FFG2414 Pharmacology II Chapter 2 Drugs for Cardiovascular System PDF

FFG2414 Pharmacology II Chapter 2 Drugs for Cardiovascular System Topics 1. Introduction to cardiovascular system 2. Antihypertensive drugs 3. Antiarrhythmic drugs 4. Antianginal drugs 5. Drugs for congestive heart failure (CHF) 6. D...

FFG2414 Pharmacology II Chapter 2 Drugs for Cardiovascular System Topics 1. Introduction to cardiovascular system 2. Antihypertensive drugs 3. Antiarrhythmic drugs 4. Antianginal drugs 5. Drugs for congestive heart failure (CHF) 6. Dyslipidemic drugs 2.1 Introduction to cardiovascular system Structure of the topic  Introduction to cardiovascular system  Autonomic Nervous System and the cardiovascular system  Anatomy of the heart  Conduction system of the heart  Cardiac cycle  The Vasculature  Regulation of Blood Pressure Introduction to cardiovascular system The cardiovascular system consists of three anatomical components: (i) the autonomic nervous system, (ii) the heart, and (iii) the vasculature. These three components interact in a complex manner to control blood flow to organs throughout the body. Autonomic nervous system and the cardiovascular system  The autonomic nervous system is widely distributed throughout the body and controls a variety of bodily functions, including blood pressure and heart rate.  The efferent peripheral autonomic nervous system is composed of two opposing subsystems, the sympathetic nervous system and the parasympathetic nervous system. (i) Classification of the Nervous System 1 9 May 2024  FFG2414 Pharmacology II 2 9 May 2024  FFG2414 Pharmacology II 3 9 May 2024  FFG2414 Pharmacology II  Sympathetic nerves become active when the body needs to expand energy and during the “fight or flight” reaction.  Parasympathetic nerves become active when the body is restoring energy during eating, digestion, sleep, and elimination of urinary and intestinal waste products.  The heart receives its nerve supply from both divisions of the autonomic nervous system.  Since the heart possesses the ability to initiate its own heartbeat, the function of the autonomic nervous system is to regulate the rate and force of contraction of the heart. (ii) Sympathetic Nervous System and the Heart  The sympathetic nervous system is diffuse and innervates many components of cardiovascular system.  How does the sympathetic nervous system act on heart?  Sympathetic nerves release norepinephrine at adrenergic nerve endings that binds to the beta-1 adrenergic receptors in SA node (increase heart rate), AV node (increase AV conduction), and myocardium (increase contractility).  Norepinephrine in the sympathetic nerve endings also binds to beta-1 receptors in the kidney to cause an increase in renin release which increases the sympathetic activity in the body and in the heart. (iii) Parasympathetic Nervous System and the Heart  The parasympathetic nervous system innervation of the cardiovascular system is essentially just the innervation of the heart by the vagus nerve.  This innervation is relatively discrete, being limited to the sino-atrial (SA) node (pacemaker) and the atrioventricular (AV) junction.  How does the parasympathetic nervous system act on heart? 4 9 May 2024  FFG2414 Pharmacology II  Parasympathetic nerves release acetylcholine at cholinergic nerve endings that binds to the cholinergic M2 receptors in the SA node (decrease heart rate) and AV node (decrease AV conduction).  The parasympathetic system has little effect on myocardial contraction. Anatomy of the heart  The heart is responsible for pumping blood through the circulatory system.  A brief description of the anatomy of the heart, the cardiac cycle, and factors affecting cardiac pumping efficiency and performance are adequate for better understanding of CVS drugs. The anatomy of the heart can be conveniently divided into five functional units:  The heart muscle (the 2 atria pump blood into the ventricles and the 2 ventricles pump blood out of the heart)  The valves of the heart which maximize the pumping action of the heart (2 atrioventricular valves: the tricuspid and mitral; 2 semi-lunar valves: the pulmonary artery and aorta)  The coronary circulation which distributes blood to the heart itself  The electrical pacemaker and conduction system which sets the normal rhythm of the heart and coordinates the contraction of the heart (sinoatrial (SA) node, atrioventricular (AV) junction, His bundle, Purkinje fibers) 5 9 May 2024  FFG2414 Pharmacology II  The autonomic nervous system innervation of the heart which regulates heart rate and contractility (sympathetic nerve endings in muscle of atria and ventricles, SA node, and AV junction; parasympathetic nerve endings mainly in atrial muscle, pacemaker, and the AV junction) Conduction system of the heart  The SA (sinoatrial) node, or pacemaker, initiates the heartbeat and causes the atria to contract on average every 0.85 second.  The AV (atrioventricular) node conveys the stimulus and initiates contraction of the ventricles.  The signal for the ventricles to contract travels from the AV node through the atrioventricular bundle to the smaller Purkinje fibers. 6 9 May 2024  FFG2414 Pharmacology II Electrophysiology of the heart  An electrocardiogram (ECG) is a recording of the electrical changes that occur in the myocardium during a cardiac cycle.  Atrial depolarization creates the P wave, ventricle depolarization creates the QRS wave, and repolarization of the ventricles produces the T wave.  P wave : atrial depolarization, contraction.  QRS complex : ventricular depolarization, contraction, atrial repolarization.  T wave : ventricular repolarization 7 9 May 2024  FFG2414 Pharmacology II 8 9 May 2024  FFG2414 Pharmacology II Five phases of the action potential (i) Rapid depolarization (Phase 0)  Rapid inward movement of Na+ due to the opening of the voltage gated sodium channels  Variation in resting membrane potential i.e. -90 mV to +15 mV (ii) Initial rapid repolarization (Phase 1)  Inactivation of sodium channels and influx of Cl-. (iii) Plateau Phase (Phase 2)  Slow but prolonged opening of voltage-gated calcium channel (iv) Repolarization (Phase 3)  Closure of calcium channels and K+ efflux through potassium channels  Return of inactivated sodium channels to resting phase Cardiac cycle  Each heartbeat is called a cardiac cycle.  When the heart beats, the two atria contract together, then the two ventricles contract; then the whole heart relaxes.  Systole is the contraction of heart chambers; diastole is their relaxation.  The heart sounds, lub-dub, are due to the closing of the atrioventricular valves, followed by the closing of the semi-lunar valves.  The cardiac cycle can be divided into three different stages: i. atrial and ventricular diastole (0.4 sec) ii. atrial systole (0.1 sec) iii. ventricular systole (0.3 sec) 9 9 May 2024  FFG2414 Pharmacology II  The proper functioning of the cardiac conduction system, with the consequent coordination of contraction and valve opening and closing in each region of the heart, is critical for efficient pumping of blood. 10 9 May 2024  FFG2414 Pharmacology II The vasculature The vasculature consists of the blood vessels responsible for distributing blood to various tissues of the body. The circulatory system consists of two separate circuits linked in series:  The pulmonary circulation (low pressure, low resistance). The right heart pumps blood into the pulmonary circulation.  The systemic circulation (high pressure, high resistance). The left heart pumps blood into the systemic circulation. 11 9 May 2024  FFG2414 Pharmacology II Blood vessels can be classified according to size, location and function:  Arteries are large diameter, thick-walled vessels that carry blood away from the heart.  Arterioles are small, thick-walled vessels that represent the major part of vascular resistance. 12 9 May 2024  FFG2414 Pharmacology II  Capillaries are extremely small, extremely thin-walled vessels (one cell thick) that allow exchange of gases, nutrients, and other small molecules between the blood stream and tissues.  Venules are small thin-walled vessels that serve to bring blood back to the heart.  Veins are large diameter thin-walled vessels that bring blood back to heart. They are distensible and (in addition to venules) contain a large fraction of the blood. Tutorial 1. Draw an organization chart for human nervous system. 2. Draw a diagram to illustrate the sympathetic and parasympathetic nerve pathways, their neurotransmitters and receptors respectively. 3. Draw and label the structure of the heart. 4. Draw a diagram to illustrate the conduction system of the heart. 5. Define systole and diastole. 6. Draw and label a diagram of electrocardiogram. 13 9 May 2024  FFG2414 Pharmacology II 2.2 Antihypertensive Drugs Structure of the topic  Definition of blood pressure and hypertension  Classification of hypertension  Factors determining blood pressure  Classification and mechanisms of action of antihypertensive drugs  Adverse effects Definition  Blood pressure is the force applied against the walls of the arteries as the heart pumps blood through the body.  Blood pressure is measured by the instrument called sphygmomanometer.  It is also possible to check blood pressure with an automatic machine.  According to Clinical Practice Guidelines: Management of Hypertension (issued by Malaysia Ministry of Health in 2018), hypertension is defined as persistent elevation of systolic BP of 140mmHg or greater, and/or diastolic BP of 90 mmHg or greater. 14 9 May 2024  FFG2414 Pharmacology II There are three forms of hypertension: (i) Essential (or primary) hypertension (95%): which has no identifiable cause. It may be due to genetic, environmental or diet (salt). (ii) Secondary hypertension (5%): which is caused by pregnancy or other disorders such as artherosclerosis, pheochromocytoma and renal diseases. (iii) Malignant hypertension: which develops quickly and reaches critical levels that can trigger lethal complications, such as cerebral edema. Classification of blood pressure Category Systolic Diastolic Normal Normal < 130 < 85 High normal 130 – 139 85 – 89 Hypertension Stage I 140 – 159 90 – 99 Stage II 160 – 179 100 – 109 Stage III ≥ 180 ≥ 110 Physiological factors regulating blood pressure  Blood pressure is closely regulated on a short-term (seconds-to-minutes) and long-term (days-to-weeks) basis  An understanding of the physiological mechanisms involved in blood pressure control is essential to understanding how many cardiovascular drugs act.  Blood pressure is mainly determined by 2 factors: - cardiac output (CO) and - peripheral resistance (PR).  Cardiac output is the amount of blood that is pumped out of the heart per minute. Two factors determine cardiac output: - the heart rate (HR) in beats per minute and - the stroke volume (SV), the amount of blood pumped per beat.  The peripheral resistance (PR) is the resistance or friction that arterioles have against the flow of blood.  The main factor that increases the peripheral resistance is vasoconstriction. Vasoconstriction and a rise in BP are produced by sympathetic stimulation (norepinephrine, epinephrine), angiotensin II, and other vasoactive factors. 15 9 May 2024  FFG2414 Pharmacology II Drugs that cause vasodilation reduce peripheral resistance.  Increasing any of the factors (HR, SV, or PR) will cause the blood pressure to rise, and stimulation of the sympathetic nervous system increase all of them.  In most cases of the essential hypertension, there is increased activity of the sympathetic nervous system, so this factor is important in the control of blood pressure. Blood pressure is regulated by an interaction between 1. Nervous control system, 2. Humoral control system and 3. Renal control system 1. Control by Nervous System  Blood pressure is controlled by the sensory receptors located in the wall of arteries.  They are pressure receptors (baroreceptors) and chemical receptors (chemoreceptors).  These receptors are present in the aorta and the common carotid arteries. (i) Baroreceptors 16 9 May 2024  FFG2414 Pharmacology II  Baroreceptors are nerve endings embedded in blood vessels that are sensitive to the stretching of vessel walls.  They are primarily located in the aortic arch and carotid artery and are regulated by two temporally different (but integrated) reflex pathways. How do the baroreceptors respond to a sudden increase/ decrease in arterial pressure and how do they alter cardiovascular control?  When the blood pressure is high, the vessel walls stretch in response to increasing blood pressure/volume.  This signals the central nervous system to inhibit the vasoconstrictor center in the medulla and to stimulate the vagal center, in turn it causes peripheral vasodilation, decreased heart rate and less vigorous contractions, thereby decreasing arterial blood pressure.  When the blood pressure is low, the baroreceptors detect decreased blood pressure.  In turn, they induce peripheral vasoconstriction, increased heart rate and more vigorous contraction, thereby increasing arterial blood pressure. (ii) Chemoreceptors  Chemoreceptors are nerve endings located in the walls of the carotid arteries, the aorta and the medullary area of the brainstem.  Responding to abnormally low levels of dissolved oxygen and carbon dioxide in the blood, the nerve endings stimulate sympathetic activity and inhibit parasympathetic activity which in turn causes a reflex increase in arterial pressure. 17 9 May 2024  FFG2414 Pharmacology II How do the chemoreceptors respond to the increase/ decrease in arterial pressure and how do they alter cardiovascular control?  When the oxygen level is low and the carbon dioxide level is high, the chemoreceptors stimulate sympathetic activity, and inhibit parasympathetic activity, causing an increase the arterial pressure. 2. Control by humoral and renal System 18 9 May 2024  FFG2414 Pharmacology II Renin-angiotensin-aldosterone system:  Renin is an enzyme released from juxtaglomerular apparatus (JG) when renal blood pressure drops.  It converts the plasma protein angiotensinogen (from liver) into angiotensin I.  Angiotensin I is converted into the vasoactive substance angiotensin II by angiotensin-converting enzyme (ACE) from mainly vasculature of lungs.  Angiotensin II is a potent vasoconstrictor which increases BP  Angiotensin II triggers release of aldosterone which increases reabsorption of sodium, chloride ions and water  Angiotensin II stimulates the secretion of antidiuretic hormone (ADH) which increases water reabsorption  Angiotensin II increases adrenaline and noradrenaline secretion and thus increases sympathetic activity  All these activities result in the increase of blood pressure. Classification of Antihypertensive Drugs 1. ACE inhibitors  Drugs in this group act on the renin-angiotensin-aldosterone system by specifically preventing the conversion of angiotensin I to angiotensin II.  As a result, blood pressure (BP) is lowered through a significant reduction in peripheral venous return.  Adverse effects: postural hypotension, nasal congestion, pupil constriction, fatigue, inhibition of ejaculation and diarrhoea.  Examples: captopril, enalapril, lisinopril, perindopril, quinopril, ramipril 19 9 May 2024  FFG2414 Pharmacology II 2. Angiotensin II antagonist  They produce their effects by blocking angiotensin II interaction with specific angiotensin II receptors.  Adverse effects: dizziness, headache, gastrointestinal disturbances.  Examples: losartan, irbesartan, eprosartan, candesartan, telmisartan p 3. Alpha adrenergic blockers  These drugs block α1 receptors located on the arterioles and venules which mediate vasoconstriction. As a result, these drugs lower PVR and lower blood pressure.  Adverse effects: postural hypotension, nasal congestion, pupil constriction, fatigue, inhibition of ejaculation and diarrhoea.  Examples: prazosin, terazosin, phentolamine, phenoxybenzamine 4. Beta adrenergic blockers  Blocks beta receptors and act by two mechanisms: - (β1 blockade) Reduces renin release and thereby prevents angiotensin II formation. - (β1 blockade) Decreases the sympathetic activity in heart.  Adverse effects: bradycardia, hypotension, cold extremities, vivid dreams, constipation  Examples: propranolol, metoprolol, esmolol, atenolol 5. Calcium channel blockers 20 9 May 2024  FFG2414 Pharmacology II  Calcium channels regulate calcium influx into heart and vascular smooth muscle cells.  Calcium channel blockers decrease the entry of Ca2+ and thus reduce the cardiac contractility, heart rate and peripheral vascular resistance.  Adverse effects: hypotension, headache, facial flushing, skin rash  Examples: verapamil, diltiazem, nifedipine, amlodipine, lercanidipine 6. Central sympatholytics  Acts by decreasing the action of the neurotransmitters of sympathetic nervous system  Adverse effects: hypotension, sedation, dryness of mouth  Examples: clonidine, methyldopa 7. Diuretics  Diuretics lower blood pressure by reducing blood volume i.e. by increasing water excretion by kidneys  Adverse effects: dehydration, hypotension, electrolyte imbalance  Examples: - Thiazides: hydrochlorothiazide, chlorthialidone - Loop Diuretics: furosemide, bumetanide, ethacrynic acid - K+ sparing diuretics: spironolactone, amiloride, triamterene 8. Vasodilators  Vasodilators reduce total peripheral resistance by relaxing vascular smooth muscle.  Adverse effects: hypotension, headache, peripheral edema, allergic rash.  Examples: - Arterial: Hydralazine, Minoxidil, Diazoxide - Arterial and Venous: Sodium nitroprusside Tutorial 1. Define blood pressure. 2. List THREE (3) types of hypertension. 3. List the factors determining blood pressure. 4. List the factors determining the cardiac output (CO). 5. Draw a diagram to illustrate the regulation of blood pressure by baroreceptors. 6. Draw a diagram to illustrate the regulation of blood pressure by chemoreceptors. 7. Where are baroreceptors and chemoreceptors located? 8. Draw a diagram to illustrate the regulation of blood pressure by humoral and renal system (renin- angiotensin-aldosterone system). 9. Classify antihypertensive drugs according to the mechanism of action and give 1 example for each class. 21 9 May 2024  FFG2414 Pharmacology II 2.3 Anti-arrhythmic Drugs Structure of the lesson  Introduction  Arrhythmias  What is arrhythmia?  Electrophysiology of Heart  Classification of anti-arrhythmic drugs  Mechanism of action  Adverse effects Normal conduction sequence  The normal sequence, called the sinus rhythm, begins in the right atrium, spreads throughout the atria and to the atrioventricular (AV) node.  From the AV node, the impulses (signals) travel down a group of specialized fibers (the ‘His- Purkinje’ system) to all parts of the ventricles.  This exact route must be followed for the heart to pump properly.  As long as the electrical impulse is transmitted normally, the heart pumps and beats at a regular pace.  A normal heart beats 60 to 100 times a minute. What is arrhythmia?  The term arrhythmia refers to any change from the normal sequence of electrical impulses, causing abnormal heart rhythms.  This can cause the heart to pump less effectively.  Some arrhythmias are so brief that the overall heart rate or rhythm isn't greatly affected.  But if arrhythmias last for some time, they may cause the heart rate to be too slow or too fast or the heart rhythm to be erratic. 22 9 May 2024  FFG2414 Pharmacology II Many factors can affect your heart's rhythm, such as  having had a heart attack,  blood chemical imbalances or  abnormal hormone levels  Some substances or medicines may also cause arrhythmias. Symptoms of arrhythmias include  Fast or slow heartbeat  Skipping beats  Lightheadedness, dizziness  Chest pain heart doesn't receive sufficient  Shortness ofOxygen breath  Paleness  Sweating There are 2 types of arrhythmias: Tachycardia  A fast heart rate is called tachycardia.  It refers to a heart rate of more than 100 beats per minute.  Tachycardias fall into two major categories: i. Ventricular tachycardia involves only the ventricles. ii. Supraventricular tachycardia involves both the atria and the ventricles.  Ventricular tachycardia is a rapid resting heart rate initiated within the ventricles, typically at 160 - 240 beats/minute.  Rapid heart beating in the ventricles can be life-threatening.  The most serious cardiac rhythm disturbance is ventricular fibrillation, where the lower chambers quiver and the heart can't pump any blood.  Collapse and sudden death follows unless medical help is provided immediately. Bradycardia  A heart rate that's too slow is called bradycardia. It refers to a heart rate of less than 60 beats per minute.  A heart rhythm that's too slow can cause fatigue, dizziness, lightheadedness, fainting or near-fainting spells.  These symptoms can be easily corrected by implanting an electronic pacemaker under the skin to speed up the heart rhythm as needed. Electrophysiology of the heart 23 9 May 2024  FFG2414 Pharmacology II The diagrams below show the normal electrophysiology of the heart. CI- Ca2 Na+ K+ Na/K exchange  This is an ECG of a person with an abnormal rhythm called an AV block.  P waves show that the top of the heart received electrical activity.  Each P wave is usually followed by the tall (QRS) waves.  QRS waves reflect the electrical activity that causes the heart to contract.  When a P wave is present and not followed by a QRS wave (and heart contraction), there is an AV block, and a bradycardia. 24 9 May 2024  FFG2414 Pharmacology II Electronic Pacemaker Pacemakers are electric activity generating devices used to treat patients with slow heart rate or symptomatic heart blocks and in patients with heart failure. 25 9 May 2024  FFG2414 Pharmacology II Classification of antiarrhythmic drugs Antiarrhythmic drugs are drugs used to restore normal cardiac rhythm. CLASS ACTION DRUGS I Sodium Channel Blockers IA Prolong repolarization Quinidine IB Shorten repolarization Lidocaine IC Little effect on repolarization Flecainide II Beta-Adrenergic Blockers Propranolol, esmolol Potassium Channel Blockade III and OtherProlong Amiodarone, bretylium Repolarization IV Calcium Channel Blockers Verapamil, diltiazem Miscellaneous Miscellaneous Actions Adenosine, magnesium Adverse effects of antiarrhythmics Most of the antiarrhythmic drugs are associated with severe and sometimes life- threatening adverse effects such as negative inotropic effects, AV block and sinus bradycardia. Tutorial 1. A normal heart beats __________ a minute. 2. Define arrhythmia. 3. Define tachycardia. 4. Define bradycardia. 5. List the factors that affect the rhythm of the heart. 6. List the symptoms of arrhythmias. 7. Classify antiarrhythmic drugs according to their mechanism of action in a table. 26 9 May 2024  FFG2414 Pharmacology II 2.4 Antianginal drugs Structure of the lesson  What is angina pectoris?  Classification of antianginal drugs What is angina pectoris?  Angina pectoris literally means chest pain and is a symptom of a condition called myocardial ischaemia.  It occurs when the heart muscle doesn’t get as much blood (hence oxygen) as it needs.  This usually happens because of the coronary artery (artery that supplies blood to the heart muscles) blocking or narrowing.  Insufficient blood supply is called ischaemia.  Angina is a specific type of pain in the chest caused by inadequate blood flow through the blood vessels (coronary vessels) of the heart muscle (myocardium). Forms of angina A. Classical/Typical Angina:  Attacks are predictably provoked by exercise, emotion, eating, coitus etc. and subside when the increased energy demand is withdrawn.  The pathophysiology: The lumen size of the coronary arteries is greatly diminished due to build-up of atherosclerotic plaque 27 9 May 2024  FFG2414 Pharmacology II B. Variant/Prinzmetal’s angina:  Attacks occur at rest or during sleep and are unpredictable  The pathophysiology: The lumen size of the coronary arteries is greatly diminished due to coronary vasospasm  Narrowing of the lumen of the coronary blood vessels due to over constriction of vessel walls. Antianginal drugs  Angina is a condition where there is a high demand for oxygen by the myocardium.  The drugs used to treat angina has two underlying mechanisms: (i) to increase oxygen (blood) supply or (ii) to decrease oxygen demand. 28 9 May 2024  FFG2414 Pharmacology II A. Drugs that increase oxygen (blood) supply: (i) Nitrates (vasodilation)  Absorbed nitrates are taken up by the endothelial cells of the blood vessel wall and converted to nitric oxide (NO). NO alters the availability of calcium and as a result the blood vessels dilate the coronary arteries to increase blood flow to ischaemic areas of the myocardium (heart).  Adverse effects (result from excessive vasodilation) - Reflex tachycardia - Hypotension - Facial flushing - Migraine-like headache - Cerebral vasodilation  Examples: a. Short acting: Glyceryltrinitrate (GTN, Nitroglycerine) b. Long acting: isosorbide dinitrate, isosorbide mononitrite B. Drugs that decrease oxygen demand: i. Beta blockers  Beta blockers reduce cardiac workload by reducing both heart rate and force of contraction.  Beta receptor blockade prevents sympathetic stimulation of heart.  Adverse effects: - Bradycardia - Dizziness - Gastrointestinal disturbances  Examples: propranolol, metoprolol, atenolol ii. Calcium channel blockers  Calcium ions are necessary for contraction of vascular smooth muscle and cardiac muscles.  So, when calcium channels are blocked, the vascular smooth muscle relaxes and coronary arteries dilate.  The force of contraction of heart is also reduced.  The ultimate effect is a fall in myocardial oxygen demand and a rise in blood flow to heart muscle.  Adverse effects: - Hypotension - Headache - Facial flushing 29 9 May 2024  FFG2414 Pharmacology II - Skin rash  Examples: verapamil, diltiazem, nifedipine iii. Potassium channel openers  Opens potassium channels in the vascular smooth muscle membrane and it allows an efflux of potassium, which leads to hyperpolarization.  And this prevents calcium channel from opening and finally causes coronary artery vasodilation.  Adverse effects: - Headache - Nausea, - Vomiting - Dizziness and weakness  Examples: picorandil, pinacidil Tutorial 1. Define angina pectoris. 2. List 2 forms of angina and outline their pathophysiology. 3. Classify antianginal drugs and give an example for each group. 30 9 May 2024  FFG2414 Pharmacology II 2.5 Drugs for Congestive Heart Failure (CHF) Structure of the lesson  Introduction  Forms  Causes  Symptoms  Diagnosis  Classification of CHF drugs Introduction  Congestive heart failure, also called heart failure, is a life-threatening condition in which the heart can no longer pump enough blood to the rest of the body.  Congestive heart failure CHF is a complex clinical syndrome characterized by impaired ventricular performance, exercise intolerance, a high incidence of ventricular arrhythmias, and shortened life expectancy.  Heart failure is almost always a chronic, long-term condition, although it can sometimes develop suddenly.  This condition may affect the right side, the left side, or both sides of the heart.  As the heart's pumping action is lost, blood may back up into other areas of the body, including the liver, the gastrointestinal tract and extremities (right-sided heart failure) and the lungs (left-sided heart failure).  With heart failure, many organs don't receive enough oxygen and nutrients, which damages them and reduces their ability to function properly.  Most areas of the body can be affected when both sides of the heart fail.  Heart failure may primarily be due to systolic dysfunction or diastolic dysfunction. Forms of Congestive Heart Failure CHF can be broadly subdivided into two distinct forms: (i) Systolic dysfunction: The ventricles are dilated and unable to develop adequate wall tension to eject significant quantity of blood. (ii) Diastolic dysfunction: The ventricular wall is thickened and unable to relax properly during diastole and as a result ventricular filling is impaired because of which output is low. 31 9 May 2024  FFG2414 Pharmacology II Causes  The most common causes of heart failure are hypertension (high blood pressure) and coronary artery disease (for example, you have had a heart attack).  Other causes of heart failure include the following: - Valvular heart disease - Congenital heart disease - Dilated cardiomyopathy - Lung disease - Heart tumor Causes – physical habits  Heart failure becomes more common with advancing age.  You are also at increased risk for developing heart failure if you are: - Overweight - have diabetes, - smoke cigarettes, - abuse alcohol, or - use cocaine 32 9 May 2024  FFG2414 Pharmacology II Symptoms of Congestive Heart Failure  Weight gain  Swelling of feet and ankles  Swelling of the abdomen  Pronounced neck veins  Loss of appetite, indigestion  Nausea and vomiting  Shortness of breath with activity, or after lying down for a while  Difficulty sleeping  Fatigue, weakness, faintness  Sensation of feeling the heartbeat (palpitations)  Irregular or rapid pulse  Decreased alertness or concentration  Cough  Decreased urine production  Need to urinate at night Classification of drugs used in congestive heart failure 1. Inotropic agents  They inhibit the Na+/K+ ATPase pump (which causes an increase in intracellular Na+), slowing the rate of the Na+/Ca2+ exchange, and thereby causing an increase in intracellular Ca2+, and the contractility of the heart.  Examples: digitalis, cardiac glycosides 2. ACE inhibitors  They inhibit the formation of Angiotensin II and decrease BP, thereby reduce the heart workload.  Examples: captopril, enalapril, lisinopril 3. Angiotensin II Receptor Antagonists  They block the Angiotensin II receptors and decrease BP, thereby reduce the heart workload.  Examples: losartan 4. Beta-Blockers - MOA  They block the β1 receptors in the heart and kidneys and causes reduction the sympathetic activity, thereby reduces heart workload  Examples: carvedilol, metoprolol, labetolol, bucindolol 5. Diuretics - MOA inhibitors  They help rid your body of fluid and sodium and decrease the workload of heart.  Examples: 33 9 May 2024  FFG2414 Pharmacology II - Thiazides: hydrochlorthiazide, chlorthialidone; - Loop diuretics: furosemide, bumetanide, ethacrynic acid; + - K sparing diuretics: amiloride, triamterene, spironolactone 6. Vasodilators - MOA  They dilate the blood vessels and reduce the heart workload. They are used mainly as concurrent therapy  Examples: hydralazine, isosorbide dinitrate 7. Calcium channel blockers  They reduce the heart workload by blocking calcium channels.  Only amlodipine and mibefradil are effective in heart failure Adverse effects of drugs used for congestive heart failure - Low blood pressure (hypotension) - Light-headedness and fainting - Lupus reaction - Headache - Gastrointestinal upset (such as nausea, heartburn, diarrhea) - Cough - Muscle cramps - Digitalis toxicity Tutorial 1. Briefly explain congestive heart failure. 2. List 2 forms of congestive heart failure. 3. List the symptoms of congestive heart failure. 4. Classify drugs used in congestive heart failure. 34 9 May 2024  FFG2414 Pharmacology II 2.6 Dyslipidemic drugs Structure of the lesson  Introduction  Lipoproteins  Dyslipidemic drugs Introduction  Lipids are necessary molecules for human life.  Cholesterol, which is an essential component of cell membranes, is the precursor to the sterol and steroid compounds that are synthesized in the body.  Triglycerides, composed of three fatty acids and glycerol, are the main storage form of fuel used to generate high-energy compounds such as adenosine triphosphate (ATP), that provide energy for muscle contraction and metabolic reactions.  Despite the vital functions of these and other lipids, elevated concentrations of cholesterol and triglycerides play an important role in the development of atherosclerotic heart disease and other disorders.  Whereas hyperlipidemia is a general term for elevated concentrations of lipids and lipoproteins in the blood, hypercholesterolemia refers specifically to high concentrations of cholesterol.  It contributes to the pathogenesis of atherosclerosis and has been associated with coronary artery disease and other atherosclerotic vascular disease.  Drugs used in the treatment of hyperlipidemia are also called as the lipid-lowering drugs. Lipoproteins  Cholesterol is derived from two main sources: (i) biosynthesis in the liver and (ii) delivery of dietary cholesterol. 35 9 May 2024  FFG2414 Pharmacology II  Because lipids are insoluble in plasma, they must be transported in the circulation in the form of lipoproteins.  There are numerous types of lipoproteins, including chylomicrons, very low-density lipoproteins (VLDL), low density lipoproteins (LDL), intermediate-density lipoproteins (IDL), high-density lipoproteins (HDL), and lipoprotein (a).  Commonly,LDL is known as “bad” cholesterol; HDL is known as “good” cholesterol.  These two types of lipids, along with triglycerides (TG), VLDL, Lp(a) cholesterol, make up the total cholesterol count, which can be determined through a blood test. Chylomicrons  Chylomicron are primarily involved in the transport of dietary lipids from the gut to the adipose tissue and liver.  When cholesterol and triglycerides are ingested, they are emulsified in the intestines by the bile acids and other bile secretions, and the emulsified lipids are combined with proteins to form chylomicrons in the gut wall.  After chylomicrons are secreted into the circulation, they deliver triglycerides to adipose tissue via the action of a lipoprotein lipase located in the vascular endothelial cells. 36 9 May 2024  FFG2414 Pharmacology II  By this processs, chylomicrons are converted to a cholesterol-rich chylomicron remnant, which transports cholesterol to the liver. Very low density and low density lipoproteins  Golgi bodies in the liver form VLDL from triglycerides, cholesterol, and protein and then secrete VLDL into the circulation.  The VLDL deliver triglycerides to adipose tissue in the same manner as do the chylomicrons.  During the process, the VLDL are transformed into IDL and LDL that contain a high percentage of cholesterol.  The LDL transport cholesterol to peripheral tissues for incorporation into cell membranes and steroids.  In this process, the LDL bind to specific LDL receptors that are located in the plasma membranes of cells. High-Density Lipoproteins  The HDL are small lipoproteins that are secreted by the gut and liver.  As the HDL circulate in the blood, they exchange apoproteins with VLDL, and they acquire cholesterol from peripheral tissues and atheromas.  The HDl also serve to transport cholesterol from atheromas and peripheral tissues to the liver. LDL cholesterol  When too much LDL cholesterol circulates in the blood, a condition known as hyperlipidemia, the LDL can slowly build up in the inner walls of the arteries that feed the heart and brain.  Together with other substances, it can form plaque, a thick, hard deposit that can narrow the arteries and make them less flexible.  This condition is known as atherosclerosis. If a clot forms and blocks a narrowed artery, this may result heart attack or stroke.  The condition of hyperlipidemia can be treated with cholesterol lowering drugs in order to prevent atherosclerosis. 37 9 May 2024  FFG2414 Pharmacology II Drugs for hyperlipidemia (Cholesterol lowering drugs) (i) HMG-CoA reductase inhibitors (Statins)  HMG-CoA reductase is an enzyme involved in the biosynthesis of cholesterol in the liver.  By Inhibiting this enzyme, HMG-CoA reductase inhibitors (statins) reduce LDL cholesterol levels and serum triglyceride levels.  Examples: lovastatin, atorvastastin, simvastatin. (ii) Resins  The bile acid-binding resins are large molecular weight polymers that can bind to bile acids.  The resins are not absorbed from the gut and are excreted in the faeces.  After the resins bind to bile acids, the bile acid-resin complex is excreted.  This action prevents the enterohepatic cycling of bile acids and prevents the absorption of dietary cholesterol.  These drugs are also known as bile sequestrants.  Example: cholestyramine 38 9 May 2024  FFG2414 Pharmacology II (iii) Ezetimibe  Ezetimibe is a unique drug that inhibits the absorption of dietary cholesterol.  After oral absorption, ezetimibe is converted to active metabolite which acts at the surface of the small intestine to block the absorption of dietary cholesterol. (iv) Niacin  Niacin, vitamin B3, or nicotinic acid and its derivatives) acts primarily by inhibiting of lipolysis in adipose tissue.  This action reduces the supply of circulating free fatty acids that liver uses to synthesize triglycerides for incorporation into VLDL.  Thus inhibits the synthesis and secretion of hepatic VLDL. (v) Fibrates  Fibrates increase synthesis of Lipoprotein Lipase (LL).  This enzyme is located in the vascular endothelium and catalyzes the hydrolysis and removal of triglycerides from VLDL, thereby lowering plasma triglyceride cholesterol levels.  Example: gemfibrozil, fenofibrate Tutorial 1. What are 2 main sources of cholesterol? 2. List 2 functions of cholesterol. 3. Dyslipidemic drugs are also called as the __________. 4. LDL stands for __________, which is also known as the __________ cholesterol. 5. HDL stands for __________, which is also known as the __________ cholesterol. 6. TG stands for __________. 7. If a clot forms and blocks a narrowed artery, it may result __________ or __________. 8. Classify dyslipidemic drugs according to their mechanism of action and give an example for each group. 39 9 May 2024  FFG2414 Pharmacology II References  Rang H.P., Dale MM, Ritter JM, Moore PK, (2003).Pharmacology (5th ed). Churchill Livingstone  Tripathi KD, Essentials of Medical Pharmacology, 2004 (5th ed) Jaypee.  Kaye M., Favaro, A. (2005). Introduction to Pharmacology (10th ed.).  WB Saunders. Holland LN, Adams MP. Core concepts in Pharmacology.2003, Prentice Hall.  Clinical Practice Guidelines: Management of Hypertension. 5th Edition. Ministry of Health Malaysia. Available at: https://www2.moh.gov.my/moh/resources/penerbitan/CPG/MSH%20Hypertension%20 CPG%202018%20V3.8%20FA.pdf (Accessed: 9 May 2024). 40 9 May 2024  FFG2414 Pharmacology II Revision A. Multiple Choice Questions 1 The conduction system of the heart consists of _________. I sino-atrial (SA) node II atrioventricular (AV) node III semi-lunar valves IV Purkinje fibers A I, II, III B I, II, IV C I, III, IV D II, III, IV 2 __________ is the contraction of heart chambers. A Cardiac cycle B Electrocardiogram C Systole D Diastole 3 Select an Angiotensin-converting enzyme (ACE) inhibitor. A Propranolol B Captopril C Losartan D Prazosin 4 Select an Angiotensin II antagonist. A Captopril B Losartan C Prazosin D Nifedipine 5 Select a β adrenergic blockers. A Losartan B Nifedipine C Captopril D Propranolol 6 __________ refers to any change from normal sequence of electrical impulses, causing abnormal heart rhythms. A Angina B Arrhythmia C Atherosclerosis D Congestive heart failure 41 9 May 2024  FFG2414 Pharmacology II 7 __________ refers to a heart rate of less than 60 beats per minute. A Hypertension B Tachycardia C Bradycardia D Angina 8 The following can be used as anti-arrhythmic drugs, EXCEPT __________. A sodium channel blockers B calcium channel blockers C potassium channel openers D diuretics 9 __________ happens due to the blocking or narrowing of coronary artery. A Heart failure B Angina C Arrhythmia D Hypertension 10 The following are drugs that decrease oxygen demand of the heart, EXCEPT __________. A Nitrates B Beta blockers C Calcium channel blockers D Potassium channel openers 11 __________ increase oxygen and blood supply to the heart. A Digitalis B Paracetamol C Propranolol D Nitrates 12 __________ is a condition where the heart can no longer pump enough blood to the rest of the body. A Heart failure B Angina C Arrhythmia D Hypertension 13 Select an inotropic agent. A Digitalis B Prednisolone C Propranolol D Captopril 14 The following drugs decrease the workload of the heart, EXCEPT __________. 42 9 May 2024  FFG2414 Pharmacology II A beta blockers B calcium blockers C ACE inhibitors D digitalis 15 __________ is also known as the bad cholesterol. A Triglyceride B Low density lipoprotein C High density lipoprotein D Chylomicron 16 Select a HMG-CoA reductase inhibitor. A Lovastatin B Propranolol C Nifedipine D Aspirin 17 __________ prevents gastro-intestinal intake of cholesterol and phytosterols. A Ezetimibe B Iron C Glyceryltrinitrate (GTN) D Nifedipine 18 Refer to diagram below, P represents __________. A atrial depolarization B ventricular depolarization C atrial repolarization D ventricular repolarization 19 Mean arterial pressure is monitored by __________. I histamine receptors II GABA receptors III baroreceptors IV chemoreceptors A I and II B I and IV 43 9 May 2024  FFG2414 Pharmacology II C II and III D III, and IV 20 When renal blood pressure drops, __________. A rennin is released from the juxtaglomerular apparatus B Care delivery C Disease type D Patient population 21 __________ refers to a heart rate of more than 100 beats per minute. A Hypertension B Tachycardia C Bradycardia D Angina 22 Refer to diagram below, phase 2 refers to __________. A rapid influx of Na+ B influx of Cl- C slow and prolonged influx of Ca2+ D K+ efflux 23 The following can be used as anti-arrhythmic drugs, EXCEPT: A sodium channel blockers B calcium channel blockers C potassium channel openers D diuretics 24 Ischaemia means __________. A elevated cholesterol in the blood B insufficient blood supply C irregular heart rate D elevated blood pressure 25 When __________ occurs, many organs do not receive enough oxygen and nutrients, which damages them and reduces their ability to function properly. A heart failure B hypertension C dyslipidemia D angina 44 9 May 2024  FFG2414 Pharmacology II 26 Select an Angiotensin-converting enzyme (ACE) inhibitor. A Propranolol B Captopril C Losartan D Paracetamol 27 Select an Angiotensin II antagonist. A Perindopril B Nifedipine C Metoprolol D Losartan 28 Select a β adrenoceptor blocker. A Rosiglitazone B Nifedipine C lovastatin D Atenolol 29 Select drugs that increase oxygen supply of the heart. A Nitrates B Beta blockers C Acarbose D Angiotensin antagonists 30 Select an inotropic agent A Digitalis B Prednisolone C Propranolol D lovastatin 31 Which of the following is involved in atherosclerosis, the formation of plaques that narrow the arteries? A LDL B HDL C VLDL D Triglycerides 32 Select a HMG Co-A reductase inhibitor. A Lovastatin B Ezetimibe C insulin lispro D Fenofibrate 45 9 May 2024  FFG2414 Pharmacology II 33 __________ increases synthesis of liproprotein lipase (LL). A Fibrates B Niacin C Metformin D Nitrates 34 Sympathetic nervous system acts on the heart through __________. I beta-1 receptors in the heart II beta-1 receptors in the kidneys III muscarinic receptors in the heart IV nicotinic receptors in the ganglion A I, II B I, IV C II, III D III, IV 35 __________ are large diameter thin-walled vessels that serve to bring blood back to the heart. A Arteries B Arterioles C Capillaries D Veins 36 __________ refers to hypertension which has no identifiable cause. It may be due to genetic, environmental or diet. A Essential hypertension B Secondary hypertension C Malignant hypertension D Peripheral hypotension 37 __________ are sensitive to the stretching of vessel walls. A Juxtaglomerular apparatus B Baroreceptors C Chemoreceptors D muscrinic receptors 38 Refer to diagram below, phase 3 refers to __________. 46 9 May 2024  FFG2414 Pharmacology II A rapid influx of Na+ B influx of Cl- C slow and prolonged influx of Ca2+ D K+ efflux 40 Calcium channel blockers reduces __________. A oxygen supply to the heart B cardiac contractility C the action of neurotransmitters D water reabsorption 41 __________ may cause collapse and sudden death and the ventricles quiver and the heart can’t pump any blood. A Bradycardia B Ventricular fibrillation C Hypertension D Hypercholesterolaemia 42 The following are anti-arrhythmic drugs, EXCEPT __________. A calcium channel blockers B potassium channel blockers C sodium channel blockers D nitrates 43 Select an INCORRECT statement related to heart rate. A A normal heart beats 60 to 100 times a minute. B The heart natural pacemaker refers to SA node. C Tachycardia refers to a heart rate of less than 60 beats per minute. D An electronic pacemaker is needed if the heart rate is too slow. 44 __________ occurs due to coronary vasospasm and usually occurs at rest or during sleep and are unpredictable. A Hypertension B Prinzmetal’s angina C Classical angina D Haemostasis 45 __________ alters the availability of calcium, causing dilation of the coronary artery and increase blood flow to the ischaemic area of the myocardium. A Beta blockers B Statins C Nitrates D Steroids 47 9 May 2024  FFG2414 Pharmacology II 46 Select a side effect of nitrates. A Facial flushing B Hypertension C Angina D Hyperuricaemia 47 The following are risk factors of congestive heart failure, EXCEPT __________. A underweight B diabetes C smoke cigarettes D alcohol abuse 48 __________ inhibits the Na+/K+/ATPase pump, slowing the rate of Na+/Ca2+ exchange, causing an increase in intracellular Ca2+ and the contractility of the heart. A Lovastatin B Propranolol C Insulin lispro D Digitalis 49 The following are drugs that reduce heart workload, EXCEPT __________. A anticoagulants B beta-blockers C calcium channel blockers D diuretics 50 Select the sources of cholesterol. I Biosynthesis in the liver II Biosynthesis in the lungs III Dietary absorption IV Reabsorption from the kidneys A I, II B I, III C II, III D II, IV 51 __________ is/are secreted by the gut and liver. They are also known as good cholesterol. A HDL B LDL C TG D Chylomicrons 52 Which of the following is a resin? 48 9 May 2024  FFG2414 Pharmacology II A Cholestyramine B Aspirin C Niacin D Vitamin K 53 __________ release norepinephrine (NE) at the SA node, AV node and myocardium. A Sympathetic nerves B Parasympathetic nerves C Somatic nerves D The adrenal glands 54 The anatomy of the heart includes __________. I the heart muscles and the valves II the coronary circulation III the pacemaker and conduction system IV the kidneys A I, II, III B I, III, IV C II, III, IV D I, II, III, IV 55 __________ is the force applied against the walls of the arteries as the heart pumps. A Blood pressure B Heart rate C Contractility of the heart D Stroke 56 __________ respond to abnormally low levels of oxygen and carbon dioxide in the blood. A Juxtaglomerular apparatus B Baroreceptors C Chemoreceptors D Beta-1 receptors 57 Refer to diagram below, phase 1 refers to __________. A rapid influx of Na+ B influx of Cl- C slow and prolonged influx of Ca2+ 49 9 May 2024  FFG2414 Pharmacology II D K+ efflux 58 Select a beta-blocker. A Propranolol B Captopril C Losartan D Verapamil 59 Angiotensin inhibitor inhibits __________. A the conversion of Angiotensinogen to Angiotensin I B the conversion of Angiotensin I to Angiotensin II C the binding of Angiotensin II to Angiotensin II receptor D The binding of aldosterone to aldosterone receptor 60 Select the factors that may affect heart rhythm. I normal hormone levels II blood chemical imbalances III having had a heart attack IV Some substances or medicines A I, II, III B I,III, IV C II, III, IV D I, II, III, IV 61 The following are anti-arrhythmic drugs, EXCEPT __________. A Propranolol B Captopril C Quinidine D Verapamil 62 Select a CORRECT statement regarding heart rate. A A normal heart beats over 100 times per minute B A normal heart beats less than 60 times per minute C The rhythm is generated by AV node D An arrhythmia is any disorder of the heart rhythm 63 __________ occurs when the heart muscle doesn’t get as much blood as it needs. A Hypertension B Myocardial ischemia C Diabetes mellitus D HPA suppression 64 Select drugs that increase oxygen supply of the heart. 50 9 May 2024  FFG2414 Pharmacology II A Nitrates B Beta blockers C Acarbose D Angiotensin antagonists 65 Beta-blockers reduce cardiac workload by __________ I reduction of heart rate II reduction of force of contraction of heart III prevents sympathetic stimulation of heart IV inhibition of sodium channels A I, II, III B I, III, IV C II, III, IV D I, II, III, IV 66 Select the consequence of heart failure. A Many organs do not receive enough oxygen and nutrients B Chest pain due to inadequate blood flow to the heart muscles C Elevated cholesterol levels in the blood D Liver fails to perform its function 67 Select the inotropic agent. A Lovastatin B Propranolol C Insulin lispro D Digoxin 68 Select the INCORRECT statement for the treatment of congestive heart failure. A Reduce urination B Reduce blood pressure C Reduce heart rate D Reduce heart workload 69 Bad cholesterol refers to __________. A HDL B LDL C TG D Chylomicrons 70 __________ serves to transport cholesterol from atheromas and peripheral tissues to the liver. A HDL 51 9 May 2024  FFG2414 Pharmacology II B LDL C TG D Chylomicron 71 __________ inhibit(s) the enzyme HMG-CoA reductase to reduce LDL cholesterol levels. A Statins B Resins C Fibrates D Niacin 72 The __________ innervates the heart by the vagus nerve. A sympathetic nervous system B parasympathetic nervous system C somatic nervous system D central nervous system 73 The right heart pumps blood into the __________. A systemic circulation B pulmonary circulation C lymphatic circulation D atmospheric circulation 74 Blood pressure is regulated by an interaction between __________. I Nervous control system II Humoral control system III Renal control system IV Motor control system A I, II, III B I, III ,IV C II, III, IV D I, II, III, IV 75 Renin is an enzyme released from __________ when renal blood pressure drops. A juxtaglomerular apparatus B liver C lung vasculature D posterior pituitary gland 76 Refer to diagram below, phase 0 refers to __________. 52 9 May 2024  FFG2414 Pharmacology II A rapid influx of Na+ B influx of Cl- C slow and prolonged influx of Ca2+ D K+ efflux 77 Select an Angiotensin II antagonist. A Propranolol B Captopril C Losartan D Verapamil 78 The following are actions of beta-blockers, EXCEPT __________. A reduce the release of renin B reduce the contractility of the heart C reduce heart rate D inhibit alpha receptors 79 The following are symptoms of arrhythmias, EXCEPT __________. A fast or slow heart beat B skipping beats C sweating D increased energy 80 Select an anti-arrhythmic drug that blocks sodium channels. A Propranolol B Captopril C Quinidine D Paracetamol 81 A very slow heart rhythm can be corrected by __________. A an electronic pacemaker B 3-day-sleep C vigorous exercise D drinking beer 82 __________ are usually provoked by exercise, emotion, eating, coitus and subside when the increased energy demand is withdrawn. 53 9 May 2024  FFG2414 Pharmacology II A Hypertension B Classical angina C Hypercholesterolemia D Hyperthyroidism 83 __________ allows potassium efflux and hyperpolarization, thus causing coronary vasodilation. A Potassium channel openers B Beta blockers C Acarbose D Oestrogen 84 The following are actions of calcium channel blockers, EXCEPT __________. A inhibition of sympathetic activities B relaxation of vascular smooth muscles C reduction of force of contraction of heart D vasodilation 85 Select the symptoms of congestive heart failure. I weight gain II swelling of feet and ankles III swelling of abdomen IV palpitations A I, II, III B I, III, IV C II, III, IV D I, II, III, IV 86 The following are drugs used in congestive heart failure, EXCEPT __________. A Digitalis B Angiotensin II Antagonists C Insulin D Diuretics 87 Select the mechanism of action of drugs used in congestive heart failure. A Reduce heart workload B Reduce urination C Increase blood pressure D Increase red blood cells 88 Which of the following are related to cholesterol. I Essential component of cell membranes II Precursor of steroid compounds 54 9 May 2024  FFG2414 Pharmacology II III Development of atherosclerotic plaques IV To reduce blood glucose levels A I, II, III B I, III, IV C II, III, IV D I, II, III, IV 89 Together with other substances, __________ forms plaque that can narrow the arteries and make them less flexible. A HDL B LDL C TG D chylomicron 90 Which of the following is a fibrate? A Gemfibrozil B Digitalis C Thiazide D Vitamin K 91 Which of the following is NOT related to the conduction system of the heart? A Sinoatrial node (SA node) B Atrioventricular node (AV node) C Atrioventricular bundle D Coronary vessels 92 The stimulation of beta-1 (β1) adrenergic receptors in the heart leads to __________. A decrease in blood pressure B increase in gastrointestinal (GI) motility C constriction of the eye-pupil D increase in heart rate 93 The M2 cholinergic receptors are responsible for __________. A increase in heart rate B increase in GI motility C constriction of the eye-pupil D decrease in heart rate 94 Which of the following locations in the heart has M2cholinergic receptors? A SA node B Coronary vessels C Semi-lunar valves D Mitral valve 55 9 May 2024  FFG2414 Pharmacology II 95 Positive inotropic effect refers to increase in __________. A myocardial force of contraction B heart rate C release of negative ions into the blood stream D release of positive ions into the blood stream 96 The form of hypertension which occurs in majority (95%) of the affected people,having no identifiable cause is known as __________ hypertension. A primary B secondary C malignant D non-essential 97 The following are TRUE about cardiac cycle, EXCEPT__________. A atrial and ventricular diastole occurs for about 4/10th of a second B atrial systole occurs for about 1/10th of a second C ventricular systole occurs for about 3/10th of a second D each cardiac cycle has 3 heart beats 98 Which of the following are TRUE about blood vessels? I Arteries are thin walled and have small diameter. II Arterioles are thick walled and have small diameter. III Capillaries are thick walled and prevent movement of small molecules. IV Veins are thin walled and carry a large portion of blood. A I and II only B II and III only C II and IV only D I, II, III and IV 99 Based on the two statements below select the correct choice of answers: 1) Vasomotor centre (VMC) in the medulla oblongata of the brain is responsible for increase or decrease of BP. 2) Cardiac centre in the medulla oblongata increases or decreases heart rate. A Statement 1) is TRUE, and statement 2) is FALSE B Statement 1) is FALSE, and statement 2) is TRUE C Both statements 1) and 2) are TRUE D Both statements 1) and 2) are FALSE 100 What is the common adverse effect of the following classes of drugs? a) Angiotensin converting enzyme (ACE) inhibitors b) Angiotensin II receptor blockers c) Beta adrenergic blockers A Hypotension 56 9 May 2024  FFG2414 Pharmacology II B Diarrhoea C Constipation D Hypertension 57 9 May 2024  FFG2414 Pharmacology II B. Short Essay Question 1 (a) Label A, B, C, D in the following diagram. (b) Diagram below shows the ECG of the heart. What do P, QRS and T indicate? 2 (a) Illustrate the renin-angiotensin-aldosterone system with a diagram. (b) Briefly explain the mechanism of angiotensin-converting enzyme (ACE) inhibitor in the reduction of blood pressure. (c) Give ONE (1) example of ACE inhibitor. 3 (a) Define heart failure. (b) Outline the mechanism of action of inotropic agents in the treatment of congestive heart failure (CHF) and give examples. (c) List 4 groups of drugs, other than inotropic agents, that are used in congestive heart failure (CHF). 4 (a) There are numerous types of lipoprotein in plasma. Indicate which one is the bad cholesterol and which one is the good cholesterol. (b) Where does cholesterol come from? List TWO (2) main sources of cholesterol in our body. (c) When too much bad cholesterol circulates in the blood, together with other substances, it can form plaque that can narrow the arteries and make them less flexible, as shown in diagram below. 58 9 May 2024  FFG2414 Pharmacology II When the coronary artery is narrowed, less blood is supplied to the heart muscles and causing chest pain. This condition is known as __________. (d) Classify drugs that are used to treat condition in (c). (e) The condition of high cholesterol in the blood can be treated with cholesterol lowering drugs to prevent atherosclerosis. Classify these drugs. 5 (a) The heart is innervated by the autonomic nervous system. Name TWO (2) branches of autonomic nervous system. (b) Name the receptors of the autonomic nervous system in the heart and their neurotransmitters. (c) Briefly explain the effects of the receptors in part (b). (d) Propranolol is a drug used in the cardiovascular disease. Briefly explain the mechanism of action of propranolol in the heart. (e) List TWO (2) clinical uses of propranolol. C. Fill in the blanks Passage 1 ____(1)______, a condition in which blood pressure (BP) in the arterial system is abnormally high, is one of the leading causes of cerebral strokes, heart attacks, and chronic heart failure. In the majority of hypertensive cases (approximately 90 percent)), the cause of hypertension is unknown. This type of hypertension is referred to as ____(2)______. Since the cause of essential hypertension is unknown, the goal of drug therapy is to lower the blood pressure back within the normal range to prevent or at least reduce the serious consequences of hypertension. There is a variety of antihypertensive drugs that can effectively lower blood pressure. These include: (i) the ____(3)______: These drugs produce hypotensive effect by increasing excretion of sodium and water. 59 9 May 2024  FFG2414 Pharmacology II Most common adverse effect of these drugs is the excessive loss of water, results in ____(4)______. Another adverse effect is ____(5)______ which is associated with the excessive loss of potassium. However, the use of _____(6)_____ may result in hyperkalaemia. (ii) the beta-blockers produce two actions in the treatment of hypertension. First, they block ____(7)______ in the heart, lowering blood pressure by decreasing CO. Second, they block the release of _____(8)_____ from the kidneys, which reduces the activation of renin-angiotensin- aldosterone mechanism. An example of beta-blocker is _____(9)_____. (iii) The alpha-blockers selectively block the alpha-1 receptors located on vascular smooth muscle. The main antihypertensive effects are vasodilation and decreased peripheral resistance. An example of alpha-blocker is: ____(10)______. (iv) ____(11)______ are drugs that interfere with the influx of calcium in cardiac and vascular smooth muscle, causing arteriolar vasodilation. This lowers peripheral resistance and blood pressure. An example for this group of drugs is _____(12)_____. (v) Several drugs interfere with the activation of the renin-angiotensin-aldosterone mechanism. The ____(13)______ inhibit the conversion of angiotensin I to angiotensin II, which then causes vasoconstriction and increase the blood pressure. Angiotensin II also stimulates the release of ____(14)______ and ____(15)______. These hormones increase the reabsorption of water and electrolytes. An example of this group of drug is ____(16)______. (vi) ____(17)______ bind to angiotensin-1 (AT1) receptor and competitively antagonize the actions of angiotensin II. An example of this is _____(18)_____. (vii) _____(19)_____ are drugs that decrease sympathetic activity and BP by an action in the central nervous system. These drugs include clonidine and methyldopa. (viii) The ____(20)______ act on vascular smooth muscle to cause relaxation. This results in vasodilation and a reduction in BP. Examples of these drugs are hydralazine, monoxidil. Essential hypertension is a chronic disease. It requires lifelong treatment and medical supervision. Passage 2 When too much LDL cholesterol circulates in the blood, it can slowly build up in the inner walls of the ____(i)______ that feed the heart and brain. Together with other substances, it can form ____(ii)______, a thick, hard deposit that can narrow the arteries and make them less flexible. This condition is known as ____(iii)______. If a clot forms and blocks a narrowed artery, this may result ____(iv)______ or ____(v)______. 60 9 May 2024