NR566_Week 3 Study Guide_includes Ch.16, Ch.28, Ch.36, Ch.39

Chapter 16: Drugs Affecting the Cardiovascular & Renal Systems Angiotensin converting enzyme inhibitors (ACEI or ACE Inhibitors) o Drugs: benazepril, captopril, enalapril, fosinopril, lisinopril, and moexipril, perindopril, quinapril, ramipril, trandolapril o Pharmacodynamics: o MOA: Slows or inhibits the angiotensin converting enzyme which then decrease how much angiotensin II (AT II) is produced thus lowering BP o Inhibit RAAS activity=decreased production of both angiotensin II and aldosterone o Act on the RAAS system: decreases peripheral vascular resistance (decreased afterload) o Indirectly reduce the secretion of aldosterone=decreased sodium and water retention, reducing extracellular fluid volume and preload o Lower vascular resistance w/o decreasing cardiac output (CO) or GFR o Do not affect CO=Do not produce reflex tachycardia o Strong evidence for CV and cerebrovascular risk reduction, HF, and slowing of renal disease o Improves oxygenation to heart muscle, decreases inappropriate remodeling of heart muscle after MI or with HF, and reduces affects of DM on the kidneys o Also plays a role in the kinin-kallikrein-bradykinin system: ACEs facilitate the breakdown of bradykinin into inactive fragments thus reducing the actions of bradykinin (pain, extravascular smooth muscle contraction, increased vascular permeability, and increased leukocyte chemotaxis) o Reno-protective for individuals with proteinuria but is not as protective in renal patients without proteinuria  Improve insulin sensitivity  Decrease proteinuria in those with CKD and help with BP control  In earliest signs of diabetic nephropathy (microalbuminuria) lisinopril is recommended  Lisinopril reduces the progression of this complication independent of BP control  Adding an ACE inhibitor to patients with known CKD commonly results in increate crt  The improvement in proteinuria happens despite this effect  Because of this, it is acceptable to have up to a 30% increase in crt with d/c of ACE inhibitor  Although crt increases acutely, GFR improved long term  d/c should only be considered for patients with progression and/or significant deterioration in renal function for patients with hyperkalemia o Pharmacotherapeutics: o Contraindications: bilateral renal artery stenosis, angioedema, and pregnancy o Use with caution:  Impaired renal function especially in older adults, hypovolemic or hyponatremic states, hepatic impairment o Contraindicated in hyperkalemia: reduced aldosterone may worsen the imbalance  Risk increased with patients with HF r/t reduced blood flow to kidneys o Contraindicated in pregnancy r/t fetal renal abnormalities in the latter half of pregnancy and cardiac abnormalities in the first trimester o Adverse drug reactions (ADRs): o ADRs are usually transient, mild, and more common in longer acting agents o ADRs increase with higher doses o dry hacking cough, usually only last a week but is often cited as the reason for discontinuance  (bradykinin and substance P after the drug interrupts the RAAS: d/c drug and see if the patient improves)  More common in African Americans and Asian population  Class phenomenon: changing to a new generation ACE has been associated with less cough o hypotension (dizziness, HA, fatigue, orthostatic hypotension) o Tachyphylaxis frequently occurs with continued use o loss of taste o Angioedema (serious)  (can be life threating, occurs with the first dose or within the first month of therapy)  More common in African Americans and Asian population o Blood dyscrasias o teratogenicity o hyperkalemia o acute renal failure (serious) o cholestatic jaundice o pancreatitis o rash (switch drugs within the class) o neutropenia that increases with high does (more common in renal impairment and collagen disease) o Photosensitivity reactions (enalapril, quinapril, and ramipril) o Drug interactions o Additive hypotension with other antihypertensives, nitrates, phenothiazines, and ETOH ingestion o Due to interference with aldosterone secretion:  Concurrent use of K supplements, K-sparing diuretics, or cyclosporine may result in hyperkalemia o Antihypertensive response is reduced by NSAIDs r/t effect o Lithium: increased lithium levels and symptoms of toxicity o Digoxin: increase peak and trough concentrations o Clinical Use and Dosing HTN o Primary HTN (no identifiable cause, Tx depends on interfering with normal physiological mechanisms that regular BP o Young Caucasian patients, DM, HF, or MI: drug of choice ACEs and ARBs o Patients with angina: prevents formation of AT II and decreased pulmonary VR by decreasing retention of sodium and water reducing extracellular fluid and preload o Diabetic patients: prevents or slows nephropathy o Not as effective for African Americans however when combined with a diuretic, race no longer an issue o Doses vary for each drug o First dose may cause a steep drop in BP, especially in those taking diuretics  Diuretics should be stopped for 2 to 3 days to allow rehydration before staring an ACE, ARB, or DRI o All three drug classes increase in effectiveness when given with a diuretic  Reintroduce diuretics after monotherapy dose has been stabilized  Thiazide diuretics are an excellent combination (foster K loss)  Start low and go slow, increase the dose at 1 to 2 week intervals until BP is controlled Hypertensive Protein-uric Diabetes o Prevent diabetic nephropathy or slow its progression, ACE or ARB (DRI use off-label) Angina and Ischemic Heart Disease • An imbalance between myocardial oxygen supply (MOS) and myocardial oxygen demand (MOD) • ACE’s affect both the MOS and MOD o Prevent formation of AT II decreased PVR thereby MOD o Decreases the thickening of coronary artery wall results in increase MOS o Decreases the thickening of ventricular wall results in decreased MOD o Reduce ECF volume and preload • Recommended for all symptomatic patients with chronic stable angina o to prevent MI or death and to reduce symptoms • Also recommended to CAD patients who also have DM or LV dysfunction • ACCF/AHA recommend that ACEs be considered in CAD patients even without LV dysfunction • ACEs and ARBs are appropriate Tx options for stable CAD • DRIs are not mixed with ACEs or ARBS because r/f hyperkalemia Post-MI • Survivors of acute MI have a r/f subsequent morbidity and mortality • Combo of an ACE, a non ISA beta blocker, antiplatelet therapy, and lipid lowering therapy after MI is appropriate • ACE: reduced AT II after myocardial injury, prevention of ventricular remodeling in noninfarcted myocytes, alteration of ventricular mass, and positive hemodynamic effects on BP and fluid and electrolyte balance • ARBS: extremely effective here r/t effect on AT II and AT I receptors • Bradykinin has cardioprotective effects and a combination of an ACE and an ARB provides complete inhibition of AT II and increased levels of bradykinin • ACE (with or w/o ARB) should be started early after MI in stable high risk patients (anterior MI, previous MI, Killip class II) o Continue indefinitely for all patients with LV dysfunction (EF <40%) or symptoms of HF and use as needed to manage BP or symptoms in all other patients • Dosages usual for treating HTN are used unless HF is present • DRI: do not have post MI indication because they do not contribute to positive outcomes more than standard care Heart Failure (HF) • CAD is the underlying cause in 2/3 of patients with LV dysfunction o begins with injury to the myocardium and progresses • Principle mechanism r/t remodeling o ACEs and ARBs are useful in treating HF r/t CAD, for their role in reducing remodeling • Another underlying cause for HF is chronic HTN o ACEs and ARBs are effective in treating this cause • DRI: do not carry indication for HF • ACEs: cornerstone therapy for HF and are recommended for patients with Hx of atherosclerotic vascular disease, DM, or HTN o Improve symptoms, decrease morbidity, and increase life expectancy o Only drugs that address all the pathological mechanisms that produce HF, appropriate for all subsets of patients unless absolute contraindication • Useful in prevention: patients who have ventricular dysfunction but no overt symptoms o (prevent development of HF) • ACEs are superior to all other drugs and drug combinations used to treat HF o Start immediately w/o waiting for symptoms to become overt • For symptomatic HF, the dose is about half that used for HTN o Start low and go slow • In CHF and low EF: the vasodilating effect of ACEs provides adequate perfusion even with SBP <90 • For patients who cannot tolerate an ACE, hydralazine in combination with a long acting nitrate has been shown to be equally effective in reducing morbidity and mortality from HF o Especially noted in African Americans • Rational Drug Selection • Short-Acting versus Long-Acting o ADRs (angioedema and renal dysfunction) occur within the first few doses o Begin therapy with captopril (short acting) which allows for rapid assessment of patient response to the drug o Captopril requires frequent dosing r/t short half-life (adherence long term is less likely) o Other ACEs have once daily dosing therefore when patient tolerance is determined, convert to another agent to improve adherence o ARBs and DRIs also allow once daily dosing • Cost o Brand name ACEs and ARBs are expensive (order generic) o Combination drug formulations can reduce costs o DRIs are expensive brand names • Difficulty in swallowing o Ramipril (Altace) is a good choice o Capsule may be opened and sprinkled on applesauce, added to apple juice, or dissolved in 4 oz of water with no change in the effectiveness o Captopril may be crushed: sulfurous odor and requires frequent dosing o Monitoring: o Baseline BP and pulse before initiating therapy and with each change in dosage o Attain weight and other indicators of fluid balance and monitor o During therapy with ACEs, ARBs, and DRIs: monitor renal function  Crt before starting therapy, after the first week of therapy, monthly during the first 3 months, and when increasing the dose  ACE dose should be reduced if serum crt is more than 2.5 o Obtain K at baseline and with other lab suggested o For patients on ACEs or ARBs that require renal dose adjustment: assess urine protein prior to initiation, every 2 to 4 weeks for the first 3 months of therapy, and regularly for up to 1 year  Increased proteinuria indicates suggests reevaluation of therapy o For patients on ARBs no change is dosage is required based on renal impairment o Initial ARB doses may be lower for patients with impaired hepatic function  LFTs prior to therapy  Dose may be increased as tolerated o DRIs need renal and K monitoring o For ACEs: WBC with diff prior to therapy, monthly for the first 3 to 6 months, and periodically for up to 1 year  Patients ARF neutropenia: renal impairment, collagen vascular disease, high doses)  d/c therapy if neutrophil count <1,000 o Patient education: o Do not double doses if one is missed, o hypotension most common ADR: reduce risk for injury o cough common with older agents o Avoid salt substitutes: high in K ACEIs & ARBs benefits in other conditions • HTN, HF, HTN with protein uric DM, angina and ischemia heart disease, and post MI • Reno protective, slow rate of progression of renal disease • LVD/post-Mi, LVD (no symptoms) Chapter 28: Chronic Stable Angina & Low Risk Unstable Angina Differentiate between myocardial oxygen supply & demand o Ischemia caused by the imbalance between myocardial oxygen supply (MOS) and myocardial oxygen demand (MOD) produces pain referred to as angina. o Ischemia occurs when demand exceeds supply Etiology, diagnosis, and risk factors • CAD, myocardial ischemia, and MI form a pathophysiological continuum that impairs the hearts ability to pump by depriving it of sufficient oxygen and nutrients • Ischemia occurs when demand exceeds supply o The most common cause of CAD and resultant ischemia is atherosclerosis: narrow the lumen impede blood flow o Chronic stable angina (exertional angina) is caused by narrowing of the arterial lumen and hardening of the arterial walls so that the affected vessels cannot dilate in response to the increased MOD associated with physical exertion or emotional stress o Risk factors for CAD are age, family Hx, smoking, HTN, hypercholesterolemia, low HDL, and DM o These risk factors are used in the Framingham equations for calculating the 10-year risk for CAD o Conditions that increase MOD and decrease MOS are also major risk factors  HF, anemia, HTN, hyperthyroidism, valvular heart disease, and morbid obesity o There are also noncardiac disorders that mimic angina because their primary symptom is chest pain.  pulmonary embolism, pneumonia, pneumothorax, gastroesophageal spasm or reflux, cholecystitis, peptic ulcer, pancreatitis, rib fractures, herpes zoster, and panic disorder.  Some of these disorders also decrease oxygen supply and can cause angina. o Women often have symptoms of angina that are atypical and may include fatigue, shortness of breath without chest pain, nausea and vomiting, back pain, jaw pain, dizziness, and weakness o Diagnosis o Initial Assessment: ECG, fasting lipids, CXR, CBC, test for DM, thyroid function, and renal function o Hx including questions about symptoms and when they occur related to exercise, smoking, physical exam, lab testing, and a resting 12 lead ECG o For abnormal ECG findings: referral to or consultation with a cardiologist is recommended Grading criteria for levels of angina o The lower the class, the more likely the patient's angina can be controlled by lifestyle modification and NTG o The higher the class, the more likely the patient will require multiple drug therapy. o The ACC/AHA guidelines have a classification system that incorporates the NYHA/CCS system and additional data. o Class I Proven coronary artery disease without symptoms o Ordinary physical activity, such as walking or climbing stairs, does not cause angina. Angina occurs with strenuous, rapid, or prolonged exertion at work or recreation. o Class II: Mild symptoms: angina and slight limitation during ordinary activity Angina only with unusually strenuous physical exertion o Slight limitation of ordinary activity. Angina occurs on walking or climbing stairs rapidly; walking uphill; walking or stair climbing after meals; in cold wind; under emotional stress; or only during the few hours after awakening. Walking more than two blocks on the level and climbing more than one flight of ordinary stairs at a normal pace and in normal conditions does not cause angina. o Class III: Angina during routine physical activity o Marked limitations of ordinary activity. Angina occurs on walking one to two blocks on the level and climbing one flight of stairs in normal conditions and at a normal pace. o Class IV: Angina during minimal activity or rest o Severe limitations: angina during minimal activity or rest. Angina during minimal activity or rest Chapter 39: Hyperlipidemia Etiology: • Obesity epidemic, uncontrolled hypertension, metabolic syndromes, and rampant consumption of nutritionally risky diets combined with high stress and lack of regular exercise are all components of the problem. • Atherosclerosis is deposits of cholesterol and lipoproteins in artery wall • Three major classes: LDL, HDL, and VLDL o Identifying risk for CAD and CBD focused on serum cholesterol above 200, fasting TG greater than 150, and LDL greater than 100 o Newest guidelines place stronger emphasis upon individual risk factors with lifestyle and pharmacological therapies individualized to reduce that risk • Lipoproteins are formed via two pathways: o Dietary or exogenous: fat and cholesterol absorbed by intestinal cells  Pharmacotherapy focuses on the pathway in which fats are absorbed, transported, and metabolized  Bile acid-binding resins: affect absorption of fat and cholesterol in the intestine  Fibric acid derivates: increase lipolysis of TG  Lifestyle modifications also affect absorption, transport, and metabolism of fats o Liver synthesis or endogenous  VLDLs are synthesized and secreted by the liver and contain TG and some cholesterol  VLDLs can become LDLs  LDL receptors in the liver are downregulated by the presence of LDL  Bile acid binding resins, statins: increases the number of LDL receptors in the liver  Niacin, fibric acid derivates: inhibit VLDL synthesis in the liver • Atherogenesis: • First step: When LDL levels exceed 100 mg/dL they cross the arterial wall, become embedded in lumen o In the lumen, undergo oxidation, taken up by macrophages, and form a plaque (fatty streak) o Atherosclerotic plaques are made up of foam cells, transformed macrophages and smooth muscle cells filled with cholesterol o HDL suppresses foam cell production (anti-inflammatory response) • Second step: o Formation of scar tissue over the fatty plaque (called a fibrous plaque) o Over time fibrous plaques become unstable and prone to rupture (leads to thrombosis) o Plaque rupture or erosion is reason for most acute coronary events Diagnosis: • Guidelines for identifying risk for CAD and CVD have traditionally focused on… • Cholesterol levels above 200 mg/dL • Fasting TG levels above 150 mg/dL • LDL levels above 100 mg/dL. Goal is 70 for those at high risk for CVD and CAD • Inflammatory marker: CRP (>2) Chapter 39: Hypertension Etiology • HTN is the most common CVD in the US, and it is also a problem worldwide • Systemic arterial pressure is a function of stroke volume, heart rate, and total peripheral resistance • Alterations in any of these factors result in changes in blood pressure. • The major organs involved in regulation of blood pressure are the heart (heart rate [HR] and stroke volume [SV]), the SNS, total peripheral resistance (TPR), and the kidney (EFV and secretion of renin) • Diminished responsiveness of baroreceptors: in the presence of long-standing HTN, baroreceptors adapt to the elevated BP levels and “reset” what the body accepts as “normal” BP. • This is one of the most significant cardiovascular effects of aging and a major factor in the lifetime risk of HTN. • Endothelial factors: vascular endothelium can produce vasoactive substances and growth factors • Nitric oxide (NO): relaxation, Endothelin: potent vasoconstrictor and vascular smooth muscle growth • Kidneys: regulate via RAAS, increases extracellular fluid and vasoconstricting via Angiotensin II • Genetic influences: BP is strongly familial, and studies of rare genetic disorders affecting BP have led to the identification of genetic abnormalities Diagnosis • Confirmation of a diagnosis of HTN is based on BP elevation documented at three different times. • Standard measurement techniques, including out-of-office or home BP measurements, can be used • Children over 3 years of age who are seen in a medical setting should have their BP measured once/yr o Preferred method is auscultation • The recommended tests are used for therapeutic decision making and baseline values for determination of progression or stabilization of the systemic impact of HTN: o A 12-lead ECG. o UA, including urinary albumin or albumin/creatinine ratio.  For those patients with diabetes or renal disease, the latter test of albumin should also be done annually.  The presence of albuminuria, including microalbuminuria, even with normal (GFR), is associated with increased cardiovascular risk. o Blood glucose and hematocrit. o Serum potassium. o Creatinine and the corresponding estimated GFR.  There is a strong relationship between decreased GFR and increases in CV morbidity and mortality o Serum calcium. o Lipid profile.