Fact-checked by Grok 2 weeks ago

Nitrovasodilator

A nitrovasodilator is a pharmaceutical agent that induces vasodilation by donating nitric oxide (NO), a potent endogenous signaling molecule that relaxes vascular smooth muscle cells.^[1] These compounds encompass organic nitrates, such as nitroglycerin (glyceryl trinitrate) and isosorbide dinitrate, as well as metal-containing agents like sodium nitroprusside.^[2] By releasing NO, nitrovasodilators activate soluble guanylate cyclase in smooth muscle cells, elevating cyclic guanosine monophosphate (cGMP) levels, which dephosphorylates myosin light chains and reduces intracellular calcium, thereby promoting arterial and venous dilation.^[1] Clinically, nitrovasodilators are cornerstone therapies for cardiovascular conditions, particularly angina pectoris, where short-acting formulations like sublingual nitroglycerin (0.3–0.6 mg) provide rapid relief by dilating coronary arteries and decreasing myocardial oxygen demand through preload reduction.^[2] They are also employed in acute heart failure to lower afterload and improve cardiac output via balanced arterial and venous effects, and in hypertensive emergencies with agents like sodium nitroprusside for controlled blood pressure reduction.^[3] Long-acting nitrates, such as isosorbide mononitrate (60–240 mg daily), serve as second-line prophylaxis for chronic stable angina after beta-blockers or calcium channel blockers.^[2] Despite their efficacy, nitrovasodilators are associated with common adverse effects including headache (incidence >10%, up to 64%), flushing, dizziness, and orthostatic hypotension due to systemic vasodilation.^[2] A major limitation is the development of tolerance with continuous exposure (after 12–24 hours), attributed to impaired biotransformation and oxidative stress, which can be mitigated by implementing nitrate-free intervals of 8–10 hours.^[2] Ongoing research explores strategies to enhance NO bioavailability and overcome tolerance for broader therapeutic applications.^[4]

General Overview

Definition and Classification

Nitrovasodilators are a class of pharmaceutical agents that induce vasodilation primarily through the donation of nitric oxide (NO), which activates soluble guanylate cyclase in vascular smooth muscle cells, leading to increased cyclic guanosine monophosphate (cGMP) levels and subsequent relaxation of smooth muscle.^[5] This NO-mediated mechanism reduces preload and afterload, distinguishing nitrovasodilators from other vasodilator classes that act via different pathways, such as calcium channel blockade.^[6] Nitrovasodilators are broadly classified into organic nitrates and other nitro compounds based on their chemical structure and NO-releasing properties. Organic nitrates, the most common subclass, contain the characteristic nitrate ester group (R-ONO₂), exemplified by nitroglycerin (glyceryl trinitrate) and isosorbide dinitrate, which require enzymatic bioactivation—primarily by mitochondrial aldehyde dehydrogenase-2 (ALDH2)—to liberate NO.^[7] In contrast, other nitro compounds, such as sodium nitroprusside, function as direct or spontaneous NO donors without needing bioactivation, releasing NO rapidly upon administration.^[5] This classification highlights their shared vasodilatory endpoint but differing pharmacokinetics and clinical handling.^[7] A key property of most nitrovasodilators, particularly organic nitrates, is the necessity for bioactivation to generate bioactive NO species, such as through denitration reactions that produce nitrite intermediates, which sets them apart from pure direct NO donors like gaseous NO or certain metal nitrosyl complexes.^[7] This bioactivation step is crucial for their therapeutic efficacy but can contribute to challenges like tolerance upon prolonged exposure.^[6]

Historical Development

The synthesis of nitroglycerin, a prototypical nitrovasodilator, occurred in 1847 when Italian chemist Ascanio Sobrero produced it by nitrating glycerol with a mixture of nitric and sulfuric acids while working in Turin under Théophile-Jules Pelouze.^[8] Sobrero recognized its explosive potential but also noted its physiological effects, including severe headaches indicative of vasodilatory action, though he deemed it too unstable for practical medical application at the time.^[9] Early explorations of its biological properties began in the mid-19th century, with homeopathic uses reported as early as 1849 by Constantin Hering, who administered small doses to induce controlled headaches.^[8] The therapeutic potential of nitrovasodilators for cardiovascular conditions emerged in the 1860s, driven by efforts to alleviate angina pectoris. In 1867, Scottish physician Thomas Lauder Brunton pioneered the clinical use of amyl nitrite, an organic nitrite, to relieve anginal pain through vasodilation, marking the first targeted application of a nitro compound in cardiology.^[9] Building on this, British physician William Murrell extended the approach to nitroglycerin in 1879, administering it to patients with angina and hypertension after observing its blood pressure-lowering effects in healthy volunteers; his work led to its inclusion in the British Pharmacopoeia by 1892.^[10] These developments established nitrovasodilators as key agents for symptom relief in coronary artery disease, with nitroglycerin transitioning from an industrial explosive—famously stabilized by Alfred Nobel for dynamite production in the 1860s—to a medical staple.^[9] Throughout the 20th century, nitrovasodilators saw widespread clinical adoption for treating cardiovascular diseases, including angina, heart failure, and hypertension, due to their rapid vasodilatory effects on coronary and systemic vessels. Sublingual nitroglycerin tablets, in use since the early 20th century, received initial U.S. Food and Drug Administration (FDA) approval in 1981 for specific formulations, formalizing their use for acute angina relief and enabling broader accessibility.^[11] A pivotal advancement came in 1977 when pharmacologist Ferid Murad demonstrated that nitrovasodilators like nitroglycerin release nitric oxide (NO), which activates guanylyl cyclase in vascular smooth muscle to produce cyclic GMP and induce relaxation, elucidating their mechanism at the molecular level.^[12] This finding connected organic nitrates to endogenous NO signaling, reinforced by Robert Furchgott's 1980 discovery of endothelium-derived relaxing factor (EDRF) and the 1987 confirmation by Louis Ignarro and Salvador Moncada that EDRF is NO, which collectively transformed understanding of vascular biology.^[13] By the 1980s, as long-acting nitrovasodilator formulations proliferated for chronic therapy, clinicians recognized the phenomenon of nitrate tolerance, where prolonged exposure diminishes vasodilatory efficacy, often necessitating dose adjustments or nitrate-free intervals to restore responsiveness.^[14] This insight, emerging from studies on sustained nitroglycerin use, refined dosing strategies and highlighted oxidative stress and neurohormonal activation as underlying causes, ensuring safer long-term application in cardiovascular management.

Clinical Applications

Medical Uses

Nitrovasodilators are primarily employed for the acute relief of angina pectoris in patients with coronary artery disease, where they rapidly reduce myocardial oxygen demand by dilating coronary arteries and peripheral veins.^[15] For instance, sublingual nitroglycerin is a first-line agent for terminating acute angina attacks, providing symptom relief within minutes by decreasing preload and afterload.^[16] They also serve to prevent angina attacks through long-term use, with oral isosorbide dinitrate commonly prescribed for chronic stable angina to improve exercise tolerance and reduce the frequency of ischemic episodes.^[17] In the management of acute heart failure, nitrovasodilators alleviate symptoms by promoting venous capacitance and reducing pulmonary congestion, particularly in cases with elevated filling pressures.^[18] Intravenous nitroglycerin is utilized in decompensated heart failure to enhance cardiac output without significantly increasing heart rate.^[19] For hypertensive emergencies, these agents provide rapid blood pressure control; sodium nitroprusside, administered intravenously, is effective in severe hypertension and acute aortic dissection due to its balanced arterial and venous dilation.^[20] Sodium nitroprusside is further indicated for inducing controlled hypotension during surgical procedures, such as neurosurgery, to minimize blood loss by maintaining mean arterial pressure at targeted levels.^[21] Off-label applications include topical nitroglycerin for anal fissures, where it relaxes the internal anal sphincter to promote healing, though this use has been partially superseded by other therapies.^[16] Historically, nitroglycerin was explored for erectile dysfunction via nitric oxide-mediated vasodilation, but it has been largely replaced by phosphodiesterase-5 inhibitors.^[15] Emerging evidence supports their potential in pulmonary hypertension, particularly inhaled formulations to selectively reduce pulmonary vascular resistance without systemic effects.^[22] As of September 2025, nebulized nitroglycerin has shown efficacy in managing persistent pulmonary hypertension of the newborn (PPHN) in neonates.^[23]

Routes of Administration

Nitrovasodilators are administered through multiple routes to achieve varying onset times and durations of action, tailored to clinical needs such as rapid relief or sustained vasodilation. The sublingual and oral routes are commonly used for nitroglycerin and isosorbide derivatives. Sublingual nitroglycerin tablets (0.3–0.6 mg) provide rapid onset within 1–3 minutes, with peak effects in 5 minutes and duration of approximately 30 minutes, making them suitable for acute scenarios like angina attacks.^[15]^[24] In contrast, oral isosorbide dinitrate (10–40 mg, three times daily) has a slower onset of 15–30 minutes and duration of 4–6 hours, ideal for prophylactic management.^[17]^[2] Transdermal and topical formulations offer sustained release for longer-term control. Nitroglycerin transdermal patches (0.2–0.8 mg/hour) or 2% ointments are applied to the skin, with onset in 5–10 minutes for ointments but typically 30–60 minutes for patches to reach steady state, providing effects over 12–14 hours when worn daily.^[15]^[25] These are particularly suited for chronic conditions requiring consistent vasodilation without frequent dosing.^[15] Intravenous administration allows for precise titration in critical settings. Sodium nitroprusside is given as a continuous IV infusion (0.5–10 mcg/kg/min), with rapid onset within 2 minutes and effects lasting about 10 minutes after discontinuation, enabling fine-tuned blood pressure control in intensive care environments.^[20] Similarly, IV nitroglycerin infusions (starting at 5 mcg/min) achieve immediate onset for acute hemodynamic management.^[26]^[25] Other routes, such as buccal or inhaled forms, are employed for specific rapid-onset requirements. Buccal nitroglycerin tablets dissolve between the cheek and gum, offering onset similar to sublingual (1–3 minutes) with duration up to 3 hours.^[27] Inhaled nitroglycerin aerosols provide quick absorption for targeted vasodilation in select cases.^[26] Pharmacokinetic variations across routes influence bioavailability and half-life, as detailed in the pharmacokinetics section.^[15]

Pharmacology

Mechanism of Action

Nitrovasodilators, such as organic nitrates, exert their vasodilatory effects through bioactivation to nitric oxide (NO), a key signaling molecule. This process involves the enzymatic denitration of the nitrate group by mitochondrial aldehyde dehydrogenase 2 (ALDH2), which serves as a high-affinity reductase converting the parent compound into bioactive NO and reactive intermediates.^[28]^[29] The simplified bioactivation can be represented as:

\text{Nitrate} \rightarrow \text{NO} + \text{reactive intermediates}

This reaction occurs primarily within vascular smooth muscle cells, independent of endothelial involvement.^[28] Once released, NO diffuses into the cytosol of smooth muscle cells and binds to the heme moiety of soluble guanylate cyclase (sGC), activating the enzyme to catalyze the conversion of guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP).^[30] Elevated cGMP levels then activate protein kinase G (PKG), which phosphorylates downstream targets, including the inhibition of myosin light chain kinase and activation of myosin light chain phosphatase. This leads to dephosphorylation of myosin light chain, reducing actin-myosin interactions and promoting smooth muscle relaxation.^[31]^[32] The net result is vasodilation, which reduces vascular tone and preload in the cardiovascular system.^[30] The vasodilatory action of nitrovasodilators demonstrates vascular selectivity based on dose. At low doses, they preferentially dilate veins, decreasing venous return and cardiac preload with minimal effects on arterial resistance.^[33] At higher doses, arterial dilation becomes more prominent, lowering systemic vascular resistance and afterload.^[34] This endothelium-independent mechanism distinguishes nitrovasodilators from endogenous NO pathways, allowing direct relaxation of vascular smooth muscle even in the presence of endothelial dysfunction.^[35]

Pharmacokinetics

Nitrovasodilators, particularly organic nitrates such as nitroglycerin and isosorbide dinitrate, undergo extensive first-pass metabolism in the liver following oral administration, resulting in low systemic bioavailability. For example, oral isosorbide dinitrate exhibits an average bioavailability of approximately 25%, with significant interindividual variability (10% to 90%) attributable to hepatic presystemic extraction.^[36] This effect is largely avoided with sublingual or intravenous routes, which enable rapid absorption and higher plasma concentrations; sublingual nitroglycerin, for instance, achieves about 40% bioavailability, influenced by mucosal metabolism and patient hydration status.^[16] Metabolism of these agents primarily involves hepatic enzymatic reduction to nitric oxide, the key bioactive species, often via denitration processes. Half-lives vary considerably across nitrovasodilators, reflecting differences in metabolic stability: nitroglycerin displays a brief plasma half-life of 1 to 4 minutes owing to rapid extrahepatic and hepatic denitration, whereas isosorbide dinitrate has a half-life of around 1 hour, with its pharmacologically active metabolite isosorbide-5-mononitrate persisting for 4 to 6 hours.^[15]^[36]^[37] Agent-specific metabolic pathways contribute to clinical variability. Nitroglycerin is swiftly converted to dinitrate and mononitrate metabolites through mitochondrial aldehyde dehydrogenase-mediated processes.^[16] In contrast, sodium nitroprusside, an inorganic nitrovasodilator administered intravenously, decomposes non-enzymatically to release nitric oxide while generating cyanide ions that bind hemoglobin, forming cyanmethemoglobin; subsequent conversion to thiocyanate requires monitoring to prevent toxicity during extended infusions.^[20]^[21] Excretion of nitrovasodilator metabolites occurs predominantly via the renal route. Denitrated products from organic nitrates, such as glyceryl mononitrates and isosorbide mononitrates, are cleared in urine, while thiocyanate from sodium nitroprusside elimination can accumulate in renal impairment, prolonging its half-life to 6 to 9 days.^[20]^[21]

Safety Profile

Contraindications

Nitrovasodilators, such as nitroglycerin and sodium nitroprusside, carry absolute contraindications in conditions where their vasodilatory effects could critically impair hemodynamics and organ perfusion. Severe hypotension, defined as systolic blood pressure below 90 mm Hg or a drop greater than 30 mm Hg from baseline, is an absolute contraindication, as these agents exacerbate the condition by further reducing vascular resistance and preload.^[38] Cardiogenic shock represents another absolute contraindication, where nitrovasodilators should neither be initiated nor continued, as they can worsen cardiac output and lead to multiorgan failure.^[39] Right ventricular infarction is contraindicated due to the preload dependence of the right ventricle; venodilation reduces venous return, potentially causing profound hypotension and decreased left ventricular filling.^[6] Similarly, hypertrophic cardiomyopathy with left ventricular outflow tract obstruction is an absolute contraindication, as vasodilation may increase the dynamic obstruction and impair cardiac performance.^[6] Relative contraindications apply in scenarios where benefits may outweigh risks but require heightened vigilance and potential dose adjustments. Recent use of phosphodiesterase-5 (PDE5) inhibitors, such as sildenafil (within 24 hours) or tadalafil (within 48 hours), is a relative contraindication due to synergistic enhancement of cyclic guanosine monophosphate, resulting in severe, potentially life-threatening hypotension.^[40] Severe anemia is also relative, as the reduced oxygen-carrying capacity of blood can be further compromised by vasodilation-induced hypotension, limiting tissue oxygenation.^[40] In special populations, nitrovasodilators demand caution in hypovolemia, where uncorrected low intravascular volume heightens the risk of excessive hypotension; fluid resuscitation is typically required beforehand.^[38] Concurrent administration with other vasodilators, such as calcium channel blockers or alpha-blockers, necessitates careful monitoring to mitigate additive hypotensive effects that could precipitate adverse outcomes.^[5] Use in pregnancy is classified as Category C by the FDA, with potential risks of maternal hypotension leading to fetal hypoxia; benefits must outweigh risks, and monitoring is essential.^[40] In pediatrics, caution is advised, particularly with sodium nitroprusside in neonates due to heightened cyanide toxicity risk; dosing adjustments and close monitoring are required.^[15] These precautions primarily aim to avert severe hypotensive episodes, as detailed in the adverse effects section.

Adverse Effects

Nitrovasodilators, such as organic nitrates and sodium nitroprusside, commonly cause side effects related to their vasodilatory properties, including headache due to cerebral vasodilation, flushing, dizziness, and reflex tachycardia.^[5] These effects arise from nitric oxide-mediated smooth muscle relaxation, leading to peripheral vasodilation and compensatory heart rate increases.^[41] Serious adverse effects include orthostatic hypotension, which can result in syncope and falls, particularly in patients with preload-dependent conditions.^[15] High-dose intravenous nitroglycerin may induce methemoglobinemia, characterized by reduced oxygen-carrying capacity of hemoglobin, presenting with cyanosis, fatigue, and hypoxemia despite normal PaO2; this is rare but requires prompt treatment with methylene blue.^[15] Sodium nitroprusside carries a risk of cyanide toxicity, especially with prolonged infusions exceeding 48 hours, high doses, or in patients with renal or hepatic impairment, manifesting as metabolic acidosis, altered mental status, seizures, and cardiovascular collapse.^[20] Many adverse effects are dose-dependent, stemming from venous pooling that reduces cardiac preload and contributes to hypotension and lightheadedness.^[5] Additionally, chronic use can lead to tolerance-related reduced efficacy, limiting therapeutic benefits over time.^[41]

Drug Interactions

Nitrovasodilators, such as nitroglycerin and isosorbide dinitrate, exhibit significant interactions with phosphodiesterase type 5 (PDE5) inhibitors like sildenafil, vardenafil, and tadalafil, which are contraindicated due to potentiation of hypotensive effects through increased cyclic guanosine monophosphate (cGMP) levels, potentially leading to severe hypotension, syncope, or myocardial ischemia.^[42]^[43] This interaction arises because nitrovasodilators release nitric oxide to activate guanylate cyclase and elevate cGMP, while PDE5 inhibitors prevent cGMP degradation, amplifying vasodilation beyond compensatory mechanisms.^[44] Concurrent use with other antihypertensives or vasodilators, including alpha-blockers and direct-acting agents like hydralazine, results in additive hypotensive effects due to synergistic reduction in systemic vascular resistance and preload.^[45] Similarly, combinations with calcium channel blockers, such as amlodipine or verapamil, can cause marked orthostatic hypotension and symptomatic blood pressure drops, necessitating careful monitoring and dose adjustments.^[46]^[47] N-acetylcysteine (NAC) enhances the vasodilatory efficacy of nitrovasodilators by providing sulfhydryl groups that facilitate nitric oxide release and bioavailability, potentially improving hemodynamic responses in conditions like angina or heart failure, though it may also increase side effects such as headache.^[48]^[49] Alcohol consumption exacerbates orthostatic hypotension with nitrovasodilators by additively impairing vascular tone and autonomic reflexes, heightening risks of dizziness and syncope.^[50]^[51] Beta-blockers, such as metoprolol or propranolol, when co-administered with nitrovasodilators, may mask reflex tachycardia induced by venodilation, potentially leading to unopposed hypotension without the usual heart rate compensation, though their combined use is often beneficial for angina management.^[52]^[53]

Nitrate Tolerance

Nitrate tolerance refers to the progressive loss of vasodilatory and anti-ischemic effects of nitrovasodilators, such as nitroglycerin (GTN), following continuous or frequent exposure, limiting their long-term efficacy in conditions like angina pectoris.^[54] This phenomenon includes rapid tolerance, which develops within hours of high-dose administration and manifests as acute tachyphylaxis to hemodynamic responses, and cross-tolerance, where desensitization extends to other organic nitrates (e.g., isosorbide dinitrate) and endothelium-derived nitric oxide pathways.^[54]^[55] The primary mechanisms involve intracellular changes that impair nitric oxide (NO) bioavailability and signaling. Depletion of sulfhydryl groups, particularly through oxidative modification of mitochondrial aldehyde dehydrogenase-2 (ALDH2), reduces the enzyme's activity in bioconverting nitrates to bioactive NO, leading to diminished vasodilation.^[54] Concurrently, nitrate exposure induces oxidative stress by elevating superoxide production via NADPH oxidase activation and mitochondrial reactive oxygen species generation, which scavenges NO to form peroxynitrite, further inhibiting soluble guanylate cyclase (sGC) and exacerbating tolerance.^[54]^[55] Prevention strategies center on interrupting continuous exposure to allow vascular recovery. Implementing nitrate-free intervals of 10-12 hours daily, such as overnight abstinence from transdermal patches, effectively restores responsiveness by enabling replenishment of sulfhydryl donors and reduction of oxidative stress.^[56]^[55] Adjunctive antioxidants like vitamin C have shown potential in preclinical models to mitigate superoxide-mediated NO scavenging, though clinical evidence remains limited and inconsistent.^[54]^[56] Dose adjustments, including eccentric dosing regimens, can also help maintain efficacy without full tolerance development.^[56] Clinically, nitrate tolerance results in attenuated anti-anginal efficacy, with reduced relief of chest pain and hemodynamic benefits after prolonged therapy, potentially increasing ischemic events and necessitating alternative treatments.^[54]^[56]

References

[1]
https://www.ahajournals.org/doi/full/10.1161/01.CIR.87.5.1461
[2]
Vasodilator Therapy: Nitrates and Nicorandil - PMC
Mechanism of Action Nicorandil exerts two distinct anti-angina mechanisms, acting as both: (1) NO donor, and (2) K+ ATP channel opener [106]. The nitrate-like ...Missing: definition | Show results with:definition
[3]
Sodium nitroprusside in 2014: A clinical concepts review - PMC
Sodium nitroprusside (SNP) is a well-known arterial and venous vasodilator used in clinical practice to lower blood pressure.Cardiac Surgery · Metabolism, Safety, And... · Antidotes: Mechanism And...
[4]
Nitrite reverses nitroglycerin tolerance via repletion of a nitrodilator ...
Jan 24, 2025 · Repeated use of nitroglycerin results in a loss of its vasodilatory efficacy which limits its clinical use for the treatment of angina pectoris.
[5]
Vasodilators - StatPearls - NCBI Bookshelf - NIH
Aug 14, 2023 · Nitrovasodilators such as nitroprusside and nitroglycerin are frequently used in hypertensive emergencies. Sodium nitroprusside administration ...
[6]
Nitrates - StatPearls - NCBI Bookshelf - NIH
Jul 10, 2023 · Nitrates are useful in the management and treatment of angina. They are a group of medications that cause vasodilation by donating nitric oxide.Missing: nitrovasodilators | Show results with:nitrovasodilators
[7]
The enigma of nitroglycerin bioactivation and nitrate tolerance
Nitroglycerin (glyceryl trinitrate; GTN) is the most prominent representative of the organic nitrates or nitrovasodilators, a class of compounds that have been ...Missing: definition | Show results with:definition
[8]
A short history of nitroglycerine and nitric oxide in pharmacology and ...
Nitroglycerine (NG) was discovered in 1847 by Ascanio Sobrero in Turin, following work with Theophile-Jules Pelouze. Sobrero first noted the 'violent ...
[9]
Nitroglycerin and Nitric Oxide — A Rondo of Themes in ...
Jul 16, 2015 · By the 1860s, the British pharmacologists and physicians T. Lauder Brunton and William Murrell were using nitrate compounds to treat patients ...<|separator|>
[10]
[PDF] Sublingual Nitroglycerin Delivery for Treatment and Prevention of ...
Nitroglycerin has been used to treat angina pectoris since 1879. It was approved by the. FDA in 1938. However, it was not until recently that its mechanism ...
[11]
The Nobel Prize in Physiology or Medicine 1998 - Press release
He called this signal molecule EDRF, the endothelium-derived relaxing factor, and his findings led to a quest to identify the factor. Ferid Murad, MD and ...
[12]
The Identification of Nitric Oxide as Endothelium-Derived Relaxing ...
Jul 5, 2013 · In 1977, Murad et al had shown that nitrovasodilators and nitric oxide (NO) activate guanylyl cyclase to effect smooth muscle relaxation and ...
[13]
Mechanisms of nitrate tolerance: A review | Cardiovascular Drugs ...
With the increased use of long-acting nitroglycerin preparations, there has been greater recognition of the problem of nitrate tolerance.
[14]
Nitroglycerin - StatPearls - NCBI Bookshelf - NIH
Off-label, non-FDA-approved uses include treatment for hypertensive urgency/emergency, coronary artery spasm, angina secondary to cocaine use, congestive heart ...Missing: nitrovasodilators | Show results with:nitrovasodilators
[15]
Nitroglycerin: Uses, Interactions, Mechanism of Action - DrugBank
Nitroglycerin is a nitrate vasodilator used to treat or prevent angina, heart failure, hypertension, and anal fissures.
[16]
Isosorbide - StatPearls - NCBI Bookshelf - NIH
May 16, 2023 · Isosorbide is a medication used to treat and prevent angina pectoris in patients with coronary heart disease. It is in the nitrate class of drugs.Continuing Education Activity · Indications · Mechanism of Action · Administration
[17]
Vasodilators in Acute Heart Failure: Review of the Latest Studies
Vasodilators play an important role in the management of acute heart failure, particularly when increased afterload is the precipitating cause of ...
[18]
The nitrovasodilators. New ideas about old drugs. | Circulation
The nitrovasodilators are a diverse group of pharmacological agents that produce vascular relaxation by releasing nitric oxide. The mechanisms by which ...Missing: definition | Show results with:definition
[19]
Sodium Nitroprusside - StatPearls - NCBI Bookshelf
May 22, 2023 · Sodium nitroprusside is a medication used in the management of acute hypertension. It is a potent vasodilator and is administered as an IV ...
[20]
Nitroprusside: Uses, Interactions, Mechanism of Action - DrugBank
Jun 13, 2005 · Nitroprusside is a direct acting vasodilator used to treat hypertension, to induce controlled hypotension to reduce postoperative bleeding, and ...
[21]
Nitrovasodilator - an overview | ScienceDirect Topics
Nitrovasodilators are defined as agents, such as sodium nitroprusside and nitroglycerin, that provide exogenous nitric oxide, leading to vascular relaxation and ...Missing: classification | Show results with:classification
[22]
Nitroglycerin Tablets, USP - DailyMed
Nitroglycerin is rapidly absorbed following sublingual administration. Its onset of action is approximately one to three minutes. Significant pharmacologic ...
[23]
Nitroglycerin Dosage Guide + Max Dose, Adjustments - Drugs.com
Aug 14, 2025 · Administer while sitting down due to rapid onset. Advise patient not to chew or swallow this medication. Use: Acute relief of an anginal attack.
[24]
Nitroglycerin Use in the Emergency Department: Current Perspectives
Jul 9, 2022 · Although nitroglycerin has historically been administered as a sublingual tablet and/or spray, it is often given intravenously in the emergency ...
[25]
Onset time of action and duration up to 3 hours of nitroglycerin in ...
Onset time of action and duration up to 3 hours of nitroglycerin in buccal, sublingual and transdermal form.
[26]
Aldehyde Dehydrogenase 2 Plays a Role in the Bioactivation of ...
Jul 28, 2005 · These data suggest that ALDH2 is involved in the bioactivation of NTG to NO in vivo in humans; but because there was incomplete inhibition of ...
[27]
Formation of Nitric Oxide by Aldehyde Dehydrogenase-2 Is ...
Aldehyde dehydrogenase-2 (ALDH2) catalyzes vascular bioactivation of the antianginal drug nitroglycerin (GTN), resulting in activation of soluble guanylate ...
[28]
Nitric Oxide-cGMP Signaling in Hypertension
Aug 24, 2020 · NO diffuses to vascular smooth muscle cells (VSMCs) where it binds sGC (soluble guanylyl cyclase). NO-bound sGC produces cGMP, a key regulator ...
[29]
Invited Review: cGMP-dependent protein kinase signaling ...
Sep 1, 2001 · cGMP is a second messenger that produces its effects by interacting with intracellular receptor proteins. In smooth muscle cells, one of the ...
[30]
The Nitric Oxide-Guanylate Cyclase Pathway and Glaucoma - PMC
NO-GC-1-cGMP Pathway and Disease Mechanisms ... In addition to inhibition of Rho A, activated PKG can directly activate myosin light chain phosphatase (MLCP).
[31]
Hemodynamic effects of nitroglycerin and long-acting nitrates
The organic nitrates produce venodilation at very low doses, with little additional vasodilation of the venous circulation with increasing dosage. Nitrates ...
[32]
Nitrate Therapy | Circulation - American Heart Association Journals
May 17, 2011 · This review summarizes the current concepts underlying tolerance and endothelial dysfunction in response to long-term therapy with different nitrates.Nitrate Tolerance · Nitrate Pseudotolerance · Sulfhydryl Group Donors
[33]
Nitric oxide and nitrovasodilators: Similarities, differences and ...
This review explores the mechanisms of action, biologic effects and potential interactions between nitrates and endothelium-derived relaxing factor.
[34]
Isosorbide dinitrate: Uses, Interactions, Mechanism of Action
Isosorbide Dinitrate is a moderate to long acting oral organic nitrate used for the relief and prophylactic management of angina pectoris. It relaxes the ...
[35]
Clinical pharmacokinetics of nitrates - PubMed
Its pharmacokinetics are unusual, with a very rapid disappearance from plasma, and large intraindividual and interindividual variations.
[36]
Contraindications to the Use of Nitroglycerin in Acute Coronary ...
"Nitrates should not be given to patients with hypotension, marked bradycardia or tachycardia, RV infarction, or 5'phosphodiesterase inhibitor use within the ...
[37]
Experts' recommendations for the management of adult patients with ...
Jul 1, 2015 · Nitrovasodilators should not be continued or introduced during cardiogenic shock (strong agreement).
[38]
[PDF] Nitrostat - accessdata.fda.gov
Sublingual nitroglycerin therapy is contraindicated in patients with early myocardial infarction, severe anemia, increased intracranial pressure, and those with ...
[39]
Nitroglycerin | C3H5(NO3)3 | CID 4510 - PubChem - NIH
Contraindications: hypersensitivity to nitroglycerin or known idiosyncratic reaction to organic nitrates ... closed-angle glaucoma. Intravenous administration ...
[40]
The Role of Nitroglycerin and Other Nitrogen Oxides in ... - PMC - NIH
The organic nitrates are commonly used in the treatment of cardiovascular disease, but clinical data limit their use mostly to the treatment of angina.
[41]
[PDF] This label may not be the latest approved by FDA. For current ...
PDE5 inhibitors: Concomitant use contraindicated (4.1, 7.1) ... In some subjects, nitroglycerin metabolites appeared only after nitroglycerin Cmax.
[42]
PDE5 Inhibitors - StatPearls - NCBI Bookshelf - NIH
Certain drugs like nitrates are absolutely contraindicated in patients taking PDE5 inhibitors, and therefore ED patients should be advised about not ...Continuing Education Activity · Indications · Adverse Effects · MonitoringMissing: nitrovasodilator | Show results with:nitrovasodilator<|control11|><|separator|>
[43]
Cardiovascular Effects of the 3 Phosphodiesterase-5 Inhibitors ...
When NO donors are given at the same time as PDE5 inhibitors, there is both an increase in the production of cyclic GMP (due to the NO donor) and an inhibition ...
[44]
Pharmacology of the nitrovasodilators. Antianginal, antihypertensive ...
The nitrovasodilators, nitroglycerin and sodium nitroprusside, cause both arterial and venous smooth muscle dilation by the intracellular release of nitric ...Missing: definition | Show results with:definition
[45]
Combined effects of calcium antagonists and nitroglycerin on large ...
Nitroglycerin and calcium antagonists are direct dilators of large coronary arteries. Their amelioration of myocardial ischemia may be in part related to ...
[46]
Drug Interactions between amlodipine and nitroglycerin - Drugs.com
Using nitroglycerin together with amLODIPine can lower your blood pressure. This can cause dizziness or feeling like you might pass out.
[47]
Combined use of nitroglycerin and N-acetylcysteine in the ... - PubMed
Previous studies in man have shown that the sulfhydryl donor N-acetylcysteine (NAC) potentiates the systemic and coronary vasodilator effects of NTG.
[48]
N-Acetylcysteine in Combination With Nitroglycerin and ...
Background N-acetylcysteine (NAC) has been shown to potentiate the effects of nitroglycerin (NTG) and to have antioxidant activity. This is the first study ...
[49]
Nitroglycerin (oral route, sublingual route) - Side effects & dosage
Nov 1, 2025 · Nitroglycerin is used to prevent angina (chest pain) caused by coronary artery disease. This medicine is also used to relieve an angina attack ...
[50]
Nitroglycerin and Alcohol/Food Interactions - Drugs.com
Nitroglycerin and ethanol (alcohol) may have additive effects in lowering your blood pressure. You may experience headache, dizziness, lightheadedness, ...
[51]
Combination of nitrates with other antianginal drugs - PubMed
Combined use of nitrates and beta-blockers is a rational approach, because the pharmacological actions of the 2 drugs produce complementary haemodynamic effects ...Missing: nitrovasodilators | Show results with:nitrovasodilators
[52]
Concomitant use of nitrates, calcium channel blockers, and beta ...
For this reason, a nitrate or a calcium channel blocker may be preferred over a beta blocker for the treatment ofpatienb in whom coro- nary artery spasm is ...
[53]
Explaining the Phenomenon of Nitrate Tolerance
Sep 30, 2005 · Nitroglycerin-induced reactive oxygen species inhibit the bioactivation of nitroglycerin by thiol oxidation of aldehyde dehydrogenase. Both ...
[54]
Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced ...
Thus, in the setting of stable angina, the preferential venodilation induced by anti-ischemic doses of nitrates results in venous pooling and therefore preload ...<|control11|><|separator|>
[55]
Amelioration of nitrate tolerance: matching strategies with mechanisms
As recently summarized in a number of reviews (8–10), two major categories of mechanism have been proposed for the development of “true” nitrate tolerance: ...Missing: nitrovasodilators | Show results with:nitrovasodilators