Cardiovascular Disorders: Coronary Heart Disease PDF

OUR LADY OF FATIMA UNIVERSITY COLLEGE OF PHARMACY Cardiovascular Disorders: Coronary Heart Disease CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS PHCP311  Ischemia Ischemia may be defined as lack of oxygen and decreased or no blood fl...

OUR LADY OF FATIMA UNIVERSITY COLLEGE OF PHARMACY Cardiovascular Disorders: Coronary Heart Disease CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS PHCP311  Ischemia Ischemia may be defined as lack of oxygen and decreased or no blood flow to the myocardium resulting from artery narrowing or obstruction. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311 OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311 OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Pathophysiology Myocardial oxygen consumption (MVO2) is primarily determined by heart rate, myocardial contractility, and wall tension. An increase in any of these requires a 50% increase in coronary flow to meet the oxygen demand. Myocardial ischemia occurs when there's an imbalance between oxygen supply and demand. The heart regulates blood flow to match its oxygen needs, influenced by factors like blood oxygen levels and coronary flow. Conditions like atherosclerosis, coronary spasm, or left ventricular hypertrophy can reduce oxygen supply, leading to ischemia. A reduction in blood oxygen-carrying capacity, such as in severe anemia, can also lower the threshold for ischemia in patients with coronary obstruction. Often, multiple factors—like increased oxygen demand due to hypertension and reduced supply due to atherosclerosis—contribute to ischemia. Microvascular angina, caused by abnormal coronary resistance vessel function, can also contribute to ischemia and angina. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Myocardial ischemia When coronary blood flow becomes inadequate to meet myocardial oxygen demand. – Dec. compensation for oxygen demand myocardial shifting from aerobic to anaerobic metabolism progressive impairment of metabolic, mechanical and electrical function OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Atherosclerosis Most common cause of epicardial coronary artery stenosis – Patients with fixed coronary atherosclerotic lesions of at least 50% show myocardial ischemia during increased myocardial metabolic demand as a result of decreased CFR. 90% fixed atherosclerotic lesions: almost no CFR Patient may experience angina at rest. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Stable Angina Atherosclerotic angina, Classic Angina, Angina on effort) – Episodic chest pain associated with exertion or other forms of increased myocardial oxygen demand. – Pain is characterized by crushing or squeezing which radiates down the left arm or the left jaw and is usually relieved by rest. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Risk Factors More common in women Increases occurrence with age – For ages 45-64, the highest prevalence was found in African-American women. – For ages 65-74, the highest prevalence was found in African American men. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Clinical Presentation chest pain precipitated by exertion or activities of daily living – squeezing, crushing, heaviness, or chest tightness/ numbness or burning in the chest – lasts from 5 to 20 minutes Ischemic symptoms may be associated with diaphoresis, nausea, vomiting, and dyspnea. – Women/ older patients – present with atypical chest pain, characterized by midepigastric discomfort, effort intolerance, dyspnea, and excessive fatigue. Patients with diabetes mellitus may have decreased pain sensation due to neuropathy. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Diagnostic Tests Obtain the medical history to identify the quality and severity of chest pain, precipitating factors, location, duration, pain radiation, and response to NTG/ rest. Assess nonmodifiable risk factors for coronary artery disease (CAD): age, sex, and family history of premature atherosclerotic disease in first-degree relatives (male onset before age 55 or female before age 65). – patients having an ischemic episode may present with tachycardia, diaphoresis, shortness of breath, nausea, vomiting, and lightheadedness. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Diagnostic Tests Stress perfusion imaging – Thalium 201 – Can diagnose multi-vessel disease, localized ischemia – Reserved for patients who have ECG abnormality Coronary angiography and cardiac catheterization – Specific and sensitive – Invasive, expensive and risky OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Nonpharmacologic Therapy 1. Risk factor modification is the primary nondrug approach for primary and secondary prevention of CAD events. 2. Lifestyle modifications include daily physical activity, weight management, dietary therapy (reduced intake of saturated fats, trans-fatty acids, and cholesterol), smoking cessation, psychological interventions – (eg, screening and treatment for depression if appropriate), limitation of alcohol intake, and avoiding exposure to air pollution. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Nonpharmacologic Therapy Surgical revascularization options for select patients include coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) with or without stent placement. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Percutaneous Transluminal Coronary Angioplasty PTCA is a treatment for patients with coronary artery disease (obstructed blood flow through the coronary arteries). The physician inserts a special catheter (a thin, flexible tube) into the femoral artery. The catheter has a balloon at its tip. X-ray is used to help the doctor thread the catheter into position at the site of the blockage in the coronary artery. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311 Coronary Artery Bypass Graft OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Pharmacologic Therapy In patients with prinzmetal angina: – Nitroglycerin – Calcium channel blockers – prevent coronary spasm Amlodipine may be preferred due to long half life OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311 OUR LADY OF FATIMA UNIVERSITY COLLEGE OF PHARMACY Neurovascular Disorders: Stroke CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS PHCP311  Stroke involves abrupt onset of focal neurologic deficit that lasts at least 24 hours and is presumed to be of vascular origin. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Ischemic Stroke Ischemic strokes (87% of all strokes) are due either to local thrombus formation or emboli occluding a cerebral artery. Cerebral atherosclerosis is a cause in most cases, but 30% are of unknown etiology. Emboli arise either from intra- or extracranial arteries. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Hemorrhagic Stroke Hemorrhagic strokes (13% of strokes) include subarachnoid hemorrhage (SAH), intracerebral hemorrhage, and subdural hematomas. SAH may result from trauma or rupture of an intracranial aneurysm or arteriovenous malformation (AVM). Intracerebral hemorrhage occurs when a ruptured blood vessel within the brain causes a hematoma. Subdural hematomas are usually caused by trauma. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Clinical Presentation Symptoms include – unilateral weakness, – inability to speak, – loss of vision, vertigo, or falling. Ischemic stroke is not usually painful, but headache may occur in hemorrhagic stroke. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311 OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Diagnosis Protein C, protein S, and Antithrombin III are best measured in steady state rather than in the acute stage. Antiphospholipid antibodies are of higher yield but should be reserved for patients younger than 50 years and those who have had multiple venous or arterial thrombotic events or livedo reticularis. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311 OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Diagnosis Computed tomography (CT) Magnetic resonance imaging (MRI) Carotid Doppler (CD) Electrocardiogram (ECG) Transthoracic echocardiogram (TTE) Transcranial Doppler (TCD) OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Nonpharmacologic Therapy Acute ischemic stroke: Surgical decompression is sometimes necessary to reduce intracranial pressure. – An interprofessional team approach that includes early rehabilitation can reduce long-term disability. – In secondary prevention, carotid endarterectomy and stenting may be effective in reducing stroke incidence and recurrence in appropriate patients. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311 OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311 OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Nonpharmacologic Therapy Hemorrhagic stroke: In SAH, surgical intervention to clip or ablate the vascular abnormality reduces mortality from re-bleeding. After primary intra-cerebral hemorrhage, surgical evacuation may be beneficial in some situations. Insertion of an external ventricular drain with monitoring of intracranial pressure is commonly performed in these patients. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Pharmacologic Therapy of Ischemic Stroke Alteplase (t-PA, tissue plasminogen activator) initiated within 4.5 hours of symptom onset reduces disability from ischemic stroke. Aspirin 160 to 325 mg/day started between 24 and 48 hours after completion of alteplase also reduces long-term death and disability. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Pharmacologic Therapy of Ischemic Stroke Cilostazol is also a first-line agent, but its use has been limited by lack of data. – Oral anticoagulation is recommended for atrial fibrillation and a presumed cardiac source of embolism. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Pharmacologic Therapy of Ischemic Stroke Statins reduce risk of stroke by approximately 30% in patients with coronary artery disease and elevated plasma lipids. – Low-molecular-weight heparin or low-dose subcutaneous unfractionated heparin (5000 units three times daily) is recommended for prevention of deep vein thrombosis in hospitalized patients with decreased mobility due to stroke and should be used in all but the most minor strokes. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Pharmacologic Therapy of Hemorrhagic Stroke There are no standard pharmacologic strategies for treating intracerebral hemorrhage. – SAH due to aneurysm rupture is often associated with delayed cerebral ischemia in the 2 weeks after the bleeding episode The calcium channel blocker Nimodipine 60 mg every 4 hours for 21 days, along with maintenance of intravascular volume with pressor therapy, is recommended to reduce the incidence and severity of neurologic deficits resulting from delayed ischemia. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311 OUR LADY OF FATIMA UNIVERSITY COLLEGE OF PHARMACY Cardiovascular Disorder: Hypertension CLINICAL PHARMACY AND PHARMACOTHERAPEUTICS PHCP311  Hypertension Common disease that is simply defined as persistently elevated arterial blood pressure. It is defined as one of the most significant risk factors for cardiovascular disease. – The Joint National Committee (JNC7), along with American Heart Association (AHA), is the most prominent evidence-based clinical guideline in the United States for the management of HTN OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Epidemiology Etiology Approx 31% has HTN Essential HTN More males have HTN – Unknown than female before the pathophysiologic etiology age 45 – Cannot be cured, can be After 55, more females controlled has HTN than males Secondary HTN In the US, more blacks – Have specific cause of have HTN HTN OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Secondary HTN Disease: – Chronic Kidney Disease, Cushing’s Syndrome, Parathyroid Disease, Pheochromocytoma, Thyroid Dse Drugs – Adrenal Steroids, Amphetamines, Decongestants, Erythropoetin, NSAIDs Street Drugs – Cocaine, Ephedra, Nicotine, Ergotamine, Anabolic Steroids Food – Sodium, Ethanol, Licorice, Tyramine-obtaining foods OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311 REGULATION OF BLOOD PRESSURE Dependent on two factors – Peripheral vascular resistance: Regulated predominantly at the level of the arterioles and is influenced by neural and hormonal inputs. – Cardiac output: strongly dependent on sodium concentration. – Resistance vessels exhibit auto regulation whereby increased blood flow would induce vasoconstriction (angiotensin II, catecholamine) to protect tissues from hyper perfusion OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Vascular changes – Functional vasoconstriction: can cause permanent structural thickening of the resistant vessel – Changes in vascular wall structure that results in increased resistance. Genetic factor – Genetic variants in the RAAS can contribute to the known racial differences in blood pressure regulation Environmental – Stress, obesity, smoking, physical inactivity, dietary sodium consumption. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Arterial Blood Pressure It is the pressure in the The difference between arterial wall measured in SBP and DBP is called the mmHg pulse pressure and is a Two typical values are measure of arterial wall systolic BP and diastolic tension BP During a cardiac cycle, SBP is achieved during two-thirds of the time is cardiac contraction and spent in diastole represents the peak value DBP is achieved after contraction when the cardiac chambers are filling OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Mechanisms of HTN RAAS Neurohormonal Regulation Peripheral Autoregulatory Components Vascular Endothelial Mechanisms Electrolytes OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311 Renin-Angiotensin-Aldosterone System Renin – Stored in the juxtaglomerular cells located in the afferent arterioles of the kidney – Release is modulated by: intrarenal factors and extrarenal factors Juxtaglomerular Cells – Function as a baroreceptor-sensing device – Decreased renal artery pressure and kidney blood flow are sensed by these cells and stimulate secretion of renin OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311 Renin-Angiotensin-Aldosterone System Cathecolamines increase renin release Decreased potassium/calcium results in secretion Renin catalyzes the conversion of angiotensinogen to angiotensin I in the blood Angiotensin I is then converted to angiotensin II by angiotensin-converting enzyme (ACE) OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311 Renin-Angiotensin-Aldosterone System Angiotensin II can elevate BP by: – Direct, VERY POTENT vasoconstrictor – Stimulation of cathecolamine release from the adrenal medulla – Would also stimulates aldosterone sythesis from the adrenal cortex This leads to sodium and water reabsorption that increases plasma volume, total peripheral resistance and ultimately BP OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311 Renin-Angiotensin-Aldosterone System OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Neurohormonal Regulation CNS/ANS – There are a number of receptors that either enhance or inhibit NE release are located on the presynaptic surface of sympathetic terminals Presynaptic a-receptors (a2) exerts a negative inhibition on NE release Stimulation of presynaptic b-receptors facilitates NE release OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Neurohormonal Regulation Adrenergic Receptors (post-synaptic) – A1 stimulation – vasoconstriction – B1 stimulation – increased HR and contractility – B2 stimulation – vasodilation of arterioles and venules OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Neurohormonal Regulation Baroreceptor Reflex System – The major negative feedback mechanism that controls sympathetic activity (for homeostasis) – Baroreceptors are nerve endings lying in the walls of large arteries, especially in the carotid arteries and aortic arch – A decrease in arterial BP stimulates baroreceptors, causing reflex vasoconstriction and increased heart rate and force of cardiac contraction – Less responsive in elderly patients and those with diabetes OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Neurohormonal Regulation The purpose of these neuronal mechanisms is to REGULATE BP and MAINTAIN HOMEOSTASIS Pathologic disturbances in any of the major components (autonomic nerve fibers, adrenergic receptors, baroreceptors) could conceivably lead to chronically elevated BP OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  PERIPHERAL AUTOREGULATORY COMPONENTS Kidney – Usually maintains BP through a volume-pressure adaptive mechanism – When BP drops, the kidneys respond by increasing retention of sodium and water – These changes lead to plasma volume expansion that increases BP Tissue oxygenation – When tissue oxygen demand is normal to low, the local arteriolar bed remains relatively vasoconstricted – However, inc demand = arteriolar vasodilation = lowered peripheral vascular resistance = increased blood flow and oxygen delivery OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  VASCULAR ENDOTHELIAL MECHANISMS Vascular endothelium and smooth muscle play important roles in regulating blood vessel tone and BP. * These functions are mediated through vasoactive substances that are synthesized by endothelial cells. – Renal endothelium produces ACE – Dysfunctions in endothelium causes, increased clot formation, increased adhesion molecules OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  VASCULAR ENDOTHELIAL MECHANISMS Deficiency in the local synthesis of vasodilating substances (prostacyclin and bradykinin) or excess vasoconstricting substances (angiotensin II* and endothelin I) contribute to essential hypertension, atherosclerosis, and other CV diseases.* Nitric oxide, A Potent vasodilator, is produced in the endothelium: intrinsic deficiency in nitric oxide will result to HTN.*  ELECTROLYTES Epidemiologic and clinical data A lack of dietary calcium have associated excess sodium hypothetically can disturb the intake with hypertension. balance between intracellular Population-based studies* and extracellular calcium, indicate that high salt diets are resulting in an increased associated with a high intracellular calcium prevalence of stroke and concentration. hypertension. This alters vascular smooth Conversely, low salt diets are muscle function by increasing associated with a low peripheral vascular resistance. prevalence of hypertension. Some studies show that dietary calcium supplementation results in a modest BP reduction in patients with hypertension. OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Clinical Presentation of HTN The px may appear very healthy or may have the presence of additional CV risk factors – Age – Diabetes Mellitus – Dyslipidemia (elevated LDL) – Microalbunemia – Family History of premature CV disease – Obesity (BMI >30kg/m2) – Physical inactivity – Tobacco use OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Clinical Presentation of HTN Laboratory Tests – BUN (indicator of kidney damage) – Fasting Lipid panel – Fasting Blood Glucose – Serum Electrolytes – Spot Urine Albumin-to-creatinine ratio OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Clinical Presentation of HTN Target Organ Damage – the px may have a previous medical history of diagnostic findings that indicate the presence of HTN-related target organ damage – Brain (Stroke, transient ischemic attack) – Eyes (Retinopathy) – Heart (Left ventricular Hypertrophy, angina or prior MI, prior coronary revascularization, HF) – Kidney (CKD) – Peripheral Vasculature(Peripheral arterial dse) OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Goal of Therapy Overall Goal Surrogate Goal – Treating HTN is to reduce – Treating px with HTN to HTN associated achieve a desired target morbidity and mortality BP value – This morbidity and – Most px have a goal BP mortality is related to of less than target-organ damage 140/90mmHg for the gen prevention of CV events – This goal is lowered to less than 130/80mmHg for px with DM, CKD OUR LADY OF FATIMA UNIVERSITY – COLLEGE OF PHARMACY – PHCP311  Non-Pharmacologic Treatment Maintain normal body weight (BMI 18.5-24.9 kg/m2) Consume a diet rich in fruits, vegetables, and low fat dairy products with a reduced content of saturated and total fat Reduce a daily dietary sodium intake as much as possible, ideally to = 65 mmol/day Regular aerobic physical activity Limit consumption to < 2 drinks/day in man and