NR566 Week 3 Study Guide

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