NR 566 Week 3 Study Guide {2020} | Chapter 16: Drugs Affecting the Cardiovascular & Renal Systems Angiotensin converting enzyme inhibitors (ACEI or ACE Inhibitors)

NR 566 Week 3 Study Guide {2020} – Chamberlain College of Nursing NR566 Week 3 Study Outline 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) Management of ACEI side effects • Angioedema: r/t increased bradykinin level must d/c o Start on captopril a short acting ACE to assess tolerance then switch to a long acting agent • ADRs are usually transient, mild and more common in longer acting agents o Taste changes usually disappear in 8 to 12 weeks • Most common: dizziness, HA, fatigue, orthostatic hypotension o Change positions slowly, not exercising in hot weather, and keeping fluid intake at more than 2 L/day • Tachyphylaxis • Dry, hacking cough: class phenomenon: changing to a newer generation ACE or change to an ARB • ACE: rash common with captopril and neutropenia that increases with high doses, renal impairment, and concomitant collagen diseases - - - - - - - - - - -- -- - - - - - - - - - - - - - - - - - - - - - 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. • Elevated levels of high-sensitivity CRP, homocysteine, and heart rate may also be considered in patients with (CVD) but without other risk factors. Risk factors o Positive relationship between HTN and CV risk o Each additional risk factor is assumed to compound the risk from HTN o TC, HDL level, smoking , DM, and LVH o Age, race, family Hx, overweight or obese, lack of physical activity, tobacco use, too much dietary sodium, too little potassium, ETOH use o Modifiable and unmodifiable risk factors o Primary HTN has not identifiable cause Clinical findings, Treatment, and rationale drug selection • Normal: 120/80 encourage lifestyle modification no drugs, • Prehypertension: 120-139/80-89 lifestyle modification, no antihypertensive but for compelling indication • Stage 1: 140-159/90-99: lifestyle thiazide type diuretic for most (ACEI, ARB, CCB, or combo) • Stage 2: 160/ 100 lifestyle, two drug combo for most, (thiazide type and ACEI or ARB, or BB, or CCB) • Diuretics lower BP by depleting the body of sodium and reducing extracellular fluid volume Agents that act in the renin-angiotensin-aldosterone system (RAAS) reduce pressure by decreasing sodium and water retention (aldosterone action), by decreasing vasoconstriction (angiotensin direct action), and by increasing vasodilation (bradykinin action). • Adrenergic blockers and other drugs acting on the SNS lower blood pressure by reducing peripheral vascular resistance, inhibiting cardiac contractility, and increasing venous pooling in capacitance vessels. • Calcium channel blockers act as vasodilators to reduce pressure by relaxing vascular smooth muscle, thereby dilating resistance vessels and increasing the area over which blood must flow, and through their negative inotropic activity to reduce cardiac output. • Direct vasodilators produce the same effect as the calcium channel blockers on vascular smooth muscle • Centrally acting agents produce vasodilation mainly through reduction in norepinephrine • Angiotensin-converting enzyme (ACE) inhibitors, for example, are drugs of choice in diabetes mellitus, heart failure, and myocardial infarction (MI) Antihypertensives contraindicated in pregnancy • ACE inhibitors and ARBs should not be prescribed for pregnant or sexually active girls because of their teratogenic effects. o ACE inhibitors, ARBs, and DRI should never be used in pregnancy. • Methyldopa has been studied the most and is typically recommended for women whose chronic hypertension is first diagnosed in pregnancy. • Beta-adrenergic blockers are equally effective and are safe during the second and third trimesters, but their use in the first trimester has been associated with growth retardation in the fetus. • Labetalol is equally effective as methyldopa and has fewer side effects. • If the hypertension is diagnosed before the pregnancy, diuretics and some antihypertensives may be continued Preferred antihypertensives for blacks • JNC-8 guidelines state that in the general black population initial antiHTN Tx should include a thiazide-type diuretic or CCB • In African Americans, calcium channel blockers are suggested as first line BP therapy in lieu of the ACE family due to a common lower renin response in this ethnic group Antihypertensive step therapy recommendations and monitoring • Initial drug choices are based on the presence or absence of compelling indications from concurrent disease processes o Set an appropriate BP goal o Be patient and work on attaining the BP goal over many weeks to months o Titrate BP medications no more often than every 4 to 6 weeks o Do not automatically assume symptoms reported are caused by the drug: what may appear to be an ADR may be something different o Plan for the use of more than one drug o Do not ignore ISH in the elderly: treat to goal SBP in older adults even if DBP is normal o ECFV may need to be controlled: diuretic • Initial drug therapy: low doses of thiazide diuretic or ACE • Stepping up to multiple drugs: o 1) max out first drug (risk for ADRs), 2) adding another drug, or 30 substitution  Adding a second drug is a better choice: synergistic effect o Always check for compliance at this point r/t pseudo resistance o Add a second drug from a different class: ACE and diuretic or diuretic and ACE • Stepping down: o After it has been controlled for at least 1 year, a decrease in the dosage and number of antihypertensive drugs may be considered. o The reduction should be deliberate, slow, and progressive and accompanied by vigilant BP monitoring. o Step-down therapy is often successful for patients who also are making lifestyle modifications. JNC 8 hypertension guidelines • Over 60 150/ 90 • Less than 60 140/90 • Greater than 18 (CKD, DM) 140/90 • Lifestyle modifications: DASH, exercise, weight reduction, quit smoking • Medications: • First line: o Thiazide diuretics (excretion of sodium and water) o ACE Inhibitors: RAAS system, decrease vasoconstriction, reduce sodium and water retention o CCB: relax blood vessels, reduces resistance o Angiotensin II Receptor Blockers: Same effect as ACE but block receptors for Angiotensin II • Second line: o Aldosterone receptor blockers ARBs (block aldosterone receptor sites) o Renin inhibitors (inhibit renin, prevents formation of aldosterone and angiotensin o Alpha-adrenergic blockers o Central adrenergic inhibitors Preferred class for initial drug therapy in hypertension treatment : Thiazides diuretics or ACEs Added benefits of beta blocker therapy for hypertension o Reduce both MOD and MOS Contraindications for beta blockers o There is increased risk of cardiogenic shock and HF with beta blockers o Can affect the lungs avoid in patients with lung disease (bronchoconstriction) o Use with caution in patients with DM: beta receptors are located in the pancreas and can cause problems for those who are prone to blood glucose imbalances Precautions and education for beta blockers • not first line therapy b/c they r weak when it comes to stroke prevention • BBs can mask the s/s of hypoglycemia (except diaphoresis): teach patient to check glucose if sweating occurs • Contraindicated for patients with respiratory conditions that include a bronchospastic component and patients with AV block. • Close monitoring of cardiac and renal status is required, not first line therapy in older adults • May precipitate or exacerbate type 2 DM-use cautiously, effects carbohydrate metabolism and mask s/s of hypoglycemia • Help patients with hyperthyroidism (increased beta adrenergic activity)-relieves palpitations, tachycardia, tremors, anxiety, and heat intolerance. Recommended for use in this population unless contraindicated. • Pregnancy category of BBs varies • Atenolol cat D • Betaxolol, acebutolol, metoprolol, nadolol, nebivolol, timolol, and propranolol Cat C • All cross placenta and can cause fetal or neonatal bradycardia, hypotension, hypoglycemia, or resp depression. Controversial during pregnancy • Sotalol and pindolol Preg Cat B-however reduced birth weight, decreased bp, and decreased HR at birth has been found. • Propranolol and metoprolol excreted in breast milk-use with caution. Use with caution • Atenolol and metoprolol better tolerated in children-Extended release found to be effective in this population.