NitroDur
From Proteopedia
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The mechanism for nitroglycerin breakdown is disputed, but it is know that nitroglycerin eventually breaks down into nitric oxide. In more recent years, nitroglycerin has been found to be broken down with the help of aldehyde dehydrogenase 2 found in the mitochondria. <ref>Mayer, B., and Beretta, M. (2008) The enigma of nitroglycerin bioactivation and nitrate tolerance. News, views, and troubles. Br. J. Pharmacol. 155, 170-184 </ref> | The mechanism for nitroglycerin breakdown is disputed, but it is know that nitroglycerin eventually breaks down into nitric oxide. In more recent years, nitroglycerin has been found to be broken down with the help of aldehyde dehydrogenase 2 found in the mitochondria. <ref>Mayer, B., and Beretta, M. (2008) The enigma of nitroglycerin bioactivation and nitrate tolerance. News, views, and troubles. Br. J. Pharmacol. 155, 170-184 </ref> | ||
There has been further proof showing that the breakdown of nitroglycerin permanently alters ALDH2 during <scene name='74/745476/Cys-302_of_aldh2_3/1'>Cys-302</scene> attack <ref name="citation23"> Lang, Barbara S., Antonius Cf Gorren, Gustav Oberdorfer, M. Wenzl, Cristina M. Furdui, Leslie B. Poole, Bernd Mayer, and Karl Gruber. "Vascular Bioactivation of Nitroglycerin: Reaction Mechanism Revealed by Crystal Structure of Aldehyde Dehydrogenase-2." BMC Pharmacology and Toxicology BMC Pharmacol Toxicol 13.Suppl 1 (2012): n. pag. Web. 1 Nov. 2016.</ref>. | There has been further proof showing that the breakdown of nitroglycerin permanently alters ALDH2 during <scene name='74/745476/Cys-302_of_aldh2_3/1'>Cys-302</scene> attack <ref name="citation23"> Lang, Barbara S., Antonius Cf Gorren, Gustav Oberdorfer, M. Wenzl, Cristina M. Furdui, Leslie B. Poole, Bernd Mayer, and Karl Gruber. "Vascular Bioactivation of Nitroglycerin: Reaction Mechanism Revealed by Crystal Structure of Aldehyde Dehydrogenase-2." BMC Pharmacology and Toxicology BMC Pharmacol Toxicol 13.Suppl 1 (2012): n. pag. Web. 1 Nov. 2016.</ref>. | ||
| - | The mechanism that is believed to happen takes nitroglycerin (GTN), bound to aldehyde dehydrogenase 2 (ALDH2) through hydrogen bonds and van der | + | The mechanism that is believed to happen takes nitroglycerin (GTN), bound to aldehyde dehydrogenase 2 (ALDH2) through hydrogen bonds and van der Waal interactions of the terminal nitrates, then Cysteine-302 (in ALDH2) attacks GTN to form a thionitrate intermediate while also releasing 1,2-glyceryl dinitrate (1,2-GDN) and a small amount of nitric oxide (NO). The thionitrate is then attacked by the surrounding cysteines (Cys-301 or Cys-303), which forms a disulfide bond and nitrite. Nitrite is then released and converted into NO. It has also been found that daidzin will inhibit GTN breakdown through competitive inhibition because the binding sites of daidzin and GTN overlap <ref name="citation23"> </ref>. Once NO is released, it is believed to activate <scene name='74/745476/Guanylate_cyclase/1'>guanylate cyclase </scene>, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in smooth muscle and other tissues. These events lead to the dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle, and results in vasodilatation. <ref>"Nitrostat (Nitroglycerin) Drug Information: Clinical Pharmacology - Prescribing Information at RxList." RxList. N.p., n.d. Web. 30 Oct. 2016.</ref> |
== Disease == | == Disease == | ||
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===Chronic Achilles Tendinopathy=== | ===Chronic Achilles Tendinopathy=== | ||
| - | Chronic Achilles Tendinopathy is characterized by pain in the | + | Chronic Achilles Tendinopathy is characterized by pain in the Achilles tendon that is caused by tendon degradation <ref>Chronic Achilles Tendon Injury: An Overview." Hospital for Special Surgery. N.p., 1 June 2011. Web. 30 Oct. 2016 </ref>. A study conducted at an Australian University Hospital looked at the effect of topical glyceryl trinitrate (in the form of a NitroDur patch) on pain management and symptoms in chronic noninsertional Achilles tendinopathy. Study participants were given an active transdermal NitroDur patch, which delivered 1.25 mg of glyceryl trinitrate over 24 hours, or a placebo treatment patch. Over the course of 24 weeks, participants applied one fourth of the NitroDur patch to their most painful site on their body. Study results showed that the NitroDur patch was more effective than placebo in reducing pain caused by chronic noninsertional Achilles tendonitis <ref>PMID: 15782065 </ref>. |
===Raynaud’s Phenomenon=== | ===Raynaud’s Phenomenon=== | ||
| - | Raynaud's | + | Raynaud's phenomenon occurs due to vasoconstriction of the capillaries, veins, and arteries in external digits <ref name="citation2"> <ref>PMCID: PMC2860448</ref>. Symptoms of Raynaud’s involves the fingers or toes turning pale, becoming numb, and then transitioning to a shade of purple or blue. These symptoms result from attacks that are characterized by spasms in the small blood vessels of the fingers and toes <ref>Haythornthwaite, Jenifer, Dr., and Fredrick Wigley, Dr. "Raynaud's, Finger and Skin Care." Scleroderma Education Program Chapter 2 Raynaud’s, Finger and Skin Care (n.d.): n. pag. Web. 16 Oct. 2016 </ref>. Patients who have been diagnosed with Raynaud’s phenomenon will occasionally need pharmacological therapy. While the NitroDur patch is not specifically prescribed, topical nitroglycerin ointment is used on these patients to decrease the occurrence and severity of vasospastic episodes <ref name="citation2"> </ref>. Nitroglycerin does this by expanding the blood vessels allowing better blood circulation <ref name="citation3"> </ref>. |
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 21:41, 4 December 2016
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