What are inotropic agents

Inotropic agents or inotropes, are medications that change the force of your heart’s contractions. There are 2 kinds of inotropes: positive inotropes and negative inotropic drugs. Positive inotropic drugs strengthen the force of the heartbeat. Negative inotropic drugs weaken the force of the heartbeat.

Both kinds of inotropic agents are used in the treatment of many different cardiovascular conditions. The kind of inotropic medication you are given depends on the condition you have.

Positive and negative inotropic drugs work in different ways.

Positive inotropic medications strengthen the heart’s contractions, so it can pump more blood with fewer heartbeats. This medicine is usually given to patients with congestive heart failure or cardiomyopathy. These medicines may also be given to patients who have had a recent heart attack. In some cases, inotropes are given to patients whose hearts have been weakened after heart surgery (in cases of cardiogenic shock).

Negative inotropic medications weaken the heart’s contractions and slow the heart rate. These medicines are used to treat high blood pressure (hypertension), chronic heart failure, abnormal heart rhythms (arrhythmias), and chest pain (angina). They are sometimes used in heart attack patients to reduce stress on the heart and prevent future heart attacks.

Talk to your doctor about your medical history before you start taking inotropic medications. The risks of taking the medicine need to be weighed against its benefits. Here are some things to consider if you and your doctor are deciding whether you should begin taking inotropic medications.

• You have aortic stenosis.
• You have bradycardia (a very slow heart rate). Certain types of inotropic drugs, especially digoxin, should not be used unless you have a pacemaker.
• You are pregnant or are thinking of becoming pregnant.
• You are breastfeeding.
• You have kidney or liver disease.
• You have thyroid disease.

How much inotropic drugs do I take?

There are many different kinds of inotropic drugs. The amount of medicine you need to take may vary. Talk to your doctor or pharmacist for more information about how and when to take this medicine.

What if I am taking other medicines?

Other medicines that you may be taking can increase or decrease the effect of inotropic drugs. These effects are called an interaction. Be sure to tell your doctor about every medicine and vitamin or herbal supplement that you are taking, so he or she can make you aware of any interactions.

The following are some of the medicines that can interact with inotropic drugs. Because there are so many kinds of medicines within each category, not every type of medicine is listed by name. Tell your doctor about every medicine that you are taking, even if it is not listed below.

• Cholesterol-lowering medicines
• Diet pills
• Laxatives or anti-diarrhea medicines
• Antacids that contain aluminum or magnesium
• Over-the-counter medicines for cough, cold, or flu
• Over-the-counter medicines for hay fever or sinusitis
• Over-the-counter eye drops for red or bloodshot eyes

You should limit drinking grapefruit juice when you are taking inotropic medications. Grapefruit juice interferes with the liver’s ability to rid your body of some substances. This could lead to a buildup of inotropic drugs in your body. Consult with your doctor about your dosage and the consumption of grapefruit.

You should also avoid alcohol and beverages that contain caffeine, such as coffee, tea, and soft drinks.

You should not take positive inotropic medications if you are already taking negative inotropic medications, such as beta-blockers, calcium channel blockers, or antiarrhythmics, unless your doctor has prescribed both. These medicines can be taken together, but only your doctor can prescribe the right balance of each.

Positive inotropic drugs

Positive inotropic drugs help the heart pump more blood with fewer heartbeats. This means that although the heart beats less, it also beats with more force to meet the oxygen demands of your body.

For example, one kind of positive inotropic drug called digoxin strengthens the force of the heartbeat by increasing the amount of calcium in the heart’s cells. (Calcium stimulates the heart to contract.) When the medicine reaches the heart muscle, it binds to sodium and potassium receptors. These receptors control the amount of calcium in the heart muscle by stopping the calcium from leaving the cells. As calcium builds up in the cells, it causes a stronger force of contraction.

Positive inotropic drugs are used to treat congestive heart failure and heart rhythm problems (atrial arrhythmias). Positive inotropic drugs can increase blood flow throughout your body and reduce swelling in your hands and ankles.

Positive inotropic agents used for increasing cardiac contractility act in different ways. The following is a brief description of those positive inotropic agents employed frequently in heart failure.

The Heart Failure Society of America has issued a number of recommendations regarding the usage of positive inotropic drugs in acute heart failure setting (see Table 2).

Table 1. Inotropic agents used in heart failure, dosings, class of recommendation and level of evidence for recommendation according to the European Society of Cardiology 2008 guidelines on diagnosis and management of acute and chronic heart failure

Inotropic agents	Bolus dosing	Infusion rate	Class of recommendation	Level of evidence
Dobutamine	No	2–20 mg/kg/min (β+)	IIa	B
Dopamine	No	<3 mg/kg/min: renal effect (dopaminergic+) 3–5 mg/kg/min: inotropic (β+) >5 mg/kg/min: inotropic (β+) and vasopressor (α+)	IIb	C
Milrinone	25–75 µg/kg over 10–20 min	0.375–0.75 µg/kg/min	IIb	B
Enoximone	0.25–0.75 mg/kg	1.25–7.5 mg/kg/min	IIb	B
Levosimendan	12 µg/kg over 10 min (optional)	0.1 µg/kg/min Which can be decreased to 0.05 or increased to 0.2 mg/kg/min	IIa	B
Norepinephrine	No	0.2–1.0 µg/kg/min	IIb	C
Epinephrine	Bolus: 1 mg can be given intravenously. During resuscitation, repeated every 3–5 min	0.05–0.5 µg/kg/min	IIb	C

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Table 2. Heart Failure Society of America 2010 guidelines on usage of inotropes in patients with acute heart failure.

Recommendation	Level of evidence
Intravenous inotropes may be considered to relieve symptoms and improve end-organ function in patients with advanced heart failure characterised by left ventricle dilation, reduced left ventricular ejection fraction, and diminished peripheral perfusion or end-organ dysfunction (low output syndrome), particularly if these patients have marginal systolic blood pressure (<90 mm Hg), have symptomatic hypotension despite adequate filling pressure, or are unresponsive to, or intolerant of, intravenous vasodilators	C
These agents may be considered in similar patients with evidence of fluid overload if they respond poorly to intravenous diuretics or manifest diminished or worsening renal function	C
When adjunctive therapy is needed in other patients with acute decompensated heart failure, administration of vasodilators should be considered instead of intravenous inotropes	C
Intravenous inotropes are not recommended unless left heart filling pressures are known to be elevated or cardiac index is severely impaired based on direct measurement or clear clinical signs	C
It is recommended that administration of intravenous inotropes in the setting of acute decompensated heart failure be accompanied by continuous or frequent blood pressure monitoring and continuous monitoring of cardiac rhythm	C
If symptomatic hypotension or worsening tachyarrhythmias develop during administration of these agents, discontinuation or dose reduction should be considered	C

[Source ² ]

Digoxin

Digoxin, the only safe and effective oral positive inotropic agent, acts by inhibiting the Na-K-ATPase pump, leading to a rise in the intracellular calcium concentration and also exerts an antiadrenergic action by inhibiting the sympathetic outflow and augmenting the parasympathetic tone ³. Digoxin withdrawal in chronic heart failure patients on digoxin and other antifailure therapies, as investigated in the PROVED and RADIANCE trials, resulted in clinical deterioration ⁴. Ever since, the DIG (Digoxin Investigators’ Group) trial has been the largest survey addressing the effect of digoxin on heart failure survival ⁵. After 3 years, there was no difference in the overall mortality rate. Patients assigned to digoxin therapy had a non-significant reduction in mortality from worsening heart failure, counterbalanced by a significant increase in non-heart failure cardiac deaths, which included death from arrhythmia. Though modest, patients assigned to digoxin enjoyed a significant decrease in hospitalisation and a significant reduction in the combined end points of death from heart failure and hospitalisation. Post hoc analyses showed a correlation between the digoxin level and patient survival ⁶, such that death and hospitalisations were reduced in patients with a serum digoxin level between 0.5 and 0.9 ng/ml, regardless of the ejection fraction or gender. It is noteworthy that digoxin did worse in women in terms of all-cause mortality and heart failure mortality and hospitalisation than in men ⁷. Digoxin can be used orally or intravenously. The dose should be adjusted according to renal function and should result in a trough serum concentration of <1 ng/ml.1 In patients with a reduced ejection fraction who continue to have signs and symptoms of heart failure, digoxin therapy should be continued in addition to other therapies during hospitalisation and after discharge. Ischaemia, hypokalaemia and hypomagnesaemia may increase the likelihood for the development of digitalis intoxication, even at the therapeutic dose ⁸.

Dobutamine

Dobutamine, the most commonly used inotropic agent worldwide, is a non-selective β1- and β2-adrenergic receptor agonist with variable activities on the α1 receptor ⁸. Prevalent β1- and β2-adrenergic receptor activation results in reduced afterload and increased stroke volume, heart rate and cardiac output at low doses. An increasing dose will add arterial and venous constriction due to α1 adrenergic receptor activation. Generally, severe tachycardia hinders clinicians in further upescalating the dobutamine dose. Clinical trials have documented excess mortality in heart failure patients receiving intermittent or continuous dobutamine infusion in spite of its beneficial effects on increasing the cardiac output and decreasing the pulmonary capillary pressure ⁹. Most heart failure specialists now agree to use dobutamine in decompensated heart failure patients with pulmonary congestion and presence of low cardiac output (hypotension, disturbed mentation and cardiorenal syndrome) and make the duration and dosage as low as possible ⁸. Precautions should also be taken when it is utilised in the elderly as well as in the presence of significant left ventricular outflow obstruction (e.g., aortic stenosis), atrial fibrillation, recent β blocker use which necessitates an increase in dose, concomitant MAO inhibitor use and state of hyperthyroidism ¹⁰. The 2008 European Society of Cardiology (ESC) guideline on heart failure management recommends that dobutamine be generally started at 2–3 µg per kilogramme per minute (mcg/kg/min) without a loading dose and increased by 2–3 mcg/kg/min not exceeding 15 mcg/kg/min ¹¹.

Dopamine

Dopamine is one example of different dose-dependent effects due to the activation of different types of receptors. Dopamine primarily binds to vascular D1 receptors in the coronary, renal and mesenteric beds at low doses (≤2 mcg/kg/min) and leads to vasodilatation and natriuresis ⁸. It has been shown that this dopaminergic dose range might vary individually. Investigators of dopamine in acute decompensated heart failure trial have shown that adding a low dose (5 mcg/kg/min for 8 h) dopamine to reduced dose diuretics might provide as much diuresis as full dose diuretics on their own in patients with acute heart failure, without the potentially kidney-damaging and the potassium-draining effects of loop diuretics.8 9 This effect appears to be due to the dilation of both large conductance and small resistance renal blood vessels ¹². Dopamine may exert this effect without significantly improving creatinine clearance ¹³. This effect is not generally affected by chronic β blocker use, which is the case in most decompensated heart failure patients ¹⁴, but may be blunted by haloperidol and other butyrophenones ¹⁵. Ibopamine, a dopamine agonist that stimulates the dopaminergic-1 and dopaminergic-2 receptors resulting in peripheral and renal vasodilatation, improved heart failure symptoms during a short-term use ¹⁶, but was associated with increased mortality in the PRIME-II trial, which evaluated 1906 patients with severe (New York Heart Association (NYHA) class III and IV) heart failure who were already receiving maximal medical therapy (25% vs 20% for placebo at approximately 1 year) ¹⁷. Intermediate doses result in the activation of myocardial β1 receptors, with positive inotropic effects ⁸. Dopamine usually increases the systolic blood pressure and heart rate, with no or minor changes in diastolic pressure and peripheral vascular resistance ⁸. At high doses (5–15 mcg/kg/min), dopamine also binds to α1 receptors and triggers vasoconstriction ⁸. The usual dose range for dopamine is 2–20 mcg/kg/min, although doses as high as 130 mcg/kg/min have been employed ¹⁸. Dopamine is most often used in hypotension due to sepsis or cardiac failure, where it should be started at 2 mcg/kg/min and then titrated to a desired physiologic effect rather than a predicted pharmacologic range. Such titration is necessary because a weight-based administration of dopamine can achieve quite different serum drug concentrations in different individuals ¹⁹.

Epinephrine

Epinephrine has potent β1 adrenergic receptor activity and moderate β2 and α1 adrenergic receptor effects. Clinically, low doses of epinephrine increase the cardiac output because of the β1 adrenergic receptor inotropic and chronotropic effects, while the α adrenergic receptor-induced vasoconstriction is prominent in higher doses ²⁰, making epinephrine a titratable vasoactive agent to support hypotension due to low cardiac output or generalised vasodilatation, which occurs not infrequently after cardiopulmonary bypass pump. Clinical trials of safety and efficacy of epinephrine in heart failure patients are lacking.

Norepinephrine

Norepinephrine acts on both α1 and β1 adrenergic receptors, thus producing potent vasoconstriction as well as a less pronounced increase in cardiac output ²¹. A reflex bradycardia usually occurs in response to the increased MAP, such that the mild chronotropic effect is cancelled out and the heart rate remains unchanged or even decreases slightly. In a multi-central, randomised trial on patients with shock, 1679 patients were randomly assigned to receive dopamine or norepinephrine. A subgroup analysis showed that dopamine, as compared with norepinephrine, was associated with an increased rate of death at 28 days among the patients with cardiogenic shock but not among those with septic or hypovolemic shock. There were more arrhythmic events among the patients treated with dopamine ²². Norepinephrine should be administered only through a central venous line because extravasation may cause tissue necrosis ⁸.

Milrinone

Milrinone, a phosphodiesterase 3 inhibitor, inhibits the breakdown of cyclic AMP in both cardiac and vascular smooth muscle cells and acts as a powerful inotrope and pulmonary vasodilator agent with little effect on systemic arterial blood pressure ²³. Initial uncontrolled observations suggested that prolonged outpatient therapy with intravenous milrinone, either continuous or weekly, could improve functional status and reduce hospitalisation ²⁴. However, this was not the case in the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-HF), a controlled trial in 949 patients admitted to the hospital with an acute exacerbation of chronic heart failure and a mean left ventricular ejection fraction of 23%; patients requiring inotropic support were excluded. Milrinone therapy was associated with significant increases in hypotension, requiring intervention and atrial arrhythmias, and with non-significant increases in mortality in hospital (3.8% vs 2.3%) and at 60 days (10.3% vs 8.9%). It is worthy of note that patients with ischemic cardiomyopathy did significantly worse with milrinone in terms of the primary end point of days of hospitalization and the combined end point of hospitalization plus death ²⁵. The Acute Decompensated Heart Failure national registry, though putting sicker patients on milrinone and dobutamine, showed clear increased mortality with these agents compared with nitrate or nesiritide ²⁶. Milrinone should be confined for those advanced heart failure patients with low cardiac output state and intolerable congestion. Pulmonary vasodilator effects give the opportunity of better tackling left-sided pulmonary hypertension. Acting distal to and independently of the β receptors might provide the chance of adding milrinone to chronic β blocker therapy. The possible long-term benefit of combined therapy was evaluated in a series of 30 patients with refractory NYHA class IV heart failure who were treated with a combination of enoximone and metoprolol: this regimen was well tolerated by 80% of patients. After a mean follow-up of 21 months, significant benefits included an increase in left ventricular ejection fraction (28% vs 18% before therapy) and improvement in NYHA class (2.8 vs 4). Approximately, half of the patients were able to discontinue enoximone. The estimated probability of survival at 1 year was 81%, a value higher than would have been expected from the results in large trials of similar patients ²⁷. Although preliminary trials with oral milrinone, like other phosphodiesterase inhibitors, have been associated with increased mortality compared with placebo (which was best demonstrated in the PROMISE trial, in which patients with NYHA class III or IV heart failure who were randomly assigned to oral milrinone faced a significant 28% increase in all-cause mortality (30% vs 24% with placebo), 34% increase in cardiovascular mortality, a greater incidence of hospitalisations, more adverse cardiovascular side effects (syncope and hypotension) and higher drug discontinuation rate) ²⁸, investigations considering milrinone inhalation are grabbing attention as a useful non-invasive route of administration ²⁹. Intravenous milrinone is generally prescribed at 0.375–0.75 mcg/kg/min without a loading dose, especially in those with baseline lower blood pressure ⁸.

Levosimendan

Levosimendan is a calcium sensitiser and ATP-dependent potassium channel opener with mild phosphodiesterase inhibitory action that has positive inotropic and vasodilatory effect, resulting in a reduction in cardiac filling pressures and an increase in the cardiac index. In a report of 146 patients with severe heart failure, 6 h of intravenous levosimendan produced an increase in stroke volume and cardiac index of 28% and 39%, respectively, and a dose-dependent reduction in pulmonary capillary wedge pressure, right atrial and pulmonary artery pressures, and symptoms of dyspnea and fatigue ³⁰. The LIDO trial compared the short-term haemodynamic effects of a 24 h intravenous infusion of levosimendan with dobutamine in 203 patients with severe, deteriorating heart failure, acute heart failure or heart failure after coronary artery bypass grafting; patients with cardiogenic shock were excluded.2 The haemodynamic end point (35% increase in cardiac index and ≥25% reduction in pulmonary capillary wedge pressure at 24 h) was more frequently achieved with levosimendan than dobutamine (28% vs 15%). The effects of levosimendan were not attenuated by concurrent therapy with a β blocker in contrast to dobutamine ⁹. The SURVIVE trial randomly assigned 1327 patients with acute decompensated heart failure and a left ventricular ejection fraction of ≤30% to intravenous levosimendan or dobutamine. After 24 h of therapy, there was no difference between the groups assigned to levosimendan or dobutamine in the percentage of patients who reported more than a mild improvement in dyspnea (82% vs 83%) or a global assessment (80% vs 81%). Patients assigned to levosimendan did have a significantly greater reduction in plasma BNP compared with patients assigned to dobutamine (631 vs 397 pg/ml). However, levosimendan use was associated with more atrial fibrillation and hypokalemia ³¹. In the REVIVE II study, an improvement in patient self-assessment, a decrease in levels of BNP and a shorter hospital stay were noted in response to levosimendan when it was added to standard therapy in patients admitted with heart failure and reduced ejection fraction. Be that as it may, compared with placebo, levosimendan use was associated with more hypotension (50% vs 34%), ventricular tachycardia (25% vs 17%) and atrial fibrillation (9% vs 2%). A trend towards increase in early mortality was also observed in the levosimendan-treated patients ³². The European Society of Cardiology guidelines recommend levosimendan to be administered as a bolus dose (3–12 mcg/kg) during 10 min, followed by a continuous infusion (0.05–0.2 mcg/kg/min for 24 h). The infusion rate may be increased once stability is confirmed. In patients with a systolic blood pressure of <100 mm Hg, the infusion should be started without a bolus dose to avoid hypotension ¹¹. A randomised clinical trial (the Pimobendan in Congestive Heart Failure (PICO) trial) employed pimobendan, another calcium sensitiser, added to conventional failure treatment in 317 patients with stable symptomatic heart failure improved exercise duration (bicycle ergometry) by 6% after 24 weeks of treatment with no significant effects on oxygen consumption and on quality of life. Nonetheless, pimobendan use was associated with an increased hazard of death, 1.8 times higher than that in the placebo group ³³.

Vesnarinone

Vesnarinone is a mixed phosphodiesterase 3 inhibitor and ion-channel modifier that has modest, dose-dependent, positive inotropic activity, but minimal negative chronotropic activity. A beneficial effect on survival in severe heart failure was shown in a small placebo-controlled clinical trial at a dose of 60 mg daily associated with a trend towards an adverse effect on survival when the dose was 120 mg per day ³⁴. Vesnarinone (30–60 mg daily) was compared with placebo in 3833 patients with NYHA class III and IV heart failure in the VEST trial. The trial was terminated prematurely due to a dose-dependent increase in mortality (12% and 23% in patients receiving 30 and 60 mg/day, respectively), primarily secondary to sudden cardiac death ³⁵.

Negative inotropic drugs

Negative inotropic drugs include beta-blockers, calcium channel blockers, and antiarrhythmic medications and they all work in different ways:

Beta-blockers “block” the effects of adrenaline on your body’s beta receptors. This slows the nerve impulses that travel through the heart. As a result, your heart does not have to work as hard because it needs less blood and oxygen. Beta-blockers also block the impulses that can cause an arrhythmia.

Calcium channel blockers slow the rate at which calcium passes into the heart muscle and into the vessel walls. This relaxes the vessels. The relaxed vessels let blood flow more easily through them, thereby lowering blood pressure.

Antiarrhythmic medications slow the electrical conduction in the heart.

Beta-blockers

Beta blockers, also known as beta-adrenergic blocking agents, are medications that reduce your blood pressure. Beta blockers work by blocking the effects of the hormone epinephrine, also known as adrenaline.

When you take beta blockers, your heart beats more slowly and with less force, thereby reducing blood pressure. Beta blockers also help blood vessels open up to improve blood flow.

Some beta blockers mainly affect your heart, while others affect both your heart and your blood vessels. Which one is best for you depends on your health and the condition being treated.

Examples of oral beta blockers include:

• Acebutolol (Sectral)
• Atenolol (Tenormin)
• Bisoprolol (Zebeta)
• Metoprolol (Lopressor, Toprol-XL)
• Nadolol (Corgard)
• Nebivolol (Bystolic)
• Propranolol (Inderal LA, InnoPran XL)

Uses for beta blockers

Doctors prescribe beta blockers to prevent, treat or improve symptoms in a variety of conditions, such as:

• High blood pressure
• Irregular heart rhythm (arrhythmia)
• Heart failure
• Chest pain (angina)
• Heart attacks
• Migraine
• Certain types of tremors

Beta blockers aren’t usually prescribed for blood pressure until other medications, such as diuretics, haven’t worked effectively. Your doctor may prescribe beta blockers as one of several medications to lower your blood pressure, including angiotensin-converting enzyme (ACE) inhibitors, diuretics or calcium channel blockers.

Beta blockers may not work as effectively for people of African heritage and older people, especially when taken without other blood pressure medications.

Beta blockers side effects and cautions

Side effects may occur in people taking beta blockers. However, many people who take beta blockers won’t have any side effects.

Common side effects of beta blockers include:

• Fatigue
• Cold hands or feet
• Weight gain

Less common side effects include:

• Shortness of breath
• Trouble sleeping
• Depression

Beta blockers generally aren’t used in people with asthma because of concerns that the medication may trigger severe asthma attacks. In people who have diabetes, beta blockers may block signs of low blood sugar, such as rapid heartbeat. It’s important to monitor your blood sugar regularly.

Beta blockers can also affect your cholesterol and triglyceride levels, causing a slight increase in triglycerides and a modest decrease in high-density lipoprotein, the “good” cholesterol. These changes often are temporary. You shouldn’t abruptly stop taking a beta blocker because doing so could increase your risk of a heart attack or other heart problems.

Calcium channel blockers

Calcium channel blockers, also called calcium antagonists, relax and widen blood vessels by affecting the muscle cells in the arterial walls. Calcium channel blockers prevent calcium from entering cells of the heart and blood vessel walls, resulting in lower blood pressure.

Some calcium channel blockers have the added benefit of slowing your heart rate, which can further reduce blood pressure, relieve chest pain (angina) and control an irregular heartbeat.

Some calcium channel blockers are available in short-acting and long-acting forms. Short-acting medications work quickly, but their effects last only a few hours. Long-acting medications are slowly released to provide a longer lasting effect.

Several calcium channel blockers are available. Which one is best for you depends on your health and the condition being treated.

Examples of calcium channel blockers include:

• Amlodipine (Norvasc)
• Diltiazem (Cardizem, Tiazac, others)
• Felodipine
• Isradipine
• Nicardipine
• Nifedipine (Adalat CC, Afeditab CR, Procardia)
• Nisoldipine (Sular)
• Verapamil (Calan, Verelan)

In some cases, your doctor might prescribe a calcium channel blocker with other high blood pressure medications or with cholesterol-lowering drugs such as statins.

Uses for calcium channel blockers

Doctors prescribe calcium channel blockers to prevent, treat or improve symptoms in a variety of conditions, such as:

• High blood pressure
• Coronary artery disease
• Chest pain (angina)
• Irregular heartbeats (arrhythmia)
• Some circulatory conditions, such as Raynaud’s disease

For people of African heritage and older people, calcium channel blockers might be more effective than other blood pressure medications, such as beta blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers.

Calcium channel blockers side effects and cautions

Side effects of calcium channel blockers may include:

• Constipation
• Headache
• Palpitations
• Dizziness
• Rash
• Drowsiness
• Flushing
• Nausea
• Swelling in the feet and lower legs

Certain calcium channel blockers interact with grapefruit products.

Antiarrhythmic medications

Antiarrhythmic medications are used to treat heart rhythm disorders, called arrhythmias, and to lessen the symptoms associated with them. Some of the common symptoms of arrhythmias include heart palpitations, irregular heartbeats, fast heartbeats, lightheadedness, fainting, chest pain, and shortness of breath.

Irregular heartbeats may be a congenital condition (you are born with it) or may develop if part of the heart muscle tissue (myocardium) is irritated or damaged, leading to a disruption or “short circuit” in the heart’s electrical system. Antiarrhythmics work in a variety of ways to slow the electrical impulses in the heart so that the heart can resume a regular rhythm.

Antiarrhythmic medicines are split into four categories:

• Class I antiarrhythmic medicines are sodium-channel blockers, which slow electrical conduction in the heart.
• Class II antiarrhythmic medicines are beta-blockers, which work by blocking the impulses that may cause an irregular heart rhythm and by interfering with hormonal influences (such as adrenaline) on the heart’s cells. By doing this, they also reduce blood pressure and heart rate.
• Class III antiarrhythmic medicines slow the electrical impulses in the heart by blocking the heart’s potassium channels.
• Class IV antiarrhythmic medicines work like class III medicines but act by blocking the calcium channels in the heart.

Digoxin is another example of a medicine that can be used as an antiarrhythmic, although it is not included in the above categories.

Because each class of medicine works in a slightly different way, there is no one medicine to treat every kind of arrhythmia. Sometimes an antiarrhythmic medicine can cause more arrhythmias or make your arrhythmia worse (called proarrhythmia). Finding which medicine works best for you may mean working closely with your doctor and trying a few different kinds of medicines. Some patients may need extra monitoring or testing, either with a Holter monitor or electrophysiology studies (EPS), which can also help doctors clarify what type of antiarrhythmic is best for the patient.

Inotropic drugs side effects

Sometimes a medicine causes unwanted effects. These are called side effects. Not all of the side effects for inotropes are listed here. If you feel these or any other effects, you should check with your doctor.

• Low blood pressure (hypotension)
• An irregular heartbeat that causes dizziness, the feeling that your heart has skipped a beat (palpitations), shortness of breath, sweating, or fainting
• Trouble with your eyesight, such as blurry eyesight, double vision, or seeing yellow, green, or white halos around objects
• Dizziness or lightheadedness
• Headache
• A loss of appetite or an upset stomach
• Fatigue
• Throwing up
• Diarrhea
• Erectile dysfunction
• Breast enlargement in men
• Decreased sex drive
• Skin rash or hives
• Eye sensitivity to light
• Nosebleeds and bleeding gums

Many of these side effects are rare. Tell your doctor right away if you have any of these side effects. Do not stop taking your medicine unless your doctor tells you to. If you stop taking your medicine without checking with your doctor, it can make your condition worse.

References

1. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, Strömberg A, van Veldhuisen DJ, Atar D, Hoes AW, Keren A, Mebazaa A, Nieminen M, Priori SG, Swedberg K, ESC Committee for Practice Guidelines (CPG). Eur Heart J. 2008 Oct; 29(19):2388-442
2. The contrasting effects of dopamine and norepinephrine on systemic and splanchnic oxygen utilization in hyperdynamic sepsis. Marik PE, Mohedin M. JAMA. 1994 Nov 2; 272(17):1354-7.
3. McMahon WS, Holzgrefe HH, Walker JD, et al. Cellular basis for improved left ventricular pump function after digoxin therapy in experimental left ventricular failure. J Am Coll Cardiol 1996;28:495
4. Packer M, Gheorghiade M, Young JB, et al. Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors. RADIANCE Study. N Engl J Med 1993;329:1
5. The effect of digoxin on mortality and morbidity in patients with heart failure. The digitalis investigation group. N Engl J Med 1997;336:525
6. Ahmed A, Rich MW, Love TE, et al. Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial. Eur Heart J 2006;27:178
7. Athore SS, Wang Y, Krumholz HM. Sex-based differences in the effect of digoxin for the treatment of heart failure. N Engl J Med 2002;347:1403
8. Gheorghiade M, Filippatos GS, Felker GM. Diagnosis and Management of Acute Heart Failure Syndromes. 9th edn Philadelphia: WB Saunders, Braunwald’s Heart Dis—A Textbook Cardiovasc Med; Chapter 27. 2011
9. Follath F, Cleland JG, Just H, et al. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet 2002;360:196
10. Oliva F, Latini R, Politi A, et al. Intermittent 6-month low-dose dobutamine infusion in severe heart failure: DICE multicenter trial. Am Heart J 1999;138:247
11. Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008. Eur Heart J 2008;29:2388–442
12. Elkayam U, Ng TM, Hatamizadeh P, et al. Renal vasodilatory action of dopamine in patients with heart failure: magnitude of effect and site of action. Circulation 2008;117:200
13. Duke GJ, Briedis JH, Weaver RA. Renal support in critically ill patients: low-dose dopamine or low-dose dobutamine? Crit Care Med 1994;22:1919
14. Giamouzis G, Rovithis D, Parisis C, et al. Beta-Blocker pretreatment does not affect the renoprotective effects of low-dose dopamine in patients with acute decompensated heart failure. J Card Fail 2010;16:S112–13
15. Dasta JF, Kirby MG. Pharmacology and therapeutic use of low-dose dopamine. Pharmacotherapy 1986;6:304
16. Dohmen HJ, Dunselman PH, Poole-Wilson PA. Comparison of captopril and ibopamine in mild to moderate heart failure. Heart 1997;78:285
17. Hampton JR, van Veldhuisen DJ, Kleber FX, et al. Randomised study of effect of ibopamine on survival in patients with advanced severe heart failure. Second Prospective Randomised Study of Ibopamine on Mortality and Efficacy (PRIME II) Investigators. Lancet 1997;349:971
18. Hannemann L, Reinhart K, Grenzer O, et al. Comparison of dopamine to dobutamine and norepinephrine for oxygen delivery and uptake in septic shock. Crit Care Med 1995;23:1962
19. MacGregor DA, Smith TE, Prielipp RC, et al. Pharmacokinetics of dopamine in healthy male subjects. Anesthesiology 2000;92:338
20. Allwood MJ, Cobbold AF, Ginsburg J. Peripheral vascular effects of noradrenaline, isopropylnoradrenaline and dopamine. Br Med Bull 1963;19:132
21. Thompson DR, Clemmer TP, Applefeld JJ, et al. Practice parameters for hemodynamic support of sepsis in adult patients in sepsis. Task force of the American College of Critical care Medicine, Society of Critical care Medicine. Crit Care Med 1999;27:639
22. Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 2010;362:779–89
23. Troitzsch D, Abdul-Khaliq H, Vogt S, et al. Critical care. 2001;5(Suppl B):P6
24. Milfred-LaForest SK, Shubert J, Mendoza B, et al. Tolerability of extended duration intravenous milrinone in patients hospitalized for advanced heart failure and the usefulness of uptitration of oral angiotensin-converting enzyme inhibitors. Am J Cardiol 1999;84:894
25. Felker GM, Benza RL, Chandler AB, et al. Heart failure aetiology and response to milrinone in decompensated heart failure: results from the OPTIME-CHF study. J Am Coll Cardiol 2003;41:997
26. Abraham WT, Adams KF, Fonarow GC, et al. In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications: an analysis from the acute decompensated heart failure national registry (ADHERE). J Am Coll Cardiol 2005;46:57
27. Shakar SF, Abraham WT, Gilbert EM, et al. Combined oral positive inotropic and beta-blocker therapy for treatment of refractory class IV heart failure. J Am Coll Cardiol 1998;31:1336
28. Packer M, Carver JR, Rodeheffer RJ, et al. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE study research group. N Engl J Med 1991;325:1468
29. Hentschel T, Yin N, Riad A, et al. Inhalation of the phosphodiesterase-3 inhibitor milrinone attenuates pulmonary hypertension in a rat model of congestive heart failure. Anesthesiology 2007;106:124–31
30. Slawsky MT, Colucci WS, Gottlieb SS, et al. Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. Study Investigators. Circulation 2000;102:2222
31. Mebazaa A, Nieminen MS, Packer M, et al. Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial. JAMA 2007;297:1883.
32. Packer M, Colucci WS, Fisher L, et al. REVIVE II: Multicenter Placebo-Controlled Trial Of Levosimendan On Clinical Status In Acutely Decompensated Heart Failure. Dallas, TX: American Heart Association Scientific Sessions, 2005
33. Lubsen J, Just H, Hjalmarsson AC, et al. Effect of pimobendan on exercise capacity in patients with heart failure: main results from the Pimobendan in Congestive Heart Failure (PICO) trial. Heart 1996;76:223–31
34. Feldman AM, Bristow MR, Parmley WW, et al. Effects of vesnarinone on morbidity and mortality in patients with heart failure. Vesnarinone Study Group. N Engl J Med 1993;329:149.
35. Cohn JN, Goldstein SO, Greenberg BH, et al. A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators. N Engl J Med 1998;339:1810