1. Pharmacology DOR 101 Abdelkader Ashour, Ph.D. 9 th Lecture

2. Cardiovascular Pharmacology

3. Heart & Blood Circulation

4. Path of blood flow through the entire cardiovascular system

5. Drugs Acting on the Cardiovascular System I.Anti-hypertensive drugs  for treatment of hypertension (high blood pressure) II.Anti-anginal drugs  for treatment of angina III.Anti-arrhythmic drugs  for treatment of arrhythmia IV.Cardiotonic drugs (e.g., digoxin)  for treatment of heart failure

6. Antihypertensive drugs, Hypertension - Introduction  Hypertension is a condition that afflicts almost 1 billion people worldwide and is a leading cause of morbidity and mortality.  More than 20% of Americans are hypertensive, and one-third of these Americans are not even aware they are hypertensive. Therefore, this disease is sometimes called the "silent killer"  SBP: systolic blood pressure  DBP: diastolic blood pressure  When the left ventricle ejects blood into the aorta, the aortic pressure rises. The maximal aortic pressure following ejection is termed the systolic blood pressure (SBP)  As the left ventricle is relaxing and refilling, the pressure in the aorta falls. The lowest pressure in the aorta, which occurs just before the ventricle ejects blood into the aorta, is termed the diastolic blood pressure (DBP)  Hypertension may defined as an abnormal elevation of either SBP or DBP *Arterial pressures less than 90/60 mmHg are considered hypotension, and therefore not normal

7. Antihypertensive drugs, Hypertension - Introduction  Causes of Hypertension: The are two basic types of hypertension: I.Primary (essential) hypertension: The majority of patients (90-95%) have essential hypertension, which is a form with no identifiable underlying cause.  This form of hypertension is commonly treated with drugs in addition to lifestyle changes (e.g., exercise, proper nutrition, weight reduction, stress reduction). II.Secondary hypertension: A smaller number of patients (5-10%) have secondary hypertension that is caused by an identifiable underlying condition such as renal artery disease, thyroid disease, primary hyperaldosteronism, pregnancy, etc.  Patients with secondary hypertension are best treated by controlling or removing the underlying disease or pathology, although they may still require antihypertensive drugs  Some causes of secondary hypertension:  Renal artery stenosis  Chronic renal disease  Primary hyperaldosteronism  Stress  Hyper- or hypothyroidism  Pheochromocytoma  Pre-eclampsia

8. Antihypertensive drugs, Introduction  Each time the heart beats, a volume of blood (stroke volume “SV”) is ejected.  This stroke volume (SV), times the number of beats per minute (heart rate “HR”), equals the cardiac output (CO); i.e., CO = SV x HR  Thus cardiac output is the volume of blood being pumped by the heart, in particular by a ventricle in a minute.  Stroke volume is expressed in ml/beat and heart rate in beats/minute. Therefore, cardiac output is in ml/minute  Peripheral resistance (PR) refers to the resistance to blood flow offered by all of the systemic vasculature, excluding the pulmonary vasculature.  Mechanisms that cause vasoconstriction increase PR, and those mechanisms that cause vasodilatation decrease PR.  Therefore, patients with primary hypertension are generally treated with drugs that: 1.reduce blood volume (which reduces central venous pressure and cardiac output) 2.reduce peripheral resistance, or 3.reduce cardiac output by depressing heart rate and stroke volume Blood Pressure = Cardiac Output X Peripheral Resistance Cardiac Output X Peripheral Resistance

9. Antihypertensive drugs, Classes, the most important ones 1.Diuretics 2.Angiotensin Converting Enzyme Inhibitors (ACE inhibitors) 3.Angiotensin Receptor blockers 4.Renin Inhibitors 5.Calcium Channel Blockers 6.Potassium Channel openers   -adrenoceptor antagonists (   -blockers) 8.Beta Blockers   -adrenoceptor agonists 10.Peripheral Vasodilators

10. Antihypertensive drugs, Classes, the most important ones 1.Diuretics:  Mechanism of action.  Diuretics act on the kidney to enhance sodium and water excretion  urine output by the kidney (i.e., promote diuresis)  blood volume  Reducing blood volume not only reduces central venous pressure, but even more importantly, reduces cardiac output  Examples:  Examples: chlorothiazide, furosemide, amioloride 2.ACE inhibitors  Mechanism of action.  Dilate arteries and veins by blocking formation of angiotensin II (AII, a vasoconstrictor)  vasodilatation, thus reduces arterial pressure, preload and afterload on the heart  Promote renal excretion of sodium and water. This reduces blood volume, venous pressure and arterial pressure  Examples:  Examples: captopril, enalapril

11. Antihypertensive drugs, Classes, the most important ones 3.Angiotensin Receptor blockers (ARBs)  Mechanism of action:  ARBs are receptor antagonists that block type 1 angiotensin II receptors on bloods vessels and other tissues such as the heart  These drugs have similar effects to ACE inhibitors and are used for the same indications (hypertension, heart failure)  Examples:  Examples: losartan, valsartan 4.Renin Inhibitors  Mechanism of action:  Renin inhibitors produce vasodilation by inhibiting the activity of renin, which is responsible for stimulating angiotensin II formation  These drugs have similar effects to ACE inhibitors and ARBs and are used for the same indications (hypertension, heart failure)  Example:  Example: aliskiren