Downloaded 40 times
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3) Stimulation of the posterior pituitary to release vasopressin (antidiuretic hormone, ADH)
also acts on the kidneys to increase water retention. If ADH production is excessive in
heart failure, Na+
level in the plasma may fall (hyponatremia), and this is a sign of
increased risk of death in heart failure patients.
4) A decrease renal protein kinase C
5) With ACE inhibitor use, the production of AII is decreased, leading to decreased blood
pressure.
6) Epidemiological and clinical studies have shown ACE inhibitors reduce the progress of
diabetic nephropathy independently from their blood pressure-lowering effect.[11]
This
action of ACE inhibitors is used in the prevention of diabetic renal failure.
Why Are They Prescribed? Or indication
Doctor may prescribe an ACE inhibitor for these other heart conditions:
Heart failure: They can prevent further weakening of heart and prolong life.
Heart attack: When given after one, some ACE inhibitors may lessen the impact on heart
strength and help you live longer.
Diabetes : Some can slow the process that leads to kidney damage in many people with type 2
diabetes.
Heart disease prevention: If at high risk, they’ve been shown to lessen chance of having a heart
attack or stroke.
What Are the Side Effects?
1. Dizziness
2. Lightheadedness
3. Itchy skin rash
4. Sore throat
5. Fever
6. Mouth sores
7. Unusual bruising
8. Fast or irregular heartbeat
9. Chest pain
10. Swelling of feet
11. Confusion
12. Irregular heartbeat
13. Nervousness
14. Numbness or tingling in hands, feet, or lips
15. Shortness of breath or difficulty breathing
16. Weakness or heaviness in your legs](https://image.slidesharecdn.com/cardiovasculardrug-200410195533/75/Cardiovascular-drug-Pdf-16-2048.jpg)
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Increased intracellular cGMP inhibits calcium entry into the cell, thereby decreasing intracellular
calcium concentrations and causing smooth muscle relaxation (click here for details). NO also
activates K+
channels, which leads to hyperpolarization and relaxation.
Mechanism of action of Nitrovasodilator
Nitrovasodilators are prodrugs that donate NO by various mechanisms. Nitrates undergo
chemical reduction, likely mediated by enzymes. Molsidomine and nitroprusside already contain
nitrogen in the right oxidation state (+2) and liberate NO without the aid of enzymes.
NO stimulates the soluble form of the enzyme guanylate cyclase in the smooth muscle cells of
blood vessels. Guanylate cyclase produces cyclic guanosine monophosphate (cGMP) from
guanosine triphosphate (GTP). cGMP in turn activates cyclic nucleotide-dependent protein
kinase G, which phosphorylates various proteins that play a role in decreasing intracellular
calcium levels, leading to relaxation of the muscle cells and thus to dilation of blood vessels.
Drug Interactions of nitrovasodilators
A number of drugs add to the low blood pressure caused by nitrovasodilators: for example, other
vasodilators, antihypertensive drugs, tricyclic antidepressantss, antipsychotics, general
anaesthetics, as well as ethanol. Combination with PDE5 inhibitors, including sildenafil
(Viagra), is contraindicated because potentially life-threatening hypotension may occur.[2] [4]](https://image.slidesharecdn.com/cardiovasculardrug-200410195533/75/Cardiovascular-drug-Pdf-22-2048.jpg)
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Cardiovascular drug Pdf
- 1. 1 Cardiovascular disease Cardiovascular disease(CVD) is a class of diseases that involve the heart or blood vessels. Cardiovascular disease includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, heart failure, hypertensive heart disease, rheumatic heart disease, cardiomyopathy, heart arrhythmia, congenital heart disease, valvular heart disease, aortic aneurysms, peripheral artery disease, thromboembolic disease. Classification of Cardiovascular disease A) Vascular diseases-Cardiovascular diseases involving the blood vessels. They are known as vascular diseases. 1) Coronary artery disease-also known as coronary heart disease and ischemic heart disease. 2) Peripheral arterial disease– disease of blood vessels that supply blood to the arms and legs 3) Cerebrovascular disease– disease of blood vessels that supply blood to the brain (includes stroke) 4) Renal artery stenosis 5) Aortic aneurysm B) Heart diseases- 1) Cardiomyopathy– diseases of cardiac muscle 2) Hypertensive heart disease– diseases of the heart secondary to high blood pressure or hypertension. 3) Heart failure- a clinical syndrome caused by the inability of the heart to supply sufficient blood to the tissues to meet their metabolic requirements. 4) Pulmonary heart disease– a failure at the right side of the heart with respiratory system involvement. 5) Cardiac dysrhythmias– abnormalities of heart rhythm. 6) Congenital heart disease– heart structure malformations existing at birth. 7) Rheumatic heart disease– heart muscles and valves damage due to rheumatic fever caused by Streptococcus pyogenes a group A streptococcal infection. What are cardiovascular agents? Cardiovascular agents are drugs, which are used in any way to treat conditions of the heart or the circulatory or vascular system. Many classes of cardiovascular agents are available to treat the various cardiovascular conditions. Types of Cardiovascular agents 1) Agents for hypertensive emergencies 2) Agents for pulmonary hypertension 3) Aldosterone receptor antagonists 4) Angiotensin converting enzyme inhibitors RAYHAN 13 th Batch Pharmacology-IV
- 2. 2 5) Angiotensin receptorblockers 6) Angiotensin receptor blockers and neprilysin inhibitors 7) Antiadrenergic agents, centrally acting 8) Antiadrenergic agents, peripherally acting 9) Antianginal agents 10) Antiarrhythmic agents 11) Anticholinergic chronotropic agents 12) Antihypertensive combinations a) ACE inhibitors with calcium channel blocking agents b) ACE inhibitors with thiazides c) Angiotensin ii inhibitors with calcium channel blockers d) Angiotensin ii inhibitors with thiazides e) Antiadrenergic agents (central) with thiazides f) Antiadrenergic agents (peripheral) with thiazides g) Beta blockers with thiazides h) Miscellaneous antihypertensive combinations i) Potassium sparing diuretics with thiazides 13) Beta-adrenergic blocking agents a) Cardioselective beta blockers b) Non-cardioselective beta blockers 14) Calcium channel blocking agents 15) Catecholamines 16) Diuretics a) carbonic anhydrase inhibitors b) loop diuretics c) miscellaneous diuretics d) potassium-sparing diuretics e) thiazide diuretics 17) Inotropic agents 18) Miscellaneous cardiovascular agents 19) Peripheral vasodilators 20) Renin inhibitors 21) Sclerosing agents 22) Vasodilators 23) Vasopressin antagonists 24) Vasopressors What Is Acute Myocardial Infarction? Myocardial infarction (MI) or acute myocardial infarction (AMI), commonly known as a heart attack, occurs when blood flow stops to a part of the heart causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may travel into the shoulder,arm, back, neck, or jaw. Often it is in the center or left side of the chest and lasts for more than a few minutes. The discomfort may occasionally feel like heartburn. About 30% of people have atypical
- 3. 3 symptoms. Women moreoften have atypical symptoms than men. Among those over 75 years old, about 5% have had an MI with little or no history of symptoms. An MI may cause heart failure, an irregular heartbeat, cardiogenic shock, or cardiac arrest. What Are the Symptoms of Acute Myocardial Infarction? While the classic symptoms of a heart attack are chest pain and shortness of breath, the symptoms can be quite varied. The most common symptoms of a heart attack include: pressure or tightness in the chest pain in the chest, back, jaw, and other areas of the upper body that lasts more than a few minutes or that goes away and comes back shortness of breath sweating nausea vomiting anxiety a cough dizziness a fast heart rate. It’s important to note that not all people who have heart attacks experience the same symptoms or the same severity of symptoms. Chest pain is the most commonly reported symptom among both women and men. What Causes Acute Myocardial Infarction? Heart is the main organ in your cardiovascular system, which also includes different types of blood vessels. Some of the most important vessels are the coronary arteries. They take oxygen-rich blood to all of the organs in the body, including heart. When these arteries become blocked or narrowed due to a buildup of plaque, the blood flow to your heart can decrease significantly or stop completely. This can cause a heart attack. Several factors may lead to a blockage in the coronary arteries- Cholesterol- Cholesterol is a colorless substance that’s found in the food we eat. Our body also makes it naturally. Not all cholesterol is bad, but LDL cholesterol can stick to the walls of our arteries and produce plaque. Plaque is a hard substance that blocks blood flow in the arteries. Blood platelets, which help the blood to clot, may stick to the plaque and build up over time. Saturated Fats-Saturated fats may also contribute to the buildup of plaque in the coronary arteries. Saturated fats are found mostly in meat and dairy products, including beef, butter, and
- 4. 4 cheese. These fatsmay lead to an arterial blockage by increasing the amount of bad cholesterol in our blood system and reducing the amount of good cholesterol; Trans Fat-Another type of fat that contributes to clogged arteries is trans fat or hydrogenated fat. Trans fat is usually artificially produced and can be found in a variety of processed foods. Increase the risk of heart attack, including: diabetes high blood pressure high cholesterol levels high triglyceride levels . Who Is at Risk for Acute Myocardial Infarction? 1. High Blood Pressure 2. High Cholesterol Levels 3. High Triglyceride Levels 4. Diabetes and High Blood Sugar Levels 5. Smoking 6. Age 7. Family History Myocardial Infarction Diagnosis 1) Electrocardiogram (EKG) may be done to measure your heart’s electrical activity. 2) An angiogram with coronary catheterization to look for areas of blockage in your arteries 3) An echocardiogram to help identify areas of your heart that aren’t working properly. Treatment of Myocardial Infarction Heart attacks require immediate treatment, so most treatments begin in the emergency room. A surgical procedure called angioplasty may be used to unblock the arteries that supply blood to the heart. During an angioplasty, surgeon will insert a long, thin tube called a catheter through artery to reach the blockage. They will then inflate a small balloon attached to the catheter in order to reopen the artery, allowing blood flow to resume. Surgeon may also place a small, mesh tube called a stent at the site of the blockage. The stent can prevent the artery from closing again. Doctor may also want to perform a coronary artery bypass graft (CABG) in some cases. In this procedure, surgeon will reroute your veins and arteries so the blood can flow around the blockage. A CABG is sometimes done immediately after a heart attack. In most cases, however, it’s performed several days after the incident so your heart has time to heal.
- 5. 5 A number ofdifferent medications can also be used to treat a heart attack: 1) Blood thinners, such as aspirin, are often used to break up blood clots and improve blood flow through narrowed arteries. 2) Thrombolytics are often used to dissolve clots. 3) Antiplatelet drugs, such as clopidogrel, can be used to prevent new clots from forming and existing clots from growing. 4) Nitroglycerin can be used to widen your blood vessels. 5) Beta-blockers lower blood pressure and relax your heart muscle. This can help limit the severity of damage to heart. 6) ACE inhibitors can also be used to lower blood pressure and decrease stress on the heart. 7) Pain relievers may be used to reduce any discomfort you may feel. How Can Acute Myocardial Infarction Be Prevented? There are many steps you can take to prevent a heart attack. One way to lower our risk is to eat a heart-healthy diet. This diet should largely consist of: whole grains vegetables fruits lean protein We should also reduce the amount of the following in your diet: sugar saturated fat trans fat cholesterol This is especially important for people with diabetes, high blood pressure, and high cholesterol. Exercising several times a week will also improve your cardiovascular health. If we had a heart attack recently, you should speak with your doctor before starting a new exercise plan. It’s also important to stop smoking if you smoke. Quitting smoking will significantly lower your risk of a heart attack and improve both our heart and lung health. You should also avoid being around secondhand smoke. Heart attack (MI) risk factors include: 1) Age. Men age 45 or older and women age 55 or older are more likely to have a heart attack than are younger men and women. 2) Tobacco 3) High blood pressure. 4) High blood cholesterol or triglyceride levels.
- 6. 6 5) Diabetes. 6) Familyhistory of heart attack. 7) Lack of physical activity. Procedure to improve blood flow 1) Coronary angioplasty. 2) Bypass surgery. 3) Stop smoking. 4) Maintain a healthy weight. 5) Control diabetes and blood pressure with prescribed medications. 6) Eat a healthy diet. 7) Keep physically active. Hypertension Hypertension also known as high blood pressure, is a long term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long term high blood pressure, however, is a major risk factor for coronary artery disease, stroke, heart failure, peripheral vascular disease, vision loss, and chronic kidney disease. Cause of Hypertension Obstructive sleep apnea Kidney problems Adrenal gland tumors Thyroid problems Certain defects in blood Certain medications, such as birth control pills, cold remedies, decongestants, over-the- counter pain relievers and some prescription drugs Illegal drugs, such as cocaine and amphetamines Alcohol abuse or chronic alcohol use Symptoms of hypertension 1) Severe headache. 2) Fatigue or confusion. 3) Vision problems. 4) Chest pain. 5) Difficulty breathing. 6) Irregular heartbeat. 7) Blood in the urine. 8) Facial flushing 9) Pounding in chest, neck, or ears
- 7. 7 Risk factors ofHigh blood pressure 1) Age. The risk of high blood pressure increases as age. Through early middle age, or about age 45, high blood pressure is more common in men. Women are more likely to develop high blood pressure after age 65. . 2) Family history. High blood pressure tends to run in families. 3) Being overweight or obese. The more weigh the more blood you need to supply oxygen and nutrients to tissues. 4) Not being physically active. Lack of physical activity also increases the risk of being overweight. 5) Using tobacco. Not only does smoking or chewing tobacco immediately raise blood pressure temporarily, but the chemicals in tobacco can damage the lining of artery walls. 6) Too much salt (sodium) in diet. Too much sodium in diet can cause body to retain fluid, which increases blood pressure. 7) Too little vitamin D in your diet. It's uncertain if having too little vitamin D in diet can lead to high blood pressure. 8) Drinking too much alcohol. Over time, heavy drinking can damage heart. 9) Stress. High levels of stress can lead to a temporary increase in blood pressure. Complications of HBP The excessive pressure on artery walls caused by high blood pressure can damage blood vessels, as well as organs in body. Uncontrolled high blood pressure can lead to: 1) Heart attack or stroke. High blood pressure can cause hardening and thickening of the arteries (atherosclerosis), which can lead to a heart attack, stroke or other complications. 2) Aneurysm. Increased blood pressure can cause blood vessels to weaken and bulge, forming an aneurysm. 3) Heart failure. To pump blood against the higher pressure in vessels, heart muscle thickens. Eventually, the thickened muscle may have a hard time pumping enough blood to meet body's needs, which can lead to heart failure. 4) Weakened and narrowed blood vessels in your kidneys. This can prevent these organs from functioning normally. 5) Thickened, narrowed or torn blood vessels in the eyes. This can result in vision loss. 6) Metabolic syndrome. This syndrome is a cluster of disorders of body's metabolism, including increased waist circumference; high triglycerides; low high-density lipoprotein (HDL) cholesterol, the "good" cholesterol; high blood pressure; and high insulin levels. These conditions make more likely to develop diabetes, heart disease and stroke. 7) Trouble with memory or understanding. Uncontrolled high blood pressure may also affect your ability to think, remember and learn.
- 8. 8 Medications to treathigh blood pressure 1) Thiazide diuretics. Diuretics, sometimes called water pills, are medications that act on your kidneys to help your body eliminate sodium and water, reducing blood volume.Thiazide diuretics include hydrochlorothiazide (Microzide), chlorthalidone and others. 2) Beta blockers. These medications reduce the workload on heart and open blood vessels, causing heart to beat slower and with less force. Beta blockers include acebutolol (Sectral), atenolol (Tenormin) and others. 3) Angiotensin-converting enzyme (ACE) inhibitors. These medications — such as lisinopril (Zestril), benazepril (Lotensin), captopril (Capoten) and others — help relax blood vessels by blocking the formation of a natural chemical that narrows blood vessels. 4) Angiotensin II receptor blockers (ARBs). These medications help relax blood vessels by blocking the action. ARBs include candesartan (Atacand), losartan (Cozaar) and others. 5) Calcium channel blockers. These medications — including amlodipine (Norvasc), diltiazem (Cardizem, Tiazac, others) and others — help relax the muscles of blood vessels. Some slow heart rate. 6) Renin inhibitors. Aliskiren (Tekturna) slows down the production of renin, an enzyme produced by kidneys that starts a chain of chemical steps that increases blood pressure. Recommend several lifestyle changes, including: 1) Eating a healthier diet with less salt 2) Exercising regularly 3) Quitting smoking 4) Limiting the amount of alcohol you drink 5) Maintaining a healthy weight or losing weight if you're overweight or obese Tests and diagnosis To measure your blood pressure, doctor or a specialist will usually place an inflatable arm cuff around arm and measure blood pressure using a pressure-measuring gauge. Blood pressure measurements fall into four general categories: 1) Normal blood pressure. Blood pressure is normal if it's below 120/80 mm Hg. 2) Prehypertension. Prehypertension is a systolic pressure ranging from 120 to 139 mm Hg or a diastolic pressure ranging from 80 to 89 mm Hg. Prehypertension tends to get worse over time. 3) Stage 1 hypertension. Stage 1 hypertension is a systolic pressure ranging from 140 to 159 mm Hg or a diastolic pressure ranging from 90 to 99 mm Hg. 4) Stage 2 hypertension. More severe hypertension, stage 2 hypertension is a systolic pressure of 160 mm Hg or higher or a diastolic pressure of 100 mm Hg or higher.
- 9. 9 Angina pectoris Angina pectoris,commonly known as angina is chest pain or discomfort that occurs if an area heart muscle doesn't get enough oxygen-rich blood. Angina may feel like pressure or squeezing in chest. The pain also can occur in shoulders, arms, neck, jaw, or back. Angina pain may even feel like indigestion. Angina isn't a disease; it's a symptom of an underlying heart problem. Angina usually is a symptom of coronary heart disease (CHD). Risk factors for Angina 1) unhealthy cholesterol levels 2) hypertension (high blood pressure) 3) tobacco smoking 4) diabetes 5) being overweight or obese 6) metabolic syndrome 7) sedentary lifestyle 8) being over 45 for men and over 55 for women 9) family history of early heart disease Causes of angina Angina isn't a disease; it's a symptom of an underlying heart problem. Angina usually is a symptom of coronary heart disease (CHD). Angina is most frequently the result of underlying coronary artery disease. The coronary arteries supply the heart with oxygen-rich blood. When cholesterol aggregates on the artery wall and hard plaques form, the artery narrows. 1. It is increasingly difficult for oxygen-rich blood to reach the heart muscle as the arteries become too narrow. 2. Damage to the arteries from other factors (such as smoking and high levels of fat or sugar in the blood) can cause plaques to build up where the arteries are damaged. 3. These plaques narrow the arteries or may break off and form blood clots that block the arteries. Types of Angina 1) Stable Angina Stable angina is the most common type of angina. It occurs when the heart is working harder than usual. Stable angina has a regular pattern. Stable angina isn't a heart attack, but it suggests that a heart attack is more likely to happen in the future.
- 10. 10 2) Unstable Angina Unstableangina doesn't follow a pattern. It may occur more often and be more severe than stable angina. Unstable angina also can occur with or without physical exertion, and rest or medicine may not relieve the pain. Unstable angina is very dangerous and requires emergency treatment. This type of angina is a sign that a heart attack may happen soon. 3) Variant Angina Variant angina is rare. A spasm in a coronary artery causes this type of angina. Variant angina usually occurs while at rest, and the pain can be severe. It usually happens between midnight and early morning. Medicine can relieve this type of angina. 4) Microvascular angina Microvascular (smallest vessels) angina are rare and can occur at rest without any underlying coronary artery disease. This angina is usually due to abnormal narrowing or relaxation (spasm) of the blood vessels, reducing blood flow to the heart. It is relieved by medicine. Beta Blockers What is beta blocker ? Mechanism of action of beta blockers ? Beta blocker, also written β-blocker, is a class of medications that are particularly used to manage cardiac arrhythmias, and to protect the heart from a second heart attack (myocardial infarction) after a first heart attack (secondary prevention). They are also widely used to treat hypertension, although they are no longer the first choice for initial treatment of most patients. Mechanism of action of beta blockers Beta blockers are competitive antagonists that block the receptor sites for the endogenous catecholamines epinephrine (adrenaline) and norepinephrine (noradrenaline) on adrenergic beta receptors, of the sympathetic nervous system, which mediates the fight-or-flight response. Some block activation of all types of β-adrenergic receptors and others are selective for one of the three known types of beta receptors, designated β1,β2 and β3 receptors. β1-adrenergic receptors are located mainly in the heart and in the kidneys. β2-adrenergic receptors are located mainly in the lungs, gastrointestinal tract, liver, uterus, vascular smooth muscle, and skeletal muscle. β3-adrenergic receptors are located in fat cells. Beta receptors are found on cells of the heart muscles, smooth muscles, airways, arteries, kidneys, and other tissues that are part of the sympathetic nervous system and lead to stress responses, especially when they are stimulated by epinephrine (adrenaline). Beta blockers interfere with the
- 11. 11 binding to thereceptor of epinephrine and other stress hormones, and weaken the effects of stress hormones. In 1964, James Black synthesized the first clinically significant beta blockers—propranolol and pronethalol; it revolutionized the medical management of angina pectoris. What do beta-blockers do? Beta-blockers block the release of noradrenalin in parts of the body. Noradrenalin is released by the nerves when they are stimulated - it is a chemical that conveys messages to other parts of the body, including muscles, blood vessels and the heart. 1) Heart problems - for a patient with heart problems beta-blockers can reduce the workload for the heart; so that it does not have to work so hard to supply all parts of the body with oxygen-rich blood. For people with angina, heart failure, or after a heart attack, reducing the heart's workload is crucial. a. Beta-blockers can also block the stimulation of the heart form electrical impulses - they can control irregular heartbeats - thus lowering the activity of the heart and slowing down the heart rate. 2) Hypertension - beta-blockers lower blood pressure by slowing down the heart rate, as well as reducing the force of the heart. Blood still gets to all parts of the body, but at reduced pressure. 3) Glaucoma - pressure within the eyeball is reduced with beta-blocker eye drops. The medication lowers the production of fluid inside the eye ball (aqueous humor). Indications for beta blockers include: 1) Angina pectoris 2) Atrial fibrillation 3) Cardiac arrhythmia 4) Congestive heart failure 5) Essential tremor 6) Glaucoma 7) Hypertension 8) Migraine prophylaxis 9) Mitral valve prolapse 10) Myocardial infarction 11) Postural orthostatic tachycardia syndrome Beta blockers have also been used for: 1) Acute aortic dissection 2) Hypertrophic obstructive cardiomyopathy 3) Prevention of variceal bleeding in portal hypertension 4) Possible mitigation of hyperhidrosis 5) anxiety disorders
- 12. 12 Adverse effects ofbeta blockers Adverse drug reactions associated with the use of beta blockers include: nausea, diarrhea, bronchospasm, dyspnea, cold extremities, exacerbation of, insomnia, nightmares, sexual dysfunction, erectile dysfunction and/or alteration of glucose and lipid metabolism, bradycardia, hypotension, heart failure, heart block, fatigue, dizziness, alopecia (hair loss), abnormal vision, hallucinations. Contraindication of beta blockers 1) Asthma. 2) Uncontrolled heart failure. 3) Very slow heart (bradycardia). 4) Low blood pressure (hypotension). 5) Certain problems with the rhythm of heart - eg, sick sinus syndrome. Calcium channel blockers (CCBs) Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are several medications that disrupt the movement of calcium through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as medications to decrease blood pressure in patients with hypertension. CCBs are particularly effective against large vessel stiffness, one of the common causes of elevated systolic blood pressure in elderly patients. Calcium channel blockers are also frequently used to alter heart rate, to prevent cerebral vasospasm, and to reduce chest pain caused by angina pectoris. CCBs have been shown to be slightly more effective than beta blockers at lowering cardiovascular mortality. Classification of Calcium channel blockers 1) Dihydropyridine Derivatives Dihydropyridine (DHP) calcium channel blockers are derived from the molecule dihydropyridine and often used to reduce systemic vascular resistance and arterial pressure. Sometimes when they are used to treat angina, the vasodilation and hypotension can lead to reflex tachycardia. e.g. Amlodipine, Aranidipine, Azelnidipine, Barnidipine, Benidipine, Cilnidipine, Clevidipine, Isradipine, Efonidipine, Felodipine, Lacidipine, Lercanidipine, Manidipine, Nicardipine, Nifedipine, Nilvadipine. 2) Non-dihydropyridine Derivatives Non-dihydropyridine or Phenylalkylamine calcium channel blockers are relatively selective for myocardium, reduce myocardial oxygen demand and reverse coronary vasospasm, and are often used to treat angina. They have minimal vasodilatory effects compared with dihydropyridines and therefore cause less reflex tachycardia, making it appealing for treatment of angina. E.g. Verapamil, Gallopamil, Fendiline.
- 13. 13 3) Benzothiazepine Derivatives Benzothiazepinecalcium channel blockers belong to the benzothiazepineclass of compounds and are an intermediate class between phenylalkylamine and dihydropyridines in their selectivity for vascular calcium channels. By having both cardiac depressant and vasodilator actions, benzothiazepines are able to reduce arterial pressure without producing the same degree of reflex cardiac stimulation caused by dihydropyridines. E.g –Diltiazem. 4) Non-selective Group While most of the agents listed above are relatively selective, there are additional agents that are considered nonselective. These include mibefradil, bepridil, flunarizine(BBBcrossing), fluspirilene and fendiline. 5) Others Group E.g – Gabapentin, pregabalin & Ziconotide. What Conditions Are They Prescribed? Below are heart conditions that calcium channel blockers might be prescribed for: High blood pressure Coronary artery disease Coronary spasm Angina (chest pain) Abnormal heart rhythms Hypertrophic cardiomyopathy Diastolic heart failure Raynaud’s syndrome Pulmonary hypertension If patient have systolic heart failure, then amlodipine and felodipine are the only calcium channel blockers that should be used. Calcium channel blockers are also used to prevent migraine headaches. What Are the Side Effects? 1) Side effects of calcium channel blockers can include: 2) Lightheadedness 3) Low blood pressure 4) Slower heart rate 5) Drowsiness. 6) Constipation 7) Swelling of feet ankles and legs 8) Increased appetite. 9) Gastroesophageal reflux disease (GERD) 10) Tenderness or bleeding of the gums.
- 14. 14 11) Sexual dysfunction 12)Weight gain. 13) Breathing difficulties. How Should Take CCBs? Calcium channel blockers should be taken with food or milk. Follow the label directions on how often to take it. While taking this medication, have blood pressure checked regularly, as advised by doctor. While taking this medication, your doctor may tell to take and record pulse daily. Doctor will tell you how rapid pulse should be. If pulse is slower than advised, contact doctor or nurse about taking calcium channel blocker that day. Do CCBs Have Food and Drug Interactions? Do not eat grapefruit or drink grapefruit juice while taking a calcium channel blocker.Avoid alcohol, as it interferes with the effects of calcium channel blockers and increases the side effects. Can Pregnant Women Take CCBs? Calcium channel blockers can be used during pregnancy to manage high blood pressure and preeclampsia. However, patient should always consult with doctor before taking calcium channel blockers during pregnancy. These drugs may pass into breast milk, but no adverse effect on breastfed infants has been found. Discuss the risks and benefits with doctor of using calcium channel blockers while breastfeeding. Can Children Take Them? The safety of calcium channel blockers in children has not been established; however, no problems have been found to date. Discuss the risks and benefits of giving child calcium channel blockers with your child's doctor. Mechanism of action of CCBs CCBs promote vasodilator activity and reduce blood pressure by reducing calcium influx into vascular smooth muscle cells by interfering with voltage operated calcium channels and to a lesser extent receptor operated channels in the cell membrane. Interference with intracellular calcium influx is also important in cardiac muscle, cardiac conduction tissue and gastrointestinal smooth muscle. In cardiac tissues, CCBs have potential for negative inotropic, chronotropic and dromotropic activity while the gastrointestinal effects predispose to constipation. These effects vary with different agents according to ability to penetrate cardiac and other tissues, relative affinity for calcium channels in different tissues and the influence of reflux cardiac stimulation secondary to peripheral vasodilation.
- 15. 15 Dihydropyridine derivatives havepronounced peripheral vasodilator properties and intense reflex cardiac stimulation overcomes any direct cardiac effects. Verapamil and diltiazem are also vasodilators but the balance of actions is such that these drugs have noticeable cardiac effects including reduced heart rate. CCBs used as medications primarily have four effects: 1. By acting on vascular smooth muscle, they reduce contraction of the arteries and cause an increase in arterial diameter, a phenomenon called vasodilation (CCBs do not work on venous smooth muscle). 2. By acting on cardiac muscles (myocardium), they reduce the force of contraction of the heart. 3. By slowing down the conduction of electrical activity within the heart, they slow down the heart beat. 4. By blocking the calcium signal on adrenal cortex cells, they directly reduce aldosterone production, which corroborates to lower blood pressure. Pharmacokinetics of CCBs Most CCBs have low and variable oral bioavailability because of extensive first pass metabolism.Half life is relatively short (<12 hours). The exception is amlodipine which, although extensively metabolised, has a substantially longer half life (> 40 hours). Diltiazem and verapamil tend to inhibit drug metabolism.This enzyme inhibitory effect is a potential source of drug interactions e.g. with cyclosporin. ACE inhibitor An angiotensin-converting-enzyme inhibitor (ACE inhibitor) is a pharmaceutical drug used primarily for the treatment of hypertension (elevated blood pressure) and congestive heart failure. This group of drugs causes relaxation of blood vessels as well as a decrease in blood volume, which leads to lower blood pressure and decreased oxygen demand from the heart. They inhibit the angiotensin-converting enzyme, an important component of the renin–angiotensin system. ACE inhibitors include benazepril, zofenopril, perindopril, trandolapril, captopril, enalapril, lisinopril, and ramipril. Mechanism of action of ACEI Under normal conditions, angiotensin II has these effects: 1) Vasoconstriction (narrowing of blood vessels) and vascular smooth muscle hypertrophy (enlargement) induced by AII may lead to increased blood pressure and hypertension. Further, constriction of the efferent arterioles of the kidney leads to increased perfusion pressure in the glomeruli. 2) Stimulation by AII of the adrenal cortex to release aldosterone, a hormone that acts on kidney tubules, causes sodium and chloride ions retention and potassium excretion.
- 16. 16 3) Stimulation ofthe posterior pituitary to release vasopressin (antidiuretic hormone, ADH) also acts on the kidneys to increase water retention. If ADH production is excessive in heart failure, Na+ level in the plasma may fall (hyponatremia), and this is a sign of increased risk of death in heart failure patients. 4) A decrease renal protein kinase C 5) With ACE inhibitor use, the production of AII is decreased, leading to decreased blood pressure. 6) Epidemiological and clinical studies have shown ACE inhibitors reduce the progress of diabetic nephropathy independently from their blood pressure-lowering effect.[11] This action of ACE inhibitors is used in the prevention of diabetic renal failure. Why Are They Prescribed? Or indication Doctor may prescribe an ACE inhibitor for these other heart conditions: Heart failure: They can prevent further weakening of heart and prolong life. Heart attack: When given after one, some ACE inhibitors may lessen the impact on heart strength and help you live longer. Diabetes : Some can slow the process that leads to kidney damage in many people with type 2 diabetes. Heart disease prevention: If at high risk, they’ve been shown to lessen chance of having a heart attack or stroke. What Are the Side Effects? 1. Dizziness 2. Lightheadedness 3. Itchy skin rash 4. Sore throat 5. Fever 6. Mouth sores 7. Unusual bruising 8. Fast or irregular heartbeat 9. Chest pain 10. Swelling of feet 11. Confusion 12. Irregular heartbeat 13. Nervousness 14. Numbness or tingling in hands, feet, or lips 15. Shortness of breath or difficulty breathing 16. Weakness or heaviness in your legs
- 17. 17 Classification of ACEI 1)Sulfhydryl containing agent- Captopril. 2) Dicarboxylate Containing agent- Enalapril, Ramipril. 3) Phosphate Containing agent- Fosinopril. 4) Natural occurring substances – Lactokinin, Lactotripeptide. ACE inhibitor equivalent doses in hypertension Angiotensin II receptor blocker (ARB) Angiotensin II receptor antagonists, also known as angiotensin receptor blockers (ARBs), AT1- receptor antagonists or sartans, are a group of pharmaceuticals that modulate the renin–angiotensin system. Their main uses are in the treatment of hypertension (high blood pressure), diabetic nephropathy (kidney damage due to diabetes) and congestive heart failure. They block activation of angiotensin II AT1 receptors, preventing angiotensin II from binding there.
- 18. 18 What are theavailable ARBs? 1) losartan 2) Olmesartan 3) azilsartan 4) candesartan 5) eprosartan 6) irbesartan 7) telmisartan 8) valsartan Mechanism of action of ARB Angiotensin II is a very potent chemical formed in the blood that causes muscles surrounding blood vessels to contract, thereby narrowing the vessels. This narrowing increases the pressure within the vessels and can cause high blood pressure (hypertension). Angiotensin II receptor blockers (ARBs) are medications that block the action of angiotensin II by preventing angiotensin II from binding to angiotensin II receptors on the muscles surrounding blood vessels. As a result, blood vessels enlarge (dilate) and blood pressure is reduced. Reduced blood pressure makes it easier for the heart to pump blood and can improve heart failure. In addition, the progression of kidney disease caused by the high blood pressure or diabetes is slowed. ARBs have effects that are similar to angiotensin converting enzyme (ACE) inhibitors, but ACE inhibitors act by preventing the formation of angiotensin II rather than by blocking the binding of angiotensin II to muscles on blood vessels. For what conditions are ARBs used? Or Indication ARBs are used for controlling high blood pressure, treating heart failure, and preventing kidney failure in people with diabetes or high blood pressure. ARGs also may prevent diabetes and reduce the risk of stroke in patients with high blood pressure and an enlarged heart. ARBs also may prevent the recurrence of atrial fibrillation. What are the side effects of ARBs? The most common side effects are cough, elevated potassium levels in the blood (hyperkalemia), low blood pressure, dizziness, headache, drowsiness, diarrhea,
- 19. 19 abnormal tastesensation (metallic or salty taste), rash, orthostatic hypotension (low blood pressure upon standing), fatigue, indigestion, and upper respiratory tract infection. Compared to ACE inhibitors, cough occurs less often with ARBs. Contraindications of ARBs ARBs have a relatively low incidence of side effects and are well-tolerated. Because they do not increase bradykinin levels like ACE inhibitors, the dry cough and angioedema that are associated with ACE inhibitors are not a problem. ARBs are contraindicated in pregnancy. Patients with bilateral renal artery stenosis may experience renal failure if ARBs are administered. Are there any differences among the different types of ARBs? ARBs are similar in action and side effects. They differ in how they are eliminated from the body and the extent to which they are distributed throughout the body. Some ARBs are converted to an active form in the body before they can exert their effects. Some ARBs are slightly better at reducing blood pressure than others; in some studies, irbesartan (Avapro) and candesartan (Atacand) were slightly more effective in reducing blood pressure than losartan (Cozaar). All ARBs usually are administered once daily for treatment of hypertension. Some patients may benefit from twice daily dosing of losartan (Cozaar) if blood pressure is not controlled with once daily dosing. With which drugs do ARBs interact? ARBs have few interactions with other drugs. The other drug fluconazole (Diflucan) reduces the conversion of losartan to its active form & Rifampin (Rifadin) reduces the blood levels of losartan. Combining ARBs with of potassium supplements, salt substitutes (which often contain potassium), or other drugs that increase potassium may result in excessive blood potassium levels, because also increase blood levels of potassium ARBs may also increase the blood concentration of lithium (Eskalith, Lithobid) and lead to an increase in side effects from lithium.
- 20. 20 What is anadvantage of using an ACEI compared to an ARB? 1. ACE inhibitor (or ACEI) stands for angiotensin-converting enzyme inhibitor. ARB stands for angiotensin-receptor blocker. Examples include losartan (Cozaar), valsartan 2. ACEI and ARBs work on the same pathway to stop high blood pressure, but each type of medication works at different spot in the process. 3. ACEIs are available as generics, which means a lower cost for the patient. Although several ARBs are now also available as generics, the cost can still be significantly higher than their ACEI counterparts. 4. A common disadvantage to using an ACEI is their potential to cause a cough. Although ACEIs and ARBs work very similarly, ARBs do not cause a cough. Drug comparison and pharmacokinetics of ARBs
- 21. 21 Vasodilator or nitrovasodilator Nitrovasodilatoris a pharmaceutical agent that causes vasodilation (widening of blood vessels) by donation of nitric oxide (NO),and is mostly used for the treatment and prevention of angina pectoris. This group of drugs includes nitrates (esters of nitric acid), which are reduced to NO in the body. Examples are glyceryl trinitrate (nitroglycerin) isosorbide mononitrate and dinitrate itramin tosilate pentaerithrityl tetranitrate propatylnitrate tenitramine trolnitrate General Pharmacology Nitric oxide (NO), a molecule produced by many cells in the body, and has several important actions (click here for details). In the cardiovascular system, NO is primarily produced by vascular endothelial cells. This endothelial-derived NO has several important functions including relaxing vascular smooth muscle (vasodilation), inhibiting platelet aggregation (anti-thrombotic), and inhibiting leukocyte-endothelial interactions (anti-inflammatory). These actions involve NO- stimulated formation of cGMP. Nitrodilators are drugs that mimic the actions of endogenous NO by releasing NO or forming NO within tissues. These drugs act directly on the vascular smooth muscle to cause relaxation and therefore serve as endothelial-independent vasodilators. There are two basic types of nitrodilators: those that release NO spontaneously (e.g., sodium nitroprusside) and organic nitrates that require an enzymatic process to form NO. Organic nitrates do not directly release NO, however, their nitrate groups interact with enzymes and intracellular sulfhydryl groups that reduce the nitrate groups to NO or to S-nitrosothiol, which then is reduced to NO. Nitric oxide activates smooth muscle soluble guanylyl cyclase (GC) to form cGMP.
- 22. 22 Increased intracellular cGMPinhibits calcium entry into the cell, thereby decreasing intracellular calcium concentrations and causing smooth muscle relaxation (click here for details). NO also activates K+ channels, which leads to hyperpolarization and relaxation. Mechanism of action of Nitrovasodilator Nitrovasodilators are prodrugs that donate NO by various mechanisms. Nitrates undergo chemical reduction, likely mediated by enzymes. Molsidomine and nitroprusside already contain nitrogen in the right oxidation state (+2) and liberate NO without the aid of enzymes. NO stimulates the soluble form of the enzyme guanylate cyclase in the smooth muscle cells of blood vessels. Guanylate cyclase produces cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP). cGMP in turn activates cyclic nucleotide-dependent protein kinase G, which phosphorylates various proteins that play a role in decreasing intracellular calcium levels, leading to relaxation of the muscle cells and thus to dilation of blood vessels. Drug Interactions of nitrovasodilators A number of drugs add to the low blood pressure caused by nitrovasodilators: for example, other vasodilators, antihypertensive drugs, tricyclic antidepressantss, antipsychotics, general anaesthetics, as well as ethanol. Combination with PDE5 inhibitors, including sildenafil (Viagra), is contraindicated because potentially life-threatening hypotension may occur.[2] [4]
- 23. 23 Nitrates increase thebioavailability of dihydroergotamine (DHE). High DHE levels may result in coronary spasms in patients with coronary disease. Therapeutic Indications The primary pharmacologic action of nitrodilators, arterial and venous dilation, make these compounds useful in the treatment of hypertension, heart failure, angina and myocardial infarction. Another beneficial action of nitrodilators is their ability to inhibit platelet aggregation. 1. Hypertension Nitrodilators are not used to treat chronic primary or secondary hypertension; however, sodium nitroprusside and nitroglycerine are used to lower blood pressure in acute hypertensive emergencies that may result from a pheochromocytoma, renal artery stenosis, aortic dissection, etc. Nitrodilators may also be used during surgery to control arterial pressure within desired limits. 2. Heart failure Nitrodilators are used in acute heart failure and in severe chronic heart failure. Arterial dilation reduces afterload on the failing ventricle and leads to an increase in stroke volume and ejection fraction. Furthermore, the venous dilation reduces venous pressure, which helps to reduce edema. Reducing both afterload and preload on the heart also helps to improve the mechanical efficiency of dilated hearts and to reduce wall stress and the oxygen demands placed on the failing heart. 3. Angina and myocardial infarction Organic nitrates are used extensively to treat angina and myocardial infarction. They are useful in Printzmetal's variant angina because they improve coronary blood flow (i.e., increase oxygen supply) by reversing and inhibiting coronary vasospasm. They are important in other forms of angina because they reduce preload on the heart by producing venous dilation, which decreases myocardial oxygen demand. It is unclear if direct dilation of epicardial coronary arteries play a role in the antianginal effects of nitrodilators in chronic stable or unstable angina. These drugs also reduce systemic vascular resistance (depending on dose) and arterial pressure, which further reduces myocardial oxygen demand. Taken together, these two actions dramatically improve the oxygen supply/demand ratio and thereby reduce anginal pain. Primary Cardiovascular Actions of Nitrodilators 1. Systemic vasculature a. vasodilation (venous dilation > arterial dilation) b. decreased venous pressure c. decreased arterial pressure (small effect)
- 24. 24 2. Cardiac a. reducedpreload and afterload b. decreased oxygen demand 3. Coronary a. prevents/reverses vasospasm b. vasodilation (primarily epicardial vessels) c. improves subendocardial perfusion d. increased oxygen delivery Adverse effect of nitrovasodilators