Rapidly developing tolerance to transdermal nitroglycerin in congestive heart failure

Jordan, Randy A.; Love, Seth; Casebolt, Penny

doi:10.1016/0883-9441(87)90171-7

Cited by 8 publications

(12 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 of Jordan's patients on 60mg/day had, after 4 hours, lower plasma concentrations than the patients on 5 mg/day. The assay used by Jordan et al (1986) was mass spectrometry, and not gas chromatography as incorrectly stated in the accompanying editorial by Abrams (1986). On application of the 'Transderm-Nitro' system in the different studies, plasma concentrations increased gradually during the first few hours, while from the second to fourth hours onwards more or less constant concentrations are seen over 24 hours.…”

Section: Rate-controlling Membrane Systemmentioning

confidence: 87%

“…for 5 to 10mg released, plasma concentrations were of the order of 0.1 to 0.2 ~g/L or somewhat higher. However, Jordan et al (1986) found for 60mg release a concentration around 1 0 ~gjL after 24 hours, which is proportionally much higher. It should be added that Jordan and colleagues also studied smaller amounts of glyceryl trinitrate for 4 hours and that the values obtained for 5 or 10mg release at 4 hours were also higher than those in other studies.…”

Section: Rate-controlling Membrane Systemmentioning

confidence: 90%

“…Packer et al (1986) argue for the presence of both counter-regulation and tolerance in congestive heart failure patients treated with transdermal glyceryl trinitrate. While a thorough discussion of counterregulation and tolerance is not within the scope of this review, there is no doubt that attenuation of the haemodynamic effects and of the antianginal efficacy of glyceryl trinitrate has been seen in a number of well controlled studies with transdermal delivery systems (Abrams 1984(Abrams , 1986Jordan et al 1986;Packer et al 1986;Parker & Fung 1984;Scheidt 1986). The attenuation of the effects of glyceryl trinitrate with time is certainly not due to a decrease in plasma concentrations over the study period.…”

Section: Is There a Relationship Between Plasma Concentrations Of Glymentioning

confidence: 95%

“…The presence of congestive heart failure with decreased hepatic blood flow has been evoked to explain the high plasma concentrations found in some studies (Armstrong et al 1980b;Jordan et al 1986), but this has never been studied systematically. For 8 other disease states, e.g.…”

Section: Influence Of Disease States and Interactions On The Pharmacomentioning

confidence: 96%

See 3 more Smart Citations

Clinical Pharmacokinetics of Glyceryl Trinitrate Following the Use of Systemic and Topical Preparations

Bogaert

1987

Clinical Pharmacokinetics

View full text Add to dashboard Cite

Glyceryl trinitrate has been used for more than a century for the treatment of angina pectoris and, more recently, for the treatment of congestive heart failure. The introduction of transdermal delivery systems has renewed the controversy regarding the efficacy of the drug, mainly in the light of the development of tolerance. With concentrations of the order of 1 microgram/L or less, the measurement of glyceryl trinitrate in plasma is not easy: gas chromatography with electron capture detection has been used widely but recently gas chromatography-mass spectrometry has provided satisfactory results. Assay problems are most likely to be responsible for some of the unexpected results reported. Further factors which may confound the results of the study of plasma concentrations are the rapid metabolism of glyceryl trinitrate in blood in vitro, adsorption to containers and infusion sets, and the uptake and/or metabolism in vessel walls. From the intravenous infusion data, the large interindividual variability in plasma concentrations of glyceryl trinitrate is apparent. The plasma half-life is about 2 to 3 minutes; plasma clearance values reported vary from 216 to 3270 L/h, indicating extensive non-hepatic metabolism. With transdermal administration, mainly with the transdermal controlled delivery systems, plasma concentrations of glyceryl trinitrate appear to be maintained for up to 24 hours, with large interindividual variations. Despite the ability to maintain, for example with the transdermal delivery systems, relatively constant concentrations of glyceryl trinitrate, it has not been possible to find a relationship between plasma concentrations and pharmacological or clinical effects. This is in part due to the attenuation of the effects with time; from the available data it is clear that this attenuation occurs at a pharmacodynamic level (reflex adaptation and tolerance) and not at the pharmacokinetic level.

show abstract

Section: Rate-controlling Membrane Systemmentioning

confidence: 87%

Section: Rate-controlling Membrane Systemmentioning

confidence: 90%

Section: Is There a Relationship Between Plasma Concentrations Of Glymentioning

confidence: 95%

Section: Influence Of Disease States and Interactions On The Pharmacomentioning

confidence: 96%

See 2 more Smart Citations

Clinical Pharmacokinetics of Glyceryl Trinitrate Following the Use of Systemic and Topical Preparations

Bogaert

1987

Clinical Pharmacokinetics

View full text Add to dashboard Cite

show abstract

“…Nitrates and sydnonimines share the common mechanism of guanylate cyclase stimulation [5], which, in the case of nitrates, requires the presence of thiol groups [5][6][7]. In spite of their favourable haemodynamic effects, the use of nitrates is encumbered by the necessity of incorporating a sufficiently long dose-free interval [8][9][10] to circumvent tolerance [6][7][8]11], which in turn, precludes therapeutic coverage throughout a 24-h treatment cycle [12][13][14][15].…”

mentioning

confidence: 99%

Haemodynamic evaluation of two regimens of molsidomine in patients with chronic congestive heart failure

Lehmann

Reiniger

Beyerle

et al. 1995

Eur J Clin Pharmacol

View full text Add to dashboard Cite

We investigated the extent and duration of the haemodynamic effects of two regimens of molsidomine, i.e. two tablets of a standard regimen consisting of 4 mg given 6 h apart and one tablet of 16 mg in sustained-release form once daily in 13 patients with chronic congestive heart failure using a placebo-controlled, randomized, double-blind and crossover protocol over a period of 12 h. Both regimens significantly affected systolic, mean and diastolic pulmonary arterial pressure (reductions of up to 15%), right atrial pressure (reductions of up to 35%) and total pulmonary resistance (reductions of up to 18%). The lower dose achieved its maximum action after about 1 h and remained effective for 2 h, whereas the higher dose in sustained-release form showed maximal efficacy at 2 h and remained active even at 12 h. In contrast, only minor changes in arterial blood pressure, systemic vascular resistance and cardiac output were observed on both regimens, almost exclusively at 2 h. Heart rate was not affected by either of the regimens tested. Neither regimen led to any untoward adverse effects. Thus, molsidomine is a potent vasodilating agent which, apart from its effects on preload, also acts on pulmonary arterial and right atrial pressures, leaving systemic circulation largely unaffected on the regimens tested. Administered on its own, it is therefore suitable for treatment of congestive heart failure.

show abstract

Nitrates: Why and how should they be used today?

Silber

1990

Eur J Clin Pharmacol

View full text Add to dashboard Cite

Nitrates are highly effective both in terminating acute attacks of angina pectoris and in the prophylaxis of symptomatic and asymptomatic myocardial ischemia. Preload reduction by venodilatation is the prevailing mechanism of nitrates in patients with chronic stable angina and is the unique feature distinguishing them from beta and calcium-channel blockers. Nitrates dilate coronary arteries not only in pre- and poststenotic vessels, but also in eccentric lesions. In patients with endothelial dysfunction, nitrates seem to be the physiological substitute for endothelium-derived relaxing factor. During the past decade, however, there has been substantial evidence of a clinically relevant loss of the anti-ischemic effects ("nitrate tolerance"). Many studies with oral dosing of isosorbide dinitrate or isosorbide-5-mononitrate at least three times daily have proven nitrate tolerance in patients with coronary artery disease and/or congestive heart failure. Complete loss of anti-ischemic effects after repetitive, continuous patch attachments has also been found. As we first showed in 1983, intermittent therapy with once-daily ingestion of high-dose sustained-release isosorbide dinitrate was successful in preventing the development of tolerance. Similarly, tolerance to isosorbide-5-mononitrate also does not develop when it is ingested once daily. It is now generally accepted that a daily low-nitrate interval is required to prevent tolerance development. Although the minimal patch-free interval required to prevent tolerance needs further investigation, a 12-h patch-free interval should prevent tolerance in most patients. The prolonged duration of action of once-daily high-dosage administration of sustained-release formulations, the improved patient compliance with a single daily administration, and the increased likelihood of maximal anti-ischemic effects are important reasons for recommending high single daily doses of isosorbide dinitrate or isosorbide-5-mononitrate.

show abstract

Rapidly developing tolerance to transdermal nitroglycerin in congestive heart failure

Cited by 8 publications

References 0 publications

Clinical Pharmacokinetics of Glyceryl Trinitrate Following the Use of Systemic and Topical Preparations

Clinical Pharmacokinetics of Glyceryl Trinitrate Following the Use of Systemic and Topical Preparations

Haemodynamic evaluation of two regimens of molsidomine in patients with chronic congestive heart failure

Nitrates: Why and how should they be used today?

Contact Info

Product

Resources

About