1.4.5.1 Antianginals, antiarrhythmics and lipid lowering agents
Antianginals are drugs that are used in the treatment of angina. They are classified according to their mechanism of action as below.
Nitrates: Nitrates dilate cardiac blood vessels and reduce the work of the heart, thus reducing cardiac oxygen demand. Examples include nitroglycerine (GoNitro, Minitran, Nitro-Bid, Nitrostat, Nitromist) and isosorbide (Isordil, Dilatrate-SR, IsoDitrate). For quick action, sublingual tablets and spray forms are available as well. Each sublingual nitroglycerine tablet may be used every 5 minutes as needed, for up to 15 minutes. It can also be taken as one tablet 5-10 minutes before starting an activity that precipitates angina, like exercise. Adverse effects include headache and dizziness. Nitrates are contraindicated with phosphodiesterase inhibitors like sildenafil (Viagra)and tadalafil(Cialis). They should not be used in people with certain types of glaucoma.
Calcium channel blockers: They were discussed earlier in antihypertensives. Diltiazem (Cardizem, Tiazac) and verapamil (Calan, Verelan) are calcium channel blockers with antianginal properties.
Beta blockers: They were discussed earlier in antihypertensives. Cardioselective beta blockers like atenolol (Tenormin) and metoprolol (Lopressor, Toprol XL) are preferred as antianginals.
Ranolazine: Ranolazine (Ranexa, Aspruzyo Sprinkle) is a sodium channel blocker. Adverse effects include dizziness, edema, tinnitus, and vertigo.
Dipyridamole: Dipyridamole (Persantine) is a phosphodiesterase inhibitor used as an antianginal and antiplatelet agent.
Antiarrhythmics are drugs used to prevent and treat irregular cardiac rhythms called arrhythmias, such as atrial fibrillation and ventricular tachycardia. Some of these drugs are also used as antihypertensives and antianginals. Depending on their mechanism of action, they are classified as follows -
Class I or Sodium channel blockers: This group includes flecainide (Tambocor), quinidine (Cardioquin, Cin-Quin, and Quinidex), and mexiletine (Mexitil). Adverse effects include worsening of arrhythmias, and cinchonism, which presents as nausea, tinnitus, and visual changes seen with quinidine and lupus-like syndrome with procainamide.
Class II or beta blockers: This group includes atenolol (Tenormin), metoprolol (Lopressor, Toprol XL), nadolol (Corgard), propranolol (Inderal), and acebutolol (Sectral). Adverse effects include bronchospasm, fatigue, bradycardia, and depression.
Class III or potassium channel blockers: This group includes amiodarone (Cordarone, Pacerone), sotalol (Betapace, Sorine) , ibutilide (Corvert) and dofetilide (Tikosyn). Adverse effects include prolongation of QTc, Torsades de Pointes, fatigue and dizziness. Amiodarone can cause dysfunction of the thyroid gland like hypothyroidism or hyperthyroidism, lung and liver damage.
Class IV or calcium channel blockers: They include verapamil (Verelan, Calan) and diltiazem (Cardizem, Tiazac). Adverse effects include hypotension, edema, constipation, headache and atrioventricular or AV conduction block.
Others: These drugs have unique mechanisms of action. Adenosine (Adenocard, Adenoscan) blocks impulse conduction between the atria and ventricles of the heart to stop arrhythmias. It is quick acting and administered intravenously to treat a type of arrhythmia called supraventricular tachycardia or SVT. Adverse effects include headache, flushing, chest tightness, and hypotension. Digitalis (Digitek, Lanoxin) blocks Na/K ATPase pump and increases cardiac contractility. Adverse effects include vision changes like yellow vision, nausea, hyperkalemia, arrhythmias, confusion, dizziness, rashes, and diarrhea. Hypokalemia or low potassium levels can exacerbate digoxin toxicity.
Lipids are fatty substances present in blood, fat cells and cell membranes. Liver plays a major role in lipid metabolism. Cholesterol and triglycerides are types of lipids. Elevation of cholesterol and/or triglyceride levels are associated with cardiovascular and pancreatic diseases. There are several classes of lipid lowering drugs, statins are the most commonly used ones.
Statins: Statins decrease the synthesis of cholesterol by inhibiting the rate-limiting enzyme of cholesterol synthesis known as HMG CoA reductase. Examples include atorvastatin (Lipitor), rosuvastatin (Crestor), simvastatin (Zocor), and lovastatin (Mevacor). Statins decrease LDL cholesterol and triglyceride levels and increase HDL levels. Adverse effects include myalgia, rhabdomyolysis, hepatotoxicity, and elevated liver enzymes. Rhabdomyolysis is the breakdown of muscle tissue, and in serious cases, it may cause renal failure. When statins are taken together with macrolide antibiotics, the risk of serious adverse effects is higher as macrolides slow down the metabolism of statins, leading to higher statin levels in the blood. FDA recommends discontinuing statins in pregnant women as it can potentially cause fetal damage.
Fibrates: They decrease triglyceride levels. Examples include gemfibrozil (Lopid), fenofibrate (Lofibra, Antara) and fenofibric acid (Fibricor). Adverse effects include muscle pain and gallstones.
Niacin: Niacin is vitamin B3. It decreases triglyceride and cholesterol levels by decreasing the synthesis of fatty acids. Adverse effects include skin flushing, hypotension, and rash. Common brand names include Niacor and Niaspan.
Ezetimibe: It decreases the absorption of cholesterol from the intestine. A commonly available brand is Zetia. It is often given in combination with a statin e.g. simvastatin plus ezetimibe (Vytorin). Adverse effects include elevated liver enzymes and diarrhea.
Bile acid sequestrants: They prevent enterohepatic recycling of bile acids which leads to decreased serum cholesterol levels. Examples include cholestyramine (Locholest, Prevalite, Questran), colestipol (Colestid) and colesevelam (WelChol). Adverse effects include nausea, gastrointestinal upset and decreased absorption of drugs and fat soluble vitamins. Medications should be taken an hour earlier or 4-6 hours after taking bile acid sequestrants to prevent interference with drug absorption.
PCSK9 inhibitors: They are relatively new medications that decrease LDL cholesterol levels. Examples include evolocumab (Repatha) and alirocumab (Praluent). Adverse effects include dementia and muscle pain.
Fish oil supplements: Omega 3 fatty acids, sold as fish oil supplements, have shown some benefit in decreasing triglyceride levels by reducing synthesis but it can increase LDL cholesterol in some patients. Taking very high doses may cause bleeding and stroke. They can interact with anticoagulants and antiplatelets and increase the risk of bleeding. They have a synergistic effect in lowering blood pressure with antihypertensives.