaying therapeutic efficiency on toxoplasmosis. Also, propranolol combined with pyrimethamine reduced the parasite load as well as significantly increased survival of mice in the pretreatment group. In the chronic phase, anti-Toxoplasma activity and decreased parasite load in tissues were observed with propranolol. In conclusion, the presented results demonstrate that propranolol, as an orally available drug, is effective at low doses against acute and latent murine toxoplasmosis, and the efficiency of the drug is increased when it is used in combination therapy with pyrimethamine.

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Section: Discussionsupporting

confidence: 81%

Evaluation of Propranolol Effect on Experimental Acute and Chronic Toxoplasmosis Using Quantitative PCR

Montazeri

Ebrahimzadeh

Ahmadpour

et al. 2016

Antimicrob Agents Chemother

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“…A noticeable feature is that in some patients the clinical condition suddenly deteriorates after a period of relative stability and that, despite treatment with /3-adrenoceptor agonists, death occurs. Hong et al (1983) and Sangster et al (1984) have suggested that properties other than @-adrenoceptor blockade might be implicated in the clinical course of the intoxication or even in the fatal outcome.…”

Section: Discussionmentioning

confidence: 99%

“…Both clinical (Frishman et al, 1979) and experimental (Strubelt, 1984) studies have shown beta sympathomimetics to be the most effective drugs in the treatment of the hemodynamic disturbances after beta-blocker overdosage. Nevertheless, in a number of clinical cases such treatment has failed to prevent a fatal outcome (Montagna and Groppi, 1980;Shore et al, 1981;Laake et al, 198 1;Hong et al, 1983;Jean et al, 1984). This has led to the assumption that other properties in addition to beta blockade determine the clincial course after an overdose of a beta blocker (Hong et al, 1983;Sangster et al, 1984).…”

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confidence: 99%

“…Nevertheless, in a number of clinical cases such treatment has failed to prevent a fatal outcome (Montagna and Groppi, 1980;Shore et al, 1981;Laake et al, 198 1;Hong et al, 1983;Jean et al, 1984). This has led to the assumption that other properties in addition to beta blockade determine the clincial course after an overdose of a beta blocker (Hong et al, 1983;Sangster et al, 1984).…”

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confidence: 99%

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Central origin of respiratory arrest in beta-blocker intoxication in rats

Langemeijer

Wildt

Groot

et al. 1987

Toxicology and Applied Pharmacology

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. 89, 399-407. Propranolol HCl(7.5 mg.kgI), timolol maleate (7.0 mg. kg-'), and sotalol HCI (10 mg. kg-') were administered intracerebroventricularly (icv) to spontaneously breathing (SB) rats. The respiratory rate declined until the rats all died from respiratory arrest. Artificial ventilation resulted in survival of the rats for a 3-hr observation period. Intravenous (iv) administration of the same doses of the three beta blockers to SB rats did not result in either respiratory depression or death. Except for a decrease in heart rate (HR) the hemodynamic and respiratory parameters remained almost constant during the 3-hr observation period after iv administration to SB rats. After icv administration to SB as well as to ventilated rats no significant differences could be observed in the initial decrease in HR in comparison with iv administration. In SB rats at the end of the experiments a further decrease in HR was observed which might be ascribed to hypoxia since it did not occur in ventilated rata. After icv administration of each drug to the ventilated rats, mean arterial blood pressure showed a significantly greater decrease at the end of the 3-hr observation period than after iv administration. Plasma concentrations of the three drugs were determined just before death after icv administration in SB rats. In the other two groups they were measured at mean survival time and at the end ofthe experimental period. The plasma concentrations showed that the route of administration rather than the concentration ofthe beta blocker in plasma determines the occurrence. of respiratory arrest. It was concluded that an overdoes of propranolol, timolol, or sotalol can cause a centrally mediated respiratory arrest. Furthermore, a central mechanism appears to be implicated in the decrease in blood pressure. 0 1987 Academic Press, Inc.

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“…Poisoning with propranolol and other ,8-blockers with marked membrane depressant action (e.g, alprenolol, oxprenolol) has several common features not usually seen with drugs lacking this property (Allely 1983;Henry & Cassidy 1986;Hong et al 1983;Khan & Muscat-Baron 1977). These include marked bradycardia (below 50 beats/min), which is often refractory to electrical pacing, and progressive heart block.…”

Section: Cardiovascular System Actions Not Mediated By Blockade Of 8mentioning

confidence: 99%

The Management of Acute Poisoning Due to β-Adrenoceptor Antagonists

Julian

Ungar

1989

Medical Toxicology

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Although many cases of beta-adrenoceptor antagonist (beta-blocker) poisoning are uneventful, a proportion develop serious and sometimes fatal cardiovascular system depression with severe hypotension. As beta-adrenergic tone is not essential for cardiovascular function in health, there is no physiological reason why total beta-adrenoceptor blockade should have serious consequences in the resting individual. The toxic actions of beta-blockers appear to be related to properties such as membrane depressant activity and possibly due to actions on beta-adrenoceptors distinct from those in the cardiovascular system. Most reports of serious adverse effects following overdosage concern beta-blockers with significant membrane depressant activity, and in particular propranolol and oxprenolol, with which progressive heart block and bradycardia are features. Sotalol toxicity, with its unique electrophysiological action, is a special case. Animal experiments confirm that beta-blockers with membrane depressant activity are more toxic than the newer more selective ones, such as atenolol and nadolol. However, experimental models also reveal that artificial ventilation markedly reduces the toxicity of all beta-blockers tested, suggesting a respiratory depressant action with very high doses. Treatment of serious overdosage in man should include maintenance of adequate ventilation. High dose intravenous glucagon is recommended, because its inotropic action depends on direct stimulation of adenylate cyclase. beta-Agonists such as isoprenaline (isoproterenol) or prenalterol may be effective, but the nature of agonist-competitive antagonist interactions may necessitate the use of unrealistically large doses to overcome very high tissue beta-blocker concentrations.

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Importance of Membrane Stabilizing Effect in Massive Overdose of Propranolol: Plasma Level Study in a Fatal Case

Cited by 21 publications

References 18 publications

Evaluation of Propranolol Effect on Experimental Acute and Chronic Toxoplasmosis Using Quantitative PCR

Evaluation of Propranolol Effect on Experimental Acute and Chronic Toxoplasmosis Using Quantitative PCR

Central origin of respiratory arrest in beta-blocker intoxication in rats

The Management of Acute Poisoning Due to β-Adrenoceptor Antagonists

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