ema: by inn us dailymed: nitric_oxide pregnancycategory au: b2 routes ofadministrationinhalationatc coder07ax01 (who) legal statuslegal status au: s4 (prescription only) us: ℞-only in general: ℞ (prescription only) identifiers iupac name nitric oxide cas number10102-43-9pubchem cid145068iuphar/bps2509drugbankdb00435chemspider127983unii31c4ky9eshkeggd00074c00533chebichebi:16480chemblchembl1200689chemical and physical dataformulanomolar mass30.006 g·mol−13d model (jsmol)interactive image smiles =o inchi inchi=1s/no/c1-2key:mwuxshhqayifbg-uhfffaoysa-n in the european union nitric oxide in conjunction with ventilatory support and other appropriate active substances, is indicated: for the treatment of newborn infants ≥34 weeks gestation with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension, in order to improve oxygenation and to reduce the need for extracorporeal membrane oxygenation; as part of the treatment of peri- and post-operative pulmonary hypertension in adults and newborn infants, infants and toddlers, children and adolescents, ages 0–17 years in conjunction to heart surgery, in order to selectively decrease pulmonary arterial pressure and improve right ventricular function and oxygenation. in the united states it is indicated to improve oxygenation and reduce the need for extracorporeal membrane oxygenation in term and near-term (>34 weeks gestation) neonates with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension in conjunction with ventilatory support and other appropriate agents. the most common side effects include thrombocytopenia (low blood platelet counts), hypokalaemia (low blood potassium levels), hypotension (low blood pressure), atelectasis (collapse of the whole, or part of a, lung), and hyperbilirubinaemia (high blood levels of bilirubin). nitric oxide was approved for medical use in the united states in december 1999 and for medical use in the european union in 2001. nitric oxide can be delivered as a pulse in the beginning of each breath to horses during anaesthesia. this is called pino (pulsed inhaled nitric oxide) and results in better matching of ventilation and perfusion and thereby improves the arterial oxygenation. associated problems there are some associated complaints with utilization of nitric oxide in neonatal patients. some of them include dose errors associated with the delivery system, headaches associated with environmental exposure of nitric oxide in hospital staff, hypotension associated with acute withdrawal of the drug, hypoxemia associated with acute withdrawal of the drug, and pulmonary edema in patients with crest syndrome. contraindications inhaled nitric oxide is contraindicated in the treatment of neonates known to be dependent on right-to-left shunting of blood. this is as the nitric oxide decreases the pulmonary circulation's resistance by dilating pulmonary blood vessels. the increased pulmonary return increases pressure in the left atrium, causing closure of the foramen ovale and reducing the blood flow through the ductus arteriosus. closing these shunts can kill neonates with heart malformations that rely on the right-to-left shunting of blood. dosage and strength in the united states, nitric oxide is a gas available in concentrations of only 100 ppm and 800 ppm. overdosage with inhaled nitric oxide will be seen by elevations in methemoglobin and pulmonary toxicities associated with inspired ·no. elevated no may cause acute lung injury. fatty liver disease nitric oxide production is associated with nonalcoholic fatty liver disease (nafld) and is essential for hepatic lipid metabolism under starvation. lung infection nitric oxide is a potential therapeutic intervention in acute and chronic lung infections. mechanism of action nitric oxide is a compound produced by many cells of the body. it relaxes vascular smooth muscle by binding to the heme moiety of cytosolic guanylate cyclase, activating guanylate cyclase and increasing intracellular levels of cyclic-guanosine 3',5'-monophosphate, which then leads to vasodilation. when inhaled, nitric oxide dilates the pulmonary vasculature and, because of efficient scavenging by hemoglobin, has minimal effect on the vasculature of the entire body. inhaled nitric oxide appears to increase the partial pressure of arterial oxygen (pao2) by dilating pulmonary vessels in better-ventilated areas of the lung, moving pulmonary blood flow away from lung segments with low ventilation/perfusion (v/q) ratios toward segments with normal or better ratios. neonatal use nitric oxide/oxygen blends are used in critical care to promote capillary and pulmonary dilation to treat primary pulmonary hypertension in neonatal patients and post-meconium aspiration related to birth defects. these are often a last-resort gas mixture before the use of extracorporeal membrane oxygenation (ecmo). nitric oxide therapy has the potential to significantly increase the quality of life and, in some cases, save the lives of infants at risk for pulmonary vascular disease. pathology people with diabetes usually have lower levels of nitric oxide than patients without diabetes. diminished supply of nitric oxide can lead to vascular damage, such as endothelial dysfunction and vascular inflammation. vascular damage can lead to decreased blood flow to the extremities, causing the diabetic patient to be more likely to develop neuropathy and non-healing ulcers, and to be at a greater risk for lower limb amputation. pediatric and adult use the primary use is in the form of nitroglycerin, either pill or liquid spray forms, which, as a prodrug, is denitrated and releases the active metabolite nitric oxide (no). as with all supplements of nitric oxide, the response is short-lived because, as a normally produced internal physiologic control mechanism, increased concentrations lead to increased rates of clearance, which is the reason that the effectiveness of sustained use of nitroglycerin for vasodilation fades to none after hours to days. in the united states, ongoing direct use of nitric oxide use is only approved for neonates. in the adult icu setting, inhaled ·no can improve hypoxemia in acute lung injury, acute respiratory distress syndrome, and severe pulmonary hypertension, although the effects are short-lived and there are no studies demonstrating improved clinical outcomes. it is used on an individualized basis in icus as an adjunct to other definitive therapies for reversible causes of hypoxemic respiratory distress. pharmacokinetics nitric oxide is absorbed systemically after inhalation. most of it moves across the pulmonary capillary bed where it combines with hemoglobin that is 60% to 100% oxygen-saturated. nitrate has been identified as the predominant nitric oxide metabolite excreted in the urine, accounting for >70% of the nitric oxide dose inhaled. nitrate is cleared from the plasma by the kidney at rates approaching the rate of glomerular filtration. pharmacology nitric oxide is considered an antianginal drug: it causes vasodilation, which can help with ischemic pain, known as angina, by decreasing the cardiac workload. by dilating (expanding) the arteries, nitric oxide drugs lower arterial pressure and left ventricular filling pressure. nitric oxide can contribute to reperfusion injury when an excessive amount produced during reperfusion (following a period of ischemia) reacts with superoxide to produce the damaging oxidant peroxynitrite. in contrast, inhaled nitric oxide has been shown to help survival and recovery from paraquat poisoning, which produces lung tissue-damaging superoxide and hinders nos metabolism. this vasodilation does not decrease the volume of blood the heart pumps, but rather it decreases the force the heart muscle must exert to pump the same volume of blood. nitroglycerin pills, taken sublingually (under the tongue), are used to prevent or treat acute chest pain. the nitroglycerin reacts with a sulfhydryl group (–sh) to produce nitric oxide, which eases the pain by causing vasodilation. there is a potential role for the use of nitric oxide in alleviating bladder contractile dysfunctions, and recent evidence suggests that nitrates may be beneficial for treatment of angina due to reduced myocardial oxygen consumption both by decreasing preload and afterload and by some direct vasodilation of coronary vessels. pulmonary embolism nitric oxide is also administered as salvage therapy in patients with acute right ventricular failure secondary to pulmonary embolism. research covid‑19 as of april 2020, studies and trials are underway that examine the possible benefits of nitric oxide in the treatment of covid-19. this research is based on the fact that nitric oxide was investigated as an experimental therapy for sars. brian strickland, md, a fellow in wilderness medicine at massachusetts general hospital who studies "acute respiratory distress" in high altitudes, is applying this research towards covid-19. he is involved in clinical trials which apply the use of inhaled nitric oxide as a treatment for covid-19. this approach was inspired by the work of associate professor of emergency medicine at the harvard medical school n. stuart harris, who has been studying the effects of altitude sickness on mountain climbers, such as those who climb mount everest. harris noticed that the consequences of high level altitude sickness on the human body mirrored covid-19's dysfunctional impact on the lungs. his focus on nitric oxide comes from its role in being able to breathe in high altitudes. according to wcvb-tv, similar trials are being conducted at tufts medical center. other studies speculate that replacing mouth breathing (which decimates no) with nasal breathing (which increases no) is a "lifestyle change" that "may also help to reduce sars-cov-2 viral load and symptoms of covid‑19 pneumonia by promoting more efficient antiviral defense mechanisms in the respiratory tract."