Nitrates as an Integral Part of Optimal Medical Therapy and Cardiac Rehabilitation for Stable Angina: Review of Current Concepts and Therapeutics

Boden, William E.; Finn, Aloke V.; Patel, Dharmesh; Peacock, W. Frank; Thadani, Udho; Zimmerman, Franklin H.

doi:10.1002/clc.21993

Cited by 29 publications

(32 citation statements)

References 77 publications

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“…The effective glyceryl trinitrate dose used was high, as 0.1 mg/h in a 20-g mouse is roughly equivalent to 80 g/kg/min. Doses given to humans using glyceryl trinitrate patches usually do not exceed 0.8 mg/h in adults (28,61), but trials with much higher doses (160 g/min to 10 mg/h) have been performed (62). These doses are still 30 to 40 times lower than those used here, and yet the side effects associated with this high dose in the mouse seemed to be relatively mild.…”

Section: Discussionmentioning

confidence: 80%

“…Glyceryl trinitrate is used for the treatment of angina and heart failure due to its dilator activity in large veins and arteries (28). Glyceryl trinitrate induced vasodilatation occurs via a biotransformation process through denitrification to yield NO, which activates soluble guanylate cyclase and thus relaxes vascular smooth muscle (29).…”

Section: Erebral Malaria (Cm) Is a Lethal Complication Ofmentioning

confidence: 99%

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Transdermal Glyceryl Trinitrate as an Effective Adjunctive Treatment with Artemether for Late-Stage Experimental Cerebral Malaria

Orjuela-Sánchez

Ong

Zaniní

et al. 2013

Antimicrob Agents Chemother

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c Cerebral malaria (CM) is associated with low nitric oxide (NO) bioavailability, cerebrovascular constriction, occlusion, and hypoperfusion. Administration of exogenous NO partially prevents the neurological syndrome and associated vascular pathology in an experimental CM (ECM) mouse model. In this study, we evaluated the effects of transdermal glyceryl trinitrate in preventing ECM and, in combination with artemether, rescuing late-stage ECM mice from mortality. The glyceryl trinitrate and/or artemether effect on survival and clinical recovery was evaluated in C57BL/6 mice infected with P. berghei ANKA. NO synthase (NOS) expression in mouse brain was determined by Western blots. Mean arterial pressure (MAP) and pial arteriolar diameter were monitored using a tail-cuff blood pressure system and a cranial window preparation, respectively. Preventative administration of glyceryl trinitrate at 0.025 mg/h decreased ECM mortality from 67 to 11% and downregulated inducible NOS expression in the brain. When administered as adjunctive rescue therapy with artemether, glyceryl trinitrate increased survival from 47 to 79%. The adjunctive therapy caused a sustained reversal of pial arteriolar vasoconstriction in ECM mice, an effect not observed with artemether alone. Glyceryl trinitrate induced a 13% decrease in MAP in uninfected mice but did not further affect MAP in hypotensive ECM mice. Glyceryl trinitrate, when combined with artemether, was an effective adjunctive rescue treatment for ECM. This treatment ameliorated pial arteriolar vasospasm and did not significantly affect MAP. These results indicate that transdermal glyceryl trinitrate has potential to be considered as a candidate for adjunctive therapy for CM.

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Section: Discussionmentioning

confidence: 80%

Section: Erebral Malaria (Cm) Is a Lethal Complication Ofmentioning

confidence: 99%

Transdermal Glyceryl Trinitrate as an Effective Adjunctive Treatment with Artemether for Late-Stage Experimental Cerebral Malaria

Orjuela-Sánchez

Ong

Zaniní

et al. 2013

Antimicrob Agents Chemother

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“…Indeed, agents that are designed to act by binding to and activating selected G protein-coupled receptors (GPCRs), including drugs such as salmeterol (for asthma) 7 or exendin-4 (for diabetes) 8 , affect cellular functions by stimulating adenylyl cyclases. Similarly, agents that promote guanylyl cyclase-catalysed synthesis of cGMP have therapeutic utility; these include nitric oxide donor drugs such as glyceryl trinitrate (for angina therapy) 9 or the natriuretic peptide-inspired drugs 10 such as nesiritide, a recombinant form of human B-type natriuretic peptide (BNP).…”

mentioning

confidence: 99%

Advances in targeting cyclic nucleotide phosphodiesterases

Maurice

Ahmad

et al. 2014

Nat Rev Drug Discov

649

766

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Cyclic nucleotide phosphodiesterases (PDEs) catalyse the hydrolysis of cyclic AMP and cyclic GMP, thereby regulating the intracellular concentrations of these cyclic nucleotides, their signalling pathways and, consequently, myriad biological responses in health and disease. Currently, a small number of PDE inhibitors are used clinically for treating the pathophysiological dysregulation of cyclic nucleotide signalling in several disorders, including erectile dysfunction, pulmonary hypertension, acute refractory cardiac failure, intermittent claudication and chronic obstructive pulmonary disease. However, pharmaceutical interest in PDEs has been reignited by the increasing understanding of the roles of individual PDEs in regulating the subcellular compartmentalization of specific cyclic nucleotide signalling pathways, by the structure-based design of novel specific inhibitors and by the development of more sophisticated strategies to target individual PDE variants.

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“…The active is most commonly supplied in the tablet form with strengths of 0.3-0.6 mg with a dose up to 1.5 mg, as needed [8]. The active may produce a slight tingling or burning sensation when placed under the tongue.…”

Section: Glyceryl Trinitrate Productsmentioning

confidence: 99%

“…The isosorbide dinitrate is only 20-25 % bioavailable when taken orally. The usual dose is 5-80 mg [8].…”

Section: Isosorbide Dinitratementioning

confidence: 99%

Tablets and Other Solid Dosage Forms for Systemic Oral Mucosal Drug Delivery

Rane¹,

Moe²

2015

Advances in Delivery Science and Technology

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Nitrates as an Integral Part of Optimal Medical Therapy and Cardiac Rehabilitation for Stable Angina: Review of Current Concepts and Therapeutics

Cited by 29 publications

References 77 publications

Transdermal Glyceryl Trinitrate as an Effective Adjunctive Treatment with Artemether for Late-Stage Experimental Cerebral Malaria

Transdermal Glyceryl Trinitrate as an Effective Adjunctive Treatment with Artemether for Late-Stage Experimental Cerebral Malaria

Advances in targeting cyclic nucleotide phosphodiesterases

Tablets and Other Solid Dosage Forms for Systemic Oral Mucosal Drug Delivery

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