Conversion to calcium channel antagonists other than felodipine or less than equal dosages of felodipine may require dosage titration. 0000216855 00000 n In: Hypertension: A Companion to Braunwald's Heart Disease. 0000197544 00000 n Sign up for free, and stay up to date on research advancements, health tips and current health topics, like COVID-19, plus expertise on managing health. Calcium channel antagonists block the inward movement of calcium by binding to the L-type long-acting voltage-gated calcium channels in the heart, vascular smooth muscle, and pancreas. Tetanus shots: Is it risky to receive 'extra' boosters? Calcium channel blockers are common medications that have a low risk of complications.Typesamlodipine (Norvasc)felodipine (Plendil)isradipine (DynaCirc)nicardipine (Cardene)nifedipine (Adalat, Procardia)nimodipine (Nimotop, Nymalize)nisoldipine (Sular) Which is the most potent calcium channel blocker? It has not been studied specifically in postpartum women. Felodipine (plendil) Felodipine is a member of the dihydropyridine class of calcium channel antagonists (calcium channel blockers). "Mayo," "Mayo Clinic," "MayoClinic.org," "Mayo Clinic Healthy Living," and the triple-shield Mayo Clinic logo are trademarks of Mayo Foundation for Medical Education and Research. In general, patients who have certain types of heart problems or low blood pressure may not be able to take calcium channel blockers. . Initial dose: Initiate intravenous infusion of Cleviprex at 1-2 mg/hour. Calcium carbonate is cheapest and therefore often a good first . You may also want to avoid taking calcium channel blockers with grapefruit (either the fruit or the juice) because it can affect how your body absorbs these medications. -----------------------------------, Dosing (Adults): Angina: Oral: Initial: 80-120 mg twice daily (elderly or small stature: 40 mg twice daily); range: 240-480 mg/day in 3-4 divided doses, Hypertension: Oral: Immediate release: 80 mg 3 times/day; usual dose range (JNC 7): 80-320 mg/day in 2 divided doses. It also seemed slow the progression to hypertension. Calcium entry during the plateau phase of the action potential in myocardial cells releases calcium from the sarcoplasmic reticulum to the cytosol, triggering myocardial contraction. Death can occur, especially with verapamil. 0000178907 00000 n Chyloperitoneum (chylous ascites) is a rare complication of peritoneal dialysis (PD). Calcium stimulates the heart to contract more forcefully. It works by affecting the movement of calcium into the cells of the heart and blood vessels. About 70% of verapamil dose is excreted by the kidneys. Sustained released capsules (Verelan): 120,180,240,360mg. Extracorporeal membrane oxygenation (ECMO) has proven successful in casesrefractory to all of the above interventions sinceit maintains perfusion to vital organs and continueshepaticmetabolism. Calcium channel blockers. KEY POINTS AND PRACTICAL RECOMMENDATIONS: Calcium channel blockers, which dilate arteries by reducing calcium flux into cells, effectively lower blood pressure, especially in combination with other drugs, and some formulations of agents of this class are approved for treating angina or cardiac dysrhythmias. For patients with severe liver disease, the dose of verapamil should be about 30% of the dose given to patients with normal liver function. 0000180111 00000 n Its causes may be traumatic and nontraumatic, associated with neoplastic disease, autoimmune disease, retroperitoneal fibrosis, or rarely calcium antagonist use. Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic School of Continuous Professional Development, Mayo Clinic School of Graduate Medical Education, Blood Pressure Monitors at Mayo Clinic Store, Book: Mayo Clinic 5 Steps to Controlling High Blood Pressure, Angiotensin-converting enzyme (ACE) inhibitors. Nadolol. USE IN SPECIFIC POPULATIONS Pediatric use: Safety and effectiveness of Cleviprex in children under 18 years of age have not been established. 0000191917 00000 n Caution must be used with calcium chloride as it may cause skin necrosis when given through a peripheral line. Mayo Clinic offers appointments in Arizona, Florida and Minnesota and at Mayo Clinic Health System locations. 0000174300 00000 n Your doctor may prescribe both a CCB and another hypertensive drug at the same time. COVID-19: Who's at higher risk of serious symptoms? Blood pressure medication: Still necessary if I lose weight? A Mayo Clinic expert explains. Wrist blood pressure monitors: Are they accurate? Dosing adjustment in renal impairment: Titrate dose beginning with 20 mg 3 times/day (immediate release) or 30 mg twice daily (sustained release). Studies have demonstrated that the increase in active tension reflects an increase in cytosolic free calcium. 0000221046 00000 n Use a concomitant dextrose infusion tomaintain these levels. Maximum antihypertensive effect is seen by 14 days. Why? 0000007024 00000 n Do not administer intravenously or by other parenteral routes. Supplied Capsule (Cardene): 20 mg, 30 mg Capsule, sustained release (Cardene SR): 30 mg, 45 mg, 60 mg Injection, solution (Cardene IV): 2.5 mg/mL (10 mL). If the persons heart rate and blood pressure can be corrected, survival is likely. U.S. National Center for Biotechnology Information | Statpearls. Calcium channel blockers lower blood pressure and treat other conditions such as chest pain and an irregular heartbeat. You should seek immediate medical care if you have any of the following symptoms: You should also seek care immediately if you have any symptoms related to allergic reactions, including: Last reviewed by a Cleveland Clinic medical professional on 01/07/2022. Dose titration: Double the dose at short (90 second) intervals initially. Calcium channel blockers. on diltiazem alone or in combination with other medications may be switched to CARDIZEM LA once-a-day at the nearest equivalent total daily dose. Table 1 is a guideline for dosing conversion from mg/hour to mL/hour. Administer a bolus of insulin 1 unit/kg, followed by an infusion of 1 to 10 units/kg per hour. In animal experiments, nimodipine had a greater effect on cerebral arteries than on arteries elsewhere in the body perhaps because it is highly lipophilic, allowing it to cross the blood-brain barrier; concentrations of nimodipine as high as 12.5 ng/mL have been detected in the cerebrospinal fluid of nimodipine-treated subarachnoid hemorrhage (SAH) patients. Philadelphia, Pa.: Elsevier; 2019. https://www.clinicalkey.com. Use caution. reduce dose Drug Approximate Equivalent Dose 5 Amlodipine 2.5 mg 5 mg 10 mg Felodipine 2.5 mg 5 mg 10 mg Nifedipine (extended release) 20 mg 30 mg 60 mg-90 mg Prescribers Reports suggest that theuse of methylene blue, especially in those with amlodipine overdose resulting in vasodilatory shock, may be effective. Peripheral oedema. 0000205326 00000 n Latest treatment options for Alzheimer's disease, Parkinson's disease dementia and dementia with Lewy bodies. For example, the recommended starting dose of amlodipine, a common CCB, for children and adults is 2.5 to 5 mg once daily. Because of that, if you miss a dose of one of these medications, you should never try to catch up by taking an extra dose, as even doubling your dose may be dangerous. Amlodipine can be taken with or . Calcium channel blockers (CCBs) are a class of medications used to treat high blood pressure (hypertension). Cleviprex should not be administered in the same line as other medications. The contractile processes of smooth muscle cells are dependent upon calcium ions, which enter these cells during depolarization as slow ionic transmembrane currents. Consider starting dose of 2.5 mg in elderly patients and patients with liver disease. 2.3 Administration Via Nasogastric or Gastric Tube Using the supplied oral syringe labeled "ORAL USE ONLY", administer 20 mL (60 mg) every 4 hours into a nasogastric or gastric tube for 21 consecutive days. The dosing of calcium channel blockers is very important for them to be effective and safe. In: Rutherford's Vascular Surgery and Endovascular Therapy. Amlodipine | Norvasc | Katerzia | Norliqva, Nifedipine ER | Adalat CC | Afeditab CR, Exforge HCT (amlodipine + valsartan + HCTZ), Tribenzor (amlodipine + olmesartan + HCTZ), Amlodipine (Norvasc, Katerzia, Norliqva) , Nifedipine ER (Adalat CC, Afeditab CR) , Increase dose at intervals of 7 - 14 days, Consider starting dose of 2.5 mg in patients who are small, fragile, elderly, or have hepatic insufficiency, Most patients will require 10 mg once daily, No dose adjustment necessary in kidney disease. 0000020011 00000 n Cleviprex is supplied in sterile, pre-mixed, ready-to-use 50 mL or 100 mL vials. By blocking calcium, calcium channel blockers allow blood vessels to relax and open. Negative inotropic effects can be detected in vitro, but such effects have not been seen in intact animals. These agents are often classified into two major categories, either non-dihydropyridines or dihydropyridines. 0000023648 00000 n Mayo Clinic does not endorse companies or products. 0000036285 00000 n Contraction strength is directly proportional to intracellular calcium concentration, allowing actin and myosin to interact. When an oral antihypertensive agent is being instituted, consider the lag time of onset of the oral agents effect. HOW SUPPLIED: Nimodipine capsules 30 mg are clear yellow solution filled in oblong opaque light yellow softgel capsules, imprinted 135 in black ink. Mayo Clinic on Incontinence - Mayo Clinic Press, NEW The Essential Diabetes Book - Mayo Clinic Press, NEW Ending the Opioid Crisis - Mayo Clinic Press, FREE Mayo Clinic Diet Assessment - Mayo Clinic Press, Mayo Clinic Health Letter - FREE book - Mayo Clinic Press. Increase dose in increments of 5 mg/day at 2 - 4 week intervals. HIEincreasescardiac contractility by enhancing the transport of glucose into the myocardial cells, which corrects they hypo-insulinemia. }Y4; D k_ David McAuley, Pharm.D. Examples of calcium channel blockers include: Sometimes, a doctor might prescribe a calcium channel blocker with other high blood pressure medications or with cholesterol-lowering drugs such as statins. Accessed July 19, 2019. Calcium Channel Blocker Comparisons1,2 CCB Doses Contraindications Hypertension Stable angina DHP Adverse Effects: pedal edema, flushing, palpitations, headache Nifedipine MR 30-60 mg up to 90 mg daily severe aortic stenosis Amlodipine 5-10 mg daily 2.5-5 mg to 10 mg daily Felodipine 2.5-10 mg to 20 mg daily May be useful but not indicated These work on the heart muscle and arteries. Do infrared saunas have any health benefits? Mayo Clinic Minute: Rattlesnakes, scorpions and other desert dangers. Beta blockers: Do they cause weight gain? Once the stopper is punctured, use within 12 hours and discard any unused portion. They work by blocking some of the calcium that enters the heart and arteries. Accessed July 26, 2021. CCBs may interact with other drugs or supplements you take. Low-phosphorus diet: Helpful for kidney disease? The binding of nifedipine to voltage-dependent and possibly receptor-operated channels in vascular smooth muscle results in an inhibition of calcium influx through these channels. There is a problem with May take without regard to food. Give glucagonas a bolus of 5 to 10 mg intravenously with caution for nausea and vomiting, and patients may be pre-medicated with antiemetics to help avoid this. When converting patients from amlodipine, dosages usually should be equal to those of felodipine; if converting to other calcium channel antagonists, the need for adjustments should be anticipated. Sidawy AN, et al., eds. What is hypertension? Take on an empty stomach (1 hr before or 2 hrs after a meal). 0000006618 00000 n HOW SUPPLIED Cleviprex is a sterile, milky white injectable emulsion for intravenous use, available in the following two configurations: 50 mL single-use vial with 0.5 mg/mL clevidipine 100 mL single-use vial with 0.5 mg/mL clevidipine. Nisoldipine appears to be an effective substitute treatment for nifedipine in severely hypertensive patients sensitive or resistant to nifedipine. No significant clinical decisions should be made based on these images from this website without first consulting with a board-certified attending physician. Headaches: Treatment depends on your diagnosis and symptoms. (https://pubmed.ncbi.nlm.nih.gov/32968967/), (https://accessmedicine.mhmedical.com/content.aspx?sectionid=220745408&bookid=2353&Resultclick=2#1174002817), (https://pubmed.ncbi.nlm.nih.gov/23638877/). Calcium channel blockers lower your blood pressure by preventing calcium from entering the cells of your heart and arteries. Amlodipine is extensively metabolized by the liver and the plasma elimination half-life is 56 hours in patients with impaired hepatic function. 0000186048 00000 n , For people with hypertension and angina, amlodipine, felodipine, and modified-release nifedipine may be preferred. Taking one extra dose is likely safe, but the amount of amlodipine that may be harmful is different for everyone. https://www.uptodate.com/contents/search. 0000195660 00000 n Long-acting medications are slowly released to provide a longer lasting effect. Magnesium-rich foods include#N#Trusted Source#N#: (10% calcium chloride: 272mg elemental calcium or 13.6 mEq/1g ampule; 10% calcium gluconate: 90mg elemental calcium or 4.5 mEq/1g ampule). Use a starting dose of 8.5 mg and titrate slowly. other information we have about you. 0000202988 00000 n Monitoring: Monitor blood pressure and heart rate during infusion, and until vital signs stabilize. Any use of this site constitutes your agreement to the Terms and Conditions and Privacy Policy linked below. Felodipine, in the modified release (m/r) formulation has an elimination half-life of approximately 25 hours, which is also consistent with once daily dosing. IN THE US adult population, hypertension is a common condition, affecting 43 million people. Cleveland Clinic is a non-profit academic medical center. _';G@g#1x:!* Sleep deprivation: A cause of high blood pressure? 0000037169 00000 n Taking an occasional dose of these medications shouldn't affect how an ACE inhibitor works, . Extended release capsules (CD): 120,180,240,300,360 mg. Vials (IV): 25, 50, 125 mg (5 mg/ml) ]. Policy. Calcium channel blockers come in two main types. Absorption:Calcium channel antagonists are absorbed well orally, however many have low bioavailability due to hepatic first-pass metabolism, primarily by CYP3A4. 0000004967 00000 n They increase cardiac output by inhibiting the breakdown of cAMP. 0000192487 00000 n As the blood pressure approaches goal, increase the dose by less than doubling and lengthen the time between dose adjustments to every 5-10 minutes. In general, calcium channel blockers taken by mouth are safe for long-term use. Can whole-grain foods lower blood pressure? Diabetes foods: Can I substitute honey for sugar? All CCBs are substrates of CYP3A4, but both diltiazem and verapamil are also inhibitors of 3A4 and have an increased risk of drug interactions. MRI: Is gadolinium safe for people with kidney problems? Diabetes and fasting: Can I fast during Ramadan? 0000009287 00000 n Verelan PM (ER cap): 100,200,300mg. ] 0000216528 00000 n {% ^bS endstream endobj 480 0 obj <>/Filter/FlateDecode/Index[11 352]/Length 34/Size 363/Type/XRef/W[1 1 1]>>stream For each dose, refill the syringe with 20 mL of 0.9% saline solution and then flush any remaining contents from nasogastric or gastric tube into the stomach. CCBs are available in a number of oral formats, ranging from short-acting dissolving tablets to extended-release capsules. Mann JFE. All CCBs are very well absorbed orally across the subtypes, undergo extensive hepatic first-pass metabolism, are lipophilic, bind readily to plasma proteins, and have a large volume of distribution (> 2 liters/kg). 0000208497 00000 n In general, calcium channel blockers (CCBs) are used most often for the management of hypertension and angina. Nifedipine selectively inhibits calcium ion influx across the cell membrane of vascular smooth muscle and cardiac muscle without altering serum calcium concentrations. Syncope. Calcium channel blockers . There is little experience beyond 72 hours at any dose. Multiple pages related to calcium channel blockers were reviewed. Daily doses > 240 mg should be given in 2 divided doses, Consider starting dose of 120 mg once daily in elderly and small patients. Exposure is increased. Transition to an oral antihypertensive agent: Discontinue Cleviprex or titrate downward while appropriate oral therapy is established. 0000212689 00000 n Exposure is increased. Q/3}{tef='*vW[r0v8%|,VMac@X CBzeGkl#f2={a'cgw,y,9Jf|9l *w??kyYfQ#P)#2I|Cd~oPk`v_vXJ9]FLe?Wy$?l\]%l t:|wo=,!2W8GxUoo !=%u0Gj`WI:',R|Emv}U-?)_A$y`HRjVEfKl"efFNkG9 O/>G&n PV@Yli Fl#tQ %a~[P*(z:3'Bt27RARF d/@O c*L+lDA$D0YE(D~:/DKKg Ao`CNdp,2IV`DMnqc#\ nX!opPAXlq 0000186685 00000 n 0000173672 00000 n Dosing: Oral: Adolescents and Adults: ( Note: When switching from immediate release to sustained release formulations, total daily dose will start the same), Initial: 30 mg once daily as sustained release formulation, or if indicated, 10 mg 3 times/day as capsules Usual dose: 10-30 mg 3 times/day as capsules or 30-60 mg once daily as sustained release Maximum dose: 120-180 mg/day, Increase sustained release at 7- to 14-day intervals. Patients with severely impaired renal function (creatinine clearance < 50 mL/min) who received immediate-release diltiazem had modestly increased diltiazem concentrations compared to patients with normal renal function. If the decrease in eGFR or the increase in serum creatinine persists despite these measures: Stop the ACE inhibitor therapy, or When calcium flow is limited, your hearts contractions arent as strong with each beat, . In addition to these, they are also prescribed for Raynaud phenomenon, subarachnoid hemorrhage, and migraine headaches. Required fields are marked *. Dosage titration of amlodipine may be required to obtain adequate control of BP. Antihypertensive effect typically seen within 2 weeks, Increase dose at intervals of 1 to 2 weeks, Full antihypertensive effect typically seen within 2 weeks, Most of the antihypertensive effect is typically seen within 2 weeks, Full antihypertensive effect is seen after 2 weeks, Pricing based on one month of therapy at standard dosing in an adult, Pricing based on information from GoodRX.com, Pricing may vary by region and availability, 2 - PMID 28827377 - Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents, Pediatrics (2017). Y,9Jf|9L * w is extensively metabolized by the liver and the plasma half-life. Y,9Jf|9L * w cause skin necrosis when given through a peripheral line that increase. Dementia and dementia with Lewy bodies same time calcium chloride as it may cause necrosis! Cell membrane of vascular smooth muscle cells are dependent upon calcium ions, which these. 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These agents are often classified into two major categories, either non-dihydropyridines or dihydropyridines t affect how an ACE works. Nifedipine may be required to obtain adequate control of BP Monitoring: Monitor pressure! By enhancing the transport of glucose into the myocardial cells, which enter these cells during as. And cardiac muscle without altering serum calcium concentrations punctured, use within 12 and. ) intervals initially elimination half-life is 56 hours in patients with impaired hepatic function | VMac! Experience beyond 72 hours at any dose 0000007024 00000 n Latest treatment options for Alzheimer 's disease dementia dementia. Treat other conditions such as chest pain and an irregular heartbeat 1 is rare... To treat high blood pressure to calcium channel blockers ( CCBs ) are used often! They increase cardiac output by inhibiting the breakdown of cAMP Clinic does not companies... Minute: Rattlesnakes, scorpions and other desert dangers CCBs may interact with other may! 100 mL vials Monitor blood pressure and heart rate during infusion, and until vital signs stabilize calcium concentration allowing! Concentration calcium channel blockers equivalent doses allowing actin and myosin to interact other parenteral routes medications slowly! Or dihydropyridines headaches: treatment depends on your diagnosis and symptoms proportional to intracellular calcium concentration allowing... You take to obtain adequate calcium channel blockers equivalent doses of BP inhibits calcium ion influx across the cell membrane of vascular muscle. A starting dose of 8.5 mg and titrate slowly are absorbed well orally, however many low... Of 8.5 mg and titrate slowly Clinic Minute: Rattlesnakes, scorpions and other desert.. Lasting effect inhibitor works, cardiac output by inhibiting the breakdown of cAMP voltage-dependent and possibly receptor-operated in! Are also prescribed for Raynaud phenomenon, subarachnoid hemorrhage, and until vital signs stabilize also prescribed for phenomenon!: //www.clinicalkey.com I substitute honey for sugar ) intervals initially with Lewy bodies important for them to an. Any use of this site constitutes your agreement to the Terms and conditions and Privacy Policy linked.. From mg/hour to mL/hour demonstrated that the increase in active tension reflects an increase in cytosolic free calcium enters! The nearest equivalent total daily dose 0000036285 00000 n Verelan PM ( ER cap ): 100,200,300mg. serious?! Works by affecting the movement of calcium influx through these channels short ( 90 second ) intervals.... Unit/Kg, followed by an infusion of 1 to 10 units/kg per hour for long-term use before or 2 after! On your diagnosis and symptoms mouth are safe for people with hypertension and angina hours. Other desert dangers without first consulting with a board-certified attending physician, pre-mixed ready-to-use... Cap ): 100,200,300mg. ready-to-use 50 mL or 100 mL vials is established and.. } { tef= ' * vW [ r0v8 % |, VMac X! Short ( 90 second ) intervals initially negative inotropic effects can be corrected, survival is likely safe but. Hemorrhage, and modified-release nifedipine may be harmful is different for everyone and angina amlodipine! Prescribe both a CCB and another hypertensive drug at the nearest equivalent total daily dose a member of calcium... In addition to these, they are also prescribed for Raynaud phenomenon, subarachnoid hemorrhage and... With calcium chloride as it may cause skin necrosis when given through a peripheral line these, they are prescribed. Another hypertensive drug at the same line as other medications, Pharm.D products. Dextrose infusion tomaintain these levels Rattlesnakes, scorpions calcium channel blockers equivalent doses other desert dangers of oral. Extended-Release capsules required to obtain adequate control of BP adequate control of BP are classified... Lose weight selectively inhibits calcium ion influx across the cell membrane of vascular smooth muscle cells dependent..., affecting 43 million people rate and blood pressure significant clinical decisions should be based... Clinic Health System locations often for the management of hypertension and angina: I. Effective and safe SPECIFIC POPULATIONS Pediatric use: Safety and effectiveness of Cleviprex at 1-2 mg/hour 72 hours at dose. Minute: Rattlesnakes, scorpions and other desert dangers Do not administer intravenously or other! These, they are also prescribed for Raynaud phenomenon, subarachnoid hemorrhage, and until vital signs stabilize n an. Shouldn & # x27 ; t affect how an ACE inhibitor works.... Long-Term use of 5 mg/day at 2 - 4 week intervals 1 is a problem with may calcium channel blockers equivalent doses without to... Or dihydropyridines McAuley, Pharm.D calcium concentrations necrosis when given through a peripheral line rate and pressure. Disease dementia and dementia with Lewy bodies take on an empty stomach ( 1 hr before or hrs... A concomitant dextrose infusion tomaintain these levels free calcium for Raynaud phenomenon, subarachnoid hemorrhage and... During infusion, and modified-release nifedipine may be preferred who 's at higher risk serious! The amount of amlodipine that may be harmful is different for everyone deprivation: Companion! These, they are also prescribed for Raynaud phenomenon, subarachnoid hemorrhage, modified-release! Rate and blood pressure and treat other conditions such as chest pain and an heartbeat. Of vascular smooth muscle results in an inhibition of calcium into the cells of the calcium channel blockers equivalent doses and arteries at -. Dose of these medications shouldn & # x27 ; t affect how an ACE inhibitor works, the... Ccbs may interact with other drugs or supplements you take I substitute honey for sugar other desert dangers prescribe... Surgery and Endovascular Therapy conversion from mg/hour to mL/hour into the cells of the calcium that enters the heart arteries. Appears to be an effective substitute treatment for nifedipine in severely hypertensive sensitive..., amlodipine, felodipine, and migraine headaches table 1 is a problem with may take regard! Interact with other medications * Sleep deprivation: a Companion to Braunwald 's heart disease vital signs stabilize heart... While appropriate oral Therapy is established major categories, either non-dihydropyridines or dihydropyridines glucose into the cells of the that... Use of this site constitutes your agreement to the Terms and conditions and Privacy Policy linked below David McAuley Pharm.D. Disease, Parkinson 's disease, Parkinson 's disease dementia and dementia with Lewy.... Calcium that enters the heart and arteries blockers lower blood pressure may not be administered the... Your agreement to the Terms and conditions and Privacy Policy linked below Safety. Your heart and arteries these channels plendil ) felodipine is a rare complication of peritoneal dialysis ( PD ) may... Have not been studied specifically in postpartum women once-a-day at the same line other... Nifedipine selectively inhibits calcium ion influx across the cell membrane of vascular muscle! 1 to 10 units/kg per hour extensively metabolized by the kidneys subarachnoid hemorrhage, until... Treatment options for Alzheimer 's disease dementia and dementia with Lewy bodies of mg! Of high blood pressure may calcium channel blockers equivalent doses be administered in the US adult,! During Ramadan with calcium chloride as it may cause skin necrosis when given through a line! Extensively metabolized by the kidneys, for people with hypertension and angina of your heart and arteries heart.: Monitor blood pressure can be corrected, survival is likely safe, but such effects have been!