NR566 Chapter 16 Complete Study Guide

CHAPTER 16: Drugs Affecting the Cardiovascular & Renal Systems

ANGIOTENSIN CONVERTING ENZYME INHIBITORS (ACEI)
 “-pril”
 Captopril (Capoten), enalapril (Vasotec), quinapril (Accupril), ramipril (Altace), lisinopril (Prinivil),
benazepril (Lotensin)

 Pharmacodynamics
o Inhibition of ACE activity results in decreased production of both angiotensin II and
aldosterone:
 Decreased vasomotor tone
 Smooth muscle relaxation
 Decreased aldosterone -> decreased Na/H 2O retention -> decreased bld volume
 Decreased BP
o Facilitates the breakdown of bradykinin into inactive fragments, reducing action ->
decreased extravascular smooth muscle relaxation.
o Reno-protective for individuals with proteinuria but is not as protective in renal patients
without proteinuria.

 Pharmacotherapeutics
o CONTRAINDICATIONS:
 Bilateral renal artery stenosis- vasodilating effect of this drug causes
inadequate perfusion that can lead to ischemic renal failure
 Angioedema
 Pregnancy
 Hyperkalemia
o CAUTIOUS USE:
 Impaired renal function
 Older adults
 Hypovolemic/hyponatremic states
 Hepatic impairment

 Clinical Use
o Hypertension
o Hypertensive proteinuric diabetes- to prevent diabetic nephropathy
o Angina and Ischemic heart disease (ACEI recommended for all symptomatic patients
with chronic stable angina to prevent MI or death and to reduce symptoms)
o Post MI
o Heart Failure (ACEIs are a cornerstone of HF therapy, and are recommended for patients
with hx of DM, atherosclerotic vascular disease, or HTN)

 Drug Interactions
o Cimetidine: increases levels of free drug
o Additive hypotensive effects: diuretics, nitrates, phenothiazines, acute ETOH ingestion
o Hyperkalemia: potassium supplements, potassium-sparing diuretics, cyclosporine
o Increased lithium levels and symptoms of toxicity
o NSAIDS: reduced antihypertensive effects

,  Adverse Drug Reactions
o Angioedema (related to increased bradykinin association with inhibition of ACE): 3- to -
4- fold higher risk among African Americans
o Cough – common (common reason of discontinuance of the drug); common among
white population
 Dry, hacking
 Usually occurs in the first week of therapy
o Hypotension
o Headache
o Fatigue
o Orthostatic hypotension
o Less common: rash (captopril), neutropenia (high doses), renal impairment,
concomitant collagen diseases
o Photosensitivity (enalapril, quinapril, ramipril)

ANGIOTENSIN RECEPTOR BLOCKERS (ARB)
 “-sartan”
 Losartan (Cozaar), telmisartan (Micardis), candesartan (Atacand), valsartan (Diovan), Olmesartan
(Benicar)

 Pharmacodynamics
o Blocks the AT II receptor that leads to:
 CNS- decreased vasopressin -> vasodilation
 Decreased aldosterone -> decreased Na/H 2O retention -> decreased bld volume
 Smooth muscle relaxation
 Decreased BP

 Pharmacotherapeutics
o CONTRAINDICATIONS:
 Bilateral renal artery stenosis- vasodilating effect of this drug causes
inadequate perfusion that can lead to ischemic renal failure
 Angioedema
 Pregnancy
 Hyperkalemia
o CAUTIOUS USE:
 Impaired renal function
 Older adults
 Hypovolemic/hyponatremic states
 Hepatic impairment

 Clinical Use
o Hypertension
o Hypertensive proteinuric diabetes- to prevent diabetic nephropathy
o Post MI

 Drug Interactions

, o CYP450 A34 and 2C9 lowers the levels of losartan and irebesartan.
o Cimetidine: increases levels of free drug
o Additive hypotensive effects: diuretics, nitrates, phenothiazines, acute ETOH ingestion
o Hyperkalemia: potassium supplements, potassium-sparing diuretics, cyclosporine
o Antacids: increases digoxin or lithium toxicity; decreased absorption of ACEI
o NSAIDS: reduced antihypertensive effects

 Adverse Drug Reactions
o Hypotension
o Headache
o Fatigue
o Orthostatic hypotension
o Photosensitivity (valsartan)


CALCIUM CHANNEL BLOCKERS (CCB)
 Dihydropyridines
o “- pine”
o Amlodipine (not recommended for children <6yo), felodipine, nifedipine, isradepine,
nicardipine
 Type 1 CCB
o Diltiazem, verapamil (also Class IV antiarrhythmic drugs)
 FIRST LINE for African Americans with HTN (also thiazide-type diurectics)

 Pharmacodynamics
o Directly block the Ca++ influx -> decreased transmembrane Ca++ content -> prolonged
vascular smooth muscle relaxation
o Relaxes arterial smooth muscles (but have little effect on venous beds) -> reduced
afterload (but limited effect on cardiac preload)
o Reduces cardiac muscle contractility (negative inotropism) and decreases SA and AV
nodal conduction velocity.
 Nifedipine (Adalat, Procardia): do not affect the rate of Ca++ channel recovery
on nodal conduction (no effect on AV conduction)
 Verapamil (Calan, Isoptin): affects openings of Ca++ channels, also decreases the
rate of recovery -> depression of SA node firing and slowing AV nodal
conduction

 Pharmacotherapeutics
o CONTRAINIDCATIONS:
 Verapamil: has the strongest negative inotropic effect and SHOULD BE AVOIDED
in HF, bradycardia, and AV block.
 Type 1 CCB: early post MI, ventricular dysfunction, SA or AV nodal conduction
disturbances, SBPs <90
 Dihydropyridines: significant peripheral edema, unstable angina

o CAUTIOUS USE:
 Severe hepatic impairment