Circulatory System Notes (PDF)

CIRCULATORY SYSTEM CIRCULATORY SYSTEM consists of a) CARDIOVASCULAR SYSTEM- Consists of HEART and BLOOD VESSELS Circulates BLOOD b) LYMPHATIC SYSTEM- Consists of LYMPH NODES and LYMPH VESSELS Circulates lymph, nutrients, waste matters, hormones CARDIOVASCULAR SYSTEM HEART...

CIRCULATORY SYSTEM CIRCULATORY SYSTEM consists of a) CARDIOVASCULAR SYSTEM- Consists of HEART and BLOOD VESSELS Circulates BLOOD b) LYMPHATIC SYSTEM- Consists of LYMPH NODES and LYMPH VESSELS Circulates lymph, nutrients, waste matters, hormones CARDIOVASCULAR SYSTEM HEART & BLOOD VESSELS Kardia (Greek): Heart Vasculum (Latin): Blood vessels WHAT IS THE ROLE? It Service the needs of tissues – It transports oxygen and nutrients to the tissues – It transports waste material away – It transports the hormones from one part of the body to another * In general to maintain an appropriate environment in all the tissue fluids of the body for optimal survival and function of the cells ANATOMY OF HEART Cone shaped -the hollow muscular organ Weight- 330 gms Sized roughly like a man’s closed fist Contracts- 100,000 times per day Pumps out 5 litres of blood per minute Situated in the thoracic cavity between the lungs ANATOMY OF HEART ANATOMY OF HEART It consists of – Chambers Valves Vessels Cardiac layers HEART HEART : INTERNAL STRUCTURE 4 Layers Pericardium (outermost covering of Heart) Epicardium (outer layer) Myocardium (middle layer) Endocardium (inner layer) 4 Chambers 2 Atria: Right Atrium & Left Atrium 2 Ventricles: Right Ventricle & Left Ventricle HEART : INTERNAL STRUCTURE 4 Vessels Vena Cava Pulmonary Artery Pulmonary Vein Aorta 4 Valves Aortic valve Pulmonary valve Tricuspid valve Bicuspid valve (Mitral valve)  LAYERS OF HEART 1 The outermost sac -Pericardium 2 The outer layer- Epicardium 3 The middle layer- Myocardium (cardiac muscle) 4 The inner layer- Endocardium Epicardium Endocardium Myocardium PROPERTIES OF CARDIAC MUSCLE I. Excitability II. Conductivity III. Contractility IV. Rhythmicity PROPERTIES OF CARDIAC MUSCLE EXCITABILITY = the ability of cardiac muscle to respond to adequate stimuli by generating an action potential followed by a mechanical contraction. CONDUCTIVITY = the ability of cardiac ms fibers to conduct the cardiac impulses that are initiated in the SA-node (the pacemaker of the heart). CONTRACTILITY = the ability of the cardiac muscle to convert chemical energy into mechanical work. RHYTHMICITY= the ability of cardiac ms to contract in a regular constant manner w/out nerve supply. ♥ It’s myogenic in origin (i.e. not neurogenic). ♥ Its initiated by the ‘pacemaker’ of the ht, the SA- node. VESSELS CONNECTED TO HEART PULMONARY PULMONARY SUPERIOR ARTERY VEIN VENA CAVA RIGHT ATRIUM LEFT ATRIUM INFERIOR VENA RIGHT LEFT CAVA VENTRICLE VENTRICLE AORTA HEART & BLOOD CIRCULATION CIRCULATION FLOWCHART Superior Vena Cava & Inferior Vena Cava (Deoxygenated blood) Right Atrium Tricuspid Valve Left Atrium Pulmonary Valve Pulmonary Artery Lungs (Exchange of gases CO2 O2 ) CIRCULATION FLOWCHART Pulmonary Vein (Oxygenated blood) Left Atrium Bicuspid Valve Left Ventricle Aortic Valve Aorta (largest artery) Different body parts CONDUCTING SYSTEM OF HEART There are small groups of specialized cells in the myocardium which initiate and conduct impulses causing coordinated and synchronized contraction of the heart muscles CONDUCTIVITY SYSTEM SA node AV node Bundle of His Right and Left Bundle of His Purkinje Fibers CONDUCTING SYSTEM OF HEART CARDIAC MUSCLE CONTRACTION Action potential over the cardiac muscle membrane Spreads to the interior Release of Ca++ ions into the muscle Ca++ ions diffuse in myofibrils Muscle contraction  CARDIAC CYCLE Sequence of events which occur in the heart during a beat It consists of two phases- Systole Phase of contraction- When heart pumps the blood Diastole Phase of relaxation- When the chambers of the heart receive blood from different sites Normal Cardiac Cycle = Systole and Diastole of both atria and both ventricles (lasts for 0.8 s) ANIMATED HEART BLOOD CIRCULATION TYPES OF BLOOD VESSELS  Artery  Vein  Capillaries  ARTERIES VEINS  Carry blood away from the heart  Carry the blood towards the heart  Usually carry deoxygenated blood  Usually carry oxygenated blood  Contains no valves  Contains valves  Walls are thicker  Walls are thinner  LAYERS OF BLOOD VESSELS 1. Tunica Externa- Outer layer- protection 2. Tunica Media- Middle layer-made up of smooth muscles- responsible for vasoconstriction and vasodilation 3. Tunica Interna- Intima/Endothelial layer  CAPILLARIES - Wall formed by a single layer of endothelial cells - Provides large filtering surface - - Exchange of gases, electrolytes ,etc, takes place at this level TWO TYPES OF CIRCULATION  CIRCULATION Aorta Artery Arterioles Capillaries (Exchange of gases between organ and blood) Venules Veins Superior and Inferior Vena cava BLOOD PRESSURE It is the lateral pressure exerted by the flowing blood on the walls of the blood vessels It is expressed as BP = Cardiac Output  Peripheral Vascular (CO) Resistance (PVR) Normal BP should be 120/80 mm/Hg BLOOD PRESSURE Arterial blood pressure varies rhythmically with the beating of the heart Rising to the maximum during the ventricular contraction (Systole) when the blood is pumped into the arteries: Systolic Blood Pressure Falling to the minimum when ventricle relaxes (Diastole): Diastolic Blood Pressure BLOOD PRESSURE Formula for Blood Pressure is – B.P = C.O x PVR (Blood Pressure) (Cardiac Output) (Peripheral Vascular Resistance) S.V X H.R X PVR (Stroke Volume) (Heart Rate) B.V X F.O.C X H.R X PVR (Blood Volume) (Force of Contraction) Hence, BP= BV X FOC X HR X PVR DEFINITIONS  CO= Cardiac Output It is the volume of blood being pumped by the heart, right ventricle in the time interval of one minute  PVR=Peripheral Vascular Resistance It is the resistance applied by the walls of blood vessels on the circulating blood  S.V= Stroke Volume It is the volume of blood pumped out of the heart with each beat/stroke Generally, its 70 mL DEFINITIONS  HR=Heart Rate It is the speed of the heartbeat, specifically the number of heartbeats per unit of time. Generally, its 72 times/minute BV= Blood Volume It is the volume of blood (both red blood cells and plasma) in the circulatory system of any individual FOC= Force of Contraction It is the force with which the heart contracts to pump out the blood Common Terminology Tachycardia: Increase in Heart Rate Bradycardia: Decrease in Heart Rate Arrhythmia: Abnormal Rhythm of Heart  Common Terminology CHRONOTROPHIC EFFECT : Effect on Heart Rate (HR) Positive Chronotropic Effect- Increased HR Negative Chronotropic Effect- Decreased HR IONOTROPHIC EFFECT: Effect on Force Of Contraction (FOC) Positive Ionotropic Effect- Increased FOC Negative Ionotropic Effect- Decreased FOC DROMOTROPHIC EFFECT: Effect on the conduction of the Cardiac Impulse Positive Dromotropic Effect- Increased Conduction Rate Negative Dromotropic Effect- Decreased Conduction Rate BLOOD VESSELS AND ORGANS Coronary Artery- Heart Carotid / Cerebral Artery- Brain Peripheral Arteries- Peripheral Organs (Legs) Can you Guess? Parameters Blood Pressure change Vasodilation ? Vasoconstriction ? Increased cardiac ? output Increased venous ? return REGULATION OF BLOOD CIRCULATION REGULATION OF BLOOD CIRCULATION  NERVOUS SYSTEM  ROLE OF KIDNEYS NERVOUS SYSTEM SYMPATHETIC Predominant role PARASYMPATHETIC Minor role  SYMPATHETIC NERVOUS SYSTEM Operates through release of nor-adrenaline/adrenaline Receptors Two types of receptors are present-   1 2 1 2 Blood Vessels CNS Heart Blood Vessels Kidney Bronchioles NERVOUS SYSTEM Receptor Tissue Response Increased  Heart Rate Cardiac 1 receptor  Force of Contraction  Atrio-Ventricular conduction Kidneys Renin release Lungs Bronchodilation 2 receptor Blood vessels Vasodilation NERVOUS SYSTEM Receptor Tissue Response  1 Receptor Blood vessels Vasoconstriction Central mediated blood  2 receptor CNS pressure depression PARASYMPATHETIC NERVOUS SYSTEM PARASYMPATHETIC Minor role Decreases Heart Rate Slightly Decreases Force of Contraction (FOC)of heart  Vasoconstrictor Agents Vasodilator Agents Noradrenaline/ Adrenaline Bradykinin Angiotensin Histamine Vasopressin (ADH)  Role of Kidneys in BP Control Hypertension Hypotension Regulate output of salt and water Release of Renin Increase Urination Stimulate RAAS Decrease BP Increase BP RENIN ANGIOTENSIN ALDOSTERON SYSTEM Angiotensinogen (Liver) Renin (Kidney) Angiotensin I ACE (Angiotensin Converting Enzyme) Angiotensin II AT1 AT2 ( Role in CVS is not clear) receptors receptors Heart Blood Vessels Kidney Adrenal gland Pituitary gland Brain  ACTION OF ANGIOTENSIN II HEART - Increase myocardial contractility BLOOD VESSELS - Vasoconstriction KIDNEY - Increase sodium and water retention, suppress Renin secretion ADRENAL GLANDS - Increase Aldosterone release PITUITARY GLAND - Increase ADH/ Vasopressin BRAIN - Increase thirsty feeling INCREASE IN BLOOD PRESSURE  HYPERTENSION The Persistent elevation (increase) in the Blood pressure than the normal which is sustained is called as Hypertension It is a chronic medical condition in which the blood pressure in the arteries is elevated  TYPES OF HYPERTENSION Hypertension is classified into two majorly :  Primary (Essential) Hypertension About 90–95% of cases are categorized as "Primary Hypertension" which means high blood pressure with no obvious underlying medical cause  Secondary (Non-essential) Hypertension 5–10% of cases (Secondary Hypertension) are caused by other conditions that affect the kidneys, arteries, heart or endocrine system. It is with known cause. E.g. Renal, Endocrinal OTHER TYPES OF HYPERTENSION  Isolated Systolic Hypertension When there is rise only in systolic BP but Diastolic BP is normal. It is defined as Systolic BP > 140 mm Hg and Diastolic BP < 90 mm Hg  White Coat Hypertension Patient’s BP is elevated when measured by a physician but normal when measured outside the health care setting  JOINT NATIONAL COMMITTEE VIII (JNC) TARGET GOAL ACHIEVEMENT Patients below 60 yrs of age- 140/90 mm/Hg Patients above 60 yrs age- 150/90 mm/Hg JOINT NATIONAL COMMITTEE VII (JNC) TARGET GOAL ACHIEVEMENT Seventh report of Joint National Committee (JNC VII) guidelines, 2004 SBP- Systolic Blood Pressure; DBP – Diastolic Blood Pressure RISK FACTORS  Age : Blood pressure rises with age in both men and women  Sex: Hypertension is less common in pre-menopausal women than in men. The cardiovascular risk in elderly men and women is similar in postmenopausal period  Family History  Salt Intake: Blood pressure increases proportionately with the salt intake RISK FACTORS  Smoking: Nicotine and carbon monoxide, in tobacco smoke, are both potent vasoconstrictors. Smoking of two cigarettes causes 16mm Hg rise of both systolic and diastolic blood pressure which does not return to pre cigarette level for about 20 minutes. Smoking is a very powerful contributor to morbidity and mortality in hypertensive patients. The incidence of stroke and coronary artery disease in hypertensive patient who smoke is 2 -3 times greater than in non-smoking patients with comparable blood pressure RISK FACTORS  Alcohol Intake: Excessive alcohol intake is an important risk factor for hypertension  Physical Inactivity: Sedentary individuals have a 20 to 50% increased risk of developing hypertension  Weight Gain: Increased weight is a major controllable risk factor for new onset of hypertension RISK FACTORS  Emotional Stress: Mental stress is known to produce an acute rise of blood pressure Diabetes: There is link between diabetes and hypertension PATHOPHYSIOLOGICAL MECHANISMS BP = Cardiac Output x PVR The development of hypertension is due to either increased Cardiac Output or elevated Vascular Resistance  SYMPTOMS OF HYPERTENSION Asymptomatic - In early stages Common Symptoms: Headache, Giddiness, Irritability and Fatigue Symptoms due to Organ Damage Heart - Breathlessness Coronary arteries - Angina, Acute MI Kidneys - Polyuria, Nocturia  COMPLICATIONS OF HYPERTENSION BLOOD VESSELS a) MACROVASCULAR Complications: Occurring in BIGGER blood vessels Heart- Myocardial Ischemia, Angina, MI (Myocardial Infarction) Brain- TIA( Transient Ischemic Attack) , Stroke Peripheral Organs- Intermittent Claudication (Painful walking), PAD/ PVD b) MICROVASCULAR Complications: Occurring in microscopic blood vessels (CAPILLARIES) Neuropathy, Nephropathy, Retinopathy, Hemorrhage HEART LVH-Left Ventricle Hypertrophy CCF- Congestive Cardiac Failure  LVH-Left Ventricular Hypertrophy Left Ventricular Hypertrophy (LVH) is the thickening of the myocardium (muscle) of the left ventricle of the heart While LVH itself is not a disease, it is usually a marker for disease involving the heart Disease processes that can cause LVH include any disease that increases the Afterload that the heart has to contract against, and some primary diseases of the muscle of the heart LVH-Left Ventricular Hypertrophy Cross-sectional Diagram  PRELOAD Preload is the end diastolic pressure that stretches the right or left ventricle of the heart to its greatest geometric dimensions under variable physiologic demand In other words, it is the initial stretching of the cardiomyocytes prior to contraction Preload is theoretically most accurately described as the initial stretching of a single cardiomyocytes prior to contraction Atrial pressure is a surrogate for preload PRELOAD Stretching of Ventricles AFTERLOAD After load is the tension or stress developed in the wall of the left ventricle during ejection In other words, it is the end load against which the heart contracts to eject blood After load can also be described as – the pressure that the chambers of the heart must generate in order to eject blood out of the heart AFTERLOAD After load is readily broken into components: It is the aortic pressure the left ventricular muscle must overcome to eject blood The greater the aortic/pulmonary pressure, the greater the after load on the left/right ventricle, respectively As After load increases, Cardiac Output decreases AFTERLOAD Ventricular Systole CHF- Congestive Heart Failure Chronic/Congestive Heart Failure (CHF) often used to mean Heart Failure (HF), occurs when the heart is unable to pump sufficiently to maintain blood flow to meet the needs of the body The terms Congestive Heart Failure (CHF) or Congestive Cardiac Failure (CCF) are often used interchangeably with chronic heart failure Heart failure is a physiological state in which Cardiac Output (CO) is insufficient to meet the needs of the body and lungs CAUSE Common causes of CHF include- CAD including - A previous Myocardial Infaraction (heart attack) - High Blood Pressure - Atrial fibrillation - Valvular Heart Disease - Cardiomyopathy These cause heart failure by changing either the structure or the functioning of the heart HF/CHF is caused by any condition which reduces the efficiency of the myocardium, or heart muscle, through damage or overloading TYPES OF CHF There are two main types of HF/CHF: - Heart Failure/CHF due to Left Ventricular Dysfunction & -Heart Failure/CHF with Normal Ejection Fraction, depending on if the ability of the left ventricle to contract is affected, or the heart's ability to relax The severity of disease is usually graded by how much the ability to exercise is decreased HF/CHF is not the same as myocardial infarction (in which part of the heart muscle dies) or Cardiac arrest (in which blood flow stops altogether) Diseases that may have symptoms similar to heart failure include: obesity, kidney problems, liver problems, anemia and thyroid disease among others EJECTION FRACTION TYPICAL NORMAL MEASURE VALUE RANGE Ejection Fraction (EF) End Diastolic represents the volumetric Volume 120 mL 65–240 mL fraction of blood pumped (EDV) End Systolic out of the left and Volume 50 mL 16 – 143 mL right ventricle with each (ESV) heartbeat or cardiac cycle Stroke 70 mL 55 – 100 mL Volume (SV) Ejection Reduction in the ejection Fraction 58% 55 – 70% fraction can manifest itself (Ef) clinically as HF/CHF Heart Rate 75 bpm 60 – 100 bpm (HR) Cardiac 5.25L/min 4 – 8 L/min Output (CO)  Left Ventricular Dysfunction (LVD) Left ventricular dysfunction (LVD) occurs as a series of compensatory mechanisms are triggered which lead to a host of structural and neuro-hormonal adaptations LVD produces many changes in the structure and function of the heart through a variety of mechanisms MICROALBUMINURIA Microalbuminuria (Urine albumin) occurs when the kidney leaks small amounts of albumin into the urine, in other words, when there is an abnormally high permeability for albumin in the renal glomerulus Albumin/Creatinine Ratio (ACR) To compensate for variations in urine concentration in spot-check samples, it is helpful to compare the amount of albumin in the sample against its concentration of creatinine This is termed the albumin/creatinine ratio (ACR) Microalbuminuria is defined as – ACR ≥3.5 mg/mmol (female) or ≥2.5 mg/mmol (male), or, with both substances measured by mass, as an ACR between 30 and 300 µg albumin/mg creatinine DIAGNOSIS The level of albumin protein produced by microalbuminuria can be detected by special albumin-specific urine Dipsticks A Microalbumin Urine Test determines the presence of the albumin in urine In a properly functioning body, albumin is not normally present in urine because it is retained in the bloodstream by the kidneys An albumin level above the upper limit values is called “Macroalbuminuria", or sometimes just Albuminuria Sometimes, the upper limit value is given as one less (such as 300 being given as 299) to mark that the higher value (here 300) is defined as Macroalbuminuria SIGNIFICANCE It is an indicator of subclinical cardiovascular disease It is a marker of vascular endothelial dysfunction It is an important prognostic marker for kidney disease in Diabetes Mellitus Hypertension Post-streptococcal glomerulonephritis Increasing microalbuminuria during the first 48 hours after admission to an ICU predicts elevated risk for acute respiratory failure, multiple organ failure, and overall mortality It is a risk factor for venous thromboembolism METABOLIC SYNDROME Metabolic Syndrome is a disorder of energy utilization and storage, diagnosed by a co-occurrence of three out of five of the following medical conditions: abdominal (central) obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides, and low high-density cholesterol (HDL) levels Metabolic syndrome increases the risk of developing CV disease particularly Heart failure, and Diabetes TREATMENT OF HYPERTENSION Lifestyle Modification: Weight reduction Alcohol restriction Regular Exercise Restricting dietary sodium Special diets Relaxation/ Reducing stress CLASSES OF ANTIHYPERTENSIVE DRUGS  Beta Blockers  Diuretics  ACE Inhibitors (ACEI)  Angiotensin - II Receptor Blockers (ARB) Calcium Channel Blockers (CCB) Other Antihypertensive drugs are-  Alpha Blockers  Central Alpha Agonists  Renin Inhibitors, including aliskiren  Vasodilators  ANTIHYPERTENSIVE DRUG CLASS BETA BLOCKERS & HYPERTENSION One of the most frequently prescribed antihypertensive agents First introduced as therapy for Angina In 1964, Propranolol was considered as an antihypertensive agent  CLASSIFICATION OF BETA BLOCKERS They are competitive blockers of beta-adrenoreceptors Properties by which Beta-Blockers differ: Propranolol Non Selective SELECTIVITY Sotalol Blocks β1 & β2 Timolol Atenolol Selective Metaprolol Blocks only β 1 PHARMACOKINETICS Solubility of BETA BLOCKERS Lipid Soluble Water Soluble Eg. Metaprolol Eg. Atenolol Timolol Sotalol Cross blood brain barrier Does not cross blood brain So side effects of fatigue, barrier Insomnia and nightmares Metabolized by liver at rapid Slowly excreted by kidney rate. MECHANISM OF ACTION (In Hypertension) Main suggested mechanisms are: a) Reduction in Cardiac Output Reduction in cardiac output is a major cause in chronic Hence, reduction of BP b) Reduction of Peripheral Vascular Resistance Due to inhibition of Renin release Hypertension In High Risk Patients In such patients, preference needs to be given to an agent with: Established long term mortality and morbidity benefits Evidence says in favor of beta blockers Beta blockers significantly reduce: - Sudden Cardiac Death - Overall Coronary events - Incidence of Stroke Hypertension With IHD BETA BLOCKERS are the drugs of choice BETA BLOCKERS - Reduces the frequency of attacks - Reduces severity of symptoms  IDEAL BETA BLOCKERS  Cardio-selective  Long acting  Simple pharmacokinetics (hydrophilic, no liver metabolism, little protein binding)  Must favorably alter mortality and morbidity Of the available beta blockers, Atenolol comes closest to this profile BETA-BLOCKERS IN ANGINA Often agents of 1st choice in angina BETA BLOCKERS  Heart Rate  Force of Contraction Reduces myocardial oxygen consumption BETA-BLOCKERS IN ANGINA  Effective in prophylactic angina  Improve angina  Reduce the frequency of attacks  Reduce severity of symptoms  Prolong the exercise tolerance endurance time  ANTIHYPERTENSIVE DRUG CLASS DIURETICS These are the drugs which increase the rate of urine formation Classification of Diuretics A. Thiazide and related diuretics e.g. Chlorthalidone, Chlorthiazide, Hydrochlorothiazide B. Loop diuretics e.g. Furosemide C. Potassium sparing diuretics e.g. Amiloride, Spironolactone, Triamterene  MECHANISM OF ACTION Elimination of edema in Depletion of plasma volume arterial walls Reduced extracellular fluid volume including plasma volume Reduces Arterial edema Cardiac Output PVR BP BP ADVANTAGES OF DIURETICS  Reduces cardiovascular morbidity and mortality in controlled treatment trials  Reduce rate of stroke  Reduce coronary artery disease events (only with low dose)  Well tolerated by most patients  Augment the effects of other antihypertensive agents  Long acting hence once daily dosing SAFETY OF DIURETICS This issue revolves around A. Metabolic Side-effects -Dyslipidemia -Hyperuricemia -Hyperglycemia B. Arrhythmogenic Side-effects -Hypokalemia All these ADRs are dose-dependent and rarely seen with low doses  ANTIHYPERTENSIVE DRUG CLASS ACEI/ ARB Angiotensinogen (Liver) Renin (Kidney) Angiotensin I ACE (Angiotensin Converting Enzyme) ACEI Angiotensin II AT1 AT2 ( Role in CVS is not clear) Receptors Receptors Heart Blood Vessels Kidney Adrenal gland ARB Pituitary gland Brain  ANTIHYPERTENSIVE DRUG CLASS ACEI ARB Examples of ACE Inhibitors are: Examples of Angiotensin- II Receptor Blockers:  Ramipril  Telmisartan  Enalapril  Losartan  Lisinopril  Olmesartan  SIDE EFFECTS OF ACE Inhibitors  Cough - This is the most common side effect and occurs in 3 - 22% of cases  Hypotension - This is more common in patients with elderly and those on diuretic therapy CONTRAINDICATION OF ARB  Pregnancy  Hyperkalaemia  Bilateral Renal Artery Stenosis  ANTIHYPERTENSIVE DRUG CLASS Calcium Channel Blockers (CCB) MECHANISM OF ACTION Amlodipine inhibits the entry of calcium ions into the vascular smooth muscle cells (of heart & blood vessels) By blocking the calcium channels which leads to Vasodilation in turn, reduction of B.P (Blood Pressure)  EFFECTS OF CCB CCBs used as medications primarily have three effects: By acting on vascular smooth muscle, they reduce contraction of the arteries & cause an increase in arterial diameter, a phenomenon called vasodialation (CCBs do not work on venous smooth muscle) By acting on cardiac muscles (myocardium), they reduce the force of contraction of the heart By slowing down the conduction of electrical activity within the heart, they slow down the heart beat  EFFECTS OF CCB Since blood pressure is determined by cardiac output and peripheral resistance, CCBs reduce blood pressure With relatively low blood pressure, the after load on the heart decreases; this decreases how hard the heart must work to eject blood into the aorta, and so the amount of oxygen required by the heart decreases accordingly Reducing the force of contraction of the myocardium is known as the negative inotropic effect of calcium channel blockers This can help ameliorate symptoms of IHD such as Angina pectoris  EXAMPLES OF CCB Dihydropyridines: E.g. Amlodipine, Nifedipine More Vascular selective Benzothiazepine: E.g. Diltiazem It has both Vascular and Cardiac activity Phenyalkylamine: E.g. Verapamil More action on Cardiac tissue  OTHER ANTIHYPERTENSIVE DRUGS  Alpha-blockers, α-blockers, or α-adrenergic-antagonists act as receptor antagonist of α-adrenoceptors - Alpha-1 blocker or antagonist acts on Alpha-1 adrenoreceptors - Alpha-1 blocker or antagonist acts on Alpha-2 adrenoreceptors Examples of non-selective α-adrenergic blockers include:  Phenoxybenzamine  Tolazoline Examples of Selective α1-adrenergic blockers include:  Tamsulosin  Prazosin Examples of Selective α2-adrenergic blockers include:  Atipamezole  Idazoxan  OTHER ANTIHYPERTENSIVE DRUGS  Renin Inhibitors bind to the active site of renin and inhibit the binding of renin to angiotensinogen, which is the rate-determining step of the RAAS cascade Examples: Pepstatin(1st RI); Aliskerin  Vasodilator agents act as blood vessel dilators (vasodilators) and open vessels by relaxing their muscular walls Examples: Nitroglycerine  WHY COMBINATIONS?? WHY COMBINATION THERAPY Different Mode of More Flexible Dosing Action Alternatives Greater Efficacy of Less Adverse Effects Combination agents (clinical or metabolic) compared to separate if both components components are in low dose Better Patient Compliance WHY COMBINATION THERAPY  The antihypertensive efficacy may be enhanced when two classes of agents are combined In addition, combination therapy enhances tolerability because one drug of fixed combination can antagonize some of the adverse effects of the second drug  Fixed-dose combination therapy simplifies the treatment regimen, preventing treatment failures that might result from missed doses (Gonzalez Maqueda I et al, Rev Esp Cardiol. 1999;52 Suppl 3:59-72) WHY COMBINATION THERAPY JNC VII report as well as standard guidelines also recommend the use of combinations in stage II hypertension BHS GUIDELINES