Pharmacodynamics of Inotropic and Chronotropic Responses to Oral Therapy with Propranolol

Boudoulas, Harisios; Beaver, Brian M.; Kates, Robert E.; Lewis, Richard P.

doi:10.1378/chest.73.2.146

Cited by 37 publications

(8 citation statements)

References 19 publications

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“…'14-7 Previous studies demonstrated that subjects with increased urinary catecholamine excretion have a short QSJ2. In addition, there is an inverse relationship between shortening of the QS2I and catecholamine excretion.14 Shortening of the QS2l caused by infusion of epinephrine or isoproterenol is directly related to the amount of drug administered in normal subjects.Y9 30 The oral glucose tolerance test results are also compatible with higher catecholamine activity. Mean blood glucose values are significantly greater in mitral valve prolapse patients than in our normal controls.…”

Section: Discussionmentioning

confidence: 80%

Metabolic studies in mitral valve prolapse syndrome. A neuroendocrine--cardiovascular process.

Boudoulas¹,

Reynolds²,

Mazzaferri³

et al. 1980

Circulation

158

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SUMMARY Symptomatic patients with mitral valve prolapse (MVP) frequently mimic thyrotoxicosis, hyperadrenergic states or hypoglycemia. Twenty symptomatic patients with auscultatory and echocardiographic MVP were studied in the clinical research unit. T8, T, and plasma cortisol were normal. Patients with MVP had normal responses to oral glucose administration but higher glucose levels than the controls (p < 0.05). Twenty-four-hour urinary epinephrine (E) and norepinephrine (NE) were greater than normal (E + NE excretion, 44 ± 2 vs 29.5 ,ug/g creatinine,p < 0.001). The short electromechanical systole corrected for heart rate (529 ± 3.9 vs normal 548 ± 2 msec, p < 0.01) also reflected high adrenergic tone. Frequent premature ventricular complexes (PVCs) with couplets and triplets were found in 14 patients. Catecholamine excretion and frequency of PVCs were parallel and both decreased significantly at night (p < 0.001). Plasma catecholamine increase with exercise was greater in patients in whom the number of PVCs increased more than 10 per minute compared with patients in whom the number of PVCs remained relatively unchanged (620 ± 80 vs 98 ± 20 msec, p <0.01).We

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Section: Discussionmentioning

confidence: 80%

Metabolic studies in mitral valve prolapse syndrome. A neuroendocrine--cardiovascular process.

Boudoulas¹,

Reynolds²,

Mazzaferri³

et al. 1980

Circulation

158

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“…1983;Wang et at. 1986)_ Studies of the concentration-response relationship for the negative inotropic effects of propranolol have produced conflicting results (Boudoulas et at. 1978;Morris et at.…”

Section: Concentration-effect Relationshipsmentioning

confidence: 99%

The Pharmacokinetics of Lignocaine and β-Adrenoceptor Antagonists in Patients with Acute Myocardial Infarction

Nattel

Gagne

Pineau

1987

Clinical Pharmacokinetics

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Lignocaine (lidocaine) and beta-adrenoceptor antagonists are widely used after acute myocardial infarction. The therapeutic value of these agents depends on the achievement and maintenance of safe and effective plasma concentrations. Lignocaine pharmacokinetics after acute myocardial infarction (MI) are controlled by a number of variables. The single most important is left ventricular function, which affects both volume of distribution and plasma clearance. Other major factors include bodyweight, age, hepatic function, the presence of obesity, and concomitant drug therapy. Lignocaine is extensively bound to alpha 1-acid glycoprotein, a plasma protein which is also an acute phase reactant. Increases in alpha 1-acid glycoprotein concentration occur after an acute MI, decreasing the free fraction of lignocaine in the plasma and consequently decreasing total plasma lignocaine clearance without altering the clearance of non-protein-bound lignocaine. Complex changes in lignocaine disposition occur with long term infusions, and therefore early discontinuation of lignocaine infusions (within 24 hours) should be undertaken whenever possible. Because the risk of ventricular tachyarrhythmia declines rapidly after the onset of an acute MI, lignocaine therapy can be rationally discontinued within 24 hours in most patients. Lignocaine has a narrow toxic/therapeutic index, so that pharmacokinetic factors are critical in dose selection. In contrast, beta-adrenoceptor antagonists' adverse effects are more related to the presence of predisposing conditions (such as asthma, heart failure, bradyarrhythmias, etc.) than to plasma concentration. The pharmacokinetics of beta-adrenoceptor antagonists are important to help assure therapeutic efficacy, to provide information about the anticipated time course of drug action, and to predict the possible role of ancillary drug effects (such as direct membrane action) and loss of cardioselectivity. Lipid solubility is the main determinant of the pharmacokinetic properties of a beta-adrenoceptor antagonist. Lipid-soluble agents like propranolol and metoprolol are well absorbed orally, and undergo rapid hepatic metabolism, with important presystemic clearance and a short plasma half-life. Water-soluble drugs like sotalol, atenolol, and nadolol are less well absorbed, and are eliminated more slowly by renal excretion. Clinical assessment of beta-adrenoceptor antagonism is more valuable than plasma concentration determinations in evaluating the adequacy of the dose of a particular beta-adrenoceptor antagonist.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…In the propranolol group the QSzI was within normal range indicating good beta blockade (5,6). The high adrenergic tone was still present two weeks after surgery.…”

Section: Discussionmentioning

confidence: 93%

“…On the other hand, there are more recent studies reporting the development of unstable angina, myocardial infarction, and even sudden death after discontinuation of propranolol -the so-called "propranolol withdrawal syndrome" (2,18,23,28). Previously we have shown that the negative inotropic effeet of propranolol is of short duration and directly parallels plasma half life (4-5 h), while chronotropic blockade persists significantly longer (5,6). Thus, in order to avoid the negative inotropic effect of propranolol it is not necessary to discontinue the drug more than 12 to 15 h. In addition, we have also shown that a transient hypersensitivity to isoproterenol is present after propranolol withdrawal (7) ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Beneficial effect of continuation of propranolol through coronary bypass surgery

Boudoulas

Lewis

Snyder

et al. 1979

Clinical Cardiology

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Summary: The safety and beneficial effect of continuation of propranolol (Pr) through coronary bypass surgery (CBS) was studied in two groups of patients. In the control group (50 patients) Pr was discontinued 24 h before CBS without reinstitution afterwards. In the propranolol group the drug was maintained up to 4 to 10 h before surgery and was restarted within 24 h afterwards. The incidence of subendocardial myocardial infarction was significantly lower in the Pr group (lout of 30 vs 10 out of 50, p < 0.05) while the incidence of transmural infarction was the same in both groups (3 out of 30, 10 %, vs 5 out of 50, 10%). The incidence of supraventricular tachycardias during the first three postoperative days was significantly lower in the propranolol group compared to control (5% vs 30%, P < 0.01). The 24 h urinary epinephrine and norepinephri ne excretion was significantly greater than normal the day before surgery (136 ± 12 vs 39 ± 4,ug/24 h, P < 0.01), and was still high two weeks after surgery (115.1 ± 14 ,ug124 h). There were no complications related to propranolol. The left ventricular function as measured from the systolic time intervals was the same preSupported in part by the Central Ohio Heart Association, Chapter of the American Heart Association. and postoperatively in both groups. The results of this study show that administration of propranolol up to 4 h before coronary bypass and reinstitution immediately afterwards is safe and beneficial.

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Pharmacodynamics of Inotropic and Chronotropic Responses to Oral Therapy with Propranolol

Cited by 37 publications

References 19 publications

Metabolic studies in mitral valve prolapse syndrome. A neuroendocrine--cardiovascular process.

Metabolic studies in mitral valve prolapse syndrome. A neuroendocrine--cardiovascular process.

The Pharmacokinetics of Lignocaine and β-Adrenoceptor Antagonists in Patients with Acute Myocardial Infarction

Beneficial effect of continuation of propranolol through coronary bypass surgery

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