ISDN has an extensive first pass metabolism in the liver, produces two major metabolites . ASK DIS: Isosorbide Dinitrate VS Isosorbide Mononitrate - Blogger . Multiple health care professionals such as cardiologists, general practitioners, nurses, pharmacists, home care workers, and dieticians can work together to overcome these challenges of isosorbide therapy. Development of a Combination Product. 4, 7 Isosorbide mononitrate is an active metabolite of isosorbide dinitrate. Treatment effect. "[~ Changing positions slowly can help lessen dizziness. Do not chew extended-release preparations. Trade Name. However, if you are pregnant or trying for a baby then you should be seen as soon as possible by a pregnancy specialist (obstetrician) and a heart specialist (cardiologist) so your heart and medicine can be reviewed. If your heart needs to work harder, during exercise for example, it needs increased blood flow to get more oxygen. The manufacturer of the fixed combination of isosorbide dinitrate and hydralazine hydrochloride states that dosage should be selected with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy. Transient flushing may occur with the nitrates, and inhalation of amyl nitrite commonly causes cutaneous flushing of the head, neck, and clavicular area. Adjust dosage of isosorbide dinitrate and isosorbide mononitrate carefully according to the patient's requirements and response; use the smallest effective dosage. Isosorbide mononitrate adalah obat untuk mencegah serangan angina pektoris pada penderita penyakit jantung koroner. Method of administration. UpToDate isosorbide mononitrate (Imdur, Ismo, Monoket) - MedicineNet In conclusion, in patients with heart failure with a preserved ejection fraction, the receipt of isosorbide mononitrate, as compared with placebo, decreased daily activity levels. you have taken too much isosorbide mononitrate or dinitrate and: If you need to go to A&E, do not drive yourself get someone else to drive you or call an ambulance. Isosorbide mononitrate (Monoket): Basics, Side Effects & Reviews - GoodRx How does isosorbide dinitrate work? Isosorbide mononitrate and dinitrate comes as tablets, or capsules. This activity will . Peripheral venous resistance is decreased via a selective action on venous capacitance vessels and results in venous pooling of blood and decreased venous return to the heart. The most common brand names of this medication are Monoket and Imdur. Two groups of coronary patients and a group of rabbits underwent treatment with the above-mentioned vasodilating drugs. Careful clinical or hemodynamic monitoring for possible hypotension or tachycardia if used in acute MI or heart failure. After therapeutic doses, cardiac output may increase transiently and then decrease. Importance of warning all patients receiving organic nitrates or nitrites about the potential interaction between the drugs and selective PDE inhibitors, even if they currently are not receiving the drugs, since there is substantial potential for patients to receive the drugs from another clinician, from a friend, with little or no clinical intervention (e.g., via the Internet), or illicitly. Do not take non-steroidal anti-inflammatory medicines (NSAIDs) regularly, such as ibuprofen, aspirin and naproxen (unless it's prescribed by your doctor). Daiber A, Mnzel T. Organic Nitrate Therapy, Nitrate Tolerance, and Nitrate-Induced Endothelial Dysfunction: Emphasis on Redox Biology and Oxidative Stress. Isosorbide-5-mononitrate must not be used in cases of: hypersensitivity to isosorbide-5-mononitrate (the active substance), other nitrate compounds or to any of the excipients acute circulatory failure (shock, circulatory collapse) cardiogenic shock, unless a sufficiently high left-ventricular end-diastolic pressure is Conventional measures in the management of angina pectoris are aimed at reducing the frequency, duration, and severity of attacks, and include coronary risk reduction (e.g., discontinuance of smoking, weight control, antilipemic strategies), rest, avoidance of precipitating circumstances (e.g., eating heavy meals, getting emotionally upset, performing strenuous exercise, exposure to cold air) and, if possible, treatment of the underlying cause. Some people need to take 2 or more medicines. Tight, light-resistant containers at room temperature (25C); do not expose to extremes in temperature. Angina is chest pain that happens when not enough blood gets to the muscles of the heart. Isosorbide dinitrate | Drugs | BNF | NICE <>stream Conversion table Original isosorbide prescription: Convert to: 10 mg twice a day at 8am and 4pm 20 mg twice a day at 8am and 4pm [2] It is taken by mouth. Maximum 40 mg of isosorbide dinitrate and 75 mg of hydralazine hydrochloride (2 tablets of BiDil) 3 times daily. Some people may be able to stop taking it after certain types of heart surgery. 1. The usage of epinephrine and other vasoconstrictors is generally not recommended. You do not need to avoid playing sports due to taking isosorbide mononitrate or dinitrate. This increases the blood supply to your heart, which gets more oxygen to your heart muscles and this reduces chest pain. Initially, (e.g., Imdur): 30 mg (as a single 30-mg tablet or as of a 60-mg tablet) or 60 mg (as a single 60-mg tablet) once daily. Nurses and general practitioners should ensure that isosorbide therapy is not an option for patients with erectile dysfunction by taking phosphodiesterase (PDE) inhibitors. Isosorbide Monograph for Professionals - Drugs.com A total of 20% of patients in the isosorbide dinitrate-oxytocin group recorded headache, and no cases of uterine tachysystole, haemorrhage or coagulopathy were recorded. ( Isosorbide mononitrate: Uses, Interactions, Mechanism of - DrugBank endobj Isosorbide Mononitrate Tablets 10 mg - Summary of Product - medicines Imdur vs. Isordil Prescription Treatment for Chest Pain - RxList Initially, isosorbide dinitrate conventional tablets (e.g., Isordil Titradose) 520 mg administered 23 times daily, followed by maintenance dosage of 1040 mg administered 23 times daily (some patients may require higher dosages). Vasodilatory effect on arteriolar resistance is not as great as the action on the venous side; as a result of this combined action, both venous filling pressure (preload) and, to a lesser extent, arterial impedance (afterload) are reduced. If this happens to you, do not drive, ride a bike or use tools or operate machinery until you feel better. Like all medicines, isosorbide mononitrate and dinitrate can cause side effects, although not everybody gets them. Extended-release tablets can be administered as whole or halved tablets, but swallow intact and do not chew or crush. When a longer . ISDN is available in immediate release (Ex: Isordil) and extended release (Ex: DilatrateSR ) forms. Isosorbide mononitrate extended-release tablets, peak: 34.5 hours. Isosorbide mononitrate. Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. Mnzel T, Steven S, Daiber A. Organic nitrates: update on mechanisms underlying vasodilation, tolerance and endothelial dysfunction. (dinitrate conventional tablets) two to three times daily. The symptoms of isosorbide overdose may arise from its vasodilating property causing profound systemic hypotension, heart block with bradycardia, syncope, nausea, vomiting, increased intracranial tension (probably along with persistent throbbing headache, fever, confusion), diaphoresis, dizziness, and palpitations. Isosorbide dinitrate: Also probably metabolized at extrahepatic sites. Tarkin JM, Kaski JC. Isosorbide dinitrate is good for chest pain, but you have to be able to stick to your dosing schedule or it won't work as well. Isosorbide mononitrate and dinitrate are types of heart medicine called nitrates. May increase dosage to 120 mg (as a single 120-mg tablet or as two 60-mg tablets) once daily after several days; 240-mg dosages rarely needed. According to pharmacokinetic data, isosorbide mononitrate has a bioavailability of about 95%, and its protein binding ability is about 5%. Nitrates in the management of chronic coronary syndrome. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. The key difference between isosorbide mononitrate and isosorbide dinitrate is that isosorbide mononitrate is primarily used in the management of chronic stable angina, whereas isosorbide dinitrate is recommended for heart failure.. Isosorbide mononitrate and isosorbide dinitrate are important medications for some heart diseases. Isosorbide mononitrate is in the class of drugs called nitrates that are used for treating and preventing angina.Other nitrates include nitroglycerin (Nitrostat, NitroQuick, Nitrolingual, Nitro-Dur and others) and isosorbide dinitrate (Isordil Titradose, Dilatrate-SR, Isochron).Nitrates are vasodilators (dilators of blood vessels). Isosorbide mononitrate (ISMN) is widely used for the prophylaxis of angina pectoris. ), which permits others to distribute the work, provided that the article is not altered or used commercially. Importance of instructing patients receiving isosorbide dinitrate for relief of acute attacks of angina pectoris to consult a clinician or go to a hospital emergency room immediately if chest pain is not relieved after 3 doses approximately every 5 minutes, because inability to relieve chest pain may indicate acute MI. If you stop taking isosorbide mononitrate or isosorbide dinitrate, your symptoms may get worse. Isosorbide Dinitrate (ISDN) is an intermediate acting nitrate approved for prevention of angina pectoris. Tolerance to the vascular and antianginal effects of individual nitrates and cross-tolerance among the drugs may occur with repeated, prolonged use. Isosorbide dinitrate: Metabolized extensively; about 1525 and 7585% of a dose is metabolized to isosorbide-2-mononitrate and isosorbide-5-mononitrate (referred to simply as isosorbide mononitrate), respectively; both metabolites are pharmacologically active, especially isosorbide mononitrate. Isosorbide Mononitrate: Uses, Dosage & Side Effects. Drugs.com. Importance of informing patients of other important precautionary information. . But it is less preferred compared to beta-blockers or calcium channel blockers. Isosorbide undergoes bioactivation in the endoplasmic reticulum through the cytochrome P450 enzymes to release NO[7], which activates the enzyme soluble guanylyl cyclase in the vascular smooth muscles, thereby increasing the levels of intracellular cGMP and the associated protein kinases such as cGMP- dependent protein kinases(cGK-I). Maximum: 80 mg 3 times/day. PDF (isosorbide mononitrate, USP) Rx Only - Food and Drug Administration The elimination half-life of isosorbide dinitrate is about 1 hour, and the excretion occurs through the kidney. The principal pharmacological action of isosorbide mononitrate is relaxation of vascular smooth endobj May need to adjust schedule for those arising earlier than 7 a.m. since early morning angina is common. In addition, the elimination time ofisosorbide mononitrate is about 5 hours whereasthe elimination time ofisosorbide dinitrate is 1 hour. It will take a few days to prevent angina symptoms. Or 30 to 60 mg (mononitrate extended-release tablets) once daily. This is because it can lower your blood pressure too much when combined with some anaesthetics. If this happens, sit or lie down and put your feet up. Isosorbide mononitrate By Vaccinationist Own work (Public Domain) via Commons Wikimedia Isosorbide dinitrate and isosorbide mononitrate are mainly excreted in the urine. Congestive heart failure: Oral: Initial: 10 mg 3 times/day. Leier CV, Huss P, Magorien RD, Unverferth DV. What is Isosorbide Mononitrate Adults: Usual adult dose is one isosorbide mononitrate XL 60 mg tablet per day (taken in the morning).If necessary, the dosage may be increased to 120 mg once daily (i.e. Adult 30-120 mg daily in divided doses. Nitrates - Knowledge @ AMBOSS Isosorbide dinitrate and isosorbide mononitrate: Organic nitrates; vasodilating agents. Selective PDE inhibitors can potentiate the hypotensive effects of organic nitrates and nitrites, possibly resulting in potentially life-threatening hypotension and/or hemodynamic compromise. Importance of informing patients receiving isosorbide dinitrate in fixed combination with hydralazine that inadequate fluid intake or excessive fluid loss due to diarrhea, vomiting, or perspiration may result in excessive hypotension, possibly leading to lightheadedness or syncope; if syncope occurs, discontinue treatment and notify clinician immediately. Sisenwine SF, Ruelius HW. By decreasing myocardial oxygen consumption, nitrates and nitrites alter the imbalance of myocardial oxygen supply and consumption which is thought to cause angina pectoris. There is no information about whether isosorbide mononitrate or dinitrate passes into breast milk, but the amounts are likely to be small. Not known whether geriatric patients respond differently than younger patients. [26]Tolerance may develop within as little as 12 to 24 hours,with a subsequent reduction in the clinical effects of isosorbide; this necessitates the need for a drug-free interval of at least 10 to 12 hours a day. Isosorbide mononitrate (Monoket) can cause headaches, dizziness, or lightheadedness. 1. Isosorbide decreases the preload and worsens the right ventricular output causing severe hypotension. This medicine is not suitable for some people. Isosorbide dinitrate in fixed combination with hydralazine hydrochloride: About 2 hours. Other medicines used to prevent angina attacks are: If you cannot take either of these medicines, you may be given another medicine such as ivabradine, nicorandil or ranolazine. Isosorbide mononitrate - UpToDate Isosorbide Mononitrate: Fungsi Obat, Dosis, dll. Hello Sehat PDF STANDARD vs. MODIFIED RELEASE ISOSORBIDE MONONITRATE Isosorbide therapy in angina and heart failure requires an interprofessional team approach to achieve optimum results. It has high . e5;O"]rQR8ku:mw/CYux:s8ofW`KMb`! Each Isosorbide mononitrate extended-release tablet, for oral administration contains 30 mg, 60 mg or 120 mg of ISMN. Product and Consumer Medicine Information. If you have darker skin your gums or the skin around your eyes may turn blue or grey, you take too many isosorbide mononitrate or isosorbide dinitrate tablets or capsules, and you feel unwell, swelling in lower legs, ankles or feet (oedema), you are having breathing difficulties that are new or worse than usual, you get weakness in your arm, or one side of your body or face, difficulty speaking, or loss of coordination these could be signs of a stroke, your mouth (lips, tongue or gums), face or skin start to look blue or grey. The tablets and capsules usually start to work within 1 hour. Drug class: Nitrates and Nitrites Particularly small stature, initially: 5 mg ( of a 10-mg tablet) twice daily, for no longer than initial 2 days. (See Selective Phosphodiesterase (PDE) Inhibitors under Cautions.). Isosorbide Dinitrate Sublingual Isosorbide Dinitrate Isosorbide 5-Mononitrate 400 mcg/min. Divakaran S, Loscalzo J. Prophylaxis and treatment of angina for isosorbide dinitrate By mouth using immediate-release medicines. Monomax XL 60 mg Prolonged Release Tablets - medicines The principal pharmacological action of ISMN and all organic nitrates in general is relaxation of vascular . Other adverse effects can be due to the reflex activity of the sympathetic nervous system due to vasodilation. All rights reserved. Isosorbide dilates the venous capacitance vessels, arterioles, and coronary arteries. Oral use. Terms of Use and Privacy Policy: Legal. %&SC*U]0l TCLg&=|G==!bT=4Er R|qB^RzA-C%#^krR(Luhiy7c+>Vour]ZOf?HV If you are taking isosorbide mononitrate or dinitrate and are bothered by side effects, speak to your doctor. <> Summarize the importance of collaboration and communication amongst the interprofessional team to enhance care delivery and improve outcomes for patients with angina pectoris receiving isosorbide. There can be some severe side effects as well, such as low blood pressure. Tell your doctor if this happens to you. Isosorbide mononitrate and isosorbide dinitrate are important medications for some heart diseases. Review the appropriate monitoring necessary with isosorbide. Passive elevation of the patient's legs to reduce the venous pooling of blood. Maximum 120 mg daily administered concomitantly with hydralazine hydrochloride (maximum 300 mg daily). Isosorbide mononitrate vs dinitrate dose conversion - no RX We can use this medication to both treat and prevent heart-related chest pain. Chronic isosorbide use without drug-free intervals may cause poor symptom control and endothelial dysfunction due to the release of excessive free radicals.[26]. Isosorbide mononitrate: Approximately 45%. Tell your doctor or pharmacist if you're taking any other medicines, including herbal medicines, vitamins or supplements. The possibility of developing orthostatic hypotension in elderly patients, The possibility of developing severe hypotension when combined with Phosphodiesterase(PDE) inhibitors in male patients, The development of tolerance during chronic isosorbide therapy and drug-free intervals, The possibility of developing anginal pain during drug-free intervals. stream It is an anti-anginal agent that works by relaxing the smooth muscles of both arteries and veins, but but predominantly veins to reduce cardiac preload. The medicine lowers blood pressure by causing veins to narrow and makes the heart more sensitive to the blood pressure (usually a very high blood pressure). A fixed-dose combination of isosorbide dinitrate and hydralazine is approved to treat congestive heart failure in African Americans. Take the first dose in the morning right after you . Comments Dose-related hypotension, sinus bradycardia, headache, methemoglo-binemia (rare with doses of 30 mcg/kg/ min). Talk to your doctor if you're not sure it's safe for you to exercise. Administer sublingually, intrabuccally, or orally. ISDN allows you to exercise for up to eight hours. Warn all patients receiving organic nitrates or nitrites about the potential interaction between the drugs and selective PDE inhibitors, even if they currently are not receiving the drugs, since there is substantial potential for patients to receive the drugs from another clinician, from a friend, with little or no clinical intervention (e.g., via the Internet), or illicitly. Nitrates | Treatment summaries | BNF | NICE Isosorbide belongs to the nitrate group of medications that acts by releasing nitric oxide (N0), thereby causing vasodilation. Patients who fail to respond to nitroglycerin lingual or sublingual: 2.55 mg of isosorbide dinitrate. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. !W#Lgy Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Answers. Figure 02: The Chemical Structure of Isosorbide Dinitrate. Nitrates in the management of acute coronary syndrome. Activation of myosin light chain phosphatase in intact arterial smooth muscle during nitric oxide-induced relaxation. When isosorbide dinitrate is used in fixed combination with hydralazine, consider the cautions, precautions, and contraindications associated with hydralazine. Concomitant use of isosorbide with PDE inhibitors will cause increased cGMP, resulting in life-threatening hypotension. Talk to your doctor if you're taking a combined hormonal contraceptive. Standard-release nitrate preparations: use an asymmetric dosing interval to maintain a daily nitrate-free time of 10-14 hours to minimize development of nitrate tolerance. http://creativecommons.org/licenses/by-nc-nd/4.0/. Isosorbide mononitrate - Wikipedia What is the difference or advantage of using isosorbide dinitrate over isosorbide mononitrate? [2] It can be used both to treat and to prevent heart-related chest pain; however, it is generally less preferred than beta blockers or calcium channel blockers. include: Impaired nitroglycerin bioconversion to 1,2-glyceryl dinitrate with decreased formation of nitric oxide. Isosorbide dinitrate is effective by mouth for the prophylaxis and treatment of angina; although the effect is slower in onset, it may persist for several hours. The approximate onset and duration of action of various dosage forms of isosorbide dinitrate (ISDN) and isosorbide mononitrate (ISMN) are as follows: Onset and duration of action following intrabuccal administration are probably similar to those after sublingual administration of isosorbide dinitrate. Imdur (IMD) is a sustained-release isosorbide 5-mononitrate preparation for the treatment of chronic stable angina pectoris. Inal ME, Egz AM. In patients with hypertrophic cardiomyopathy, isosorbide decreases the preload and, hence, the left ventricular volume, worseningleft ventricular outflow tract obstruction.[11]. Nitrates as an integral part of optimal medical therapy and cardiac rehabilitation for stable angina: review of current concepts and therapeutics. Sublingual or intrabuccal nitrates may be inadequately absorbed, with resultant decreased efficacy, in patients with dry oral mucous membranes (e.g., xerostomia). Because of this decrease in the heart's workload, myocardial oxygen demand becomes reduced. This medication belongs to a class of drugs known as nitrates . Your doctor may increase your dose as needed. Elantan long (EL) is the only long-acting isosorbide mononitrate formulation based on a controlled membrane principle. Learn how we can help. <>>> Postural hypotension may occur and may cause dizziness, weakness, and other signs of cerebral ischemia. However, do not take medicines for erection problems if you are taking isosorbide mononitrate or dinitrate. But Its maximal effect is seen in venous capacitance vessels. Isosorbide Mononitrate - what is the difference between isosorbide This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Long-acting nitrates. Talk to your doctor if you are having problems with your sex life. Roman S, Kahrilas PJ. [22], Isosorbide releases NO, which stimulates the soluble guanylate cyclase. 5. Fung HL. Isosorbide Dinitrate - Uses, Side Effects, and More - WebMD When the transdermal route is used, the patch should be left in place for 12 hours. Differences between nitrates: role of isosorbide 2-mononitrate Isosorbide dinitrate is used to prevent chest pain ( angina) in patients with a certain heart condition ( coronary artery disease ). There is no clear evidence that isosorbide mononitrate or dinitrate affects fertility in men or women. Modified-release preparations can have a duration of action up to 12 hours. Your email address will not be published. The challenges of isosorbide therapy are drug interactions, adverse effects, and the development of tolerance during chronic isosorbide therapy. How can lifestyle changes help the health of my heart? Isosorbide dinitrate was synthesized in the United States in the 1950s by Harris and colleagues. PDF Cardiovascular Drugs and Therapies NITRATES COMPARISON CHART Conventional tablets (e.g., Monoket): Tight, light-resistant containers at 1530C. Isosorbide mononitrate. They are similar medicines that work in the same way, but the doses are different so you'll need to take the type that you're prescribed. If you are trying to get pregnant, talk to your doctor. Severe hypotension, particularly in upright position, can occur even with low doses. Manufacturers state that selective phosphodiesterase (PDE) inhibitors (e.g., sildenafil, tadalafil, vardenafil) are contraindicated in patients receiving nitrates. The elimination half-life of isosorbide dinitrate is 1 hour, while the elimination half-life of isosorbide mononitrate is 5 to 6 hours. Your doctor may advise you to stop taking isosorbide mononitrate or dinitrate before surgery. What intervals in oral therapy of isosorbide dinitrate in various doses are sufficient to prevent nitrate tolerance? Therecommended drug-free intervals for preventing the development of tolerance for oral sustained-release isosorbide dinitrate are as follows[27]: The patients should understand the possibility of developing anginal episodes during the drug-free interval. Molecular formula: C6H8N2O8C6H9NO6 Isosorbide mononitrate and dinitrate can be taken by most adults aged 18 years and above. Therefore, the concomitant use of isosorbide with riociguat (a soluble guanylate cyclase stimulator) will cause an increased level of cGMP resulting inlife-threatening hypotension.[24]. 2 0 obj After several days, dosage may be increased to 120 mg (given as single 120-mg tablet or two 60-mg tablets) once daily. Usual initial dosage of conventional tablets (e.g., Monoket): 20 mg twice daily, with the 2 doses administered 7 hours apart. Isosorbide is a medication used to treat and prevent angina pectoris in patients with coronary heart disease. ;6YXZp2k>!'Z)IfFW`VG@Y!b /r980t ~pE Dr. Rick Koch answered. How much isosorbide mononitrate or dinitrate you take depends on your symptoms, the brand of medicine and the type of tablets or capsules you are taking. @media (max-width: 1171px) { .sidead300 { margin-left: -20px; } } It is as safe as other forms of exercise with similar levels of effort. DailyMed - ISOSORBIDE MONONITRATE ER tablet, extended release Principal pharmacologic property is relaxation of vascular smooth muscle, resulting in generalized vasodilation. Sublingual: 2.5-10 mg every 4-6 hours. The trade name of this drug is Isordil. Heart failure - Treatment - Hydralazine and Isosorbide Dinitrate It's important to stay active if you have angina or heart failure. The easiest way to lookup drug information, identify pills, check interactions and set up your own personal medication records. Visit Yellow Card for further information. The patent was approved, leading to the production of BiDil, a single-pill equivalent to the generic H-ISDN. Komicki M, Sadowski Z, Szwed H, Kowalik I. However, nitrate tolerance develops rapidly with persistent exposure and these agents are given in a way that allows for an 8 to 12 hour nitrate free period to restore efficacy. Importance of warning all patients taking either selective PDE inhibitors or organic nitrates or nitrites of the potentially severe and life-threatening hemodynamic consequences of taking the drugs within close proximity (e.g., within 24 hours of sildenafil; possibly more prolonged periods of risk with longer-acting PDE inhibitors) of taking a nitrate- or nitrite-containing preparation. It has high bioavailability and a longer half-life (4-6 hours) than ISDN. With a mind rooted firmly to basic principals of chemistry and passion for ever evolving field of industrial chemistry, she is keenly interested to be a true companion for those who seek knowledge in the subject of chemistry. Some of the patient education strategies include educating regarding the following: Home care workers can help elderly patients prone to developing orthostatic hypotension with Home safety measures. Complete avoidance may not be possible, provided sufficient time elapses between use of the drugs. Next review due: 1 July 2024, Isosorbide mononitrate and isosorbide dinitrate. Posology. PI. Distribution into human body tissues and fluids has not been fully characterized. Copyright 2023, Selected Revisions February 7, 2017. Similarly, sustained or repeated oral administration of isosorbide dinitrate for the prophylaxis of angina does not improve the exercise duration as much with a single use (2 hours vs. 6 to 8 hours), in spite of much higher plasma concentration [21].Eccentric or asymmetric dosing is one way to circumvent this.
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