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Antihypertensive drugs Dr. M. Kheir Mulki What is the Blood Pressure ? • Blood pressure (BP) is the pressure exerted by circulating blood upon the walls of blood vessels. • Blood pressure (BP) is one of the principal vital signs. BP = CO x PR BP = blood pressure CO = cardiac output PR = peripheral resistance • Cardiac output is the volume of blood pumped by the heart per minute (mL blood/min). • Cardiac output is a function of heart rate and stroke volume. Under conditions of rest: the parasympathetic fibers release acetylcholine, which acts to slow the pacemaker potential of the SA node and thus reduce heart rate. Under conditions of physical or emotional activity : 1. Sympathetic nerve fibers release norepinephrine 2.The adrenal medulla release epinephrine, which acts to speed up the pacemaker potential of the SA node thus increasing heart rate. • An average person has a resting heart rate of 70 beats/minute and a resting stroke volume of 70 mL/beat. • The cardiac output for this person at rest is: Cardiac Output = 70 (beats/min) X 70 (mL/beat) = 4900 mL/minute. • The total volume of blood in the circulatory system of an average person is about 5 liters (5000 mL). • According to our calculations, the entire volume of blood within the circulatory sytem is pumped by the heart each minute (at rest). • During vigorous exercise, the cardiac output can increase up to 7 fold (35 liters/minute). What is the Essential hypertension ? Essential hypertension (also called primary or idiopathic hypertension) is the form of hypertension that by definition, has no identifiable cause. It is the most common type of hypertension, affecting 95% of hypertensive patients What is secondary hypertension ? • Secondary hypertension (inessential hypertension) is a type of hypertension which by definition is caused by an identifiable underlying secondary cause. • It is much less common(affecting only 5% of hypertensive patients). • It has many different causes including : • Disorders of the adrenal gland (Cushing's syndrome ,hyperaldosteronism and pheochromocytoma) • Kidney disease (polycystic kidney disease, kidney tumor, kidney failure, narrow or blocked main artery supplying the kidney) • Drugs : (corticosteroids, NSAID ,weight loss drugs , decongestants, birth control pills (the estrogen component), and migraine medications) • Sleep apnea • Thyroid and parathyroid problems What is the classification of Blood pressure ? Isolated systolic hypertension: increased systolic blood pressure at normal or decreased diastolic BP Pseudohypertension : rigid arteries in old age. White coat hypertension : induced by stress at physical examination. Masked hypertension : false finding of normal blood pressure during the examination; opposite of white coat hypertension. What are the symptoms of hypertension ? • Often, patients diagnosed with essential hypertension have no symptoms. • Sometimes patients will experience a : •Mild headache •Tiredness •Shortness of breath •Confusion •Dizziness •Anxiety •Visual changes •Nausea and vomiting •Perspiration •Nose bleeds •Pale or red skin •An angina-like pain in the chest •Rarely, the first symptom may be a stroke What is the physiological mechanisms to maintain normal blood pressure ? 1. Autonomic nervous system responses. 2. Hormonal responses The autonomic nervous system is the most rapidly responding regulator of blood pressure and receives continuous information from the baroreceptors situated in the carotid sinus and the aortic arch. This information is relayed to the brainstem to the vasomotor centre (VMC). Hormonal mechanisms Hormonal mechanisms exist both for lowering and raising blood pressure. They act in various ways including vasoconstriction, vasodilatation and alteration of blood volume. The principal hormones raising blood pressure are: 1. Adrenaline and noradrenaline secreted from the adrenal medulla in response to sympathetic nervous system stimulation. They increase cardiac output and cause vasoconstriction and act very rapidly. 2. Renin- Angiotensin- Aldosterone axis : Renin production is increased in the kidney when stimulated by hypotension . Angiotensin is converted in the lung to Angiotensin II, which is a potent vasoconstrictor. In addition these hormones stimulate the production of aldosterone from the adrenal cortex which decreases urinary fluid and electrolyte loss from the body. Why Hypertension should be Treated ? To decrease: • Cerebrovascular Accidents 35-40% • Coronary events 20-25% • Heart failure 50% • Progression of renal disease • Progression to severe hypertension Therefore decreasing mortality rate City Pharma Medical supprt dept. Lifestyle Modification Modification Weight reduction Approximate SBP reduction (range) 5–20 mmHg/10 kg weight loss Adopt DASH eating plan 8–14 mmHg Dietary sodium reduction 2–8 mmHg Physical activity 4–9 mmHg Moderation of alcohol consumption 2–4 mmHg Dietary Approaches to Stop Hypertension (DASH) What can the patient do? -Change lifestyle -Stop smoking -Lose weight -Exercise regularly -Cut down on alcohol -Eat a varied diet -Reduce stress by trying different relaxation techniques, or by avoiding stressful situations. Only 53% Only 24% of hypertensive patients are being treated, have their hypertension under control. Antihypertensive agents Anti hypertensive agents 1. 2. 3. 4. 5. 6. 7. ACE inhibitor ARBS Beta blockers Calcium channel blockers Central agents Diuretics vasodilators Peter S. Sever, and Franz H. Messerli Eur Heart J 2011;eurheartj.ehr177 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2011. For permissions please email: [email protected] Diuretics • Diuretics ( water pills ) treat a variety of conditions, such as : • High blood pressure. • Glaucoma. • Edema. • Heart failure. • Kidney and liver problems • and sometimes in weight loss. The most common types of diuretic are: • Thiazides (eg hydrochlorthiazide) • Loop diuretics (eg furosemide) • Potassium-sparing diuretics (eg spirenolacton) • Others : carboanhydrase inhibitors (acetazolamid) Vasodilators • Vasodilator drugs relax the smooth muscle in blood vessels, which causes the vessels to dilate. • Dilation of arterial (resistance) vessels leads to a reduction in systemic vascular resistance, which leads to a fall in arterial blood pressure. • Examples of vasodilators are Hydralazine and Minoxidil . • The vasodilator Hydralazine also may be used to control high blood pressure in pregnant women or to bring down extremely high blood pressure in emergency situations. • A liquid form of Minoxidil, used to promote hair growth in people with certain kinds of baldness and is applied directly to the scalp, is sold without a prescription. Beta blockers Beta blockers block the action of endogenous catecholamines (epinephrine (adrenaline) and norepinephrine (noradrenaline) in particular), on β-adrenergic receptors, part of the sympathetic nervous system . Beta-blockers are often prescribed for these heart conditions: • Compensated congestive heart failure • High blood pressure • Angina • Abnormal heart rhythms • Heart attack( post myocardial infarction ) • In addition, beta-blockers are sometimes prescribed for glaucoma, migraine headaches, and hyperthyroidism. • Some beta-blockers are selective, which means that they block beta 1 receptors more than they block beta 2 receptors. • Nonselective beta-blockers block both beta 1 and beta 2 receptors. Non-selective agents Oxprenolol • Penbutolol • Pindolol • Propranolol • Sotalol • Timolol • • • • • • Alprenolol Carteolol Levobunolol Mepindolol Metipranolol Nadolol β1-Selective agents • • • • • Atenolol Acebutolol Betaxolol Bisoprolol[1] Esmolol • • • • • Metoprolol Nebivolol Amosulalol Landiolol Tilisolol Angiotensin Converting Enzyme Inhibitors ACEi ACE inhibitors can be divided into three based on their molecular :groups structure • Sulfhydryl-containing agents Captopril Zofenopril • Dicarboxylate-containing agents Enalapril Ramipril Quinapril Perindopril Lisinopril Benazepril • Phosphonate-containing agents Fosinopril Angiotensin receptor blockers (ARBs) • ARBs prevent angiotensin II from binding to the angiotensin II receptor on blood vessels and other tissues. Calcium channel blockers 1. Dihydropyridines : (high vascular selectivity) Amlodipine – Nicardipine - Nifedipine . Non-Dihydropyridines : 2. Verapamil (phenylalkylamine class): selective for the myocardium. 3 . Diltiazem (benzothiazepine class): intermediate between Verapamil and Dihydropyridines. JNC 8 (2014 Hypertension Guideline Management Algorithm) 1 JAMA. 2013;():. doi:10.1001/jama.2013.284427 2014 Hypertension Guideline Management Algorithm SBP indicates systolic blood pressure; DBP, diastolic blood pressure; ACEI, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; and CCB, calcium channel blocker.aACEIs and ARBs should not be used in combination.bIf blood pressure fails to be maintained at goal, reenter the algorithm where appropriate based on the current individual therapeutic plan. JNC 8 (2014 Hypertension Guideline Management Algorithm) 2 JAMA. 2013;():. doi:10.1001/jama.2013.284427 2014 Hypertension Guideline Management Algorithm SBP indicates systolic blood pressure; DBP, diastolic blood pressure; ACEI, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; and CCB, calcium channel blocker.aACEIs and ARBs should not be used in combination.bIf blood pressure fails to be maintained at goal, reenter the algorithm where appropriate based on the current individual therapeutic plan. JNC 8 (2014 Hypertension Guideline Management Algorithm) 3 JAMA. 2013;():. doi:10.1001/jama.2013.284427 2014 Hypertension Guideline Management Algorithm SBP indicates systolic blood pressure; DBP, diastolic blood pressure; ACEI, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; and CCB, calcium channel blocker.aACEIs and ARBs should not be used in combination.bIf blood pressure fails to be maintained at goal, reenter the algorithm where appropriate based on the current individual therapeutic plan. Questions Thank you