Pharmacology study guide 21-24

Electrolytes Potassium Calcium

Actions of digoxin are affected by changes in the serum electrolytes, particularly potassium and calcium. Hypokalemia (low potassium) sensitizes the heart to the toxic effects of digoxin. Decrease in serum potassium may cause an increased incidence of arrhythmias, which can lead to ventricular fibrillation and sudden death. Hyperkalemia (high serum potassium) antagonizes the therapeutic effect of digoxin. Hypercalcemia (high serum calcium) enhances the action of digoxin and can lead to arrhythmias.

Cinchonism

Adverse syndrome produced by quinidine in overdosage or in patients who are sensitive to the drug. This condition is characterized by ringing in the ears (tinnitus), dizziness, salivation, headache and hallucinations.

Beta Adrenergic Blockers Mechanism of action Adverse effects

Antagonize or reverse the effects of sympathetic activation caused by exercise and other physical and mental exertions. Increase heart rate, force of myocardial contractions and oxygen consumption. Indicated for long-term chronic management of angina pectoris. Can be used in combination with nitrates in patients that require more than one drug to control angina. Adverse effects drowsiness, tiredness, and GI disturbancs such as nausea and diarrhea. Excessive dosage cause bradycardia, hypotension and possible development of heart failure.

CHF

Chronic Heart Failure, the contractile ability of the heart to pump blood is decreased so that the heart pumps out less blood than it receives. Blood accumulates inside the chambers, causing enlargement (dilatation) of the heart. Less blood circulating in the blood vessels to supply the body organs. Causing fluid retention and edema. The kidneys respond by releasing a substance called renin. Renin stimulates the enzymatic conversion of a precursor protein from the liver, angiotensiongen, to angiotensin I. An enzyme produced by the lungs, angiotensin-converting enzyme (ACE), converts angiotensin I into angiotensin II. Angiotensin II is a potent vasoconstrictor and also stimulates the release of aldosterone from the adrenal cortex and antifiuretic hormone (ADH) from the hypothalamus and pituitary gland. RAA Renin-Angiotensin_Aldosterone mechanism.

Conduction System Autorhythmicity

Composed of a specialized type of nervous tissue that is located in specific areas of the heart. Conduction tissue has a unique property known as autorhythmicity, this allows the heart to initiate its own electrical stimulation. ECG electrocardiogram records the electrical ativity of the heart from 12 different body locations.

Glycosides Clinical Indications Toxic effects Digitalis - toxic effects

Compounds originally obtained from the plant leaves of DIgitalis purpurea and Digitalis lanata. Digitalis also refers to these drugs. The action of these drugs is to increase cardiac contractility. Digoxin (Lanoxin) is the only drug of this class that is still available in the United States. Increases the force of myocardial contractions (also referred to as a positive inotropic effect) in CHF without causing an increase in oxygen consumption. The efficiency of the heart is improved, restoring normal blood circulation. Digoxin increases the force of myocardial contractions by increasing the concentration of calcium ions inside cardiac muscle cells. It inhibits the enzyme Na/K adenosine triphosphatase (Na/K ATPase) which energizes the sodium/potassium pump. Increase sodium ions inside heart muscles reduces the activity of another ion exchange mechanism. Resulting increased intracellular calcium concentrations increase the formation of the contractile protein actinomyosin, resulting in greater myocardial contraction. The main use of digoxin is the treatment of CHF, to increase the force of contractions. It is also used in some cases of atrial flutter and atrial fibrillation. Digoxin Immune Fab (Digibind) is a preparation of antidigoxin antibodies that is administered parenterally. Development of cardiac arrhythmias. Usually there is an apperance of extra heartbeats (ectopic beats). Premature ventricular contractions (PVCs). Which lead to ventricular tachycardia, ventricular fibrillation and cardiac arrest.

Adenosine

Considered a miscellaneous antiarrhythmic drug that is only used in emergency and acute situations. Naturally occurring metabolite of adenosine triphosphate (ATP). Administered intravenously to terminate episodes of paroxysmal supraventricular tachycarida. Decreases the activity of calcium ions in the SA and AV nodes. Causes slowing of the heart rate and AV conduction which usually terminates the episode of tachycardia. The duration of action is extremely short 15 to 30 seconds and may require repeated administrations. Adverse effects are brief and include asystole, respiratory difficulties (bronchospasm) and hypotension.

CAD

Coronary Artery Disease is a general term for several cardiac conditions. Insufficient flow of blood through the coronary arteries to the heart is common factor in arteriosclerosis, atherosclerosis and angina pectoris.

Cardizem

Diltiazem (Cardizem) are similar to verapamil, but considered to be a more potent vasodilator then verapmil. SA and AV nodes, it deceases AV node conduction.

ECG

Electrocardiogram records the various cardiac arrhythmia's. Extremely valuable for determining abnormalities in cardiac rhythm and conduction. Heart rate can be determined by counting the number of QRS waves that occur within a 1-minute period.

Verapamil

Major effect is on the SA and aV nodes of the heart. Decreases SA nde activity, resulting in a slight decrease in heart rate. Decreases AV node conduction. Makes it very useful in treating various types of rapid AV nodal arrhythmias and other supraventricular tachycardias. Administered PO and IV in emergency situations. Produces vasodilation and is used in treatment of angina pectoris and hypertension. Adverse effects of verapamil include headache, dizziness, and minor GI disturbances, especially constipation. Produces hypotension, especially when patients change position. Serious complications include cardiac depression leading to heart failure and various degrees of heart block, especially if is taken with other cardiac depressant drugs. Heart failure

Patient Education

Since they are unpredictable, it is important for patients to carry the prescribed medications at all times. It is volatile and tablets lose potency if exposed to air or light so need to be carried in a light-resistant airtight containers and under 6 months old.

Lidocaine

Mild block of sodium (Na) channels, mild decrease in Phase O depolarization, decrease in ventricular automaticity. Synthetic drug used primarily as a local anesthetic agent. It is widely used for ventricular arrhythmias, especially those resulting from a myocardial infarction or arrhythmias occurring during surgery. As a rule it is ineffective in atrial arrhythmias and is therfore not recommended for use in these conditions. Disadvantage is that it must be administered parenterally (IV or IM). Given as an intravenous infusion to maintain the antiarrhythmic action. toxic blood levels of lidocaine usually produce CNS depression (anesthetic effect) and possible cardiac and respiratory arrest.

V-fib

Most serious arrhythmia, which constitutes a medical emergency. During fibrillation the electrical activity of the ventricles is severely disturbed and the ventricles cannot contract efficiently enough to maintain adeuate circulation. If not treated immediately, cardiac arrest and death will result.

Quinidine

Natural product obtained from the bark of the cinchona tree. Dates back to the eighteenth century, when patients suffered from malaria. Cardiac depressant that decreases myocardial contraction in addition it produces anticholinergic and alpha-blocking effects. Adverse effects include nausea, vomiting, and diarrhea due to irritation of the GI tract.

Nitrites/Nitrates Mechanism of action Clinical use Sublingual Ointment Transdermal Extended-release capsules

Once known as coronary dilators, but research has shown that during angia these drugs do not produce significant effects on cornonary arteris that are atherosclerotic and hardened by arteriosclerosis. Ischemia itself is a potent vasodilator so that during attacks of angia the coronary arteries are already maximally dilated. Main effect is to produce a general vasodilation of systemic veins and arteris. This reduced cardiac work and oxygen consumption. First they are used during attack of angina to relieve the intense pain. Most common is sublingual. Drugs in this group have an almost immediate onset of action, although their duration is short. Second they are administered prophylactically on a daily basis to prevent attacks of angina. Mechanism of Action: These drugs relax vascular smooth muscle. Main effect are a decreased in venous return to the heart (decrease in pre-load) and a decrease in blood pressure (decrease in after-load) Consquently cardiac work is reduced. Sublingual tablet and spray relief are available. Sublingual means under the tongue Ointment is applied topically to an area of the chest or abdomen and is covered with a plastic dressing. Transdermal is an adhesive patch that is applied on the torso. Slowly and uniformly released into the bloodstream over a 24-hour period. Extended-release capsules of 2.5, 6.5 and 9.0 that release the drug gradually over a prolonged period. Duration is 8 to 12 hours.

Ectopic foci

Originate below the AV node are referred to as ventricular arrhythmias. Ectopic foci, areas of abnormal impulse generation, may appear when electrical impulses traveling through the conduction system are delayed or blocked

PAC, PVC

Premature Atrial Contractions (PACs), classified as a supraventricular arrhythmia. Premature Ventricular Contractions (PVCs). Depolarizes the ventricle before the SA node and atrium. The electrical impulse travels up the conduction system (instead of down) toward the atrium. The result is a QRS wave that is inverted and that disrupts normal ventricular contraction.

Nitrates Adverse Effects

Related to vasodilating action. Cutaneous flushing, dizziness, headache, weakness, and fainting. Sudden or excessive drops in blood pressure can cause reflex tachycardia.

Nerve Supply Sympathetic Parasympathetic involvement

The heart receives its nerve supply from both divisions of the autonomic nervous system. Sympathetic nerves release norepinephrine at adrenergic nerve endings that go to the SA node (increasing the heart rate), AV node (increase contractility). Sympathetic nerves become active when the body needs to expend energy and during the "fight or flight" reaction. Parasympathetic nerves release acetylocholine at cholinergic nerve endings that go to the SA node (decrease heart rate) and AV node (decrease AV conduction). The parasympathetic system has little effect on myocardial contraction. They become active when the body is restoring energy during eating, digestions, sleep and elimination of urinary and intestinal waste products.

Cardiac muscle Myocardium Blood Supply

The pumping ability of the heart is due to the arrangement of heart muscle. Heart muscle Through the coronary arteries that branch off the aorta immediately after the aorta leaves the heart. Blood flow in the coronary arteries is dependent upon the force of myocardial contractions. Any interference with the normal function of the myocardium results in ISCHEMIA and a decreased capacity of the heart of contract.

Calcium Channel Blockers Adverse effects Mechanism of action

To block the influx of calcium ions into vascular smooth muscle. Contraction of vascular smooth muscle is very dependent on calcium influx (movement from extracellular to intracellular sites) Which normally occurs during membrane depolarization (action potential) of smotth muscle. They relax arterial smooth muscle and have little effect on veins. Primary effect is srteriolar vasodilation and reduction of blood pressure. Adverse effects include headache, facial flushing, dizziness, hypotension, and minor gastrointestinal GI disturbances. Constipation is one of the more common side effect. overdosage can cause bradycardia, AV block, and decreased myocardial contraction that can lead to heart failure. Excessive cardiac depression and heart failure.

Amiodorone

Very potent antiarrhythmic drug that has multiple sites of action. In addition to blocking potassium channels, amiodarone blocks sodium (class 1) and calcium (class 4) channels. It has blocking actions on both beta- (class 2) and alpha-adrenergic receptors. Structurally similar to the thyroid hormone thyroxine, contains iodine, and can interfere with thyroid function. Can be administered both orally and intravenously. Oral absorption is incomplete and variable. Must be carefully regulated and periodic monitoring of serum drug levels is advised. Dizziness, tremors, and ataxia. hypo or hyperthyroidism are possible adverse side effects. Toxic include bradycardia, heart block, heart failure, and generation of proarrhythmias such as torsade de pointes.

Arteriosclerosis

is a disease of the aging process in which there is a hardening (fibrosis) and narrowing of the arteries. These changes result in a decreased blood flow.

Types of Arrythmias

is any abnormality in heart rate or rhythm of electrical conduction through the heart. It disturbs the electrical activity of the heart and interrupt the normal sequence of atrial and ventricular activation and contraction.

Myocardial Infarction

occurs when an area of the heart muscle is deprived of blood flow. The area deprived of blood dies unless immediate treatment is administered to restore blood flow. Blockage of blood flow is caused by the formation of a blood clot in one of the coronary arteries. Usually forms in a vessel where there are atherosclerotic plaques. Antiocoagulant and fibrinolytic drugs can be administered to dissolve the clot to prevent further blockage

Atherosclerosis

primarily caused by abnormally high cholesterol levels in the blood. Cholesterol forms the fatty deposits (plaque) that decrease blood flow.

Angina pectoris

the clinical condition characterized by chest pain caused by insufficient coronary blood flow. Arteriosclerosis, atherosclerosis, and corornary artery spasms are the major causes.