Intravenous propranolol in patients with inflammation.

Waller, Derek G.; Smith, C. Wayne; Renwick, A. G.; George, C. F.

doi:10.1111/j.1365-2125.1982.tb01426.x

Cited by 8 publications

(4 citation statements)

References 6 publications

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“…iinistration of propranolol with inflammation was, here too, markedly smaller ts and in rats with inflam-than in control rats. The total concentrations of propranolol after intravenous administration were more than doubled in the rats with inflammation, Rats with which is in agreement with results in rats with adjuvant Control rats inflammation induced arthritis Barber et al, 1983) and in patients with various inflammatory 0.9 ± 0.1 19.7+2.1*diseases (De Leve & Piafsky 1981;Waller et al, 1982).…”

Section: Intravenous Administrati Antagonistssupporting

confidence: 87%

“…After oral administration the serum concentrations of propranolol and oxprenolol are higher when inflammation is present, in man (Schneider et al, 1976;Kendall et al, 1979) as well as in animals (Belpaire et al, 1981;Bishop et al, 1981;Barber et al, 1983). After intravenous administration, there is still a difference between serum concentrations of the P-adrenoceptor blockers in healthy and diseased individuals, in man (De Leve & Piafsky, 1981;Waller et al, 1982) and experimental animals (Belpaire et al, 1981;Bishop et al, 1981;Barber et al, 1983), but it is less pronounced.…”

Section: Introductionmentioning

confidence: 99%

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Binding to serum α₁‐acid glycoprotein and effect of β‐adrenoceptor antagonists in rats with inflammation

Belpaire

Bogaert

Mugabo

et al. 1986

British J Pharmacology

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1 The P-blocking effect of 4 P-adrenoceptor antagonists with different pharmacokinetic properties was studied after intravenous and intraportal administration to control rats and to rats with experimental inflammation. 2 In rats with inflammation the effects of propranolol and oxprenolol, which are mainly bound to a,-acid glycoprotein (ax-AGP), were significantly less after intravenous administration, but not after intraportal administration. In contrast, for metoprolol and atenolol, which are only negligibly serum bound, no difference was observed between control rats and rats with inflammation for either route of administration. 3 Total and unbound serum concentrations of propranolol were measured 20 min after intravenous and intraportal administration. 4 After intravenous administration, in the rats with inflammation total concentrations of propranolol were more than twice, and unbound concentrations less than half those of control rats. After intraportal administration the total concentrations were 8 times, and the unbound concentrations 3 times higher in the rats with inflammation. 5There was a significant correlation between the P-blocking effect and the unbound concentrations of propranolol after intravenous administration, but not after intraportal administration. The latter finding is probably because the unbound concentrations were supramaximal.

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Section: Intravenous Administrati Antagonistssupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Binding to serum α₁‐acid glycoprotein and effect of β‐adrenoceptor antagonists in rats with inflammation

Belpaire

Bogaert

Mugabo

et al. 1986

British J Pharmacology

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“…Herein, we report the pharmacokinetics and pharmacodynamics of verapamil in IBD (Crohn's disease), a condition for which a convenient and relatively robust method exists for grading of the disease severity [25]. Due to its inflammatory nature, Crohn's disease is expected to alter both drug plasma protein binding and the hepatic metabolism of certain drugs, resulting in reduced clearance [26–28]. The effect of the disease on response to cardiovascular drugs is, however, unknown.…”

Section: Introductionmentioning

confidence: 99%

Drug−disease interaction: Crohn's disease elevates verapamil plasma concentrations but reduces response to the drug proportional to disease activity

Sanaee

Clements

Waugh³

et al. 2011

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Inflammatory conditions such as Crohn's disease are associated with cardiovascular complications. Inflammation also substantially reduces clearance of some cardiovascular drugs. It has also been shown that in rheumatoid arthritis, an elevation in verapamil concentration does not result in increased response. WHAT THIS STUDY ADDS • A reduced response upon increased verapamil concentration in another inflammatory condition, inflammatory bowel disease, with different aetiology from arthritis was found. Interestingly, however, a mere affliction with the disease is not sufficient to alter pharmacokinetics and pharmacodynamics since we found that the alteration is a function of disease severity. There is a remarkable reverse correlation between the disease severity and response to verapamil. Our observation suggests a complex relationship between pharmacokinetics and pharmacodynamics which may have implications beyond the disease and the drug studied herein. AIM Inflammation is involved in the pathogenesis of cardiovascular diseases that includes reduced response to pharmacotherapy due to altered pharmacokinetics and pharmacodynamics. It is not known if these effects exist in general in all inflammatory conditions. It also remains unknown whether in a given population the effect is a function of disease severity. We investigated whether pharmacokinetics and pharmacodynamics of a typical calcium channel inhibitor are influenced by Crohn's disease (CD), a disease for which the disease severity can be readily ranked. METHODS We administered 80 mg verapamil orally to (i) healthy control subjects (n= 9), (ii) patients with clinically quiescent CD (n= 22) and (iii) patients with clinically active CD (n= 14). Serial analysis of verapamil enantiomers (total and plasma unbound), blood pressure and electrocardiograms were recorded over 8 h post dose. The severity of CD was measured using the Harvey‐Bradshaw Index. RESULTS CD substantially and significantly increased plasma verapamil concentration and in a stereoselective fashion (S, 9‐fold; R, 2‐fold). The elevated verapamil concentration, however, failed to result in an increased verapamil pharmacodynamic effect so that the patients with elevated verapamil concentration demonstrated no significant increase in response measured as PR interval and blood pressure. Instead, the greater the disease severity, the lower was the drug potency to prolong PR interval (r= 0.86, P < 0.0006), CONCLUSIONS CD patients with severe disease may not respond to cardiovascular therapy with calcium channel blockers. Reducing the severity increases response despite reduced drug concentration. This observation may have therapeutic implication beyond the disease and the drug studies herein.

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“…The APRP chosen were xl-acid glycoprotein (AGP), al-anti-trypsin (AAT) and C-reactive protein (CRP) because in inflammatory disorders, for which timegadine would be prescribed, the concentration of these proteins is Correspondence: Mr S. George, Department of Clinical Pharmacology, Groby Road Hospital, Groby Road, Leicester, UK. significantly elevated (Piafsky et al, 1978;Waller et al, 1982;Walker et al, 1983). These increases could affect the binding of timegadine and so the rate of elimination together with the duration of action may be altered.…”

Section: Introductionmentioning

confidence: 99%

The protein binding of timegadine determined by equilibrium dialysis.

George¹,

McBurney²,

Ward³

1984

Brit J Clinical Pharma

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The protein binding of timegadine to albumin, serum, plasma and plasma enriched with the acute phase reactants alpha 1‐acid glycoprotein, alpha 1‐anti‐trypsin and C‐reactive protein was determined by equilibrium dialysis. The effects of other analgesic and anti‐ inflammatories (indomethacin, ketoprofen, paracetamol and sodium salicylate) and other basic drugs (disopyramide, lignocaine, propranolol and quinidine) on the binding of timegadine were also determined. Timegadine binding was concentration‐dependent up to 0.5 micrograms/ml, but independent above this level up to 10.0 micrograms/ml, the mean and standard error being 93.8 +/‐ 0.5%. Albumin accounted for only 32.4% of timegadine bound to plasma. Plasma enrichment with the acute phase reactants led to significant increases in timegadine binding. Simultaneous dialysis with other drugs caused significant decreases in timegadine binding.

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Intravenous propranolol in patients with inflammation.

Cited by 8 publications

References 6 publications

Binding to serum α₁‐acid glycoprotein and effect of β‐adrenoceptor antagonists in rats with inflammation

Binding to serum α₁‐acid glycoprotein and effect of β‐adrenoceptor antagonists in rats with inflammation

Drug−disease interaction: Crohn's disease elevates verapamil plasma concentrations but reduces response to the drug proportional to disease activity

The protein binding of timegadine determined by equilibrium dialysis.

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Intravenous propranolol in patients with inflammation.

Cited by 8 publications

References 6 publications

Binding to serum α1‐acid glycoprotein and effect of β‐adrenoceptor antagonists in rats with inflammation

Binding to serum α1‐acid glycoprotein and effect of β‐adrenoceptor antagonists in rats with inflammation

Drug−disease interaction: Crohn's disease elevates verapamil plasma concentrations but reduces response to the drug proportional to disease activity

The protein binding of timegadine determined by equilibrium dialysis.

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Binding to serum α₁‐acid glycoprotein and effect of β‐adrenoceptor antagonists in rats with inflammation

Binding to serum α₁‐acid glycoprotein and effect of β‐adrenoceptor antagonists in rats with inflammation