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Continuing Education:
Cardiac Drugs – Lecture II The most common groups of drugs used to treat angina are the
nitrates, calcium channel blockers, and beta blockers. Nitrates are the oldest and possibly still
the most common treatment for angina.
They work by liberating nitric oxide, which causes smooth muscle to
relax producing vasodilation [1]. The
vasodilation is more pronounced in the venous system than in the arterial system. Venodilation reduces preload (amount of
tension/stretch on heart muscle before it begins to contract; related to volume
of blood entering the heart chambers) due to venous pooling, which decreases
end diastolic volume and end diastolic pressure. Arterio-vasodilation decreases systemic
vascular resistance and systolic blood pressure, which decreases afterload
(amount of tension the heart muscle must achieve before it can start to
contract; the resistance the left ventricle must overcome to eject blood into
the arterial system). The overall effect
is a decrease in myocardial workload and, therefore, myocardial oxygen
demand. Since they produce a decrease in
preload, heart rate (HR) may increase to compensate for the decrease in cardiac
output (Q). Recall that a decrease in
preload produces a decrease in stroke volume (SV). Blood pressure should decrease at rest and
during exercise. An important therapeutic effect of the nitrates is improved perfusion of the subendocardium due to coronary vessel dilation and reduced preload. Consequently, ischemic ECG changes are less likely to occur at rest and during exercise. Metabolic efficiency is also improved. When taken prior to a treadmill stress test, they delay the onset of ST depression and decrease the magnitude. They may even prevent ST changes altogether. It may be desirable to withhold them for an appropriate time period prior to testing, depending on the purpose of the testing. If vasodilation is excessive, undesirable effects may
occur. These include orthostatic
hypotension, tachycardia, flushing sensations, and severe headache. Nitrates are used to treat angina (stable,
variant, unstable) and congestive heart failure. Patients can develop tolerance. They are contraindicated if intracranial
pressure is elevated. Abrupt withdrawal
of long-term nitrate therapy is also contraindicated. Examples include Nitroglycerin
(Nitro-Bid, Nitrostat, Nitro-Dur), Isosorbide
dinitrate (Isordil, Sorbitrate), Amyl nitrate
(Aspirols, Vaporole), and Peritrate.
Nitrates may be administered in pill forms (swallowed, chewed,
sublingual or buccal), topical ointment or transdermal patch, or as a spray [2]. Calcium channel blockers do just what the term implies. They prevent calcium from being transported
through the muscle cell membrane (cardiac and smooth muscle). Without calcium, muscle contraction does not
occur. As a result, coronary vessels
dilate, which increases coronary blood flow and reduces coronary
vasospasm. Peripheral vessels also
dilate resulting in reduced systemic vascular resistance and, consequently,
lower blood pressure. Calcium channel
blockers have negative chronotropic, inotropic, and dromotropic effects, all of
which reduce myocardial oxygen consumption (MVO2). Verapamil also has significant antiarrhythmic
properties; other calcium channel blockers do not. These drugs delay the time of onset of ST
depression, but if BP drops too much, exercise tolerance may be decreased. A number of undesirable effects may occur with calcium
channel blockers, although these effects vary somewhat with specific drugs in
this group. Such effects include
hypotension, dependent edema (below the knees), bradycardia, heart failure, GI
disturbances, dizziness, flushing, nausea.
The reflex sympathetic response is particularly interesting. It is attributed to reduced BP caused by
dilation of the peripheral vessels.
Heart rate, contractility, and Q increase in response to the lower BP. Angina (stable, variant, unstable), supraventricular
tachycardias, atrial fibrillation or flutter, and hypertension may be treated
with calcium channel blockers. A number
of conditions may preclude the use of calcium channel blockers or at least
certain members of the group. They
should not be used to treat patients with congestive heart failure (CHF), SA node
or AV
node conduction disturbances, or low BP due to their negative
chronotropic, inotropic, and dromotropic effects. Some calcium channel blockers may actually
increase HR in persons with Wolff-Parkinson-White syndrome or a history of
myocardial infarction (MI). Verapamil is
contraindicated for atrial tachycardia caused by digitalis toxicity due to drug
interactions. Generally, calcium channel
blockers should not be used with beta-blockers or quinidine. Verapamil (Calan, Isoptin), nifedipine (Adalat, Procardia, Cardilate), diltiazem (Cardizem), mibefradil (Posicor) are commonly used to treat angina. Other calcium channel blockers include amlodipine (Norvasc), felodipine (Plendil), nisoldipine (Sular), nimodipine (Nimotop), nicardipine (Cardene), isradapine (Dynacirc), bepridil (Vascor). Another group of cardiac drugs used to treat angina are
beta-blockers or beta-adrenergic blockers.
Like the calcium channel blockers, their group name also describes their
mechanism of action. They block beta-adrenergic receptors. In doing so, they decrease HR, BP, and
myocardial contractility, which decreases MVO2 at rest, submaximal
exercise, and maximal exercise. As HR
decreases, diastolic filling time of the coronary arteries increases, thus
allowing for an increase in myocardial O2 supply (i.e., increased
perfusion). The decrease in BP is likely
due primarily to decreased Q, although beta-blockers may also suppress rennin
release from the kidneys and central nervous system discharge. Some beta-blockers are cardioselective in that they
preferentially bind to beta1-receptors. This allows for fewer side effects and allows
patients with peripheral vascular disease/bronchospasm to use
beta-blockers. The term
“cardioselectivity” is relative, meaning that it is only selective at low to
moderate doses. Labetolol blocks beta-adrenergic and alpha1 adrenergic receptors with a 3:1
ratio of beta:alpha antagonism. The beta-blockers have negative inotropic and chronotropic effects which reduces myocardial workload. End-diastolic volume and ejection time are increased due to slowing of the HR. They are also antihypertensive due to effects on the heart, blood vessels, and possibly other unknown CNS actions. They decrease renin production and labetalol reduces BP by dilating both resistance (arterial) and capacitance (venous) vessels. Overall, beta-blockers improve exercise tolerance in
patients with angina, but may decrease maximum exercise capacity in patients
with significant left ventricular dysfunction (with or without angina) due to
their negative inotropic effect.
Otherwise, the patient’s exercise capacity or VO2max can
increase with training. Many patients
exercise longer and have less ST segment depression and less angina. Beta-blockers do not change the relationship
between % VO2max and % HRmax.
Thus, the usual methods to calculate target HR for exercise prescription
can be used. Generally, beta-blockers
decrease VO2max and HRmax, but they will not obscure ischemic ST
segment depression in patients with epicardial coronary narrowing. There are several adverse effects that may be produced by beta-blockers. These include: 1. Vasospasm - beta-blockers leave the vasoconstricting effects of alpha receptors unopposed, and thus may produce peripheral arteriolar constriction by blocking the vasodilating SNS fibers and allowing the unopposed vasoconstricting fibers to constrict. Hence, patients with claudication may worsen with resultant complaints of cold extremities. The same theory is used to explain the side effect of coronary artery vasoconstriction and worsening of coronary artery spasm. 2. Worsening of bronchospasm (increased airway resistance) due to inhibition of beta2-receptor-mediated relaxation of bronchial smooth muscle. Non-selective beta-blockers leave the constricting effect of the parasympathetic system on the lungs unopposed. 3. Congestive heart failure due to depression of myocardial contractility. 4. Bradycardia or AV block due to effects on AV conduction. 5. May complicate hypoglycemia in diabetics due to inhibition of SNS response to signs of decreased blood glucose. 6. CNS effects: fatigue, depression, vivid/bizarre dreams. 7. May increase plasma triglycerides and decrease HDL-cholesterol. 8. Labetalol may produce orthostatic hypotension (particularly in fasting, volume-depleted, salf-restricted, or elderly patients, or patients on other antihypertensives), sexual dysfunction. Beta-blockers are used to treat angina pectoris (stable and unstable), hypertension, previous MI, arrhythmia, migraine headaches, and CHF [3] in some patients. Due to possible adverse effects beta-blockers are contraindicated in the following conditions: 1. Peripheral vascular disease and claudication. 2. Coronary artery spasm (vasospastic angina). Due to the indirect vasospastic effects of beta-blockers they can aggravate or precipitate angina with a vasospastic component. 3. Sinus node disease, slow heart rate, or AV node conduction problems. 4. Asthma. Beta1 selective drugs are better than non-selective drugs, but remember beta1 selectivity is not complete. 5. Insulin dependent diabetes. Beta-blockers can slow recovery from a hypoglycemic episode; beta1 selective drugs are preferred. It is also worth noting that abrupt withdrawal of
beta-blocker therapy may accelerate angina, tachycardia, MI, sudden death,
hypertension (called the “propanolol withdrawal rebound phenomenon”). As stated above, beta-blockers should not be
used concurrently with calcium channel blockers (could result in AV block). Examples of cardioselective beta-blockers include acebutolol
(Sectral), atenolol (Tenormin), metaprolol (Lopressor, Toprol), esmolol (Brevibloc),
bisoprolol (Zebeta),
nebivolol (Nebilet), betaxolol (Betoptic,
Kerlone).
Non-cardioselective beta-blockers include nadolol (Corgard), propanolol
(Inderal), penbutolol (Levatol), pindolol (Visken), timolol (Blocadren, Timoptic),
carvedilol (Coreg), carteolol (Cartrol), labetalol
(Normodyne, Trandate). References 1. http://heartdisease.about.com/cs/cardiacdrugs/index.htm 3. Lehne, R. A. (1998). Pharmacology for Nursing Care, 3rd Ed. Philadephia: W. B. Saunders Co. 5. http://www.pdrhealth.com/drug_info/rxdrugprofiles/alphaindexa.shtml |
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