Drugs Affecting the Cardiovascular and Renal System

DRUGS AFFECTING THE CARDIOVASCULAR AND RENAL SYSTEM

Inotropic drugs- drugs that increase the force of myocardial contraction.

Chronotropic drugs- drugs that increase the rate at which the heart beats.

Dromotropic drugs- drugs that accelerate conduction

2 Main Classes of Positive Inotropic Drugs

1. Cardiac glycosides2. Phosphodiesterase Inhibitors

CARDIAC GLYCOSIDES

Cardiac Glycosides- one of the eldest and most effective groups of cardiac drugs.

They were originally obtained from either the Digitalis purpurea or Digitalis Ianata plant, both commonly referred to as foxglove. For this reason, cardiac glycosides are sometimes referred to as digitalis glycosides. Critically ill patients can often be restored to near-normal states within hours after initiating digoxin therapy, a process known as digitalization.

MECHANISM OF ACTION AND DRUG EFFECTS

The primary beneficial effect of a cardiac glycoside is thought to be an increase in myocardial contractility. This occurs secondarily to the inhibition of the sodium-potassium ATPase pump. When the action of this enzyme complex is inhibited, the cellular sodium concentration and subsequently the calcium concentration increase. The overall result is enhanced myocardial contraction.

INDICATION

Cardiac glycosides are primarily used in the treatment of heart failure and supraventricular dysrhytmias. In heart failure the therapeutic effects of digoxin are secondary to its ability to increase the force of contraction-its positive inotropic action. Because more blood is ejected with each contraction of the heart, less blood remains in the ventricle and thus less pressure builds up. With this, the symptoms of pulmonary edema, pulmonary hypertension, and right-sided ventricular failure subside, and tissue perfusion improves.

Another benefit of this positive inotropic action is that it promotes diuresis by ensuring that adequate blood is supplied to the kidneys. As a result, fluids are more completely filtered and waste products removed, which relieves shortness of breath and pulmonary edema.

CONTRAINDICATIONS

Drug allergy 2nd or 3rd degree heart block Atrial fibrillation Ventricular tachycardia or fibrillation Heart failure resulting from diastolic dysfunction Subaortic stenosis

ADVERSE EFFECTSThe primary cardiac glycoside in use today is digoxin, and close monitoring of the patients development of toxic symptoms is essential. Digoxin has a narrow therapeutic index; that is, the range of blood drug levels that is considered therapeutic is small. Monitoring of digoxin levels after the drug reaches steady state is necessary only if there is suspicion of toxicity, noncompliance, or deteriorating renal function. Low potassium levels can increase the potential for toxicity, know specifically for this drug as digitoxicity. Therefore, frequent serum electrolyte level checks are also important.

TOXICITY AND MANAGEMENT OF OVERDOSE

Body SystemCommon adverse effects

cardiovasculardysrhythmia, (bradycardia or tachycardia

central nervousheadache, fatigue, malaise, confusion, convulsions

eyecolored vision (i.e., green, yellow, or purple) halo vision, or flickering lights

gastrointestinalanorexia, nausea, vomiting, diarrhea

DIGOXIN TOXICITY: STEP-BY-STEP MANAGEMENT

1Discontinue administration of drug.2Begin continuous ECG monitoring for cardiac dysrhythmias; administer antidysrhythmic drugs as ordered.3Determine serum digoxin and electrolyte levels.4Administer potassium supplements for hypokalemia in indicated, as ordered.5Institute supportive therapy for gastrointestinal symptoms.6Administer digoxin antidote (digoxin immune Fab) if indicated, as ordered.

INTERACTIONS

INTERACTING DRUGSMECHANISMRESULT

antidysrthymics calcium(parenteral) reserpineincrease cardiac irritabilityincreased digoxin toxicity

sympathomimetics amphotericin B chlorthalidoneloop diureticlaxativessteroids(adrenal)thiazides (diuretics)produce hypokalemiaincreased digoxin toxicity

antacids, antidiarrhealscholestyraminecolestipolsucralfatedecrease oral absorptionreduced therapeutic effect

quinidineverapamilamiodaronedecrease clearanceincrease digoxin levels (2x); digoxin dose should be reduced 50%

anticholinergics

increase oral absorptionincreased therapeutic effect

barbiturates

induce enzymereduced therapeutic effect

calcium channel blockersblock calcium channels in myocardiumenhanced bradycardic and negative inotropic effects of digoxin

-blockers

block b1 receptors in heartenhanced bradycardic effect of digoxin

The herbal supplement hawthorne can reduce theeffectiveness of cardiac glycosides. Hawthorne is used for hypertension and angina.

DRUG PROFILES

Normal therapeutic levels of digoxin should be between 0.5-2 ng/ml. Levels higher than 2 ng/ml are typically desirable for the treatment of atrial fibrillation.Digoxin is available in oral and injectable forms.

PHOSPODIESTERASE INHIBITORS

Phosphodiesterase inhibitors (PDIs)- group of inotropicDrugs that work by inhibiting the action of an enzyme called phosphodiesterase.

The inhibition of this enzyme results in two very beneficial effects in an individual with heart failure: a positive inotropic response and vasodilation. For this reason this class of drugs may also be referred to as inodilators (inotropics and dilators).

There are presently only two U.S. drugs in this category: inamrinone and milrinone.

Inodilators are more specific for phosphodiesterase type III, which is especially common in the heart and vascular smooth muscles.


Inhibition of phosphodiesterase results in the availability of more calcium for the heart to use in muscle contraction. It also results in dilation of systemic or pulmonary blood vessels, which in return decreases the workload of the heart. The effects on the heart muscle lead to an increase in the force of contraction.

INDICATIONS

PDIs are primarily used for the short-term management of heart failure. Traditionally, PDIs are given to patients who can be closely monitored and who have not responded adequately to digoxin, diuretics, and/or vasodilators.

CONTRAINDICATIONS

Drug allergy Presence of severe aortic or pulmonary valvular disease Heart failure resulting from diastolic dysfunction

ADVERSE EFFECTS

The adverse effect that is most worrisome with inamrinone is thrombocytopenia. The primary adverse effect seen with milrinone therapy is dysrhythmia. Milrinone-induced dysrthymias are mainly ventricular.


No specific antidote exists for an overdose of either inamrinone or milrinone. Hypotension secondary to vasodilation is the primary effect seen with excessive doses of both drugs.

The recommendation is to reduce the dose or temporarily discontinue the PDI if excessive hypotension occurs. This should be done until the patients condition is stabilized.

INTERACTIONS

Concurrent administration of diuretics may cause significant hypovolemia and reduced cardiac filling pressure. Furosemide must not be injected into intravenous lines of inamrinone or milrinone because it will precipitate immediately.

NURSING CONSIDERATIONS

Before a cardiac glycoside or other positive inotropic drug is administered, a thorough assessment of the patient is required.

Patients need to be aware of conditions that predispose to digitalis toxicity, including hypokalemia, hypercalcemia, hypothyroid states, renal dysfunction and advanced age.

Patients must be educated to measure pulse rate, and daily weight with daily journaling. Nurses should always take an apical pulse for 1 full minute when digoxin is administered, and patients should be instructed on taking radial pulses when at home.

Patients should be encouraged to notify the health care provider immediately at the first signs of anorexia, nausea, or vomiting, or the occurrence of bradycardia with a pulse rate below 60 beats/min if the patient is taking digoxin.

If more than 12 hours have passed, the patient should know to not skip that dose, not double up on the next digoxin dose, and to contact the health care provider immediately for further instructions.

Patients should not abruptly stop their digoxin because this could precipitate more cardiac problems and complications.

Patients should avoid using antacids or eating ice cream, milk products, yogurt, or cheese for 2 hours before or after taking medication to avoid interference with the drug.

Nurses must be aware that hypotension, dysrthythmias, and thrombocytopenia are major adverse effects of inamrinone and milrinone use.

ANTIDYSRHYTHMIC DRUGS

The SA node, AV node, and bundle of His- Purkinje cells are all areas in which there is automaticity. The SA node is the pacemaker because it can spontaneously depolarize easier and faster than the other areas.

Antidysrthythmic drugs are used to correct dysrthythmias; however, they may also cause dysrthythmias and for this reason are said to be prodysrthythmic.

Vaughan Williams classification- this system is based on the electrophysiologic effect of particular drugs on the action potential.

VAUGHAN WILLIAMS CLASSIFICATION AND MECHANISM OF ACTION

CLASSIFICATIONMECHANISM OF ACTION

Class I (Moricizine)Ia: quinidine, procainamideIb: lidocaine, phenytoinIc: flecainide, propafenonemembrane- stabilizing drugs

Class II (- blockers)propanolol

-adrenergic blockers that depress phase 4 depolarization

Class III: Amiodaronedrugs that prolong repolarization in phase 3

Class IV: Verapamilcalcium channel blockers that depress phase 4 depolarization

INDICATION

DRUG CLASSINDICATIONS

Class Isymptomatic ventricular and life-threatening dysrthythmias

Class IaAtrial fibrillation, premature atrial contractions, premature ventricular contractions, ventricular tachycardia, Wolff- Parkinson- White Syndrome

Class Ib

Class IbVentricular dysrthythmias only; Atrial and ventricular tachydysrthythmias caused by digitalis toxicity; long QT syndrome

Class Icsevere ventricular tachycardia and supraventricular tachycardia dysrthythmias, atrial fibrillation and flutter

Class IIBoth supraventricular and ventricular dysrthythmias

Class IIILife- threatening ventricular tachycardia or fibrillation; atrial fibrillation or flutter resistant to other drug therapy

Class IVParoxysmal supraventricular tachycardia; rate control for atrial fibrillation and flutter

CONTRAINDICATIONS Drug allergy Structural heart damage

ADVERSE EFFECTS Hypersensitivity reactions Nausea Vomiting Diarrhea Dizziness Headache Blurred vision


The main toxic effects of the antidysrthythmics involve the heart, circulation, and central nervous system. Specific antidotes are not available, and the management of an overdose involves maintaining adequate circulation and respiration using general support measures and providing any required symptomatic treatment.

INTERACTIONS

Antidysrthythmic drugs can interact with many different categories of drugs. The most serious drug interactions are the ones that can result in dysrthythmias, hypotension, respiratory distress, or any excessive therapeutic or toxic drug effects. Drug interaction occur when the presence of one drug strengthens or weakens the pharmacologic effects of another. This is most commonly seen when the first drug affects the activity of the enzymes that metabolize the second drug, either speeding or slowing its elimination.

One particular interaction common to many antidysrthythmics is the potentiation of anticoagulant activity with warfarin (Coumadin). Because many patients receiving antidysrthythmic therapy also need warfarin, prothrombin time and international normalized ratio should be monitored appropriately and necessary adjustments made to warfarin dosage.


Nursing actions for the various anti dysrthythmics include astute nursing assessment and close monitoring of heart rate, blood pressure, heart rhythms, general well-being, skin color, temperature, and heart and breath sounds.

The therapeutic response to antidysrthythmics include a decrease in blood pressure in hypertensive patients, a decrease in edema, and restoration of a regular pulse rate or pulse rate without major irregularities or with improved regularity compared to the irregularity that existed before therapy.

Patient education about the dosage schedule and the adverse effects the patient should report to the physician is important for safe and effective therapy.

Inform patients that a daily or weekly journal of symptoms, adverse effects, daily weights, a rating of how they feel, activity tolerance, blood pressure, and pulse rates will help with therapy. Also encourage them to weigh the same time every day and while wearing the same amount of clothing.

Instruct the patient to call the physician immediately if there is a weight gain of 2 lb or more in 24 hours or 5 lb or more in 1 week.

The patient should be cautioned to change position slowly because postural hypotension can be an adverse effect of these drugs. Moving too quickly may lead to dizziness, syncope, and subsequent injury or falls.

Instruct the patient that they should not abruptly discontinue their medication and should continue taking it as prescribed.

With amiodarone, photosensitivity is an adverse effect, so the patient should avoid sun exposure and should wear sun-protective clothing and dark glasses when going outside. The patient should be instructed on the need to report any blue-gray discoloration of the skin (often after 1 year, and especially on the face, neck, and arms) immediately to the healthcare provider.

ANTIANGINAL DRUGS

3 Main Classes of Drugs1. Nitrates and nitrites2. - blockers3. Calcium channel blockers (CCB)

3 Main Therapeutic Objectives1. Minimize the frequency of attacks and decrease the duration and intensity of the angina pain;2. Improve the patients functional capacity with as few adverse effects as possible;3. Prevent or delay the worst possible outcome, MI. The overall goal of antianginal drug therapy is to increase blood flow to ischemic myocardium, decrease myocardial oxygen demand, or both.

NITRATES AND NITRITES

This class of antianginal drugs was first discovered by Sir Thomas Lauder Brunton in England. They are available in a wide variety of preparations, including sublingual, chewable, and oral tablets; capsules; ointments; patches; a translingual spray; and intravenous solutions. The following are the rapid and long-acting nitrates available for clinical use: Amyl nitrate (rapid acting) Nitroglycerin (both rapid and long acting) Isosorbide dinitrate (both rapid and long acting) Isosorbide mononitrate ( primarily long acting)


Medicinal nitrates and nitrites, more commonly referred to simply as nitrates, dilate all blood vessels. These vasodilatory effects are the result of relaxation of the smooth muscle cells that are part of the wall structure of veins and arteries. This causes redistribution of blood and therefore oxygen to previously ischemic myocardial tissue and reduction of angina symptoms.

INDICATIONS

The nitrates are used for stable, unstable, and vasoplastic (Prinzmetals) angina. Long-acting dosage forms are used more for prevention of anginal episodes. Rapid-acting dosage forms, most often sublingual nitroglycerin tablets, or an intravenous drip in the hospital setting, are used to treat acute angina attacks.

CONTRAINDICATIONS

Drug allergy Severe anemia Closed-angle glaucoma Hypotension Severe head injury

This is because the vasodilatory effects of nitrates can worsen these latter conditions. In anemia, a drug-induced hypotensive episode can further compromise already reduced tissue oxygenation.

ADVERSE EFFECTS

The most common undesirable effect is headache, which generally diminishes in intensity and frequency soon after the start of therapy. Other cardiovascular effects include tachycardia and postural hypotension.

If nitrate-induced vasodilation occurs too rapidly, the cardiovascular system overcompensates and increases the heart rate, a condition referred to as reflex tachycardia.

INTERACTIONS

Nitrate antianginal drugs can produce additive hypotensive effects when taken in combination with alcohol, -blockers, CCBs, phenothiazines, and erectile- dysfunction drugs such as sildenafil (Viagra).

- BLOCKERS

- blockers approved as antianginal drugs: Atenolol Metropolol Nadolol Propanolol


When receptors are blocked by - blockers, the rate by which the pacemaker (sinoatrial node) fires decreases, and the time it takes for the node to recover increases. The - blockers also slow conduction through the atrioventricular node and reduce myocardial contractility (negative inotropic effect). Both of these effects serve to slow the heart rate (negative chronotropic effect). These effects reduce myocardial oxygen demand, which aids in the treatment of angina by reducing the workload of the heart.

The - blockers also suppress the activity of the hormone renin, a potent vasoconstrictor released by the kidneys when they sense that they are not adequately perfused.

INDICATIONS

The -blockers are most effective in the treatment of typical exertional angina.

The -blockers are also approved for the treatment of: MI Hypertension Cardiac dysrhythmias Essential tremor

CONTRAINDICATIONS

Systolic heart failure and serious conduction disturbances Bronchial asthma Diabetes mellitus Reduced mental alertness Peripheral vascular disease

ADVERSE EFFECTS

BODY SYSTEMADVERSE EFFECTS

Cardiovascularbradycardia, hypotension, 2nd or 3rd degree heart block, heart failure

Central Nervousdizziness, fatigue, mental depression, lethargy, drowsiness

Metabolicaltered glucose and lipid metabolism

Otherwheezing, dyspnea, impotence

INTERACTIONS

INTERACTING DRUGMECHANISMRESULT

Anticholinergics, cimetidineAntagonistc effect; decreased metabolismdecreased level of -blocker; increased levels and pharmacodynamic effects of propanolol and metoprolol

Diuretics and antihypertensivesadditive effectshypotension

phenothiazineadditive hypotensive effectshypotension and cardiac arrest

Phosphodiesterase type 5 inhibitors (e.g. Viagra)additive hypotensive effectspotentially life-threatening hypotension

Insulin and oral diabetic drugsadditive hypoglycemic effectshypogylemia; possibly requiring dosage adjustment of -blocker or antidiabetic drugs

CALCIUM CHANNEL BLOCKERS

The 3 chemical classes of calcium channel blockers:1. Phenylalkylamines (Verapamil)2. Benzothiazepines (Diltiazem)3. Dihydropyridines (Amlodipine, nicardipine, nifedipine)


Calcium plays an important role in the excitation-contraction coupling process that occurs in the heart and vascular smooth muscle cells, as well as in skeletal muscle. Preventing calcium from entering into this process therefore prevents muscle contraction and promotes relaxation instead. Relaxation of the smooth muscles that surround the coronary arteries causes them to dilate. This increases blood flow to the ischemic heart which in return increases the oxygen supply and helps shift the supply and demand ratio back to normal.INDICATIONS

CCBs are considered first-line drugs for the treatment of such conditions as: Angina, Hypertension, and Supraventricular tachycardia.

The CCBs are also used for short-termmanagement of: Atrial fibrillation and flutter Migraine headaches Raynauds disease

CONTRAINDICATIONS

Drug allergy Acute MI 2nd or 3rd degree atrioventricular block (unless the patient has a pacemaker) Hypotension

ADVERSE EFFECTS


Cardiovascularhypotension, palpitation, tachycardia or bradycardia, heart failure

GastrointestinalConstipation, nausea

Otherdermatitis, dyspnea, rash, flushing, peripheral edema, wheezing

INTERACTIONS

INTERACTING DRUGMECHANISMRESULT

-blockeradditive effectsbradycardia and atrioventricular block

Digoxininterference with eliminationpossible increased digoxin levels

blockersdecreased clearanceelevated levels of calcium channel blockers


The patient should be instructed that keeping a journal is a very good way of documenting how the patient feels, including how many anginal episodes occur, what happens, the character and intensity of pain, frequency, and precipitating and relieving factors. Encourage the patient to also make notes about how the medication is tolerated.

If patients are taking capsules or extended-dosage forms, encourage them to not chew, crush, or alter the dosage form.

Educate the patient about the best place to keep the medication away from moisture, light, heat, and cotton filler and to keep the medication in its original packaging (e.g., nitroglycerin in amber-colored glass container). Inform the patient to expect burning or stinging once the medication is placed under the tongue; it is does not burn, then the drug may have lost its potency and a new prescription must be obtained.

It is important to emphasize that the medication is only potent for 3 to 6 months. Remind the patient to always have a fresh supply of the drug on hand, to plan ahead if traveling and (no matter the dosage form) to be seated or lie down when taking the medication to avoid falls secondary to a drop in blood pressure.

Educate the patient that while taking antianginals, they should avoid alcohol, hot environment temperatures, saunas, hot tubs, and excessive exertion because these will lead to worsening of vasodilation with hypotension, possible fainting, or other cardiac events.

If the physician prescribes it, educate the patient to take the nitroglycerin before stressful activities or events such as emotional situations, consumption of large meals, or sudden increase in activity (e.g., sexual intercourse). The patient should be instructed to follow the physicians directions very closely.

ANTIHYPERTENSIVE DRUGS

There are essentially seven main categories of pharmacologic drugs:1. Adrenergic drugs2. Angiotensin- converting enzyme inhibitor3. Angiotensin II receptor blockers4. Calcium channel blockers5. Diuretics6. Vasodilators

ADRENERGIC DRUGS Centrally and peripherally acting adrenergic neuron blockers


The central acting adrenergic drugs work by stimulating the -adrenergic receptors in the brain. The -adrenergic receptors are unique in that receptor stimulating actually reduces sympathetic outflow, in this case from the central nervous system. The resulting lack of norepinephrine production reduces blood pressure.

In the periphery the -blockers doxazosin, prazosin, and terazosin also modify the function of the SNS. However, they do so by blocking the -adrenergic receptors, which, when stimulated by circulating norepinephrine, produce increased blood pressure. Thus, when these receptors are blocked, blood pressure is decreased. The -blockers also increase urinary flow rates and decrease outflow obstruction by preventing smooth muscle contractions in the bladder neck and urethra.

INDICATIONS

The drugs mentioned are used primarily for the treatment of hypertension, either alone or in combination with other antihypertensive drugs.

CONTRAINDICATIONS

Drug allergy Acute heart failure Concurrent use of monoamine oxidase inhibitors Severe mental depression Peptic ulcer Colitis Severe liver or kidney diseaseADVERSE EFFECTS

The most common adverse effects of these drugs are: Bradycardia with reflex tachycardia Postural and postexercise hypotension Dry mouth Drowsiness Sedation Dizziness Edema Constipation Sexual dysfunction

Other effects include: Headaches Sleep disturbances Nausea Rash Peripheral pooling of blood Palpitations

There is also a high incidence of orthosthatic hypotension. This can even lead to a situation known as first-dose syncope, in which the hypotensive effect is severe enough to cause the patient to lose consciousness with even the first dose of medication.

INTERACTIONS

Adrenergic drugs interact primarily with CNS depressant such as alcohol, benzodiazepines, and opioids. The additive effects of these combinations of drugs increase CNS depression.

ANGIOTENSIN- CONVERTING ENZYME INHIBITORS

The available ACE inhibitors are: Captopril (Capoten) Benazepril (Lotensin) Enalapril (Vasotec) Fosinopril (Menopril) Lisinopril (Prinivil, Zestril) Moexipril (Univasc) Perindopril (Aceon) Quinapril (Accupril) Ramipril (Altace), and Trandolapril (Mavik)

These drugs are very safe and efficacious and are often used as first-line drugs in the treatment of both heart failure and hypertension.

Captopril has the shortest half-life and therefore must be dosed more frequently than any of the other ACE inhibitors. Enalapril is the only ACE inhibitor that is available in a parenteral preparation. All other drugs are available only in oral form.


They inhibit angiotensin- converting enzyme, which is responsible for converting AI to AII. AII is a potent vasoconstrictor and induces aldosterone secretion by the adrenal glands. The ACE inhibitors are beneficial in the treatment of heart failure because they prevent sodium and water resorption by inhibiting aldosterone secretion. This causes dieresis, which decreases blood volume and return to the heart.

INDICATIONS

They are excellent antihypertensive and adjunctive drugs for the treatment of heart failure.

CONTRAINDICATIONS

Drug allergy,especially a previous reaction of angioedema (laryngeal swelling) to an ACE inhibitor Patients with a baseline potassium of level of 5 mEq/L or higher may not be a suitable candidate because these drugs can promote hyperkalemia.

ADVERSE EFFECTS

Major CNS effects of the ACE inhibitors include: Fatigue Dizziness Mood changes Headaches

A characteristic dry, nonproductive cough is reversible with discontinuation of the therapy. A first-dose hypotensive effect can cause a significant decline in blood pressure. In patients with severe heart failure whose renal function may depend on the activity of the rennin-angiotensin-aldosterone system, treatment with ACE inhibitors may cause acute renal failure. ACE inhibitors tent to promote potassium resorption in the kidney, although they also promote sodium excretion due to their reduction of aldosterone secretion. One rare, but potentially fatal, adverse effect is angioedema, a strong vascular reaction involving inflammation of submucosal tissues, which can progress to anaphylaxis.


The most pronounced symptom of an overdose of an ACE inhibitor is hypotension. Treatment is symptomatic and supportive and includes the administration of intravenous fluids to expand the blood volume.

INTERACTIONS

Nonsteroidal anti-inflammatory drugs- can reduce the antihypertensive effect Concurrent use of ACE inhibitor and other antihypertensives or diuretics- can have hypotensive effects Lithium + ACE inhibitors= lithium toxicity!

ANGIOTENSIN II RECEPTOR BLOCKERS

ARBs are one of the newest classes of antihypertensives. Losartan (Cozaar) Eprosartan (Teveten) Valsartan (Diovan) Irbesartan (Avapro) Candesartan (Atacand) Olmesartan (Benicar) Telmisartan (Micardis)


ARBs block the binding of A II to type 1 A II receptors . ARBs block vasoconstriction and the secretion of aldosterone.

Clinically, ACE inhibitors and ARBs appear to be equally effective for the treatment of hypertension. Both are well tolerated, but ARBs do not cause cough.

INDICATIONS

Antihypertensive Adjunctive treatment of heart failureThese drugs are used primarily in patients who have been intolerant of ACE inhibitor.

CONTRAINDICATIONS

Drug allergy Pregnancy and lactation

ARBs such as losartan should be used very cautiously in elderly patients with renal dysfunction.

ADVERSE EFFECTS

Most common adverse effects of ARBs are: Upper respiratory infections Headache

Occasionally: Dizziness Inability to sleep Diarrhea Dyspnea Heartburn Nasal congestion Back pain Fatigue

Rarely: Anxiety Muscle pain Sinusitis Cough Insomnia

TOXICITY AND MANAGEMENT

Overdose may manifest as hypotension and tachycardia; bradycardia occurs less often. Treatment is symptomatic and supportive and includes the administration of intravenous fluids to expand the blood volume.

INTERACTION

DRUGMECHANISMRESULT

cimetidinecompetes for metabolismincreased ARB effect

lithiuminhibits lithium eliminationincreased lithium concentration

Phenobarbital, rifampinincreased metabolismdecreased ARB effect

DIURETICS

The diuretics are a highly effective class of antihypertensive drugs. Their primary therapeutic effect is decreasing the plasma and extracellular fluid volumes, which results in decreased preload. This leads to a decrease in cardiac output and total peripheral resistance, all of which decrease the workload of the heart. The thiazide diuretics are the most commonly used diuretics for hypertension.

VASODILATORS

Vasodilators act directly on arteriolar and/or venous smooth muscle to cause relaxation (e.g., IV diazoxide and sodium nitroprusside).


The particular mechanism of action of the direct-acting vasodilators that makes them useful as antihypertensive drugs is their ability to directly elicit peripheral vasodilation. In general, the most notable effect of the vasodilators is their hypotensive effect.

INDICATIONS

All of the vasodilators can be used to treat hypertension, either alone or in combination with other antihypertensives.

CONTRAINDICATIONS

Drug allergy Hypotension Cerebral edema Head injury Acute MI CAD

ADVERSE EFFECTS

Diazoxide: Dizziness Headache Orthostatic hypotension Dysrthythmias Sodium and water retention Nausea Vomiting Acute pancreatitis(rare) Hyperglycemia (in diabetic patients)

Hydralazine: Dizziness Headache Anxiety Tachycardia Edema Nasal congestion Dyspnea Anorexia Nausea Vomiting Diarrhea Anemia Agranulocytosis Hepatitis Peripheral neuritis Systemic lupus erythematosus Rash

Minoxidil: T-wave electrocardiographic echanges Pericardial effusion or tamponade Angina Breast tenderness Rash Thrombocytopenia

Sodium nitroprusside: Bradycardia Decreased platelet aggregation Rash Hypothyroidism Hypotension


The main symptom of diazoxide overdose or toxicity is hypotension, which can usually be controlled by placing the patients bed in Trendelenbrug position.

Minoxidil overdose or toxicity can precipitate excessive hypotension. Treatment is supportive and symptomatic and includes the administration of IV fluids.

The main symptom of sodium nitroprusside overdose or toxicity is excessive hypotension. This drug is normally administered only to patients receiving intensive care. Treatment for the hypotension is supportive and symptomatic.


Educate patients to take medications exactly as prescribed by the physician.

The patient should be informed about the fact that successful therapy requires compliance to medications as well as any dietary restrictions (e.g., decreasing fatty foods or those high in cholesterol and salty foods).

The patient should always monitor stress levels and use biofeedback, imagery, and/or relaxation techniques or massage, as the management of hypertension and serves to relieve stress and is usually inclusive of supervised, prescribed exercise.

The patient should avoid smoking and excessive alcohol intake as well as excessive exercise, hot climates, saunas, hot tubs, and hot environments.

Blood pressure should be recorded, including postural blood pressures. The patient should be sure he or she feels comfortable in taking his or her own blood pressure and pulse rate.

The patient should inform all health providers (e.g., dentist, surgeon) that he or she in taking antihypertensive drugs.

The patient should be sure to move purposefully and cautiously and to change positions slowly because of the possible adverse effect of postural hypotension and associated risk for dizziness. Lightheadedness, and possible fainting and falls.

With successful therapy, the patients condition will improve; however , the patient should be cautioned not to stop taking the medication just because he or she is feeling better. Lifelong therapy is required.

Encourage patient to use saliva substitutes, sugar-free hard candy, or frequent fluids for management of dry mouth.

Share with the patient measures to help with constipation, such as forcing fluids, increasing fiber and roughage, and contacting the physician if there is no relief of this adverse effect.

Patients should know to never abruptly stop taking the medication for any reason, including sexual problems, because of the risk of severe hypertensive rebound.

DIURETIC DRUGS

The potency of these diuretics is a function of where they work in the nephron to inhibit sodium and water resorption. The more sodium and water they inhibit from resorption , the greater the amount of dieresis and therefore the greater the potency.

CLASSIFICATION OF DIURETICS

CLASSDRUGS

Carbonic anhydrase inhibitorsAcetazolamide, dichlorphenamide, methazolamide

Loop diureticsBumetanide, ethacrynic acid, furosemide, torsemide

Osmotic diureticsMannitol

Potassium- sparing diureticsAmiloride, spirolactone, triamterene

Thiazide and thiazide-like diureticsChlorothiazide, hydrochlorotiazide

CARBONIC ANHYDRASE INHIBITORS

The site of action of the CAIs is the location of the carbonic anhydrase enzyme system along the nephron, primarily in the proximal tubule.

MECHANISM OF ACTION

The carbonic anhydrase system in the kidney is located just distal to the glomerulus in the proximal tubules, where roughly two thirds of all sodium and water is resorbed in the blood. For sodium and thus water to be resorbed back into the blood, hydrogen must be exchanged for it. Without hydrogen, this cannot occur, and the sodium and water will be eliminated with the urine. Carbonic anhydrase helps to make the hydrogen ions.

When its actions are inhibited by a CAI such as acetazolamide, little sodium and water can be resorbed into the blood and they are eliminated with the urine.

The metabolic acidosis induced by CAIs is beneficial in the prevention of certain seizures.

INDICATIONS

They are commonly used in the treatment of: Glaucoma Edema Epilepsy High-altitude sickness

CONTRAINDICATIONS

Drug allergy Hyponatremia Hypokalemia Severe renal or hepatic dysfunction

ADVERSE EFFECTS

The more common undesirable effects with CAIs Acidosis HypokalemiaThese drugs may also cause: Drowsiness Anorexia Paresthesias Hematuria Urticaria Photosensitivity Melena

INTERACTIONS

Increase in digitalis toxicity when CAIs and digitalis are given together, stemming from the hypokalemia that CAIs may induce. Concomitant use of CAIs and corticosteroids may also cause hypokalemia. Their use with oral hypoglycemic drugs and quinidine may induce greater activity or toxicity of the latter drug.

LOOP DIURETICS

Loop diuretics (bumetanide, ethacrynic acid, furosemide, and torsemide) are very potent diuretics.

MECHANISM OF ACTION

Their renal effects are their major mechanism of action. These drugs act primarily along the thick ascending limb of the loop of Henle, blocking chloride and, secondarily, sodium resorption. Loop diuretics are particularly useful when rapid dieresis is needed, because of their rapid onset of action. In addition, the diuretic effect last at least 2 hours.

The resulting decreased fluid volume leads to a decreased return of blood to the heart, or decreased filling pressures. This has the following cardiovascular effect: Reduces blood pressure Reduces pulmonary vascular resistance Reduces systemic vascular resistance Reduces central venous pressure

INDICATIONS

Edema associated with heart failure and hepatic or renal disease Control hypertension Increase the renal excretion of calcium in patients with hypercalcemia

CONTRAINDICATIONS

Drug allergy Hepatic coma Severe electrolyte loss

COMMON ADVERSE EFFECTS


Central nervousDizziness, headache, tinnitus, blurred vision

GastrointestinalNausea, vomiting, diarrhea

HematologicAgranulocytosis, thrombocytopenia, neutropenia

MetabolicHypokalemia


Electrolyte loss and dehydration, which can result in circulatory failure, are the main toxic effects of loop diuretics that require attention. Treatment involves electrolyte and fluid replacement.

INTERACTIONS

INTERACTING DRUGMECHANISMRESULTS

Aminoglycosides,Capreomycin,Chloroquine,Vancomycin,Additive effectIncreased neurotoxicity, especially ototoxicity

Corticosteroids,DigoxinHypokalemiaAdditive hypokalemia,Increased digoxin toxicity

LithiumDecrease in renal excretionIncreased lithium toxicity

NSAIDsInhibition of renal prostaglandinsDecreased diuretic activity

SulfonylureasDecrease in glucose toleranceHyperglycemia

OSMOTIC DIURETICS

The osmotic diuretics include mannitol, urea, organic acids, and glucose. Mannitol, a nonabsorbable solute, is the most commonly used of these drugs.


Mannitol works along the entire nephron. Its major action, however, is the proximal tubule and descending limb of the loop of Henle. It produces osmotic pressure in the glomerular filtrate, which in turn pulls fluid, primarily water, into the renal tubules from surrounding tissues. This process also inhibits the tubular resorption of water and solutes, which produces rapid diuresis.

Mannitol may induce vasodilation and in doing so increase both glomerular filtration and renal plasma flow. This makes it an excellent drug for preventing kidney damage during acute renal failure. It is also often used to reduce intracranial pressure and cerebral edema resulting from head trauma.

INDICATIONS

Mannitol is the osmotic drug of choice. It is commonly used in the treatment of patients in the early, oliguric phase of acute renal failure.

CONTRAINDICATIONS Drug allergy Severe renal disease Pulmonary edema (loop diuretics are used instead) Active intracranial bleeding

ADVERSE EFFECTS Convulsions Thrombophlebitis Pulmonary congestion

INTERACTIONS

There are no drugs that interact significantly with mannitol.

POTASSIUM- SPARING DIURETICS

The currently available potassium- sparing diuretics are amiloride, spironolactone, and triamterene.


Spironolactone competitively binds to aldosterone competitively binds to aldosterone receptors and therefore blocks the resorption of sodium and water that is induced by aldosterone secretion. These receptors are found primarily in the distal tubule.

Amiloride and triamterene do not bind to aldosterone receptors. However, they inhibit both aldosterone-induced and basal sodium reabsorption, working in both the distal tubule and collecting ducts. They are often prescribed for children with heart failure, because pediatric cardiac problems are frequently accompanied by an excess secretion of aldosterone.

INDICATIONS

Spironolactone and triamterene are used to treat: Hyperaldosteronism Hypertension Reverse potassium loss caused by potassium wasting (e.g., loop, thiazide) diuretics. The uses for amiloride are similar to those spironolactone and triamterene, but amiloride is less effective in the long term.

CONTRAINDICATIONS

Drug allergy Hyperkalemia (serum potassium level exceeding 5.5 mEq/L) Severe renal failure or anuriaTriamterene use may also be contraindicated in cases of severe hepatic failure.

ADVERSE EFFECTS


Central nervousDizziness, headache

Gastrointestinal Cramps, nausea, vomiting, diarrhea

Other Urinary frequency, weakness, hyperkalemia

INTERACTIONS

The administration of ACE inhibitors or potassium supplements in combination with potassium-sparing diuretics can result in hyperkalemia.

When lithium and potassium-sparing diuretics are given together, lithium toxicity can result.

NSAIDs can inhibit renal prostaglandins, decreasing blood flow to the kidneys and therefore decreasing the delivery of diuretic drugs to this site of action. This in turn can lead to a diminished diuretic response.

THIAZIDES AND THIAZIDE-LIKE DIURETICS

Hydrochlorothiazide is undoubtedly the most commonly prescribed and the least expensive of the generic preparations.

The thiazide diuretics include: bendroflumethiazide, chlorothiazide, methyclothiazide, and trichlormethiazide.

The thiazide-like diuretics are very similar in action to the thiazides and include: chlorthalidone, indapamide, and metolazone.

Of all of the drugs just mentioned, hydrochlorothiazide and metolazone are by far the most commonly prescribed in practice.


The primary site of action of thiazides and thiazide-like diuretics is the distal convoluted tubule, where they inhibit the resorption of sodium, potassium, and chloride. This results in osmotic water loss.

Thiazides generally should not be used if creatinine clearance is less than 30 to 50 mL/min. Normal creatinine clearance is 125 mL/min. The only exception is metolazone, which remains effective to a creatinine clearance of 10 mL/min.

INDICATIONS

Edematous states Diabetes insipidus HypertensionThis group of diuretics may also be useful as adjunct drugs in the treatment of: Edema related to heart failure, Hepatic cirrhosis, Corticosteroid or estrogen therapy

CONTRAINDICATIONS

Drug allergy Hepatic coma (metolazone) Anuria Severe renal failure

ADVERSE EFFECTS


Central nervousDizziness, headache, blurred vision, presthesia, decreased libido

GastrointestinalAnorexia, nausea, vomiting, diarrhea, pancreatitis, cholecystitis

Genitourinary Impotence

Hematologic Jaundice, leukopenia, purpura, agranulocytosis, aplastic anemia, thrombocytopenia

Integumentary Urticaria, photosensitivity

Metabolic Hypokalemia, glycosuria, hyperglycemia, hyperuricemia


An overdose of these drugs can lead to an electrolyte imbalance resulting from hypokalemia. Symptoms include: Anorexia Nausea Lethargy Muscle weakness Mental confusion HypotensionTreatment involves electrolyte replacement.INTERACTIONSINTERACTING DRUGMECHANISMRESULTS

Corticosteroids Additive effect Hypokalemia

Diazoxide Additive effect Hyperkalemia

Digoxin Hypokalemia Increased digoxin toxicity

Lithium Decreased clearanceIncreased lithium toxicity

NSAIDsInhibition of renal prostaglandinsDecreased diuretic activity

Oral hypoglycemicsAntagonism Reduced therapeutic hypoglycemic effect


Patient should maintain proper nutrition intake and fluid volume status with attention to eating potassium-rich foods, except when contraindicated or when taking potassium- sparing diuretics.

Foods high in potassium include bananas, oranges, dates, plums, fresh vegetables, potatoes (white and sweet), meat, fish, apricots, whole grain cereals, and legumes.

Patients need to change positions slowly and to rise slowly after sitting or lying to prevent dizziness and possible fainting (syncope).

Prevent constipation with an increase in fiber, bulk, roughage, and fluids if not contraindicated.

For patients with diabetes mellitus who are also taking thiazide and/or loop diuretics, educate them about close monitoring of blood glucose levels. These diuretics may cause elevation of blood glucose.

FLUIDS AND ELECTROLYTES

CONDITIONS LEADING TO FLUID LOSS OR DEHYDRATION AND ASSOCIATED CORRESPONDING SYMPTOMS

CONDITIONASSOCIATED SYMPTOMS

Bleeding Tachycardia and hypotension

Bowel obstruction Reduced perspiration and mucous secretions

DiarrheaReduced urine output (oliguria)

Fever Dry skin and mucous membrane

Vomiting Reduced lacrimal (tears) and salivary secretions

When fluid that has been lost must be replaced, there are three categories of agents that can be used to accomplish this:1. Crystalloids2. Colloids3. Blood products

CRYSTALLOIDS

Crystalloids are fluids given by intravenous injection that supply water and sodium to maintain osmotic gradient between the extravascular and intravascular compartments. NS Hypertonic saline Lactated Ringers W Plasma-Lyte


Because crystalloids work by osmosis, hypertonic saline (3% sodium chloride) is more efficient than normal saline (NS) (0.9% sodium chloride) for expanding the PV.

Crystalloid solutions contain fluids and electrolytes that are normally found in the body. They do not contain proteins (colloids), which are necessary to maintain the colloid osmotic pressure and prevent water from leaving the plasma compartment.

Crystalloids are also distributed faster into the interstitial and intracellular compartments, which makes them better for treating dehydration than for expanding the PV alone, such as in hypovolemic shock.

INDICATIONS

Crystalloid solutions are most commonly used as maintenance fluids. They are used to compensate for insensible fluid losses, to replace fluids when there are body-fluid deficits. Manage specific fluid and electrolyte disturbances. Less expensive than colloids and blood products.

Following are the common indications for either crystalloid or colloid replacement therapy: Acute liver failure Acute nephrosis Adult respiratory distress syndrome Burns Cardiopulmonary bypass Hypoproteinemia Reduction of the risk for deep vein thrombosis (DVT) Renal dialysis Shock

CONTRAINDICATIONS

Drug allergy Hypervolemia Severe electrolyte disturbance

ADVERSE EFFECTS

Because they contain no large particles, such as proteins, they do not stay within the blood vessels and can leak out of the plasma into the tissues and cells. This may result in edema anywhere in the body, due to osmosis from the crystalloid itself. Peripheral edema and pulmonary edema are two common examples.

INTERACTIONS

Interactions with crystalloid solutions are rare because they are very similar if not identical to normal physiologic substances.

COLLOIDS

Colloids are protein substances that increase the capillary osmotic pressure and effectively move fluid from the interstitial compartment to the plasma compartment by pulling the fluid into the blood vessels.Commonly used colloids: Dextran 70 Dextran 40 Hetastarch 5% Albumin 25% Albumin


The mechanism of action of colloids is related to their ability to increase COP. Because colloids increase the blood volume, they are sometimes called plasma expanders.

INDICATIONS

Colloids are superior to crystalloids in their ability to maintain PV for a longer term.

CONTRAINDICATIONS

Drug allergy Hypervolemia Severe electrolyte disturbance

ADVERSE EFFECTS

Colloids are relatively safe agents, although there are some disadvantages to their use. They have no oxygen-carrying ability and contain no clotting factors, unlike blood products. Because of this, they can alter the coagulation system through dilutional effect, resulting in: Impaired coagulation and, possibly Bleeding.

INTERACTIONS

Because colloids are so compatible with many drugs, they are sometimes used as medium for delivering them.

BLOOD PRODUCTS

Blood products can be thought of as biologic drugs. All of them can augment the PV. Red blood cell (RBC)- containing products can also improve tissue oxygenation, as well as augment PV.

Blood products are also expensive and are less available than crystalloids and colloids because they are natural products and require human donor.

MECHANISM OF ACTION AND DRUG EFFECTS Red blood cell (RBC) products have the ability to carry oxygen. They can maintain the COP for several hours to days, and because they come from human donors, they have all the benefits (and hazards) that human blood products have. They are administered when a persons body is deficient in these products.

BLOOD PRODUCTS: INDICATIONS

BLOOD PRODUCTINDICATION

Cryoprecipitate and plasma protein fractions (PPF)To manage acute bleeding

Fresh frozen plasma (FFP)To increase clotting factor levels in patients with a demonstrated deficiency

Packed red blood cell (PRBC)To increase oxygen-carrying capacity in patients with substantial hemoglobin deficits, and in patients who have lost up to 25% of their total blood volume

Whole bloodSame as for PRBCs, except that whole blood is more beneficial in cases of extreme (>25%) loss of blood volume since whole blood also contains plasma, the chief fluid volume of the blood; it also contains plasma proteins, the chief osmotic component, which help draw fluid back into blood vessels from surrounding tissues

CONTRAINDICATIONS

There are no absolute contraindications to the use of blood products. However, because of the risk for transfer of infectious disease, although remote, their use should be based on careful clinical evaluation of the patients condition.

ADVERSE EFFECTS

Because these products come from other humans, they can be incompatible with the recipients immune system. These incompatibilities are tested for before the administration of the particular blood product by determining the respective blood types of the donor and recipient and by doing cross-matching tests to screen for incompatibility between selected blood proteins.

These products can also transmit pathogens from the donor to the recipient. Examples of such pathogens are hepatitis and HIV.

INTERACTIONS

They interact with very few substances.

POTASSIUM

Potassium is the most abundant cationic (positively charged) electrolyte inside the cells (intracellular space), where the normal concentration is approximately 150 mEq/L. The potassium content outside the cells in the plasma ranges from 3.5 to 5 mEq/L.

Potassium is obtained from a variety of foods, the most common being fruit and juices, fish, vegetables, poultry, meats, and dairy products.

SYMPTOMS OF HYPOKALEMIA

Early Anorexia Hypotension Lethargy Mental confusion Muscle confusion Nausea

Late Cardiac dysrthythmias Neuropathy Paralytic ileus Secondary alkalosis

MECHANISM OF ACTION AND DRUG EFFECTS Functions of potassium in our body: Muscle contraction Transmission of nerve impulse Regulation of heartbeats

INDICATIONS

Potassium replacement therapy is called for in the treatment or prevention of potassium depletion in patients whenever dietary measures prove inadequate.

CONTRAINDICATIONS

Drug allergy Hyperkalemia Severe renal disease Acute dehydration Severe hemolytic disease

ADVERSE EFFECTS

Gastrointestinal (occur with oral administration) Diarrhea Nausea Vomiting GI bleeding UlcerationOccur with parenteral administration Pain at the injection site Phlebitis


The toxic effects of potassium are the result of hyperkalemia. Symptoms include: Muscle weakness Paresthesia Paralysis Cardiac rhythm irregularities

The treatment instituted depends on the degree of the hyperkalemia and ranges from regimens for reversible life-threatening problems to simple dietary restrictions.

In the event of severe hyperkalemia, intravenous administration of sodium bicarbonate, calcium gluconate or chloride, or dextrose solution with insulin is often required. These drugs correct severe hyperkalemia by causing rapid intracellular shift of potassium ions, thus reducing the serum potassium concentration.

INTERACTIONS

Concurrent use of potassium-sparing diuretics and ACE inhibitors can produce a hyperkalemic state. Concurrent use of diuretics, amphotericin B, and mineralosteroids can produce a hypokalemic state.

SODIUM

Sodium is the principal cation outside the cell. The normal concentration of sodium outside cells is 135-145 mEq/L, and it is maintained through dietary intake of sodium in the form of sodium chloride, which is obtained from salt; fish; meats; and other foods flavored, seasoned, or preserved with salt.

HYPONATREMIA SYMPTOMS

Lethargy Hypotension Stomach cramps Vomiting Diarrhea Seizures Excessive perspiration(occurring during hot weather or physical work) Prolonged diarrhea or vomiting (especially in young children) Renal disorders Adrenocortical impairment

HYPERNATREMIA SYMPTOMS

Edema Hypertension Red, flushed skin Sticky mucous membranes Increased thirst Temperature elevation Decreased or absent urination


Sodium is principally involved in the control of water distribution, fluid and electrolyte balance, and osmotic pressure of body fluids. Sodium is also capable of causing diuresis.

INDICATIONS

Sodium is primarily administered in the treatment or prevention of sodium depletion when dietary measures have provided inadequate.

Pronounced sodium depletion is treated with NS or lactated Ringers solution administered intravenously.

CONTRAINDICATIONS

Drug allergy Hypernatremia

ADVERSE EFFECTS

Oral administration: Gastric upset Nausea Vomiting CrampsParenteral administration Venous phlebitis


Treatment consists of increased fluid intake and dietary restrictions.

INTERACTIONS

Sodium is not known to interact significantly with any drugs.


Blood products may cause hemolysis of RBCs, and, therefore, adverse reactions such as fever, chills, and back pain should be watched for continually.

Hematuria may occur if the hemolysis reaction is present.

If noted, the nurse should notify the physician immediately, the IV infusion discontinued, and the nature of the reaction and all actions taken documented.

Blood products should be given only with NS 0.9% because W will cause hemolysis of the blood product.

As needed, educate the patient about the difference in signs and symptoms of hyponatremia and hypernatremia, hypokalemia and hyperkalemia.

COAGULATION MODIFIER DRUGS

These drugs can be broken down into several main categories based on their actions:

Anticoagulants- inhibit the action or formation of clotting factors and, therefore, prevent clots from forming.

Antiplatelet- prevent platelet plugs from forming by inhibiting platelet aggregation, which can be beneficial in preventing heart attacks and strokes. These are sometimes referred to as hemorrheologic drugs.

Antifibrinolytic drugs- also known as hemostatic drugs, have the opposite effect of these other classes of drugs; they actually promote blood coagulation and are helpful in the management of conditions which excessive bleeding would be harmful.

Thrombolytic drugs- lyse (break down) clots, or thrombi, that have already formed.

ANTICOAGULANTS

Drug classes of anticoagulants include older drugs such as unfractioned heparin and warfarin.

MECHANISM OF ACTION

Heparin works by binding to a substance called antithrombin III (AT-III) which turns off 3 main activating factors: activated II (also called thrombin), activated X, and activated IX.

Warfarin (Coumadin) also works by inhibiting vitamin K synthesis by bacteria in the gastrointestinal tract.

INDICATIONS MI Unstable angina Atrial fibrillation Indwelling devices such as mechanical heart valves Conditions in which blood flow may be slowed and blood may pool

CONTRAINDICATIONS

Drug allergy Acute bleeding Thrombocytopenia Leukemia or other blood dyscrasias Pregnancy GI obstruction Serious inflammation Infection

ADVERSE EFFECTS

Bleeding is the main complication of anticoagulant therapy, and the risk increases with increasing dosages. Such bleeding may be localized or systemic.

INTERACTIONS

The main interaction mechanisms responsible for increasing anticoagulant activity include the following: Enzyme inhibition of biotransformation Displacement of the drug from inactive protein- binding sites Decrease in vitamin K absorption or synthesis by the bacterial flora of the large intestines Alteration in the platelet count or activity


Symptoms that may be attributed to toxicity or an overdose of anticoagulants are: Hematuria Melena Petechiae Ecchymoses Gum or mucous membrane bleeding

In the event of either heparin or warfarin toxicity, the drug should be discontinued immediately. In severe cases or when large doses have been given intentionally, IV injection of protamine sulfate is indicated.

ANTIPLATELET DRUGS

Aspirin Clopidogrel Dipyridamole Pentoxifylline Cilostazol Anagrelide Abciximab Tirofiban Eptifibatide

MECHANISM OF ACTION

Many of the antiplatelet drugs affect the cyclooxygenase pathway, which is one of the common final enzymatic pathways in the complex arachidonic acid pathway that operates within platelets and on blood vessel walls.

INDICATIONS

Aspirin: Officially recommended for stroke prevention by the American Stroke Society

Clopidogrel: Used for reducing the risk for fatal and nonfatal thrombotic stroke Used for prophylaxis against transient ischemic attacks as well as post-MI thromboprevention.Dipyridamole Used as adjunct to warfarin in the prevention of postoperative thromboembolic complications. Also used to decrease platelet aggregation in various other thromboembolic disorders.

Pentoxifylline Indicated for peripheral vascular disease

Cilostazol Indicated specifically for intermittent claudication (pain and cramping in the calf muscle associated with walking)

CONTRAINDICATIONS

Drug allergy Thrombocytopenia Active bleeding Leukemia Traumatic injury GI ulcer Vitamin K deficiency Recent stroke

ADVERSE EFFECTS


Aspirin

Central nervousStimulation, drowsiness, dizziness, confusion, flushing

GastrointestinalNausea, vomiting, GI bleeding, diarrhea, heartburn

HematologicThrombocytopenia, agranulocytosis, leucopenia,neutropenia, hemolytic anemia,bleeding

Clopidogrel

CardiovascularChest pain, hypertension, edema

Central nervousFlulike symptoms, headache, dizziness, fatigue

GastrointestinalAbdominal pain, dyspepsia, diarrhea, nausea

MiscellaneousEpistaxis and integumentary disorders, including rash and pruritis

INTERACTIONS

The concurrent use of dipyridamole, with aspirin, clopidogrel, and/or nonsteroidal anti-inflammatory drugs (NSAIDs) produces additive antiplatelet activity and increased bleeding potential.

The combined use of aspirin and steroids or NSAIDs can increase the ulcerogenic effects of aspirin.

When aspirin is given with oral antidiabetic drugs, the patient can experience a loss of diabetic control.

ANTIFRIBINOLYTIC DRUGS

The term antifibrinolytic refers to what these drugs can do, which is to prevent the lysis of fibrin; in doing so, they actually promote clot formation.

There are three synthetic antifibrinolytics:1. Aminocaproic acid2. Tranexamic acid3. Desmopressin

One natural antifibrinolytic drug:1. Aprotinin


Aminocaproic acid, tranexamic acid, and aprotinin prevent breakdown of fibrin, which prevents the destruction of the formed platelet clot.

Desmopressin causes a dose-dependent increase in the concentration of plasma factor VIII (von WIlleband factor), along with an increase in the plasma concentration of tissue plasminogen activator.

INDICATIONS

Antifibrinolytics are useful in both prevention and treatment of excessive bleeding resulting from systemic hyperfibrinolysis or surgical complications. They also have proved successful in arresting excessive oozing from surgical sites such as chest tubes.

Desmopressin may also be used in patients who have hemophilia A or type I von Willebrands disease.

CONTRAINDICATIONS Drug allergy Disseminated intravascular coagulation

ADVERSE EFFECTS


Cardiovascular Dysrhythmias, orthostatic hypotension, bradycardia

Central nervousHeadache, dizziness, fatigue, hallucination, psychosis, convulsions

GastrointestinalNausea, vomiting, abdominal cramps, diarrhea

INTERACTIONS Concurrent use of drugs such as estrogens or oral contraceptives with aminocaproic acid, tranexamic acid, and aprotinin may have an additive effect, resulting in increased coagulation.

THROMBOLYTIC DRUGSThrombolytics are coagulation modifiers that lyse thrombi in the blood vessels that supply the heart with blood, the coronary arteries.


Thrombolytics accomplish its action by activating the conversion of plasminogen to plasmin, which breaks down, or lyses, the thrombus. This reestablishes blood flow to the blood-starved heart muscle. If the blood flow is reestablished early, the heart muscle and left ventricular function can be saved. If blood flow is not reestablished early, the affected area of the heart muscle becomes ischemic, and eventually necrotic and nonfunctional.

INDICATIONS

Acute MI Arterial thrombosis DVT Occlusion of shunts or catheters Pulmonary embolism Acute ischemic stroke

CONTRAINDICATIONS

Drug allergy Concurrent use with other drugs that alter clotting

ADVERSE EFFECTS

The most common undesirable effect of thrombolytic therapy is internal, intracranial and superficial bleeding.

Other problems include: Hypersensitivity Anaphylactoid reactions Nausea Vomiting Hypotension

These drugs can also induce cardiac dysrthythmias.

TOXICITY AND MANAGEMENT

Acute toxicity primarily causes an extension of the adverse effects of the thrombolytic agent. Treatment is symptomatic.

INTERACTIONS

The most common effect of drug interactions is an increased bleeding tendency resulting from the concurrent use of anticoagulant, antiplatelet, or other drugs that affect platelet function.


Subcutaneous heparin injections After thorough checking the physicians order, assess the patient for the existence of any allergies, contraindications, cautions, or drug interactions. Check injection site for bleeding or bruising and document any pertinent information. The nurse should not massage or rub the injection. Do not aspirate before injecting to avoid/prevent the occurrence of hematoma.

Intravenous heparin administration Always double-check the specific physicians order for dosage, rate of infusion, and time and route before beginning the therapy.

For continuous IV administration of heparin, an IV pump must be used to ensure a precise rate of infusion.

Intermittent infusions of heparin are usually ordered to be given every 4 to 6 hours because of heparins short half-life. Intermittent infusions and all other types of IV infusions include use of needle-less system.

For intermittent infusions, a heparin lock was used in the past. Heparin locks are now referred to as intermittent infusion locks or salinelocks (because the locks are flushed with isotonic saline and nit heparin).

Oral anticoagulant administration It is important to recheck the physicians orders and the patients medication and medical history before administering the drug. Always check to make sure the patient has no known hypersensitivity to the drug.

Dosages of warfarin are calculated based upon INR blood values. INRs are also used to monitor the effectiveness of therapy, remember, however, dosing is highly individualized.

ANTILIPEMIC DRUGS

The decision to prescribe hyperlipemic drugs as an adjunct to diet therapy in patients with an elevated cholesterol level should be based on the patients clinical profile.

When the decision to institute drug therapy has been made, the choice of drug should then be determined by the specific lipid profile of the patient.

There are currently 4 established classes of drugs used to treat dyslipidemia:1. HMG-CoA reductase inhibitors (statins)2. Bile acid sequestrants3. B- vitamin niacin (vitamin , also known as nicotinic acid)4. Fibric acid derivatives (fibrates)

In addition to all of these drugs, the newest drug, ezetimibe (Zetia), is cholesterol absorption inhibitor.

HMG-CoA REDUCTASE INHIBITORS

The rate-limiting enzyme in cholesterol synthesis is known as HMG-CoA reductase. This class of medication competitively inhibits this enzyme. They are the most potent of the drugs available for reducing plasma concentrations of LDL cholesterol.

Lovastatin- the first drug in this class to be approved for use, and this occurred in 1987.

Since that time, 6 other HMG-CoA reductase inhibitors have become available on the U.S. market: Pravastatin Simvastatin Atorvastatin Cerivastatin Fluvastatin Rosuvastatin

MECHANISM OF ACTION AND DRUG AFFECTS

Statins lower the blood cholesterol level by decreasing the rate of cholesterol production. The liver requires HMG-CoA reductase to produce cholesterol. It is the rate-limiting enzyme in the reactions needed to make cholesterol. The statins inhibit this enzyme, thereby decreasing cholesterol production.INDICATIONS

First-line drug therapy for hypercholesterolemia, the most common and dangerous form of dyslipidemia.

These drugs also appear to be equally effective in their ability to reduce LDL cholesterol concentrations.

CONTRAINDICATIONS

Drug allergy Pregnancy Liver disease Elevation of liver enzymes

ADVERSE EFFECTS


Central nervousHeadache, dizziness, blurred vision, opthalmoplegia, fatigue, nightmares, insomnia

GastrointestinalConstipation, cramps, diarrhea, nausea,changes in bowel function

Other Myalgias, skin rashes


Very limited data are available on the nature of toxicity and overdose in patients taking HMG-CoA reductase inhibitors. Treatment, if needed, is supportive and based on presenting symptoms.

INTERACTIONS

HMG-CoA reductase inhibitors should be used cautiously in patients taking oral anticoagulants.

BILE ACID SEQUESTRANTS

Bile acid sequestrants, also called bile acid-binding resins and ion-exchange resins, include: Cholestyramine Colestipol Colesevelam


Bile acids are necessary for the absorption of cholesterol from the small intestine, yet are also synthesized from cholesterol by the liver. This is one natural way that the liver excretes cholesterol from the body. The more the bile acids are excreted in the feces, the more the liver converts cholesterol to bile acids. This reduces the level of cholesterol in the liver, and thus, the circulation as well.

CONTRAINDICATIONS

Drug allergy Biliary or bowel obstruction

ADVERSE EFFECTS


Gastrointestinal Constipation, heartburn, nausea, belching, bloating

OtherBleeding, headache, tinnitus, burnt odor of urine


Because the bile acid sequestrants are not absorbed, an overdose could cause obstruction of the GI tract. Therefore, treatment of an overdose involves retoring gut motility.

INTERACTIONS

All drugs should be taken at least 1 hour before or 4 to 6 hours after the administration of ion-exchange resins. In addition, high doses of a bile sequestrants will decrease the absorption of fat-soluble vitamins (A, D, E and K).

NIACIN

Niacin, or nicotinic acid, is not only a very unique lipid-lowering drug, it is also a vitamin. It is often given in combination with other antilipemic drugs to enhance the lipid-lowering effects.


Although the exact mechanism of action of niacin is unknown, the beneficial effects are believed to be related to its ability to inhibit lipolysis in adipose tissue and increase the activity of lipoprotein lipase.

CONTRAINDICATIONS

Drug allergy Liver disease Hypertension Peptic ulcer disease Any active hemorrhagic disease

ADVERSE EFFECTS


Gastrointestinal Abdominal discomfort, GI distress

Integumentary Cutaneous flushing, pruritus, hyperpigmentation

Other Blurred vision, glucose intolerance, hyperuricemia, dry eyes(rare), hepatotoxicity

INTERACTIONS

The major drug interactions associated with niacin are minimal. One interaction of note: when niacin is taken concomitantly with an HMG-CoA reductase inhibitor, the likelihood of myopathy development is increased.

FIBRIC ACID DERIVATIVES

Current fibric acid derivatives include gemifibrozil and fenofibrate. They are often collectively referred to as fibrates.


Fibric acid drugs are believed to work by activating lipoprotein lipase, an enzyme responsible for the breakdown of cholesterol.

CONTRAINDICATIONS

Drug allergy Severe liver or kidney disease, cirrhosis Gallbladder disease

ADVERSE EFFECTS


Gastrointestinal Nausea, vomiting, diarrhea, gallstones, acute appendicitis

Genitourinary Impotence, decreased urine output, hematuria, increased risk for urinary hematuria, increased risk for UTI and viral infections

Other Drowsiness, dizziness, rash, pruritus, alopecia, eczema, vertigo, headache


The management of fibrate overdose, which is uncommon, is supportive care based on presenting symptoms. GI contamination or use of gastric lavage may be indicated for large overdoses.

INTERACTIONS

Gemfibrozil can also enhance the action of oral anticoagulants, thus also necessitating careful dose adjustment of these latter drugs.

The risk for myalgia, myositis, and rhabdomyolysis is increased when either gemfibrozil or fenofibrate is given with a statin.


Educate patients about the need for eating plentiful amounts of raw vegetables, fruit and bran and at least 2000mL of fluids a day to prevent the constipation that is commonly experienced with antilipemics.

Inform patients to engage in moderate daily exercise as ordered by their physician and to exchange positions slowly.

If patients are taking a bile acid sequestrant, make sure they contact their health care provider immediately if they notice their stool appear black and tarry.

With statin drugs Take the medication with at least 6 oz of water with meals to help minimize gastric upset.

It may take several weeks before therapeutic results are seen, and frequent laboratory testing will occur at about every 3 to 6 months.

If taking one of the statin drugs, an ophthalmic examination is needed prior to and during therapy due to the problems reported with visual acuity.

Other side effects may include decreased in libido, severe muscle pain, chest pain, or other unexplained pain, patients should contact their physician immediately.

All patients should receive nutritional consultation and menu planning assistance related to a low-fat diet.Page | 27

Drugs Affecting the Cardiovascular and Renal System

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