- Email: [email protected]
Nitrates
14 Nitrates Chapter Objectives 1. Introduce the purpose and use of nitrate drugs. 2. Understand the patient's history, differential diagnosis, clinical workup, and treatment approaches that resulted in the use of nitrate drugs. 3. Introduce the traditional Chinese medicine formulas and nutritional supplements that may be used singly or in connection with nitrate drugs. 4. Discuss the treatment perspectives for patients during the acute and chronic stages. 5. Discuss the treatment perspectives for patients during the recovery and prevention stages.
Background See Chapters 5 and 8e10. Metabolic syndrome includes several diseases grouped together to predict the chances of coronary artery disease (CAD) and ultimately heart disease and prognosis. The diseases commonly present include: Gender specific: • Abdominal waist circumference: • Men >40 in at any age • Women >35 in with close monitoring especially during perimenopausal stage and after menopause • HDL cholesterol levels decreased, often lower than LDL levels: • Men <40 mg/dL at any age • Women <50 mg/dL especially closely before and after menopause Gender inclusive: • Hypertension (130/85 mmHg) • Hypertriglyceridemia (>150 mg/dL) Note: See New York Heart Association Symptoms of Heart Failure charts in Chapter 10. Syndrome X is a metabolic syndrome described as a condition that mainly happens to post menopausal women. It involves Herbal, Bio-nutrient and Drug Titration According to Disease Stages in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817580-4.00014-7 Copyright © 2020 Elsevier Inc. All rights reserved.
173
174
Chapter 14 Nitrates
estrogen deficiency, the same neurogenic problems as in angina pectoris, common findings in stress testing such as changes in the ST segment on EKG, and myocardial perfusion, normal flow through coronary arteries yet characteristic microvascular angina. The vascular problems of syndrome X include microcirculation fibrosis, endothelial dysfunction, and vasoconstriction. Nitrates are the drug of choice for use in relieving angina pectoris. In addition, metabolic syndrome is characterized as symptoms of insulin resistance, hypertension, low blood sugar at times, and heart disease. Heart failure gradually develops because of many causative factors. One of the factors is metabolic syndrome, which leads to CAD. Another is a deficiency of oxygen requirements and myocardial and systemic blood supply at hemoglobin is <8 g/ dL), which is severe anemia. Severe anemia can also be caused by syndrome X, coronary spasms, Takayasu arteritis, myocardial ischemia, and other conditions. Anginal chest pain is caused by a process where the cardiac afferent nerve A1 receptors are stimulated by adenosine breakdown of ATP, left ventricular hypertrophy with increased diastolic pressure. It can be a warning symptom of many cardiovascular disorders. Stable angina happens during movement when the heart is working hard to push blood through narrowed arteries. Unstable angina happens anytime, even at rest or sleep, and is one of the signs of myocardial infarction. Anginal chest pain is a major feature in heart failure. Nitrates are the choice pharmaceutical drugs to relieve anginal chest pain, a sign of vessel constriction and increasing heart workload. It dilates all blood vessels to increase blood flow throughout the body toward the heart, and arteries that exclusively provide blood to the heart. Patients who visit physicians and practitioners of traditional Chinese medicine commonly do so at a complicated point in their health condition when life has changed direction toward a point of inability to return to normal well-being. Patients may be in noncompliance with medication use or the advancing disease condition may be on the brink of not responding to aggressive medical therapy. After receiving a thorough intake, discovering why they seek natural medicine is because of the reduction in quality of life with juggling medication intake. Managing patients on prescribed medication for chronic and complicating heart failure includes monitoring for sudden death. For this reason alone, it may be necessary to refer the patient back to their main physician to avoid liability.
Chapter 14 Nitrates
Considering the side effects and toxicity of many of these drugs range from symptomatic problems presented in routine clinical visits to life-threatening consequences, it is best to understand how drugs used for diseases that contribute to heart failure work. Further, it is crucial to understand what symptoms could be presented in the clinic as part of routine management, what should be referred out or back to a specialist, and what constitutes an emergency alert to first responders. The main reasons for study of heart failure are for the purposes of realizing what compromised patients will often face in the future and how to help patients avoid such with careful measures. The purpose of traditional Chinese medicine is to address early signs caused by symptoms of coronary artery disease, syndrome X, and diabetes during the prevention stage. Therapeutic principles are to free stagnated qi and invigorate blood, nourish blood and break blood stasis, resolve phlegm and dampness, and balance shen.
History and physical examination According to patient narrative, angina occurs because of eating, movement, emotions, and severe temperature exposure. Symptoms occur in an unlimited combination, but usually involve such qualities in specific areas: • Pain is usually reported to last 5 minutes or less and does not increase in intensity by respiration, coughing, or changing body position • Pain that aches without relief in localized areas of the mandible, both sides of the neck, and upper back • Pain that radiates in a downward motion in both shoulders and one or both arms • Pain lingering without relief behind the sternum and described as squeezing, heaviness, and choking the air passages and epigastrium • Pain that is relieved with two rounds of nitroglycerine under the tongue and by resting supine or in the Fowlers position Physical Examination • Xanthelasma and xanthomas, seen commonly around the eyelids • Ophthalmic examination: • Increased light reflexes • Arteriovenous nicking Patient presently experiencing symptoms of anginal chest pain requiring emergency assistance: • No peripheral pulses
175
176
Chapter 14 Nitrates
• Left ventricular systolic and diastolic dysfunction: third and fourth heart sounds • Mitral regurgitation • Carotid bruit
Differential diagnosis Diseases and symptoms of less serious diseases or disorders can have the same physical symptoms, and should be ruled out: • Acute gastritis • Anemia • Anxiety or panic disorders • Cholecystitis • Coronary spasm • Diabetes types 1 and 2 • Esophageal spasm or rupture • Embolism • Familial hypercholesterolemia • Gastroesophageal reflux disease and peptic ulcers • Hernia • Herpes zoster virus • Lupus • Pneumonia • Pulmonary arterial hypertension • Scleroderma • Takayasu arteritis
Diagnosis See Chapters 5 and 8e10.
Clinical workup • Exercise stress testing: This is the most widely used test for the evaluation of patients presenting with chest pain and can be performed alone and in conjunction with • Echocardiography • EKG monitoring • EKG • Nuclear imaging: myocardial perfusion scintography • Ambulatory monitoring: prinzmetal and silent ischemia • Radiography • Pericardial effusion • Previous myocardial infarction as seen in cardiomegaly • Cardiomyopathy • Pulmonary edema
Chapter 14 Nitrates
• CT scan • Coronary artery calcium scoring • Framingham risk scoring • Angiography • Percutaneous intervention • Possible stenting
Treatment approaches Basic • Address the hyperlipidemia, hypertension, blood sugar/diabetes mellitus • Modification of the diet: herbal therapy, nutritional supplementation, meal planning, and movement or exercise • Lower serum LDL cholesterol levels: • Serum LDL cholesterol level goals set of <70 mg/dL to <200 mg/dL • Sustain HDL levels when normal and raise when higher
Moderate • Pharmaceutical drug therapy • Angiotensin-converting enzyme inhibitor • Beta blockers • Calcium channel blockers • Clopidogrel • Replacing or supplementing male or female gender designated hormones • Paracetamol • Nitroglycerine (nitrates)
Severe (poor prognosis) • The criteria for such patients include advancing diabetes lesions found in 1e3þ arteries and LCA >50% stenosed • Main coronary revascularization procedures e Angioplasty and intraaortic balloon or enhanced external counterpulsation e Percutaneous intervention with drug eluting stenting e Coronary artery bypass grafting e Laser transmyocardial procedure • Human CD34 þ stem cell therapy e Granulocyte colony-stimulating factor or intramyocardial injections U Reduced incidence of ventricular tachycardia U Reduced incidence of ventricular fibrillation
177
178
Chapter 14 Nitrates
e
Patients with coronary artery disease U Incidence of anginal chest pain U Evidence of myocardial ischemia U Resistant to revascularization U Incidence of poor response to medical therapy e Induces neovascularization in ischemic myocardium e Enhances perfusion and heart function e Common signs and symptoms U Eliminates incidence of myocardial infarction U Reduces elevation of cardiac enzymes U Eliminates perforation U Eliminates incidence of pericardial effusion • Coronary Sinus Reducer Device e Patients with coronary artery disease U Incidence of anginal chest pain U Evidence of myocardial ischemia U Resistant to revascularization e Reduces myocardial ischemia U Redistributes concentration of blood to ischemic sections from nonischemic areas U Percutaneous implantable device that raises coronary sinus pressure
Traditional Chinese medicine See Chapters 5 and 8e10.
Nutritional supplements Two main nutrients that assist the vessel dilation action of nitrates are vitamin C and amino acid N-acetyl cysteine.
Vitamin C Origin: Ascorbic and citric acid Benefits: • Increases capillary strength to maintain nitroglycerin dilation response • Sustains and balances cholesterol levels • Improve glucose tolerance • Reduces urinary protein loss • Reduces sorbitol levels to preserve the function of the nerves, kidneys, and eyes
Chapter 14 Nitrates
Caution: Should not take as a doping measure during treatment of advanced diseases cases, as too much intake of >5 g per day could increase levels of blood sugar and the chances of developing retinopathy.
N-acetyl cysteine Origin: Amino acid protein of meat origin Benefits: • Antioxidant • Improves effect of nitroglycerine on vessel dilation • Decreases tissue damage after myocardial infarction Caution: More than 1.2 g daily may cause nerve toxicity, oxidative stress, and gastrointestinal upset and an increase in zinc and copper excretion in urine. See Chapters 5 and 8e10.
Pharmaceutical drugs Nitrates Nitrates are drugs used to treat advanced and serious cardiovascular disease caused by factors that weaken functioning. They can also be used at the time of emergency when one or more factors have caused the vessels to constrict to the point that the heart is overworked to the point of ultimate exhaustion. They immediately cause the vascular system to dilate so that the
Nitrate use in heart failure Nitrate
Delivery
Isosorbide dinitrate
Oral
Isosorbide mononitrate Nitroglycerin
Oral
Angina pectoris
Congestive heart Myocardial failure Hypertension infarction
Prophylactic Acute Chronic Chronic
Chronic
Chronic
Acute Chronic
Not indicated
Not indicated
Not indicated
Chronic
Chronic
Acute Chronic
Prophylactic Oral Acute Parenteral Chronic Sublingual Topical transdermal
179
180
Chapter 14 Nitrates
oxygen-rich blood can flow, and the heart can work less and at a more optimal pace. When used as a prophylactic or in chronic treatment, nitrates can help keep vessels dilated so that oxygen, vital components, and nutrients and drugs that prevent or treat blood disorders can help keep it flowing through. Other drugs used for coronary artery disease, diabetes/blood glucose, and hypertension as factors in heart failure: See Chapters 5 and 8e10. Use with caution with other pharmaceutical drugs for diseases associated with impending or confirmed heart failure.
Chronic stages Clinical management of advancing heart failure with CAD and metabolic syndrome as causative factors involves disease surveillance, balancing health factors within subjective yet acceptable ranges. Therapies utilizing aggressive pharmacological and nonpharmacological therapies are for maintaining: • Blood levels: confirmed chronic anemia • Blood sugar: confirmed diabetes • Blood lipids: confirmed LDL, HDL, and cholesterols at unacceptably high and low levels • Blood pressure: confirmed hypertension
Pharmacological therapy Patients at the chronic stage and taking nitrates for confirmed diagnoses will have a prior history of serious noncompliance. They may likely not be indicated for Chinese herbal medicine and nutritional supplements, especially vitamin C and cysteine. The effectiveness is still subjective to findings in lab studies, disease stage, body constitution, and overall prognosis. None will have satisfactory clinical effects of much significance over the long term because of concentric remodeling in confirmed and advancing disease states do not present reversal. Pharmacodynamics of nitrates can increase blood pressure and the likelihood of anginal chest pains and emergency events if interacted with other ingested pharmaceutical drug or Chinese herbal medications. Men are especially affected as certain blood pressure medications, with side effects that enhance experiences during sexual encounters, can experience excessively dangerous drops in blood pressure, which can be fatal.
Chapter 14 Nitrates
Common findings during therapy that often complicate care or have poor prognosis with resulting palliation: • Left main coronary artery stenosis >50% • Left ventricular dysfunction affecting the mitral valve and blood movement through the aorta to the rest of the body • Confirmed diabetes • Patients continue severe symptoms despite maximum medical therapy • Atherosclerotic lesions in left coronary artery and left ascending artery and condition that is unstable and beyond benefit of percutaneous intervention • Unstable angina developing • Baseline epicardial adipose tissue thickness (EAT) ¼> 7 mm revealed during a revascularization procedure is a predictor of future unstable angina, myocardial infarction necessitating revascularizations, and sudden death
Recovery and prevention stages Recovery Clinical management of angina due to problems with poor microvascular circulation in Syndrome X often includes lifestyle modification practices. • Changing food and beverage items to those that are conducive to meeting therapeutic goals • Adopting an exercise practice that helps to strengthen heart muscles and promote blood flow • Balancing blood lipid levels • Reducing body fat • Reducing and eliminating factors that lead to confirmed diabetes Patients taking nitrates often experience side effects that may linger or resolve after completing a medication course: Qi, blood, phlegm, and dampness issues: • Dizziness • Headache • Lightheadedness • Low blood pressure • Nausea • Skin flushing around the face and neck Symptoms to prompt emergency assistance: • Vision blurring • Trouble breathing • Swelling of the face and lips and inside of the mouth
181
182
Chapter 14 Nitrates
• Persistent headache • Skin rash including hives When weaning from nitrates to a modified lifestyle that may involve the use of other medications. When indicated, alternate Chinese medicine formula(s) that recover after illness with pharmaceutical drugs. Administer within 3 hours before or after pharmaceutical drug doses. Chinese medicine formulas: • Modified yue jian cao you jiao wan • Modified bao jian mei jian fei cha • Modified xi huang wan • Modified zhi gan cao decoction • Modified shen fu decoction • Modified gui pi decoction Continue a traditional Chinese medicine formula that recovers after illness and within 2 weeks after weaning from nitrates and pharmaceutical drugs, incorporate formula(s) that address rhythm activity, phlegm, and blood sugar: • Modified yu quan wan • Modified zuo gui wan • Modified liu wei di huang wan • Modified zhi gan cao decoction Continue a traditional Chinese medicine formula that recovers after illness while monitoring vitals such as blood sugar, cholesterol, blood pressure, and so forth. At optimal results in clinical examination, incorporate formula(s) that address blood nourishment, opening of channels, and calming shen: • Modified xue fu zhu yu tang • Modified mao dong qing jiao nang • Modified huo xue tong mai pian • Modified mu xiao jiu xin wan • Modified dan shen yin
Prevention Lifestyle factors to consider: • Abstain from smoking cigarettes and tobacco use • Limit the amount of any kind or form of sugar in daily and weekly meal planning • Check hormonal levels regularly and adjust needs according to milestones at middle age such as menopause and andropause • Check CBC at regular levels, especially for early detection of anemia and lipid levels • Check blood sugar daily • Check blood pressure daily
Chapter 14 Nitrates
• Suggest a dietary plan that is conducive to maintaining control of health and well-being • Use proper measures to completely recover from infections and get tested within suggested timeframes after courses of medicines to be sure Formulas to consider: • Modified xue fu zhu yu tang • Modified mao dong qing jiao nang • Modified huo xue tong mai pian • Modified mu xiao jiu xin wan • Modified dan shen yin • Modified liu wei di huang wan
Further reading Al-Mohammad A. Hydralazine and nitrates in the treatment of heart failure with reduced ejection fraction. ESC Heart Fail. 2019;6(4):878e883. https://doi.org/ 10.1002/ehf2.12459. Battas A, Gaidoumi AE, Ksakas A, Kherbeche A. Adsorption study for the removal of nitrate from water using local clay. ScientificWorldJournal. 2019;2019: 9529618. https://doi.org/10.1155/2019/9529618. Published 2019 Feb 3. Górski J, Dragon K, Kaczmarek PMJ. Nitrate pollution in the Warta river (Poland) between 1958 and 2016: trends and causes. Environ Sci Pollut Res Int. 2019; 26(3):2038e2046. https://doi.org/10.1007/s11356-017-9798-3. Lu L, Rao X, Cong R, et al. Design, synthesis and biological evaluation of nitrate derivatives of sauropunol a A and b B as potent vasodilatory agents. Molecules. 2019;24(3):583. https://doi.org/10.3390/molecules24030583. Published 2019 Feb 6. Smith K, Muggeridge DJ, Easton C, Ross MD. An acute dose of inorganic dietary nitrate does not improve high-intensity, intermittent exercise performance in temperate or hot and humid conditions. Eur J Appl Physiol. 2019;119(3): 723e733. https://doi.org/10.1007/s00421-018-04063-9. Tatarczak-Michalewska M, Flieger J, Kawka J, et al. HPLC-DAD determination of nitrite and nitrate in human saliva utilizing a phosphatidylcholine column. Molecules. 2019;24(9):1754. https://doi.org/10.3390/molecules24091754. Published 2019 May 6. Zhang M, Shi JC, Wu LS. Factors influencing the accuracy of the denitrifier method for determining the oxygen isotopic composition of nitrate. J Zhejiang Univ Sci B. 2019;20(1):49e58. https://doi.org/10.1631/ jzus.B1800197.
183
Background See Chapters 5 and 8e10. Metabolic syndrome includes several diseases grouped together to predict the chances of coronary artery disease (CAD) and ultimately heart disease and prognosis. The diseases commonly present include: Gender specific: • Abdominal waist circumference: • Men >40 in at any age • Women >35 in with close monitoring especially during perimenopausal stage and after menopause • HDL cholesterol levels decreased, often lower than LDL levels: • Men <40 mg/dL at any age • Women <50 mg/dL especially closely before and after menopause Gender inclusive: • Hypertension (130/85 mmHg) • Hypertriglyceridemia (>150 mg/dL) Note: See New York Heart Association Symptoms of Heart Failure charts in Chapter 10. Syndrome X is a metabolic syndrome described as a condition that mainly happens to post menopausal women. It involves Herbal, Bio-nutrient and Drug Titration According to Disease Stages in Integrative Cardiovascular Chinese Medicine. https://doi.org/10.1016/B978-0-12-817580-4.00014-7 Copyright © 2020 Elsevier Inc. All rights reserved.
173
174
Chapter 14 Nitrates
estrogen deficiency, the same neurogenic problems as in angina pectoris, common findings in stress testing such as changes in the ST segment on EKG, and myocardial perfusion, normal flow through coronary arteries yet characteristic microvascular angina. The vascular problems of syndrome X include microcirculation fibrosis, endothelial dysfunction, and vasoconstriction. Nitrates are the drug of choice for use in relieving angina pectoris. In addition, metabolic syndrome is characterized as symptoms of insulin resistance, hypertension, low blood sugar at times, and heart disease. Heart failure gradually develops because of many causative factors. One of the factors is metabolic syndrome, which leads to CAD. Another is a deficiency of oxygen requirements and myocardial and systemic blood supply at hemoglobin is <8 g/ dL), which is severe anemia. Severe anemia can also be caused by syndrome X, coronary spasms, Takayasu arteritis, myocardial ischemia, and other conditions. Anginal chest pain is caused by a process where the cardiac afferent nerve A1 receptors are stimulated by adenosine breakdown of ATP, left ventricular hypertrophy with increased diastolic pressure. It can be a warning symptom of many cardiovascular disorders. Stable angina happens during movement when the heart is working hard to push blood through narrowed arteries. Unstable angina happens anytime, even at rest or sleep, and is one of the signs of myocardial infarction. Anginal chest pain is a major feature in heart failure. Nitrates are the choice pharmaceutical drugs to relieve anginal chest pain, a sign of vessel constriction and increasing heart workload. It dilates all blood vessels to increase blood flow throughout the body toward the heart, and arteries that exclusively provide blood to the heart. Patients who visit physicians and practitioners of traditional Chinese medicine commonly do so at a complicated point in their health condition when life has changed direction toward a point of inability to return to normal well-being. Patients may be in noncompliance with medication use or the advancing disease condition may be on the brink of not responding to aggressive medical therapy. After receiving a thorough intake, discovering why they seek natural medicine is because of the reduction in quality of life with juggling medication intake. Managing patients on prescribed medication for chronic and complicating heart failure includes monitoring for sudden death. For this reason alone, it may be necessary to refer the patient back to their main physician to avoid liability.
Chapter 14 Nitrates
Considering the side effects and toxicity of many of these drugs range from symptomatic problems presented in routine clinical visits to life-threatening consequences, it is best to understand how drugs used for diseases that contribute to heart failure work. Further, it is crucial to understand what symptoms could be presented in the clinic as part of routine management, what should be referred out or back to a specialist, and what constitutes an emergency alert to first responders. The main reasons for study of heart failure are for the purposes of realizing what compromised patients will often face in the future and how to help patients avoid such with careful measures. The purpose of traditional Chinese medicine is to address early signs caused by symptoms of coronary artery disease, syndrome X, and diabetes during the prevention stage. Therapeutic principles are to free stagnated qi and invigorate blood, nourish blood and break blood stasis, resolve phlegm and dampness, and balance shen.
History and physical examination According to patient narrative, angina occurs because of eating, movement, emotions, and severe temperature exposure. Symptoms occur in an unlimited combination, but usually involve such qualities in specific areas: • Pain is usually reported to last 5 minutes or less and does not increase in intensity by respiration, coughing, or changing body position • Pain that aches without relief in localized areas of the mandible, both sides of the neck, and upper back • Pain that radiates in a downward motion in both shoulders and one or both arms • Pain lingering without relief behind the sternum and described as squeezing, heaviness, and choking the air passages and epigastrium • Pain that is relieved with two rounds of nitroglycerine under the tongue and by resting supine or in the Fowlers position Physical Examination • Xanthelasma and xanthomas, seen commonly around the eyelids • Ophthalmic examination: • Increased light reflexes • Arteriovenous nicking Patient presently experiencing symptoms of anginal chest pain requiring emergency assistance: • No peripheral pulses
175
176
Chapter 14 Nitrates
• Left ventricular systolic and diastolic dysfunction: third and fourth heart sounds • Mitral regurgitation • Carotid bruit
Differential diagnosis Diseases and symptoms of less serious diseases or disorders can have the same physical symptoms, and should be ruled out: • Acute gastritis • Anemia • Anxiety or panic disorders • Cholecystitis • Coronary spasm • Diabetes types 1 and 2 • Esophageal spasm or rupture • Embolism • Familial hypercholesterolemia • Gastroesophageal reflux disease and peptic ulcers • Hernia • Herpes zoster virus • Lupus • Pneumonia • Pulmonary arterial hypertension • Scleroderma • Takayasu arteritis
Diagnosis See Chapters 5 and 8e10.
Clinical workup • Exercise stress testing: This is the most widely used test for the evaluation of patients presenting with chest pain and can be performed alone and in conjunction with • Echocardiography • EKG monitoring • EKG • Nuclear imaging: myocardial perfusion scintography • Ambulatory monitoring: prinzmetal and silent ischemia • Radiography • Pericardial effusion • Previous myocardial infarction as seen in cardiomegaly • Cardiomyopathy • Pulmonary edema
Chapter 14 Nitrates
• CT scan • Coronary artery calcium scoring • Framingham risk scoring • Angiography • Percutaneous intervention • Possible stenting
Treatment approaches Basic • Address the hyperlipidemia, hypertension, blood sugar/diabetes mellitus • Modification of the diet: herbal therapy, nutritional supplementation, meal planning, and movement or exercise • Lower serum LDL cholesterol levels: • Serum LDL cholesterol level goals set of <70 mg/dL to <200 mg/dL • Sustain HDL levels when normal and raise when higher
Moderate • Pharmaceutical drug therapy • Angiotensin-converting enzyme inhibitor • Beta blockers • Calcium channel blockers • Clopidogrel • Replacing or supplementing male or female gender designated hormones • Paracetamol • Nitroglycerine (nitrates)
Severe (poor prognosis) • The criteria for such patients include advancing diabetes lesions found in 1e3þ arteries and LCA >50% stenosed • Main coronary revascularization procedures e Angioplasty and intraaortic balloon or enhanced external counterpulsation e Percutaneous intervention with drug eluting stenting e Coronary artery bypass grafting e Laser transmyocardial procedure • Human CD34 þ stem cell therapy e Granulocyte colony-stimulating factor or intramyocardial injections U Reduced incidence of ventricular tachycardia U Reduced incidence of ventricular fibrillation
177
178
Chapter 14 Nitrates
e
Patients with coronary artery disease U Incidence of anginal chest pain U Evidence of myocardial ischemia U Resistant to revascularization U Incidence of poor response to medical therapy e Induces neovascularization in ischemic myocardium e Enhances perfusion and heart function e Common signs and symptoms U Eliminates incidence of myocardial infarction U Reduces elevation of cardiac enzymes U Eliminates perforation U Eliminates incidence of pericardial effusion • Coronary Sinus Reducer Device e Patients with coronary artery disease U Incidence of anginal chest pain U Evidence of myocardial ischemia U Resistant to revascularization e Reduces myocardial ischemia U Redistributes concentration of blood to ischemic sections from nonischemic areas U Percutaneous implantable device that raises coronary sinus pressure
Traditional Chinese medicine See Chapters 5 and 8e10.
Nutritional supplements Two main nutrients that assist the vessel dilation action of nitrates are vitamin C and amino acid N-acetyl cysteine.
Vitamin C Origin: Ascorbic and citric acid Benefits: • Increases capillary strength to maintain nitroglycerin dilation response • Sustains and balances cholesterol levels • Improve glucose tolerance • Reduces urinary protein loss • Reduces sorbitol levels to preserve the function of the nerves, kidneys, and eyes
Chapter 14 Nitrates
Caution: Should not take as a doping measure during treatment of advanced diseases cases, as too much intake of >5 g per day could increase levels of blood sugar and the chances of developing retinopathy.
N-acetyl cysteine Origin: Amino acid protein of meat origin Benefits: • Antioxidant • Improves effect of nitroglycerine on vessel dilation • Decreases tissue damage after myocardial infarction Caution: More than 1.2 g daily may cause nerve toxicity, oxidative stress, and gastrointestinal upset and an increase in zinc and copper excretion in urine. See Chapters 5 and 8e10.
Pharmaceutical drugs Nitrates Nitrates are drugs used to treat advanced and serious cardiovascular disease caused by factors that weaken functioning. They can also be used at the time of emergency when one or more factors have caused the vessels to constrict to the point that the heart is overworked to the point of ultimate exhaustion. They immediately cause the vascular system to dilate so that the
Nitrate use in heart failure Nitrate
Delivery
Isosorbide dinitrate
Oral
Isosorbide mononitrate Nitroglycerin
Oral
Angina pectoris
Congestive heart Myocardial failure Hypertension infarction
Prophylactic Acute Chronic Chronic
Chronic
Chronic
Acute Chronic
Not indicated
Not indicated
Not indicated
Chronic
Chronic
Acute Chronic
Prophylactic Oral Acute Parenteral Chronic Sublingual Topical transdermal
179
180
Chapter 14 Nitrates
oxygen-rich blood can flow, and the heart can work less and at a more optimal pace. When used as a prophylactic or in chronic treatment, nitrates can help keep vessels dilated so that oxygen, vital components, and nutrients and drugs that prevent or treat blood disorders can help keep it flowing through. Other drugs used for coronary artery disease, diabetes/blood glucose, and hypertension as factors in heart failure: See Chapters 5 and 8e10. Use with caution with other pharmaceutical drugs for diseases associated with impending or confirmed heart failure.
Chronic stages Clinical management of advancing heart failure with CAD and metabolic syndrome as causative factors involves disease surveillance, balancing health factors within subjective yet acceptable ranges. Therapies utilizing aggressive pharmacological and nonpharmacological therapies are for maintaining: • Blood levels: confirmed chronic anemia • Blood sugar: confirmed diabetes • Blood lipids: confirmed LDL, HDL, and cholesterols at unacceptably high and low levels • Blood pressure: confirmed hypertension
Pharmacological therapy Patients at the chronic stage and taking nitrates for confirmed diagnoses will have a prior history of serious noncompliance. They may likely not be indicated for Chinese herbal medicine and nutritional supplements, especially vitamin C and cysteine. The effectiveness is still subjective to findings in lab studies, disease stage, body constitution, and overall prognosis. None will have satisfactory clinical effects of much significance over the long term because of concentric remodeling in confirmed and advancing disease states do not present reversal. Pharmacodynamics of nitrates can increase blood pressure and the likelihood of anginal chest pains and emergency events if interacted with other ingested pharmaceutical drug or Chinese herbal medications. Men are especially affected as certain blood pressure medications, with side effects that enhance experiences during sexual encounters, can experience excessively dangerous drops in blood pressure, which can be fatal.
Chapter 14 Nitrates
Common findings during therapy that often complicate care or have poor prognosis with resulting palliation: • Left main coronary artery stenosis >50% • Left ventricular dysfunction affecting the mitral valve and blood movement through the aorta to the rest of the body • Confirmed diabetes • Patients continue severe symptoms despite maximum medical therapy • Atherosclerotic lesions in left coronary artery and left ascending artery and condition that is unstable and beyond benefit of percutaneous intervention • Unstable angina developing • Baseline epicardial adipose tissue thickness (EAT) ¼> 7 mm revealed during a revascularization procedure is a predictor of future unstable angina, myocardial infarction necessitating revascularizations, and sudden death
Recovery and prevention stages Recovery Clinical management of angina due to problems with poor microvascular circulation in Syndrome X often includes lifestyle modification practices. • Changing food and beverage items to those that are conducive to meeting therapeutic goals • Adopting an exercise practice that helps to strengthen heart muscles and promote blood flow • Balancing blood lipid levels • Reducing body fat • Reducing and eliminating factors that lead to confirmed diabetes Patients taking nitrates often experience side effects that may linger or resolve after completing a medication course: Qi, blood, phlegm, and dampness issues: • Dizziness • Headache • Lightheadedness • Low blood pressure • Nausea • Skin flushing around the face and neck Symptoms to prompt emergency assistance: • Vision blurring • Trouble breathing • Swelling of the face and lips and inside of the mouth
181
182
Chapter 14 Nitrates
• Persistent headache • Skin rash including hives When weaning from nitrates to a modified lifestyle that may involve the use of other medications. When indicated, alternate Chinese medicine formula(s) that recover after illness with pharmaceutical drugs. Administer within 3 hours before or after pharmaceutical drug doses. Chinese medicine formulas: • Modified yue jian cao you jiao wan • Modified bao jian mei jian fei cha • Modified xi huang wan • Modified zhi gan cao decoction • Modified shen fu decoction • Modified gui pi decoction Continue a traditional Chinese medicine formula that recovers after illness and within 2 weeks after weaning from nitrates and pharmaceutical drugs, incorporate formula(s) that address rhythm activity, phlegm, and blood sugar: • Modified yu quan wan • Modified zuo gui wan • Modified liu wei di huang wan • Modified zhi gan cao decoction Continue a traditional Chinese medicine formula that recovers after illness while monitoring vitals such as blood sugar, cholesterol, blood pressure, and so forth. At optimal results in clinical examination, incorporate formula(s) that address blood nourishment, opening of channels, and calming shen: • Modified xue fu zhu yu tang • Modified mao dong qing jiao nang • Modified huo xue tong mai pian • Modified mu xiao jiu xin wan • Modified dan shen yin
Prevention Lifestyle factors to consider: • Abstain from smoking cigarettes and tobacco use • Limit the amount of any kind or form of sugar in daily and weekly meal planning • Check hormonal levels regularly and adjust needs according to milestones at middle age such as menopause and andropause • Check CBC at regular levels, especially for early detection of anemia and lipid levels • Check blood sugar daily • Check blood pressure daily
Chapter 14 Nitrates
• Suggest a dietary plan that is conducive to maintaining control of health and well-being • Use proper measures to completely recover from infections and get tested within suggested timeframes after courses of medicines to be sure Formulas to consider: • Modified xue fu zhu yu tang • Modified mao dong qing jiao nang • Modified huo xue tong mai pian • Modified mu xiao jiu xin wan • Modified dan shen yin • Modified liu wei di huang wan
Further reading Al-Mohammad A. Hydralazine and nitrates in the treatment of heart failure with reduced ejection fraction. ESC Heart Fail. 2019;6(4):878e883. https://doi.org/ 10.1002/ehf2.12459. Battas A, Gaidoumi AE, Ksakas A, Kherbeche A. Adsorption study for the removal of nitrate from water using local clay. ScientificWorldJournal. 2019;2019: 9529618. https://doi.org/10.1155/2019/9529618. Published 2019 Feb 3. Górski J, Dragon K, Kaczmarek PMJ. Nitrate pollution in the Warta river (Poland) between 1958 and 2016: trends and causes. Environ Sci Pollut Res Int. 2019; 26(3):2038e2046. https://doi.org/10.1007/s11356-017-9798-3. Lu L, Rao X, Cong R, et al. Design, synthesis and biological evaluation of nitrate derivatives of sauropunol a A and b B as potent vasodilatory agents. Molecules. 2019;24(3):583. https://doi.org/10.3390/molecules24030583. Published 2019 Feb 6. Smith K, Muggeridge DJ, Easton C, Ross MD. An acute dose of inorganic dietary nitrate does not improve high-intensity, intermittent exercise performance in temperate or hot and humid conditions. Eur J Appl Physiol. 2019;119(3): 723e733. https://doi.org/10.1007/s00421-018-04063-9. Tatarczak-Michalewska M, Flieger J, Kawka J, et al. HPLC-DAD determination of nitrite and nitrate in human saliva utilizing a phosphatidylcholine column. Molecules. 2019;24(9):1754. https://doi.org/10.3390/molecules24091754. Published 2019 May 6. Zhang M, Shi JC, Wu LS. Factors influencing the accuracy of the denitrifier method for determining the oxygen isotopic composition of nitrate. J Zhejiang Univ Sci B. 2019;20(1):49e58. https://doi.org/10.1631/ jzus.B1800197.
183