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Shine Stephen

Angina Pectoris
Most common condition involving tissue

ischemia ISCHEMIA Chest pain caused by accumulation of metabolites resulting from myocardial ischemia Strangling or pressure-like pain caused by myocardial ischemia

Angina Pectoris
Located substernally but sometimes perceived in the neck, shoulder or epigastrium Primarily caused by imbalance between the oxygen requirement of the heart and oxygen supplied to it by the coronary vessels

Determinants of Oxygen
DIASTOLIC FACTOR Blood volume Venous tone SYSTOLIC FACTOR Peripheral resistance Heart rate Ejection time

INTRAMYOCARDIAL FIBER TENSION Myocardial Oxygen requirement

Pathophysiology of Angina
Variables that contribute to muscle tension

1. PRELOAD (diastolic filling pressure) 2. AFTERLOAD (arterial blood pressure) 3. HEART RATE double product 4. CARDIAC CONTRACTILITY ejection time (relationship to oxygen requirement and force of contraction)

Types of Angina
1. Atherosclerotic angina Angina of effort or Classic angina Associated with atheromatous plaques that partially occlude one or more of the coronaries Constitutes 90% of cases Rest leads to relief of pain in 5-15 minutes

Types of Angina
2. Vasospastic angina Rest angina, Variant angina or Prinzmetals angina Involves reversible spasm of coronaries, usually at the site of an atherosclerotic plaque Spasm may occur anytime, even during sleep May deteriorate to unstable angina

Types of Angina
3. Unstable angina Crescendo angina, Acute coronary syndrome Increased frequency and severity of attacks that result from atherosclerotic plaques, platelet aggregation at fractured plaques and vasospasm Immediate precursor of myocardial infarction (MI) Medical emergency

Pathophysiology of Angina
C. Therapeutic strategies
The defect that causes anginal pain is inadequate

O2 delivery relative to myocardial oxygen requirement Can be corrected in 2 ways

1. Increasing O2 delivery 2. Reducing O2 requirement 3. Efficiency of O2 utilization

Pathophysiology of Angina
Newer investigational approach Shifting the energy substrate

reference of the heart from fatty acid to glucose Partial fatty acid oxidation inhibitors (Eg, Ranolazine, Trimetazidine)


NITRATES NITROGLYCERINE (NTG) Active ingredient in dynamite Most important of the nitrates Available forms
Sublingual (10-20 min) Transdermal (8-10 h)

Effect of sublingual NTG results from unchanged

drug because it avoids first-pass effect

Rapidly denitrated in the liver and smooth

muscle Nitroglycerin (Glyceryl) Dinitrate Mononitrate First-pass effect is 90% (because of high enzyme activity in the liver) Efficacy of oral (swallowed) NTG results from high levels of glyceryl dinitrate (which have a significant vasodilating effect)

MECHANISM OF ACTION Denitration causes release of nitric oxide (NO) within smooth muscle cells which stimulates guanyl cyclase and causes an increase in cGMP leading to smooth muscle relaxation

ISOSORBIDE DINITRATE Another commonly used nitrate Available in sublingual and oral form Rapidly denitrated in the liver and smooth muscle to isosorbide mononitrate which is also active

ISOSORBIDE MONONITRATE Available as a separate drug Oral form AMYL NITRITE Volatile and rapidly acting vasodilator Inhalational route Rarely prescribed


1. Cardiovascular System
Smooth muscle relaxation

peripheral venodilation reduced cardiac size and CO through reduced preload Reduced afterload because of arteriolar dilation increase in ejection and further decrease in cardiac size Sensitivity veins >> arteries > arterioles

decreased diastolic heart size and fiber tension

Arteriolar dilation
reduced peripheral resistance and BP

Overall reduction in myocardial fiber tension,

O2 consumption and double product No direct effects on the cardiac muscle Can cause reflex tachycardia and increased force of contraction when reducing BP

2. Other smooth muscle effect
Relaxation of the smooth muscle of the

bronchi, GIT, GUT Effects are too small to be clinically significant 3. Action on platelets Decrease platelet aggregation 4. Nitrite ion + hemoglobin methemoglobin Methemoglobin has low affinity for oxygen Pseudocyanosis, tissue hypoxia, death

D. CLINICAL USES Sublingual tablet Standard form for treatment of acute anginal pain Duration of action 10-30 minutes Oral (Swallowed) Normal-release Duration of action 4-6 hours Sustained-release Longer duration

Transdermal formulations Ointment or patch Maintains blood level up to 24 hours Tolerance develops after 8-10 hours with rapidly diminishing effectiveness Remove after 10-12 hours to allow recovery of sensitivity to the drug

Toxicities Tachycardia (baroreceptor reflex) Orthostatic hypotension Throbbing headache (from meningeal artery vasodilatation) Interact with Sildenafil (Viagra) and similar drugs promoted for erectile dysfunction Synergistic relaxation of vascular smooth muscle with potentially dangerous hypotension and hypoperfusion of critical

Monday disease
Contamination of nitrates in the workplace Alternating development of tolerance (during work

week) and loss of tolerance (over the weekend) for the vasodilating action Headache, tachycardia, dizziness Occurs every Monday Nitrites cause methemoglobinemia at high blood concentration, therefore potential antidote for cyanide poisoning


Prophylactic therapy in effort and vasospastic angina

Nifedipine has also been used to abort acute anginal attacks

Combined with nitrates in the treatment of

atherosclerotic angina Migraine Preterm labor Stroke Raynauds phenomenon Nimodipine is used for hemorrhagic stroke


TOXICITY Constipation, pretibial edema, nausea flushing and dizziness Heart failure, AV blockade and sinus node depression (Verapamil) Torsade de pointes (Bepridil)


Nifedipine, Dihydropyridine, Diltiazem, Verapamil
Differ markedly in structure but all are orally active with

half-lives of 3-6 hours

Member of the dihydropyridine family

Approved only for the treatment of stroke associated

with subarachnoid hemorrhage

Similar structure to verapamil, Longer duration of action,

Greater cardiovascular toxicity


MECHANISM OF ACTION Block voltage-gated L-type calcium channels (channel most important in cardiac and smooth muscle) Reduce intracellular calcium concentration and muscle contractility Mibefradil
Blocks cardiac T-type and L-type channels


EFFECTS Relax blood vessels, and to a lesser extent, the uterus, bronchi and the gut Diltiazem and Verapamil
Reduce cardiac rate and contractility (block Ca-

dependent conduction in the AV node of the heart) May be used to treat AV nodal arrythmia

Nifedipine and other dihydropyridines Evoke greater vasodilation

The resulting sympathetic reflex prevents bradycardia and increases heart rate


Prophylaxis of atherosclerotic anginal attacks Reduce the double product

Beneficial effects
Decreased heart rate Decreased cardiac force Decreased BP

Detrimental effects
Increased heart size Longer ejection period


CLINICAL USE Only for prophylactic therapy No value for acute attacks Prevents exercise-induced angina but not the

vasospastic form Combination with nitrates reduces the undesirable compensatory effects like tachycardia and increased cardiac force


NONPHARMACOLOGIC THERAPY Myocardial revascularization Coronary artery bypass grafting (CABG) Percutanous transluminal coronary angioplasty (PTCA) Increase coronary flow in atherosclerotic angina

Nursing Responsibilities
Check blood pressure and heart rate before each dose of an antianginal drug. Withhold the drug if systolic blood pressure is below 90

mm Hg. If the dose is omitted, record and report to the health care provider. Give antianginal drugs on a regular schedule, at evenly spaced intervals. If oral nitrates and topical nitroglycerin are being used concurrently, stagger times of administration.

For sublingual nitroglycerin and isosorbide dinitrate, instruct the client to place the tablets under the tongue until they dissolve. For oral isosorbide dinitrate, regular and chewable tablets are available. Be sure each type of tablet is taken appropriately. For sublingual nitroglycerin, check expiration date on the container.


To apply nitroglycerin ointment, use the

special paper to measure the dose. Place the ointment on a nonhairy part of the body, and apply with the applicator paper. Cover the area withplastic wrap or tape. Rotate application sites and wipe off previous ointment before applying a new dose. For nitroglycerin patches, apply at the same time each day to clean, dry, hairless areas on the upper body or arms. Rotate sites. Avoid applying below the knee or elbow or in areas of skin irritation or scar tissue.

For intravenous (IV) nitroglycerin, dilute the drug and give by continuous infusion, with frequent monitoring of blood pressure and

heart rate. Use only with the special administration set supplied by the manufacturer to avoid drug adsorption onto tubing. With IV verapamil, inject slowly, over 23 min.

Observe for therapeutic effects

Relief of chest pain with acute attacks
Reduced incidence and severity of acute

attacks with prophylactic antianginal drugs Increased exercise tolerance

Observe for adverse effects

With nitrates, observe for hypotension, dizziness, light headedness, tachycardia, palpitations, and headache. With beta-adrenergic blocking agents, observe for hypotension, bradycardia, bronchospasm, and heart failure.

With calcium channel blockers, observe for hypotension, dizziness, lightheadedness, weakness, peripheral edema, headache,

heart failure, pulmonary edema, nausea, and constipation. Bradycardia may occur with verapamil and diltiazem; tachycardia may occur with nifedipine and nicardipine.


Determinants of Oxygen
DIASTOLIC FACTOR Blood volume Venous tone SYSTOLIC FACTOR Peripheral resistance Heart rate Ejection time

INTRAMYOCARDIAL FIBER TENSION Myocardial Oxygen requirement