Download Angina - WordPress.com

Angina
PHCP 403
Samirah Abdu-Aguye
Introduction
• The term angina pectoris is applied to varying forms of transient chest
discomfort that are attributable to insufficient myocardial oxygen
• It is characterized by discomfort in the chest, jaw, shoulder, back, or arms,
typically caused by exertion or emotional stress and relieved by rest or
nitroglycerin.
• Characteristically, the discomfort (it is often not described by the patient as
a pain) occurs after a predictable level of exertion, classically when
climbing hills or stairs, and resolves within a few minutes on resting.
• Unfortunately, the clinical manifestations of angina vary. Many
patients mistake the discomfort for indigestion. Some patients,
particularly diabetics and the elderly, may not experience pain at all
but present with breathlessness or fatigue; this is termed silent
ischemia.
• Angina can occur in patients with valvular heart disease, uncontrolled
hypertension, as well as in non-cardiac organ systems such as the
chest wall, esophagus, or lungs.
Etiology
The processes, singly or in combination, that produce IHD include
decreased blood flow to the myocardium, increased oxygen demand,
and decreased oxygenation of the blood.
1. Decreased blood flow : caused by atherosclerosis, or Coronary
artery spasms.
2. Increased oxygen demand usually in the presence of restricted
oxygen supply
3. Reduced blood oxygenation. The oxygen-carrying capacity of the
blood may be reduced, as occurs in various forms of anemia or
hypoxemia.
Types
1. Stable (classic) angina
• This is the most common form of the condition. Stable angina is characteristically the result of a
fixed obstruction in a coronary artery
• Here, the condition has a more predictable pattern, which is brought on by exertion, emotional
stress, or a heavy meal, which is usually relieved by rest, nitroglycerin, or both.
• The Pain is often referred to as “squeezing,” “grip-like,” “pressure-like,” “suffocating,” and “heavy”
and is usually referred to as a discomfort rather than “pain.”
• The anginal episode typically lasts for “minutes” and is usually sub-sternal but has a tendency to
radiate to the neck, jaw, epigastrium, or arms.
• Characteristically, the discomfort builds to a peak, radiating to the jaw, neck, shoulder, and arms,
and then subsides without residual sensation.
• Angina is normally related to physical exertion, and the discomfort usually subsides quickly (i.e., in
3 to 5 mins) with rest; if precipitated by emotional stress, the episode tends to last longer (i.e.,
about 10 mins).
2. Unstable angina.
• Angina is considered unstable and requires further evaluation if
patients experience angina at rest( usually lasting longer than 20
minutes ).
• The discomfort in this case usually does not respond to rest or
nitroglycerin.
• Unstable angina confers a higher short-term risk for an MI, and
should be reported promptly to a physician.
3. Angina decubitus (nocturnal angina)
• This angina occurs in the recumbent position and is not specifically related to either rest
or exertion.
• Gravitational forces shift fluids within the body with a resultant increase in ventricular
volume, which increases oxygen needs and produces angina decubitus.
• Paroxysmal nocturnal dyspnea (PND) is associated with angina decubitus
• PND refers to a condition where fluid accumulation in the lungs, normally due to
gravitational forces when one is in the recumbent position, making it very difficult for a
patient to breath.
• Sleeping with several additional pillows might allow gravity to reduce symptoms.
However, the underlying cause needs to be corrected or the PND will remain.
• Diuretics alone or in combination effectively reduce left ventricular volume and may aid
the patient.
4. Prinzmetal angina (vasospastic or variant angina)
• A coronary artery spasm that reduces blood flow precipitates this angina.
• It usually occurs at rest (i.e., pain may disrupt sleep) rather than with
exertion or emotional stress, and usually resolves without progression to
an acute MI.
• However, if the attack is prolonged, MI, life-threatening arrhythmias, and
sudden cardiac death can occur.
• Characteristically, an electrocardiogram (EKG/ECG) taken during an attack
reveals a transient ST-segment elevation, which returns toward normal
after the acute attack.
• Nitroglycerin may not provide relief, depending on the cause of vasospasm.
Calcium-channel blockers are most effective for this form of angina.
Diagnosis
• Physical examination is usually not useful, especially between
attacks. However, the patient’s history, risk factors, and full
description of attacks can aid diagnosis
• ECG/EKG
• Exercise/ Stress testing
• Pharmacological stress testing
• Coronary angiography is regarded as the gold standard for diagnosis.
It involves the passage of a catheter through the arterial circulation
and the injection of radio-opaque contrast media into the coronary
arteries.
Goals of Treatment
There are 2 Goals of Treatment in stable angina.
1. Relieve or prevent symptoms.
2. To remove or reduce cardiac risk factors, Thereby Improving
prognosis by preventing MI and death.
CARDIAC RISK FACTORS AND WAYS TO
MODIFY THEM
RISK FACTOR
MODIFICATION
1. Smoking
Smoking Cessation and avoidance of second hand smoke
2. High Blood Pressure
Blood pressure control: Blood pressure should be reduced to less than
140/90 mm Hg or less than 130/90 mm Hg if chronic kidney disease
or diabetes mellitus are present
3. Elevated Blood Lipid levels
4. Physical Inactivity
Participate in at least 30 minutes of physical activity most days of the
week
5. Overweight/ Obesity
Maintain Body mass index (BMI) of 18.5 to 24.9 kg/m2 with waist
circumference of less than
35 inches (women) and less than 40 inches (men).
6. Diabetes Mellitus
Achieve and maintain glycosylated hemoglobin (HbA1c) level of less
than 7%
PHARMACOTHERAPY
1. Nitrates
• Nitrates are valuable in angina because they dilate veins and thereby
decrease preload, and dilate arteries to a lesser extent thereby decreasing
afterload. Their role in providing symptom relief is well established.
• They can be used to treat acute attacks and in prophylaxis
• Three main nitrates are available: GTN/ Nitroglycerin, isosorbide dinitrate
and isosorbide mononitrate. All are effective if given in appropriate doses
at suitable dose intervals
• There are many dosage forms available, including intravenous infusions,
conventional or slow-release tablets and capsules, transdermal patches,
sublingual tablets and sprays.
• Tolerance is one of the main limitations to the use of nitrates. This
develops rapidly, and a ‘nitrate-free’ period of a few hours in each
24h period is beneficial in maintaining the effectiveness of treatment.
The nitrate-free period
• Major side effects include postural hypotension and headaches
2. Beta-blockers: Various studies have demonstrated the beneficial
mortality effect of β-blockers in angina and they are now considered
first-line agents. They are particularly useful in patients with other
cardiac co-morbidities e.g. previous MI or heart failure.
• Mechanism of action. Beta-Blockers reduce oxygen demand, both at
rest and during exertion, by decreasing the heart rate and myocardial
contractility, which also decreases arterial blood pressure.
• Indications: These agents reduce the frequency and severity of
exertional angina that is not controlled by nitrates. All beta blockers
are effective for angina, however “cardioselective” agents such as
atenolol, bisoprolol and metoprolol are preferred.
Precautions and monitoring effects
(1) Doses should be increased until the anginal episodes have been reduced or until unacceptable
side effects occur.
(2) Beta-Blockers should be avoided in Prinzmetal angina (caused by coronary vasospasm) because
they increase coronary resistance and may induce vasospasm.
(3) Asthma is a relative contraindication because all beta-blockers increase airway resistance
and have the potential to induce bronchospasm in susceptible patients.
(4) Patients with diabetes and others predisposed to hypoglycemia should be warned that
beta-blockers mask tachycardia, which is a key sign of developing hypoglycemia.
(5) Patients should be monitored for excessive negative inotropic effects. Findings such as
fatigue, shortness of breath, edema, and paroxysmal nocturnal dyspnea may signal developing
Cardiac failure.
(6) Sudden cessation of beta-blocker therapy may trigger a withdrawal syndrome that can
exacerbate anginal attacks.
3. Calcium-channel blockers
Mechanisms of action.
(1) These agents prevent and reverse coronary spasm by inhibiting calcium influx into
vascular smooth muscle and myocardial muscle.
(2) Calcium-channel blockers increase coronary blood flow, and decrease cardiac inotropy,
resulting in decreased myocardial oxygen demand.
Indications
• Calcium-channel blockers are used in stable (exertional) angina that is not controlled by
nitrates and beta-blockers and in patients for whom beta-blocker therapy is inadvisable.
Combination therapy—with nitrates, beta-blockers, or both—may be most effective.
• These agents, alone or with a nitrate, are particularly valuable in the treatment of
Prinzmetal angina. They are considered the drug of choice in treatment of angina at rest
• Both dihydropyridine and non-dihydropyridine CCB can be used for this purpose
Diltiazem and verapamil
• These drugs produce negative inotropic effects, and patients must be monitored
closely for signs of developing cardiac failure (i.e., fatigue, SOB, edema, and PND).
• When co-administered with beta-blockers or other agents that produce negative
inotropic effects e.g., several antiarrhythmics, the negative effects are additive.
• Patients should be monitored for signs of developing bradyarrhythmias and heart
block because these agents have negative chronotropic effects.
• Verapamil frequently causes constipation that must be treated as needed to
prevent straining at stool, which could cause an increased oxygen demand
4. Antithrombotic/ Anti-Platelet drugs
• One of the major complications arising from the presence of plaques
in arteries is thrombus formation.
• This causes an increase in plaque size and may result in myocardial
infarction.
• Antiplatelet agents, in particular aspirin, are effective in preventing
platelet activation and thus thrombus formation.
• Other agents used in this class include clopidogrel, prasugrel,
ticlopidine and Dipyridamole
• The optimal maintenance dose for aspirin lies between 75–150 mg
/day with lower doses having limited cardiac risk protection and
higher doses increasing the risk of gastro-intestinal side effects.
• Dyspepsia is relatively common in patients taking aspirin and patients
should be advised to take the medicine with or immediately after
food.
• Adverse reactions to aspirin include allergies and bronchospasm.
• Clopidogrel is useful as an alternative to aspirin in patients who are
allergic or cannot tolerate aspirin. A loading dose of 300 mg is given
once, then 75 mg daily.
5. Other drugs
• Ivabradine : is similar in efficacy to atenolol and CCBs and may be of
particular use in patients in whom β-blockers are contraindicated. Its major
side effects are visual disturbances.
• Nicorandil: Nicorandil is indicated for ‘add-on’ treatment to combinations
of antianginals such as β-blockers, CCBs and long-acting nitrates in high risk
patients with stable angina. Its main benefit for patients may be a
reduction in unplanned admission to hospital with chest pain
• Ranolazine: has been shown to increase exercise tolerance, reduce anginal
episodes and reduce the use of GTN. Side effects include dizziness,
constipation, nausea, and the potential for prolongation of the QTc
interval.
Case Study 1
• Mr AG, a 57-year-old taxi driver of Indian origin, attends your
community pharmacy with a new prescription for: glyceryl trinitrate
(GTN) spray 400 micrograms one or two puffs as required.
• You dispense this item and speak with him and he tells you that his
GP thinks he has angina and has asked him to use the spray the
next time he gets any minor chest pain or tightness.
• You counsel Mr AG on the correct use of the spray. Mr AG returns a
few days later complaining of a headache following the use of the
spray. He is reluctant to use the spray again. He asks your advice on
managing his headache.
• He also smokes about five cigarettes a week and asks if he should
now stop.
Questions
1. What typical symptoms could a patient with angina present with?
2. What are the risk factors for developing angina?
3. What, if any, risk factors does Mr AG have for developing stable angina?
4. What group of drugs does GTN spray belong to?
5. What are the side-effects of GTN spray?
6. How would you counsel Mr AG on the use of his spray?
7. What other formulations of GTN are available? List their advantages and
disadvantages.
8. Mr AG’s headache may be caused by his use of GTN spray. What can you
recommend to him to help manage his headache?
9. What advice would you give Mr AG in relation to his smoking?
Case Study 2
• ST is a 65 year old obese and asthmatic Asian man with a largely sedentary
lifestyle who has suffered from stable angina for several years. His current
medication are
GTN Spray 2 puffs prn
Verapamil 80mg TDS
1. He still suffers from symptoms on exertion, Suggest additional drug
therapy for him.
2. Comment on ST’s drug therapy( Hint: what drug class is missing from his
current drug regimen). Suggest a suitable agent to be added for him
3. He has recently been prescribed an antiarrhythmic agent, what sort
of monitoring is required?
4. He also complains of severe constipation. What could be the cause?
Suggest measures to reduce this problem.
5. Suggest drug treatment for ST if he had presented with
a. Vasospastic angina
b. Angina decubitus
REFERENCES
1. Mutnick A.H. Coronary Artery Disease. In: Shargel L, Mutnick A,
Souney P, Swanson L, ed. by. Comprehensive pharmacy review for
NAPLEX. 8th ed. Philadelphia: Lippincott williams & wilkins; 2013. p.
566-571.
2. McRobbie D. Coronary Heart Disease. In: Walker R, Whittlesea C,
ed. by. Clinical Pharmacy & Therapeutics. 5th ed. China: Elsevier;
2012. p. 315-320
3. Bhalla N. Cardiovascular case studies. In: Dhillon S, Raymond R, ed.
by. Pharmacy case studies. UK: Pharmaceutical Press; 2009. p. 2021