PHARMACOLOGY OF THE

CARDIOVASCULAR SYSTEM
DRUGS FOR ANGINA, MI & CVA
Kirsten Culver,
PhD
Science Lead
BScN Program
 ATHEROSCLEROSIS
 When the arterial blood supply is compromised due to narrowing,
cardiovascular and cerebrovascular functioning becomes impaired
 Heart, brain and other organs are deprived of oxygen and nutrients
 Angina pectoris
coronary artery disease
 Acute myocardial infarction
 Cerebrovascular accident
 Atherosclerosis; presence of plaque within arterial walls
 Plaque: accumulation of fatty, fibrous material that narrows arteries,
increases TPR, and reduces vascular elasticity
 ATHEROSCLEROSIS
 Endothelial injury and inflammation stimulates:
 Migration of immune cells (e.g., monocytes) to the site of injury (tunica
intima)
 Loosening of tight junctions between endothelial cells (now permeable to
LDL)
 Monocytes differentiate into macrophages once inside the intima
 Macrophages, nitrous oxide & lipoxygenase oxidize LDL
 Macrophages engulf oxidized LDL by phagocytosis and become “foam cells”
 Cells rupture, causing inflammation and recruitment of more immune cells to
site of injury
 T-lymphocytes secrete cytokines - inducing smooth muscle migration;
ATHEROSCLEROSIS
 ANGINA PECTORIS
 Acute chest pain arising from inadequate oxygen supply to the
myocardium (lactic acid accumulation)
 Characterized by a steady, intense pain that is sometimes accompanied
by a crushing/constricting sensation
 Pain typically radiates across the left shoulder and down the left arm,
but can move up to the jaw, or across to the thoracic region of the back;
can also be experienced in the mid-epigastric or abdominal area
 Panic, pallor, dyspnea, diaphoresis, tachycardia and elevated blood
pressure are also common
 ANGINA PECTORIS
 Onset typically associated with physical exertion or emotional excitement
 Increased oxygen demand
 Symptoms improve with rest, stress reduction and nitroglycerin
 Episode lasts approximately 10 – 15 minutes after rest
 Stable angina
 Predictable frequency, duration and intensity, no associated myocardial
damage; relief with rest
 Unstable angina
 Variable intensity, occurs during periods of rest, increased frequency, no
associated myocardial damage
 Associated with an increased risk of MI
 NON-PHARMACOLOGICAL
MANAGEMENT OF STABLE ANGINA
PECTORIS
Client should understand the causes of angina, identify the conditions and
situations that trigger it, and develop motivation to modify behaviors linked to the
disease
 Abstain from alcohol, or limit alcohol intake to less than 2 drinks/day
 Eliminate foods high in cholesterol, saturated fats and sodium
 Control hyperlipidemia
 Control hypertension
 Regular exercise & maintenance of optimal weight
 Control blood glucose levels
 Abstain from using tobacco products
Healthy lifestyle habits can prevent CAD and slow the progression in those with
atherosclerosis
 PHARMACOLOGICAL MANAGEMENT
OF STABLE ANGINA PECTORIS
Therapeutic Goals
 Reduce the intensity and frequency of attacks
 Extend lifespan by preventing heart failure, MI and dysrhythmias
 Terminate an attack once it begins
 Drug therapies reduce myocardial oxygen demand or improve oxygen supply
to the myocardium
 Slow heart rate
 Reduce force of cardiac contraction
 Dilate veins (reduce volume of blood sent to heart; preload)
 Dilate arterioles (reduce TPR; afterload)
 Nitrates, beta-blockers & calcium channel blockers
PHARMACOLOGICAL MANAGEMENT
OF STABLE ANGINA PECTORIS
 ANGINA PECTORIS - NITRATES
First line therapy for terminating an angina attack
Facilitate the formation of nitric acid; a potent vasodilator for vascular smooth
muscle
 Relax coronary arteries and venous smooth muscle
 Dilation of venous smooth muscle
 Decreases amount of blood returning to the heart (preload)
 Decreases cardiac output, workload and oxygen demand
 Risk of hypotension
 Dilation of arterial smooth muscle
 Increases blood flow to myocardium Greater effect on healthy coronary arteries
 Improves oxygen supply to myocardium
 ANGINA PECTORIS - NITRATES
Short-acting, sublingual route (tablet & spray) e.g., Nitroglycerin
 Used to terminate an angina attack (or just prior to physical activity)
 Protocol; rest, take drug & wait 5 min. If no improvement, take another dose &
wait 5 min to a maximum of 3 doses in 15 min. If symptoms persist, seek
medical attention
Long-acting, oral & transdermal routes e.g., Isosorbide dinitrate
 Decreases intensity and frequency of angina attacks; no longer a first line
therapy for preventing angina; does not reduce morality in clients with CAD
 Remove patch for 16-12 hrs/day or withhold nighttime oral dose to delay
tolerance, slow withdrawal from medication to prevent risk of MI
 ANGINA PECTORIS - NITRATES
 Short-acting nitroglycerin also available in PO, IV, topical and extended-
release forms
 Adverse effects; related to vasodilation and decrease in blood flow
 Throbbing headache, dizziness, hypotension, reflex tachycardia
 Caution in those with hypotension, hypovolemia, and pre-existing conditions
that limit cardiac output
 Drug interactions; alcohol (vasodilation), drugs for the treatment of erectile
dysfunction (phosphodiesterase-5 inhibitors e.g., sildenafil/Viagra) may
cause life-threatening hypotension
 ANGINA PECTORIS
BETA ADRENERGIC ANTAGONISTS
 First line therapy for prevention of chronic stable angina
 Reduces cardiac workload; slows heart rate & reduces contractility;
ultimately decreasing oxygen demand
 Ideal for clients with hypertension & CAD; reduces risk of MI
 Used to decrease frequency & intensity of angina attacks; no tolerance risk
 Use with caution in those with asthma, COPD (use beta 1 -selective
antagonists), depression & diabetes
 Adverse effects; related to SANS blockade
 Fatigue, weakness, bradycardia (activity intolerance), hypotension, sleep
disturbances; rapid withdrawal worsens angina - reduce dose over 1-2 weeks
 ANGINA PECTORIS
CALCIUM CHANNEL BLOCKERS
 Used for the prevention of chronic stable angina in clients who cannot
tolerate beta-blockers
 Decrease myocardial oxygen demand
 Relax arteriolar smooth muscle lowering blood pressure; decreasing afterload
 Decrease heart rate (non-selective CCBs only)
 Increase myocardial oxygen supply; dilate coronary arteries
 Adverse effects related to effects on cardiac output and vascular smooth muscle;
dizziness, light-headedness, fatigue, bradycardia, flushing, nausea
 Monitor for hypotension and reflex tachycardia
 Avoid grapefruit juice; increases serum CCB levels
 ACUTE CORONARY SYNDROMES
 Unstable angina occurs when the atherosclerotic plaque is disrupted,
exposing the injured endothelium to platelet and coagulation factors
 Results in transient occlusion of the affected the vessel
 MI occurs when coronary artery is completely ischemic…
 Myocytes begin to die in ~20 minutes, unless blood supply is restored
 Necrotized tissues release enzyme markers of tissue injury (troponin) which
can be used to confirm MI vs unstable angina
 MYOCARDIAL INFARCTION
Result of advanced coronary artery disease
 Plaque rupture and hemorrhage; exposed plaque activates coagulation cascade;
additional clots develop; occluding coronary artery leading to myocardial ischemia
and necrosis
 Pieces of unstable plaque break away and block small vessels that supply parts of
the myocardium
Goals of therapy
 Reduce myocardial oxygen demand
 Restore blood supply to the damaged myocardium
 Control dysrhythmias
 Reduce post-MI mortality with antiplatelet drugs, anti-coagulant therapy, statins
 Control pain with analgesics
 PHARMACOLOGICAL MANAGEMENT
OF MI
1. Restore blood supply to the damaged myocardium
 Thrombolytics (within 12 hrs of onset; ideally 30 min) and/or surgery
2. Reduce myocardial oxygen demand
 Nitrates, beta-blockers, ACE inhibitors to prevent further infarction
3. Control or prevent MI-associated dysrhythmias
 Beta-blockers slow impulse conduction, suppressing dysrhythmias
4. Reduce post-MI mortality
 Aspirin, beta-blockers, ACE inhibitors and statins
5. Manage severe pain and anxiety with analgesics
 Opiates
6. Prevent enlargement of the thrombus
 Anticoagulant and antiplatelet drugs
 CEREBROVASCULAR ACCIDENT (CVA)
Stroke
 80% thrombotic strokes, 20% hemorrhagic strokes
 Same risk factors as hypertension and coronary artery disease
 Signs and symptoms dependent on brain areas affected
Warning signs of stroke
1. Paralysis (weakness) on one side
2. Vision problems
3. Dizziness
4. Speech problems
5. Headache
 PHARMACOLOGICAL MANAGEMENT
OF CVA
Thrombotic CVA
 Prevention
 Lifestyle management
 Antihypertensive drugs
 Antiplatelet therapy
 Anticoagulant therapy
 Treatment
 Thrombolytics
 Administration within 3 hours of brain attack can completely restore
function in affected brain areas