Bile acid-binding resins
| Drug: Cholestyramine (generic, Questran ®) |
| Drug Class: Hypolipidemic |
| Mechanism of Action: a large polymeric cationic exchange resin that binds bile acids in the intestinal lumen & prevents their reabsorption. The resin itself is not absorbed. The increased fecal loss of bile acids leads to an increased oxidation of cholesterol to bile acids, a decrease in beta lipoprotein or low density lipoprotein plasma levels and a decrease in serum cholesterol levels. Increased uptake of LDL and IDL from plasma results from up-regulation of LDL receptors, particularly in the liver. |
| Indications: useful for treating patients having an isolated increase in LDL |
| Contraindications: ineffective in patients with homozygous familial hypercholesterolemia who have no functional LDL receptors. |
| Pharmacokinetics: not absorbed |
| Side Effects: constipation |
| Major drug interactions: may delay or reduce the absorption of concomitant oral medication such as phenylbutazone, warfarin, thiazide diuretics (acidic) or propranolol (basic), as well as tetracycline penicillin G, phenobarbital, thyroid and thyroxine preparations, estrogens and progestins, and digitalis. Because cholestyramine binds bile acids, cholestyramine resin may interfere with normal fat digestion and absorption and thus may prevent absorption of fat soluble vitamins such as A, D, E, and K |
Reference: www.rxlist.com |
| Drug: Colestipol (Colestid ®) |
| Drug Class: Hypolipidemic (decreases LDL, increases HDL & TGs) |
| Mechanism of Action: Colestipol hydrochloride binds bile acids in the intestine forming a complex that is excreted in the feces. This nonsystemic action results in a partial removal of the bile acids from the enterohepatic circulation, preventing their reabsorption. The increased fecal loss of bile acids due to colestipol hydrochloride administration leads to an increased oxidation of cholesterol to bile acids. This results in an increase in the number of low- density lipoprotein (LDL) receptors, increased hepatic uptake of LDL and a decrease in beta lipoprotein or LDL serum levels, and a decrease in serum cholesterol levels |
| Indications: as adjunctive therapy to diet for the reduction of elevated serum total and LDL in patients with primary hypercholesterolemia (elevated LDL) who do not respond adequately to diet. |
| Contraindications: drug hypersensitivity |
| Pharmacokinetics: not absorbed |
| Side Effects: Constipation. Genereally there is no clinically significant effect on serum triglycerides, but triglyceride levels may be raised in some patients. |
| Major drug interactions: colestipol binds anionic compounds & may prevent their absorption - including the absorption of chlorothiazide, tetracycline, furosemide, penicillin G, hydrochlorothiazide, and gemfibrozil . Bile acid binding resins may also interfere with the absorption of oral phosphate supplements and hydrocortisone |
Reference: www.rxlist.com |
Nicotinic acid (Niacin)
| Drug: Nicotinic acid (generic, Niacor ®) |
| Drug Class: Hypolipidemic (decreases VLDL, LDL & TGs, HDL may increase) |
| Mechanism of Action: Niacin (Vit B3) inhibits VLDL secretion from hepatocytes, which in turn decreases the production of LDL. Increased clearance of VLDL via the LPL pathway contributes to triglyceride reduction. Niacin has no effect on bile acid production. Excretion of neutral sterols in the stool is increased acutely as cholesterol is mobilized from tissue pools and a new steady state is reached. The catabolic rate for HDL is decreased. Niacin inhibits the intracellular lipase of adipose tissue via receptor-mediated signaling, possibly reducing VLDL production by decreasing the flux of free fatty acids to liver. |
| Indications: In combination with a resin or reductase inhibitor, niacin normalizes LDL in most patients with heterozygous familial hypercholesterolemia & other forms of hypercholesterolemia. In severe mixed lipemia that is incompletely responsive to diet, niacin often produces marked reductions of triglycerides, an effect enhanced by marine omega-3 fatty acids. It is clearly the most effective agent for increasing levels of HDL. It is effective in patients with combined hyperlipoproteinemia & in those with familial dysbetalipoproteinemia. |
| Contraindications: patients with acanthosis nigricans because of an association with insulin resistance. Contraindicated in patients with severe peptic disease. |
| Pharmacokinetics: rapid absorption from the gastrointestinal tract and a short plasma elimination half-life of 20 to 45 minutes. |
| Side Effects: a harmless cutaneous vasodilation & sensation of warmth after each dose when the drug is started or the dose is increased (taking aspirin or ibuprofen beforehand can blunt this effect). Tachyphylaxis to flushing typically occurs within a few days. Nausea & abdominal discomfort. Reversible elevations in aminotransferases up to 2 X normal. Liver function should be monitored regularly due to a risk of sever hepatic dysfunction. Carbohydrate tolerance may be impaired (typically moderate & reversible unless the patient has latent diabetes). Hyperuricemia that can precipitate gout. |
| Major drug interactions: the effect of antihypertensives may be potentiated by niacin (requiring adjustment of their dosage). |
Reference: www.rxlist.com & Katzung's text |
Fibric acid derivatives
| Drug: Gemfibrozil (generic, Lopid ®) |
| Drug Class: Hypolipidemic (decreases VLDL, TGs & possibly LDL) |
| Mechanism of Action: function as ligands for the nuclear transcription receptor "peroxisome proliferator - activated receptor alpha (PPAR-alpha)". Increases lysis of lipoprotein triglyceride via LPL. Intracellular lipolysis in adipose tissue is decreased. Levels of VLDL decrease, in part as a result of decreased secretion by the liver. Only modest decreases in LDL occur in most patients. Patients with combined hyperlipidemia may experience an increase in LDL as TGs are reduced. HDL levels increase moderately.(due to reduced TG levels & consequent reduced exchange of TG into HDL in place of cholesteryl esters). |
| Indications: hypertriglyceridemias in which VLDL predominate & in dysbetalipoproteinemia. Treatment of hypertriglyceridemia resulting from treatment with viral protease inhibitors. |
| Contraindications: patients with hepatic or renal dysfunction, patients with biliary tract disease. |
| Pharmacokinetics: absorbed from the GI tract & undergoes enterohepatic circulation. Most (70%) is eliminated unchanged through the kidneys. Half life is 1.5 hrs. |
| Side Effects: rare cases of rash, GI symptoms, myopathy, arrhythmias, hypokalemia & high aminotransferase or alkaline phosphatase levels, risk of cholesterol gallstones. |
| Major drug interactions: fibric acid derivatives potentiate the effect of coumarin & indanedione anticoagulants. |
Reference: www.rxlist.com & Katzung's text |
HMG-CoA Reductase Inhibitors (decrease LDL & VLDL)
Common Characteristics:
| Drug Class: HMG-CoA Reductase Inhibitors |
| Mechanism of Action: specific inhibitors of HMG-CoA reductase, the enzyme which catalyzes the conversion of HMG-CoA to mevalonate. The conversion of HMG-CoA to mevalonate is an early step in the biosynthetic pathway for cholesterol. Other effects include decreased oxidative stress & vascular inflammation with increased stability of atherosclerotic lesions. These drugs decrease cholesterol synthesis & upregulate LDL receptors. The upregulation of LDL receptors increases both the catabolic rate of LDL & the livers extraction of LDL precursors (VLDL remenants), thus reducing plasma LDL. |
| Indications: Useful alone, or in combination with resins, niacin in reducing LDL levels. It is standard therapy to initiate reductase inhibitor therapy immediately after myocardial infarction, irrespective of lipid levels. |
| Contraindications: women who are pregnant, lactating or likely to become pregnant should not take these agents. Use in children is restricted to those with homozygous familial hypercholesteremia & selected patients with heterozygous familial hypercholesteremia. |
| Pharmacokinetics: Because cholesterol synthesis occurs predominantly at night, reductase inhibitors - except atrorvastatin , should be given in the evening . Absorption is enhanced if taken with food (with the exception of pravastatin).. Reductase inhibitors are metabolized by CYP 3A4 or CYP2C9. |
| Side Effects: elevations of serum aminotransferase activity (up to 3x normal) occur in some patients & are usually not associated with other evidence of hepatic toxicity. In ~2% of patients (some of whom have underlying liver disease or alcohol abuse) may have > 3x elevations in aminotransferase levels. This effect portends more severe hepatic toxicity. Such patients may present with malaise, anorexia & precipitious decreases in LDL. Medication should be discontinued immediately in such patients. |
| Major drug interactions: Drugs that inhibit or compete for CYP 3A4 or CYP2C9 will increase the plasma concentrations of statins. Drugs that induce CYP will reduce plasma statin levels (see below). Concomitant use of amiodarone or verapamil causes an increased risk of myopathy. |
Reference: Katzung's text |
Drug Specific Characteristics:
| Drug: Lovastatin (generic, Mevacor ®) |
| Drug Class: HMG-CoA Reductase Inhibitors |
| Pharmacokinetics: give in the evening (because cholesterol synthesis occurs predominantly at night). Absorption is enhanced if taken with food.. Metbolized by CYP 3A4. |
| Major drug interactions: Drugs that inhibit or compete for CYP 3A4 cause increased levels of lovastatin (e.g. macrolide antibiotics, cyclosporin, ketoconazole & analogs, HIV protease inhibitors, tacrolimus). Drugs that induce CYP 3A4 reduce lovastatin levels (e.g. phenytoin, griseofulvin, barbiturates, rifampin, thiazolidinediones). Concomitant use of amiodarone or verapamil causes an increased risk of myopathy. |
Reference: www.rxlist.com & Katzung's text |
| Drug: Atorvastatin (Lipitor ®) |
| Drug Class: HMG-CoA Reductase Inhibitors |
| Mechanism of Action: HMG-CoA reductase inhibitor. Not a prodrug. |
| Pharmacokinetics: Metbolized by CYP 3A4. |
| Major drug interactions: Drugs that inhibit or compete for CYP 3A4 cause increased levels of lovastatin (e.g. macrolide antibiotics, cyclosporin, ketoconazole & analogs, HIV protease inhibitors, tacrolimus). Drugs that induce CYP 3A4 reduce lovastatin levels (e.g. phenytoin, griseofulvin, barbiturates, rifampin, thiazolidinediones). Concomitant use of amiodarone or verapamil causes an increased risk of myopathy. |
Reference: www.rxlist.com |
| Drug: Pravastatin (Provachol ®) |
| Drug Class: HMG-CoA Reductase Inhibitors |
| Pharmacokinetics: Not a prodrug. While the presence of food in the gastrointestinal tract reduces systemic bioavailability, the lipid-lowering effects of the drug are similar whether taken with, or 1 hour prior, to meals. pproximately 20% of a radiolabeled oral dose is excreted in urine and 70% in the feces. Metabolized by non-P450 pathways . |
Reference: www.rxlist.com & Katzung's text |
| Drug: Digoxin (generic, Lanoxicaps, Lanoxin ®) |
| Drug Class: Cardiac glycoside (positive inotrope) |
| Mechanism of Action: digoxin inhibits sodium-potassium ATPase, an enzyme that regulates the quantity of sodium and potassium inside cells. Inhibition of the enzyme leads to an increase in the intracellular concentration of sodium and thus (by stimulation of sodium-calcium exchange) an increase in the intracellular concentration of calcium. |
| Indications: digoxin is indicated for the treatment of mild to moderate systolic heart failure, and is particularly effective in the setting of atrial fibrillation and congestive heart failure. Digoxin is usually given after ACE inhibitors. |
| Contraindications: digitalis glycosides are contraindicated in patients with ventricular fibrillation or in patients with a known hypersensitivity to digoxin. Also contraindicated in patients with diastolic heart failure (~40% of patients with CHF have diastolic failure vs. systolic failure). |
| Pharmacokinetics: Can be given orally or by i.v. injection. Digoxin elimination follows first-order kinetics. Following intravenous administration to healthy volunteers, 50% to 70% of a digoxin dose is excreted unchanged in the urine. Renal excretion of digoxin is proportional to glomerular filtration rate and is largely independent of urine flow. In healthy volunteers with normal renal function, digoxin has a half-life of 1.5 to 2.0 days. |
| Side Effects: the adverse reactions of digoxin are dose-dependent and typically occur at doses higher than those needed to achieve a therapeutic effect. They include: fatigue, anorexia, nausea, vomiting, visual & psychic complaints, diarrhea, dreams, muscular weakness, 2nd or 3rd degree AV conduction block, various arrhythmias. Note: Digoxin's TI is relatively low (~2). |
| Major drug interactions: potassium depleting diuretics. Calcium, particularly if administered rapidly by the intravenous route, may produce serious arrhythmias in digitalized patients. Quinidine, verapamil, amiodarone, propafenone, indomethacin, itraconazole, alprazolam, and spironolactone raise the serum digoxin concentration due to a reduction in clearance and/or in volume of distribution of the drug, with the implication that digitalis intoxication may result. Erythromycin and clarithromycin (and possibly other macrolide antibiotics) and tetracycline may increase digoxin absorption in patients who inactivate digoxin by bacterial metabolism in the lower intestine, so that digitalis intoxication may result. |
Notes: Digoxin increases left ventricular ejection fraction and improves heart failure symptoms as evidenced by increased exercise capacity and decreased heart failure-related hospitalizations and emergency care, while having no effect on mortality. Where possible, digoxin should typically be used with a diuretic and an angiotensin-converting enzyme inhibitor. |
| Reference: www.rxlist.com & Katzung's text |
| Drug: Digitoxin |
| Pharmacokinetics: Eliminated primarily by hepatic metabolism, half-life is ~ 1 week. |
Notes: no longer commercially available in the US. |
| Drug: Digoxin Immune Fab (Digibind ®) |
| Drug Class: Digoxin antidote |
| Mechanism of Action: Digoxin immune Fab are antibodies that bind to digoxin. In cases of digoxin toxicity, the antibodies bind to digoxin and the complex is excreted through the kidneys. |
| Indications: Life-threatening digoxin toxicity (or digitoxin toxicity). Symptoms of serious digoxin toxicity include severe sinus bradycardia, second- or third-degree heart block which does not respond to atropine, ventricular tachycardia, ventricular fibrillation. |
| Contraindications: Use in infants only if benefits outweigh risks. Clients sensitive to products of sheep origin may also be sensitive to digoxin immune Fab. |
| Pharmacokinetics: Injection: 10 mg/mL. Onset of action is less than 1 min. Improvement in signs of toxicity occurs within 30 min. t1/2: 15-20 hr (after IV administration). Each vial contains 38 mg of pure digoxin immune Fab, which will bind approximately 0.5 mg digoxin or digitoxin. |
| Side Effects: worsening of CHF or low CO, atrial fibrillation (all due to withdrawal of the effects of digoxin) |
| Major drug interactions: |
Notes: cardiac arrest can be expected if a healthy adult ingests more than 10 mg digoxin or a healthy child ingests more than 4 mg. |
| Reference: www.rxlist.com |
Nitrates
(Nitrates are the mainstay of therapy for the immediate relief of angina)
| Drug: Nitroglycerin (Nitrogard, Minitran, Nitro-Dur, Nitrol ®, others) |
| Drug Class: antianginal, vasodilator |
| Mechanism of Action: Direct relaxation of vascular smooth muscle is the principal pharmacologic action of nitroglycerin. Although venous effects predominate at low doses, nitroglycerin produces, in a dose-related manner, dilation of both arterial and venous beds. Dilation of the postcapillary vessels, including large veins, promotes peripheral pooling of blood and decreases venous return to the heart, reducing left ventricular end-diastolic pressure (preload). Arteriolar relaxation reduces systemic vascular resistance and arterial pressure (afterload). Myocardial oxygen consumption or demand is decreased by both the arterial and venous effects of nitroglycerin, and a more favorable supply-demand ratio can be achieved. May cause redistribution of coronary blood flow from normal to ischemic tissue. Nitrates (and calcium channel blockers) may also increase myocardial oxygen delivery in variant angina by reversing coronary arterial spasm. |
| Indications: 1) effort-associated (classic), variant & unstable forms of angina pectoris, 2) CHF associated with acute myocardial infarction, 3) control of blood pressure in hypertension associated with surgical procedures, 4) production of controlled hypotension during surgical procedures. |
| Contraindications: 1) known hypersensitivity, 2) hypotension or uncorrected hypovolemia, 3) increased intracranial pressure (head trauma), 4) inadequate cerebral circulation, 5) constrictive pericarditis or pericardial tamponade. |
| Pharmacokinetics: Several formulations exist including: extended release oral tablets, sublingual tablets, ointments, transdermal delivery system, intravenous (after dilution to 5% in dextrose). Very short half life of 1-4 minutes. Tolerance can develop if doses are given within 10-12 hours. |
| Side Effects: headache (2% incidence), tachycardia, nausea. |
| Major drug interactions: |
Reference: www.rxlist.com |
| Drug: Isosorbide dinitrate (generic, Isordil, Sorbitrate ®) |
| Drug Class: antianginal, vasodilator |
| Mechanism of Action: same as nitroglycerin. |
| Indications: same as nitroglycerin |
| Contraindications: drug allergy |
| Pharmacokinetics: Absorption of isosorbide dinitrate after oral dosing is nearly complete, but bioavailability is highly variable (10% to 90%), with extensive first-pass metabolism in the liver. Half life is about 1 hour. Tolerance can develop if doses are given more frequently than every ~14 hours. |
| Side Effects: headache, methemoglobinemia (rare) |
| Major drug interactions: |
Reference: www.rxlist.com |
Calcium Channel Blockers
(Used for prophylaxis in angina)
| Drug: Nifedipine (Procarida ®) |
| Drug Class: antianginal, vasodilator, antihypertensive |
| Mechanism of Action: L-type calcium channel blocker. Chronic (effort - associated) stable angina: nifedipine reduces arterial pressure at rest and at a given level of exercise by dilating peripheral arterioles and reducing the total peripheral resistance (afterload) against which the heart works. This unloading of the heart reduces myocardial energy consumption and oxygen requirements. Prinzmetal's, variant or vasospastic angina: Nifedipine dilates the main coronary arteries and coronary arterioles, both in normal and ischemic regions, and is a potent inhibitor of coronary artery spasm, whether spontaneous or ergonovine-induced. This property increases myocardial oxygen delivery in patients with coronary artery spasm. Hypertension: nifedipine reduces arterial blood pressure by directly causing peripheral arterial vasodilatation, leading to a reduction in peripheral vascular resistance. |
| Indications: For prophylactic treatment of both angina of effort & Prinzmetal's (variant) angina pectoris & hypertension. (Calcium channel blockers can be "tried" in refractory cases of unstable angina, but otherwise are not drugs of first or second choice in this condition). |
| Contraindications: known hypersensitivity to nifedipine |
| Pharmacokinetics: oral administration, available in immediate release & extended release formulations. Nifedipine is extensively converted to inactive metabolites and approximately 80% of nifedipine and metabolites are eliminated via the kidneys. The half-life of nifedipine in plasma is approximately 2 hours. Since hepatic biotransformation is the predominant route for the disposition of nifedipine, the pharmacokinetics may be altered in patients with chronic liver disease. |
Side Effects: dizziness, flushing, headache, transient hypotension, peripheral edema |
| Major drug interactions: cimetidine (80% increase in nifedipine plasma levels) |
Reference: www.rxlist.com |
| Drug: Verapamil (Calan, Isoptin ®) |
| Drug Class: Calcium channel blocker (Class 4 antiarrhythmic, antihypertensive, antianginal) |
| Mechanism of Action: Blocks L-type calcium channels |
| Indications: 1) For prophylactic treatment of both both vasospastic & effort-associated angina (calcium channel blockers can be "tried" in refractory cases of unstable angina, but otherwise are not drugs of first or second choice in this condition), 2) essential hypertension, 3) prophylaxis for repetitive paroxysmal supraventricular tachycardia, 4) in association with digitalis for the control of ventricular rate in patients with chronic atrial fibrillation/flutter |
| Contraindications: severe hypotension, second- or third-degree AV block, cardiogenic shock, severe CHF, sick sinus syndrome (unless client has artificial pacemaker), severe LV dysfunction. |
| Pharmacokinetics: Taken orally. A nonlinear correlation between the verapamil dose administered and verapamil plasma levels does exist. The mean elimination half-life in single-doses studies ranged from 2.8 to 7.4 hours. In these same studies, after repetitive dosing, the half-life increased to a range from 4.5 to 12.0 hours (after less than 10 consecutive doses given 6 hours apart). Bioavailability of verapamil is higher and half life longer in older (>65 yrs) subjects. Lean body weight also affects its pharmacokinetics inversely. |
| Side Effects: constipation, bradycardia, AV conduction block, asystole |
| Major drug interactions: Verapamil undergoes biotransformation by predominantly CYP3A4, however CYP1A2 and members of the CYP2C subfamily are involved in its metabolism. Verapamil can produce additive effects with other antihypertensive drugs.& with cardiac effects of beta blockers. |
Reference: www.rxlist.com |
| Drug: Diltiazem (Cardizem ®) |
| Drug Class: Calcium channel blocker (Class 4 antiarrhythmic, antihypertensive, antianginal) |
| Mechanism of Action: Blocks L-type calcium channels |
| Indications: 1) for prophylactic treatment of angina (both vasospastic & effort-associated), 2) antihypertensive, 3) control of ventricular rate in atrial fibrillation of flutter. |
| Contraindications: hypotension. Second- or third-degree AV block and sick sinus syndrome except in presence of a functioning ventricular pacemaker. Acute MI, pulmonary congestion. Lactation. |
| Pharmacokinetics: taken orally. Plasma elimination half-life following single or multiple drug administration is approximately 3.0 to 4.5 hours. |
| Side Effects: hypotension, AV conduction block, bradycardia |
| Major drug interactions: diltiazem can produce additive effects with other antihypertensive drugs.& with cardiac effects of beta blockers. |
Reference: www.rxlist.com |
| Drug Class: Beta Blockers |
| Mechanism of Action: The relevant effect in angina is to block cardiac beta-1 receptors to produce a decreased heart rate, contractility, and blood pressure, which thereby decrease myocardial oxygen requirements at rest and during exercise. Beta blockers may also be valuable in reducing "silent" ischemia. Randomized trials in patients with stable angina have shown better outcome & symptomatic improvement with beta-blockers compared to calcium channel blockers. |
| Indications: Angina of effort |
| Contraindications: asthma & other bronchospastic conditions, severe bradycardia, AV block, severe unstable LV failure. |
| Pharmacokinetics: |
| Side Effects: increase in end-diastolic volume & increased ejection time, which ends up increasing oxygen requirements, which partially offsets the beneficial effects to reduce oxygen demands. This can be balanced by the concomitant use of nitrates. Others - fatigue, impaired exercise tolerance, insomnia, unpleasant dreams, erectile dysfunction. |
Reference: Katzung's text |
| Summary of Maintenance Therapy for Angina |
Chronic Stable Angina of Effort: mono or combination therapy with:
|
Vasospastic (Variant) Angina: mono or combination therapy with:
|
Unstable Angina:
|
Related drugs:
| Drug: Dipyridamole (Persantine ®) |
| Drug Class: vasodilator, platalet adhesion inhibitor |
| Mechanism of Action: Vasodilator: dilates resistance vessels in coronary beds to increase flow without increasing oxygen demand. Thromboembolism: Dipyridamole has been found to lengthen abnormally shortened platelet survival time in a dose-dependent manner. The mechanism is unclear but may involve inhibition of adenosine uptake by RBCs (adenosine is an inhibitor of platelet reactivity) & phosphodiesterase inhibition. |
| Indications: an adjunct to coumarin anticoagulants in the prevention of postoperative thromboembolic complications of cardiac valve replacement. |
Reference: www.rxlist.com |
| Drug: Papaverine |
| Drug Class: vasodilator |
| Mechanism of Action: believed to be due to inhibition of phosphodiesterase, leading to an increase in intracellular cAMP. |
| Indications: for the relief of cerebral and peripheral ischemia associated with arterial spasm and myocardial ischemia complicated by arrhythmias It also dilates coronary arteries. |
| Contraindications: complete AV block |
Reference: www.rxlist.com, healthdigest.org |
| Drug: Sildenafil (Viagra ®) |
| Drug Class: erectile dysfunction drug |
| Mechanism of Action: a selective inhibitor of phosphodiesterase type 5 (PDE5). PDE5 is responsible for degradation of cGMP in the corpus cavernosum. When sexual stimulation causes local release of NO, inhibition of PDE5 by sildenafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum. |
| Indications: treatment of erectile dysfunction |
| Contraindications: patients taking nitrates (e.g. nitroglycerin) |
| Pharmacokinetics: Sildenafil metabolism is principally mediated by the cytochrome P450 (CYP) isoforms 3A4 (major route) and 2C9 (minor route). Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance. |
| Side Effects: headache, flushing, abnormal color tinge to vision (mild and transient) |
| Major drug interactions: sildenafil citrate was shown to potentiate the hypotensive effects of nitrates, and its administration to patients who are using organic nitrates either regularly and/or intermittently in any form is therefore contraindicated. After patients have taken sildenafil citrate, it is unknown when nitrates, if necessary, can be safely administered (e.g. it may take longer than 24 hrs). |
Reference: www.rxlist.com |
| Drug: Sodium nitrate & amyl nitrite |
| Drug Class: nitrates- obsolete antianginal drugs |
| Mechanism of Action: these drugs, or their metabolites are vasodilators |
| Indications: "illicit" use - to enhance or prolong erectile function |
| Pharmacokinetics: amyl nitrite is a highly volatile liquid that is packaged in fragile glass ampules. Crushing the ampule with the fingers results in the rapid release of inhalable vapors through a cloth covering. The inhalation route provides for rapid absorption & avoids the hepatic first pass effect. Once aborbed, the duration of action is 2-8 minutes. |
| Side Effects: dizziness, giddiness, tachycardia, hypotension, flushing of the skin, pregnancy (just kidding). |
Reference: Katzung's text |
| Drug: Hydrochlorothiazide (generic, Microzide ®) |
| Drug Class: diuretic, antihypertensive |
| Mechanism of Action: blocks the Na/Cl transporter in the distal convoluted tubule, resulting in decreased NaCl reabsorption from the luminal side of epithelial cells, and eventual reduced blood volume, reduced venous pressure & reduced preload. Thiazides enhance Ca reabsorption in the distal convoluted tubule, perhaps by Na/Ca exchange. |
| Indications: hypertension, heart failure, nephrolithiasis due to idiopathic hypercalciuria & nephrogenic diabetes insipidus. |
| Contraindications: excessive use in hepatic cirrhosis, borderline renal failure, or heart failure |
| Pharmacokinetics: |
| Side Effects: hypokalemic metabolic alkalosis, hyperuricemia, impaired carbohydrate tolerance, hyperlipidemia (5-15% rise in serum chlosterol & increased LDL), hyponatremia, allergic reactions. |
| Major drug interactions: the effects of diuretics are dependent on renal prostaglandin production & can be inhibited by NSAIDs under certain conditions. |
Notes: the prototypical thiazide diuretic |
| Reference: www.rxlist.com |
| Drug: Furosemide (generic, Lasix ®) |
| Drug Class: loop diuretic |
| Mechanism of Action: selectively inhibit NaCl reabsorption in the thick ascending limb of the loop of Henle, resulting in reduced blood volume, reduced venous pressure & reduced preload. Loop diuretics also induce renal prostaglandin synthesis, which participate in their renal actions. Furosemide also increases renal blood flow & (by an unknown mechanism) reduces pulmonary congestion and left ventricular filling pressure in heart failure (this effect occurs prior to producing a change in urinary output, and also in anephric patients). |
| Indications: acute pulmonary edema, other edematous conditions, acute hypercalcemia, hyperkalemia, acute renal failure, anion overdosage (e.g. toxic ingestion of fluoride, bromide, iodide). |
| Contraindications: patients who are allgeric to sulfonamides. Do not use "overzealously" in hepatic cirrhosis or borderline renal failure or heart failure. |
| Pharmacokinetics: rapidly absorbed, eliminated by tubular secretion & glomerular filtration. Duration of effect is 2-3 hours (half life depends on renal function). NSAIDs and probenecid compete for secretion. |
| Side Effects: hypokalemia. Toxicity: hypokalemic metabolic alkalosis, ototoxicity (dose related & usually reversible), hyperuricemia, hypomanesemia, allergic reactions (skin rash, eosinophilia). |
| Major drug interactions: NSAIDs (eg. indomethacin) can interfere with the actions of loop diuretics by interfering with prostaglandin synthesis. This interference is minimal in norma subjects, but may be significant in patients with nephrotic syndrome or hepatic cirrhosis. |
Reference: www.rxlist.com, Katzung's text |
| Drug: Torsemide (Demadex ®) |
| Drug Class: loop diuretic |
| Mechanism of Action: Torsemide inhibits the Na/K/Cl carrier system in the loop of Henle and increases the urinary excretion of sodium, chloride, and water, but it does not significantly alter glomerular filtration rate, renal plasma flow, or acid-base balance. |
| Indications: the treatment of edema associated with congestive heart failure, renal disease, or hepatic disease (same as for furosemide). It will reduce preload via reduced blood volume. |
| Contraindications: (same as for furosemide) |
| Pharmacokinetics: duration of effect is 4-6 hours (twice that of furosemide) |
| Side Effects: (same as for furosemide) |
| Major drug interactions: (same as for furosemide) |
Reference: www.rxlist.com |
| Drug: Dopamine (generic) |
| Drug Class: dopaminergic & sympathomimetic |
| Mechanism of Action: Dose related. Dopamine selectively stimulates dopamine receptors at low rates of infusion (0.5-2 ug/kg/min). These dopamine receptors are distinct from alpha- and beta- adrenoceptors, and are found in the renal, mesenteric, coronary, and intracerebral vascular beds. At these dopamine receptors, haloperidol is an antagonist. The vasodilation in these vascular beds is accompanied by increased glomerular filtration rate, renal blood flow, sodium excretion, and urine flow. Dopamine also stimulates beta1-adrenoceptors at intermediate rates of infusion (2-10 ug/kg/min), resulting in improved myocardial contractility, increased SA rate and enhanced impulse conduction in the heart. Dopamine stimulates alpha receptors at higher rates of infusion (10-20 ug/kg/min), with consequent vasoconstrictor effects and a rise in blood pressure, which can override and reverse the renal dilation and naturesis produced at lower doses. At high doses dopamine may mimic the effects of epinephrine. |
Indications: Simultaneous i.v. administration of sodium nitroprusside & intermediate dosing rates of dopamine have been found to be useful in the treatment of severe CHF. At intermediate doses, dopamine causes both vasodilation (dopamine receptor stimulation) and increased myocardial contractility (beta-1 receptor stimulation). Thus afterload reduction is combined with inotropic stimulation, which produces a greater CO. Also indicated for the correction of hemodynamic imbalances present in the shock syndrome due to myocardial infarction, trauma, endotoxic septicemia, open-heart surgery, renal failure, and chronic cardiac decompensation as in congestive failure. |
| Contraindications: in patients with pheochromocytoma, uncorrected tachyarrhythmias or ventricular fibrillation. |
| Pharmacokinetics: intravenous administration, plasma half life of ~2 minutes. Dopamine is metabolized in the liver, kidney, and plasma by MAO and COMT. About 25% of the dose is taken up into specialized neurosecretory vesicles (the adrenergic nerve terminals), where it is hydroxylated to form norepinephrine. |
| Side Effects: high doses can induce ventricular arrhythmia, tachycardia, hypertension. |
| Major drug interactions: MAO inhibitors - if dopamine is given within 2-3 weeks after an MAOI, reduce loading dose of dopamine to 1/10th normal. Tricyclic antidepressants can potentiate the pressor effects of dopamine. Beta blockers and alpha blockers antagonize the cardiac and systemic vascular effects of dopamine. Dopamine-induced renal and mesenteric vasodilation is not antagonized by either alpha-or beta-adrenergic blocking agents. |
Reference: www.rxlist.com |
| Drug: Dobutamine (generic) |
| Drug Class: beta-1 selective sympathomimetic |
| Mechanism of Action: a direct-acting inotropic agent whose primary activity results from stimulation of cardiac beta-receptors while producing comparatively mild chronotropic, hypertensive, arrhythmogenic, and vasodilative effects. |
| Indications: indicated when parenteral therapy is necessary for short term inotropic support in patients with cardiac decompensation due to depressed contractility resulting either from organic heart disease or from cardiac surgical procedures. |
| Contraindications: idiopathic hypertrophic subaortic stenosis, patients with previous manifestations of hypersensitivity |
| Pharmacokinetics: Intravenous administration. The onset of action of dobutamine is within 1 to 2 minutes; however, as much as 10 minutes may be required to obtain the peak effect of a particular infusion rate. The plasma half-life of dobutamine in humans is 2 minutes. |
| Side Effects: A 10- to 20- mm increase in systolic blood pressure and an increasein heart rate of 5 to 15 beats/minute have been noted in most patients |
| Major drug interactions: beta blockers |
Notes: www.rxlist.com |
| Drug: Digoxin (Lanoxin ®) |
| Drug Class: cardiac glycoside (positive inotrope) |
| Pharmacology: (see digitalis section) |
Notes: Digoxin increases left ventricular ejection fraction and improves heart failure symptoms as evidenced by increased exercise capacity and decreased heart failure-related hospitalizations and emergency care, while having no effect on mortality. Where possible, digoxin should typically be used with a diuretic and an angiotensin-converting enzyme inhibitor. |
| Reference: www.rxlist.com |
| Drug: Nitroglycerin (Nitrogard, Minitran, Nitro-Dur, Nitrol ®, others) |
| Drug Class: antianginal, vasodilator |
| Mechanism of Action: Direct relaxation of vascular smooth muscle is the principal pharmacologic action of nitroglycerin. Although venous effects predominate at low doses, nitroglycerin produces, in a dose-related manner, dilation of both arterial and venous beds. Dilation of the postcapillary vessels, including large veins, promotes peripheral pooling of blood and decreases venous return to the heart, reducing left ventricular end-diastolic pressure (decreased preload). Arteriolar relaxation produced at higher doses reduces systemic vascular resistance and arterial pressure (decreased afterload). Myocardial oxygen consumption or demand is decreased by both the arterial and venous effects of nitroglycerin, and a more favorable supply-demand ratio can be achieved. May cause redistribution of coronary blood flow from normal to ischemic tissue. |
| Pharmacology: (see antianginal drugs) |
Reference: www.rxlist.com |
| Drug: Isosorbide dinitrate (generic, Isordil, Sorbitrate ®) |
| Drug Class: antianginal, vasodilator |
| Mechanism of Action: same as nitroglycerin. |
| Indications: same as nitroglycerin |
Reference: www.rxlist.com |
| Drug: Hydralazine (generic, Apresoline ®) |
| Drug Class: antihypertensive, vasodilator |
| Mechanism of Action: hydralizine causes the relaxation of vascular smooth muscle by an unknown mechanism. It preferentially dialates arterioles vs. venous blood vessels, and thereby does not tend to result in sigifnicant postural hypotension. Hydralazine lowers blood pressure & promotes an increase in cardiac output via afterload reduction. |
| Indications: Essential hypertension |
| Contraindications: Hypersensitivity to hydralazine; coronary artery disease; mitral valvular rheumatic heart disease. |
| Pharmacokinetics: oral or parenteral administration. Plasma levels of hydralazine vary widely among individuals. Hydralazine undergoes hepatic metabolism that is subject to polymorphic acetylation. Fast acetylators have lower plasma levels of hydralazine and require lower doses to control blood pressure. |
| Side Effects: headache, anorexia, vomiting, angina, tachycardia |
| Major drug interactions: MAO inihibitors should be used with caution in patients on hydralazine |
Notes: www.rxlist.com |
| Drug Category: ACE Inhibitors |
| Drugs: Captopril (generic, Capoten ®), Enalapril - a prodrug -(Vasotec ®) |
Pharmacological Effects:
|
| Drug Category: Beta Blockers |
| Drugs: Propranolol (generic, Inderal ®), Metoprolol (Lopressor ®), Carvedilol (Coreg ®) |
Pharmacological Effects: Beta blockers can reduce morbidity & mortality in systolic CHF, attributed to reversal or prevention of cardiac remodeling caused by chronicly elevated sympathetic tone. Beta blockers are also indicated in the treatment of diastolic CHF where they help facilitate diastolic filling by improving myocardial relaxation. |
| Drug Category: Calcium Channel Blockers |
| Drugs: Diltiazem (Cardizem ®) , Verapamil (Calan, Isoptin ®) |
| Pharmacological Effects: Used in the treatment of diastolic heart failure (along with beta blockers) to help improve diastolic filling. |
Reference: www.rxlist.com |
| Drug: Spironolactone (generic, Aldactone ®) |
| Drug Class: diuretic (potassium sparing) |
| Mechanism of Action: a specific pharmacologic antagonist of aldosterone (see diuretic section below for additional information). Aldosterone can worsen CHF by causing edema. In addition, evidence also suggests that aldosterone may cause direct effects on the heart to produce cardiac remodeling that impairs contractility and diastolic relaxation. |
Indications: 1) treatment of CHF. The RALES trial (1995-98) showed that spironolactone administration in patients with severe heart failure reduced mortality by 27%, and also reduced the rate of hospitalization, and improved symptoms. 2) Other indications: primary hyperaldosteronism, edematous conditions, essential hypertension, hypokalemia |
| Major drug interactions: can produce severe hyperkalemia when used in combination with ACE inhibitors or Bactrim ® (trimethoprim/sulfamethoxazole). Caution is warranted since hyperkalemia can be lethal. |
Reference: www.rxlist.com |
Class I (Na Channel Blockers)
| Drug: Lidocaine (Xylocaine ®) |
| Drug Class: class 1b antiarrhythmic, local anesthetic (amide), |
| Mechanism of Action: blocks voltage sensitive sodium channels in nerves and cardiac tissue. |
| Clinical Indications: treatment of ventricular cardiac arrhythmias (esp. post- MI), production of local or regional anesthesia. Not effective against suprventricular arrhythmias. |
| Contraindications: patients with history of hypersenstivity to amide local anesthetics |
| Side Effects: (related to overdose) lightheadedness, tinnitus, metalic taste, blurred vision, numbness, twitching, convulsions, hypotension |
| Pharmacokinetics: Administered i.m. or i.v.. Not effective orally. hepatic metabolism, half life 1.5-2 hrs. Patients with CHF or hepatic disease will have higher plasma levels. |
| Major drug Interactions: MAOIs or ergot alkaloids (when using epinephrine containing solutions). Phenothiazines may reduce the pressor effects of epinephrine |
| Notes: lidocaine is also packaged in combination with epinephrine for local anesthetic use to prolong the duration of local anesthesia |
| Reference: www.rxlist.com |
| Drug: Quinidine (generic) |
| Drug Class: Antiarrhythmic class IA, antimalarial |
| Mechanism of Action: Mixed Na channel blocker & K channel blocker, decreased ectopic pacemaker activity. |
| Indications: atrial fibrillation/flutter (to restore sinus rhythm in patients who are not adequately controlled by drugs that reduce the ventricular response, or to reduce the frequency of relapse into atrial fib/flutter). Patients with symptomatic atrial fibrillation/flutter should be treated with quinidine only after ventricular rate control (e.g., with digitalis or B-blockers) has failed to provide satisfactory control of symptoms. Suppression of recurrent documented potentilly life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia. Because of the proarrhythmic effects of quinidine, its use with ventricular arrhythmias of lesser severity is generally not recommended, and treatment of patients with asymptomatic ventricular premature contractions should be avoided. Reserved for use in patients with no significant organic/structural heart disease (yet are arrhythmic). |
| Contraindications: Use cautiously when initiating quinidine therapy in patients with atrial tachyarrhythmias due to it's anticholinergic side effects that can decrease the AVN ERP. Quinidine is also contraindicated in patients who, like those with myasthenia gravis, might be adversely affected by an anticholinergic agent. Contraindicated in patients whose cardiac rhythm is dependent upon an ectopic pacemaker. |
| Side Effects: diarrhea (24%), fever (6%), rash (6%), arrhythmia (3%). Cinchonism: a syndrome of headache, dizziness & tinnitus at toxic concentrations. Rare idiosyncratic reactions such as thrombocytopenia & hepatitis. Note: quinidine has significant antimuscarinic effects. Syncope, prolonged QTc & torsade de pointes. |
| Pharmacokinetics: usuallly taken orally. Can be given i.v. but with caution due to alpha receptor blocking action that can cause severe hypotension & sinus tachycardia. The elimination half-life is 6-8 hours in adults and 3-4 hours in children. |
| Major drug interactions: drugs that alkalinize the urine (Na bicarb), quinidine levels are increased by coadministration of amiodarone or cimetidine, hepatic elimination is increased by drugs that induce P450 3A4 (phenobarbital, phenytoin & rifampin). Quinidine decreases the clearance & increases the Vd of digoxin, resulting in a ~doubling of digoxin plasma levels. Quinidine's anticholinergic, vasodilating, and negative inotropic actions may be additive to those of other drugs |
Reference: www.rxlist.com |
| Drug: Procainamide (Pronestyl ®, generic) |
| Drug Class: Antiarrhythmic class IA |
| Mechanism of Action: Na channel blocker (NAPA metabolite is a K channel blocker) |
Indications: the treatment of documented life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia. Because of the proarrhythmic effects of procainamide, its use with lesser arrhythmias is generally not recommended. Also effective against atrial arrhythmias. Treatment of patients with asymptomatic, ventricular premature contractions should be avoided. A drug of second choice (after lidocaine) in most coronary care units for treatment of ventricular arrhythmias associated with myocardial infarction. |
| Contraindications: patients with complete heart block, systemic lupus erythematosus, patients with a history of torsade de pointes. |
| Side Effects: hypotension when given i.v. A lupus erythematosus-like syndrome is common after prolonged use. Rare: agranulocytosis (0.5%). Negative inotropic effects (use caustiously in CHF). Weak ganglionic blocker (use cautiously in patients with atrial tachyarrhythmias). |
| Pharmacokinetics: administered orally, im or iv. |
| Major drug interactions: additive effect when given with other antiarrhythmics. |
Reference: www.rxlist.com |
| Drug: Amiodarone (Cordarone ®) |
| Drug Class: Antiarrhythmic (miscellaneous or Class III) |
| Mechanism of Action: broad spectrum: a prodominant K channel blockade, significant Na channel blockade & weak adrenergic & calcium channel blockade. |
| Indications: preventing the reoccurance of life-threatening ventricular arrhythmias. Low doses are effective in maintaining sinus rhythm in patients with atrial fibrillation. It's use is not associated with an increase in mortality in patients with coronary artery disease or heart failure (in contrast to many other agents). Maybe used as an adjuvant therapy to decrease the frequency of uncomfortable ICD discharges (ICDs have in many cases succeeded drug therapy as the primary treatment for VT). |
| Contraindications: Amiodarone is contraindicated in severe sinus-node dysfunction, causing marked sinus bradycardia; second- and third-degree atrioventricular block; and when episodes of bradycardia have caused syncope (except when used in conjunction with a pacemaker). Amiodarone is contraindicated in patients with a known hypersensitivity to the drug. |
| Side Effects: Amiodarone accumulates in many tissues (up to 10-50 times greater than plasma). Dose-related potentially fatal pulmonary fibrosis, exacerbation of arrhythmia, and rare serious liver injury. Neurologic problems (e.g. malaise), GI complaints (nausea, vomiting, constipation). Can produce bradycardia & heart block in patients with sinus or AV nodal disease. Gray-blue skin discoloration in sun-exposed areas, asymptomatic corneal microdeposits in most patients. Rarely optic neuritis may progress to blindness Amiodarone blocks the peripheral conversion of thyroxine (T4) to tiiodothyronine (T3). Can cause either hypo- or hyper-thyroidism. |
| Pharmacokinetics:oral or i.v. administration. Complex elmination half life - half is eliminated with a half-life of 3-10 days and the remainder with a half-life of several weeks. Effects are maintained for 1-3 months after drug discontinuation, and tissue levels are detectible for up to a year. |
| Major drug interactions: Many. All other medications being taken should be reviewed prior to initiating amiodarone therapy. Amiodarone is a substrate for P-450 CYP3A4. Drugs that inhibit this enzyme (e.g. cimetidine) or induce it (e.g. rifampin) will alter amiodarone plasma levels. Amiodarone inhibits most other cytochrome cytochrome enzymes & may result in elevated levels of drugs that are substrates for these enzymes (e.g. warfarin). Amiodarone can elevate digoxin plasma levels. |
Reference: www.rxlist.com |
| Drug: Propranolol (generic, Inderal ®) |
| Drug Class: beta blocker (nonselective) |
| Mechanism of Action: blocks beta1 & beta2 adrenergic receptors |
| Indications: to reduce mortality & sudden death after myocardial infarction, paroxysmal atrial tachycardia (esp. those induced by catecholamines), persistent sinus tachycardia, arrhythmias related to thyrotoxicosis, control of ventricular rate in atrial fibrillation/flutter when digoxin is contraindicated, treatment of hypertension & migraines, essential tremor, pheochromocytoma, resistant ventricular tachycardias due to catecholamines after surgery or ventricular arrhythmias that don't respond to other measures. |
| Contraindications:cardiogenic shock, sinus bradycardia & greater than 1st degree AV block, asthma, CHF (unless secondary to tachyarrhythmias). |
| Pharmacokinetics: taken orally, significant 1st pass effect, half-life of 4 hrs. There is no simple correlation between dose or plasma level and therapeutic effect, and the dose-sensitivity range as observed in clinical practice is wide. The principal reason for this is that sympathetic tone varies widely between individuals. |
| Side Effects: with overdosage: bradycardia, cardiac failure, h ypotension, bronchospasm. Other: depression, insomnia, light-headedness. |
| Major drug interactions: patients taking reserpine or a calcium channel blocker should be carefully watched. Combination with haloperidol may cause hypotension & cardiac arrest. Aluminum hydroxide gel reduces GI absorption of propranolol. Phenytoin & rifampin increase propranolol's clearance. Cimetidine decreases propranolol's clearance. |
Reference: www.rxlist.com |
| Drug: Atenolol (Tenormin ®) |
| Drug Class: beta blocker (beta-1 selective) |
| Mechanism of Action: selective beta-1 receptor blocker |
| Indications: Atenolol is indicated in the management of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality, hypertension, angina |
| Contraindications: Atenolol is contraindicated in sinus bradycardia, heart block greater than first degree, cardiogenic shock, and overt cardiac failure. |
| Pharmacokinetics: taken orally or i.v.; half-life of 6-7 hrs |
| Side Effects: with overdosage: bradycardia, hypotension, reversible depression, disorder of respiratory drive |
| Major drug interactions: additive effects with reserpine or calcium channel blockers. |
Reference: www.rxlist.com |
| Drug: Metoprolol (Lopressor ®) |
| Drug Class: beta blocker (beta-1 selective) |
| Mechanism of Action: selective beta-1 receptor blocker |
| Indications: hypertension, post-myocardial infarction, angina |
| Contraindications: Metoprolol is contraindicated in sinus bradycardia, heart block greater than first degree, cardiogenic shock, and overt cardiac failure. Metoprolol is contraindicated in patients with a heart rate <45 beats/min; second- and third-degree heart block; significant first-degree heart block (P-R interval >0.24sec); systolic blood pressure <100 mmhg; or moderate-to-severe cardiac failure. |
| Pharmacokinetics: oral or i.v. administration; half-life 3-7 hrs. |
| Side Effects: with overdosage: bradycardia, hypotension, bronchospasm, and cardiac failure. |
| Major drug interactions: reserpine or calcium channel blockers may produce additive effects. |
Reference: www.rxlist.com |
| Drug: Sotalol (Betapace ®) |
| Drug Class: Class II & Class III Antiarrhythmic |
| Mechanism of Action: one stereoisomer is a non-selective beta blocker & both are isomers are K channel blockers |
| Indications: ventricular arrhythmias |
| Contraindications: sinus bradycardia, 2nd or 3rd degree AV block, long QT syndrome, heart failure, cardiogenic shock, drug hypersensitivity, asthma. |
| Pharmacokinetics:sotalol is excreted predominantly in urine and its terminal elimination half-life is prolonged in conditions of renal impairment |
| Side Effects: torsade de pointes (~2%). With overdosage: bradycardia, hypotension, bronchospasm, and cardiac failure, hypoglycemia |
| Major drug interactions: Class Ia antiarrhythmic drugs, such as disopyramide, quinidine and procainamide and other Class III drugs (e.g., amiodarone) are not recommended as concomitant therapy with sotalol, because of their potential to prolong refractoriness (QT). Use with caution with calcium channel blockers. Symptoms of hypoglycemia may be masked in diabetics. |
| Reference: www.rxlist.com |
Class IV (Ca Channel Blockers)
| Drug: Verapamil (Calan, Isoptin ®) |
| Drug Class: Calcium channel blocker (Class 4 antiarrhythmic, antihypertensive, antianginal) |
| Mechanism of Action: Blocks L-type calcium channels |
| Indications: 1) in association with digitalis for the control of ventricular rate in patients with chronic atrial fibrillation/flutter, 2) prophylaxis for repetitive paroxysmal supraventricular tachycardia, 3) angina (both vasospastic & effort-associated), 4) essential hypertension |
| Contraindications: severe hypotension, second- or third-degree AV block, cardiogenic shock, severe CHF, sick sinus syndrome (unless client has artificial pacemaker), severe LV dysfunction. |
| Pharmacokinetics: Taken orally. A nonlinear correlation between the verapamil dose administered and verapamil plasma levels does exist. The mean elimination half-life in single-doses studies ranged from 2.8 to 7.4 hours. In these same studies, after repetitive dosing, the half-life increased to a range from 4.5 to 12.0 hours (after less than 10 consecutive doses given 6 hours apart). Bioavailability of verapamil is higher and half life longer in older (>65 yrs) subjects. Lean body weight also affects its pharmacokinetics inversely. |
| Side Effects: constipation, bradycardia, AV conduction block, asystole |
| Major drug interactions: Verapamil undergoes biotransformation by predominantly CYP3A4, however CYP1A2 and members of the CYP2C subfamily are involved in its metabolism. Verapamil can produce additive effects with other antihypertensive drugs.& with cardiac effects of beta blockers. |
Reference: www.rxlist.com |
| Drug: Diltiazem (Cardizem ®) |
| Drug Class: Calcium channel blocker (Class 4 antiarrhythmic, antihypertensive, antianginal) |
| Mechanism of Action: Blocks L-type calcium channels |
| Indications: control of ventricular rate in atrial fibrillation of flutter, angina (both vasospastic & effort-associated), antihypertensive, prophylaxis for paroxysmal supraventricular tachycardia |
| Contraindications: hypotension. Second- or third-degree AV block and sick sinus syndrome except in presence of a functioning ventricular pacemaker. Acute MI, pulmonary congestion. Lactation. |
| Pharmacokinetics: taken orally. Plasma elimination half-life following single or multiple drug administration is approximately 3.0 to 4.5 hours. |
| Side Effects: hypotension, AV conduction block, bradycardia |
| Major drug interactions: diltiazem can produce additive effects with other antihypertensive drugs & with cardiac effects of beta blockers. |
Reference: www.rxlist.com |
| Drug: Amiodarone (Cordarone ®) |
| Drug Class: Antiarrhythmic (miscellaneous or Class III) |
| Mechanism of Action: broad spectrum: a prodominant K channel blockade, significant Na channel blockade & weak adrenergic & calcium channel blockade. |
| Indications: preventing the reoccurance of life-threatening ventricular arrhythmias. Low doses are effective in maintaining sinus rhythm in patients with atrial fibrillation. It's use is not associated with an increase in mortality in patients with coronary artery disease or heart failure (in contrast to many other agents). Maybe used as an adjuvant therapy to decrease the frequency of uncomfortable ICD discharges (ICDs have in many cases succeeded drug therapy as the primary treatment for VT). |
| Contraindications: Amiodarone is contraindicated in severe sinus-node dysfunction, causing marked sinus bradycardia; second- and third-degree atrioventricular block; and when episodes of bradycardia have caused syncope (except when used in conjunction with a pacemaker). Amiodarone is contraindicated in patients with a known hypersensitivity to the drug. |
| Side Effects: Amiodarone accumulates in many tissues (up to 10-50 times greater than plasma). Dose-related potentially fatal pulmonary fibrosis, exacerbation of arrhythmia, and rare serious liver injury. Neurologic problems (e.g. malaise), GI complaints (nausea, vomiting, constipation). Can produce bradycardia & heart block in patients with sinus or AV nodal disease. Gray-blue skin discoloration in sun-exposed areas, asymptomatic corneal microdeposits in most patients. Rarely optic neuritis may progress to blindness Amiodarone blocks the peripheral conversion of thyroxine (T4) to tiiodothyronine (T3). Can cause either hypo- or hyper-thyroidism. |
| Pharmacokinetics:oral or i.v. administration. Complex elmination half life - half is eliminated with a half-life of 3-10 days and the remainder with a half-life of several weeks. Effects are maintained for 1-3 months after drug discontinuation, and tissue levels are detectible for up to a year. |
| Major drug interactions: Many. All other medications being taken should be reviewed prior to initiating amiodarone therapy. Amiodarone is a substrate for P-450 CYP3A4. Drugs that inhibit this enzyme (e.g. cimetidine) or induce it (e.g. rifampin) will alter amiodarone plasma levels. Amiodarone inhibits most other cytochrome cytochrome enzymes & may result in elevated levels of drugs that are substrates for these enzymes (e.g. warfarin). Amiodarone can elevate digoxin plasma levels. |
Reference: www.rxlist.com |
| Drug: Adenosine (Adenocard ®) |
| Drug Class: endogenous nucleotide "antiarrhythmic" |
| Mechanism of Action: slows conduction time through the A-V node, can interrupt the reentry pathways through the A-V node, and can restore normal sinus rhythm in patients with paroxysmal supraventricular tachycardia (PSVT), including PSVT associated with Wolff-Parkinson-White Syndrome. |
| Indications: Acute conversion to sinus rhythm of paroxysmal supraventricular tachycardia (PSVT), including that associated with accessory bypass tracts (Wolff-Parkinson-White Syndrome). When clinically advisable, appropriate vagal maneuvers (e.g., Valsalva maneuver), should be attempted prior to Adenocard administration. |
| Contraindications: Second- or third-degree A-V block (except in patients with a functioning artificial pacemaker). Sinus node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients with a functioning artificial pacemaker). Known hypersensitivity to adenosine. |
| Pharmacokinetics: Adenocard ® (adenosine) is a sterile solution for rapid bolus intravenous injection. Intravenously administered adenosine is rapidly cleared from the circulation (half life of less than 10 seconds) via cellular uptake, primarily by erythrocytes and vascular endothelial cells. This process involves a specific transmembrane nucleoside carrier system |
| Side Effects: The usual intravenous bolus dose of 6 or 12 mg adenosine will have no systemic hemodynamic effects. When larger doses are given by infusion, adenosine decreases blood pressure by decreasing peripheral resistance. Facial flushing, lightheadness, dyspnea occur occasionally. |
| Major drug interactions: Adenocard is antagonized competitively by methylxanthines such as caffeine and theophylline, and potentiated by blockers of nucleoside transport such as dipyridamole. Adenocard is not blocked by atropine. |
Notes: Adenocard does not convert atrial flutter, atrial fibrillation, or ventricular tachycardia to normal sinus rhythm. |
| Reference: www.rxlist.com |