Pimobendan
Encyclopedia
Pimobendan or pimobendane. It is a calcium sensitizer with positive inotropic and vasodilator effects. It is also a selective inhibitor
of phosphodiesterase
III (PDE3
).
Pimobendan is used in the management of heart failure in dogs, most commonly caused by myxomatous mitral valve disease (also known as endocardiosis), or dilated cardiomyopathy
. Research has shown that pimobendan increases survival time and improves quality of life in patients with congestive heart failure
secondary to mitral valve disease when compared with benazepril
, an angiotensin-converting-enzyme (ACE) inhibitor
. Under the trade name Acardi, it is available for human use in Japan
.
. It sensitizes and increases the binding efficiency of cardiac myofibril
to the calcium ions that are already present without increasing the consumption of oxygen and energy. Pimobendan also causes peripheral vasodilation
by inhibiting the function of phosphodiesterase III
. This results in decreased pressure, translating into smaller cardiac preload and afterload
(decreases the failing heart's workload).
of 60-65%. It is metabolized into its active form by the liver
. The half-life
of pimobendan in the blood is 0.4 hours and the half-life of its metabolite is 2 hours. Elimination is by excretion in the bile and then feces. Pimobendan is 90–95% bound to plasma proteins
in circulation. This has implications in patients suffering from low blood protein levels (hypoproteinemia
/hypoalbuminemia
) and with patients that are on concurrent therapies that are also highly protein bound.
Other drugs may also be used as required to manage certain arrhythmias that are often associated with heart disease.
:
Phosphodiesterase inhibitor
A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase , therefore preventing the inactivation of the intracellular second messengers cyclic adenosine monophosphate and cyclic guanosine monophosphate by the respective PDE...
of phosphodiesterase
Phosphodiesterase
A phosphodiesterase is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below...
III (PDE3
PDE3
PDE3 is a phosphodiesterase. The PDEs belong to at least eleven related gene families, which are different in their primary structure, substrate affinity, responses to effectors, and regulation mechanism....
).
Pimobendan is used in the management of heart failure in dogs, most commonly caused by myxomatous mitral valve disease (also known as endocardiosis), or dilated cardiomyopathy
Dilated cardiomyopathy
Dilated cardiomyopathy or DCM is a condition in which the heart becomes weakened and enlarged and cannot pump blood efficiently. The decreased heart function can affect the lungs, liver, and other body systems....
. Research has shown that pimobendan increases survival time and improves quality of life in patients with congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
secondary to mitral valve disease when compared with benazepril
Benazepril
Benazepril, brand name Lotensin, is a medication used to treat high blood pressure , congestive heart failure, and chronic renal failure...
, an angiotensin-converting-enzyme (ACE) inhibitor
ACE inhibitor
ACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...
. Under the trade name Acardi, it is available for human use in Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
.
Mechanism of action
Pimobendan is a positive inotropeInotrope
An inotrope is an agent that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions...
. It sensitizes and increases the binding efficiency of cardiac myofibril
Myofibril
A myofibril is a basic unit of a muscle. Muscles are composed of tubular cells called myocytes or myofibers. Myofibers are composed of tubular myofibrils. Myofibrils are composed of long proteins such as actin, myosin, and titin, and other proteins that hold them together...
to the calcium ions that are already present without increasing the consumption of oxygen and energy. Pimobendan also causes peripheral vasodilation
Vasodilation
Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...
by inhibiting the function of phosphodiesterase III
PDE3
PDE3 is a phosphodiesterase. The PDEs belong to at least eleven related gene families, which are different in their primary structure, substrate affinity, responses to effectors, and regulation mechanism....
. This results in decreased pressure, translating into smaller cardiac preload and afterload
Afterload
Afterload is the tension or stress developed in the wall of the left ventricle during ejection. Following Laplace's law, the tension upon the muscle fibers in the heart wall is the product of the pressure within the ventricle, multiplied by the volume within the ventricle, divided by the wall...
(decreases the failing heart's workload).
Pharmacokinetics
Pimobendan is absorbed rapidly when given via the oral route and has a bioavailabilityBioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
of 60-65%. It is metabolized into its active form by the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
. The half-life
Half-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...
of pimobendan in the blood is 0.4 hours and the half-life of its metabolite is 2 hours. Elimination is by excretion in the bile and then feces. Pimobendan is 90–95% bound to plasma proteins
Plasma protein binding
A drug's efficiency may be affected by the degree to which it binds to the proteins within blood plasma. The less bound a drug is, the more efficiently it can traverse cell membranes or diffuse. Common blood proteins that drugs bind to are human serum albumin, lipoprotein, glycoprotein, α, β‚ and γ...
in circulation. This has implications in patients suffering from low blood protein levels (hypoproteinemia
Hypoproteinemia
Hypoproteinemia is a condition where there is an abnormally low level of protein in the blood.One common cause is due to excess protein in the urine , which can be a medical sign of nephrotic syndrome....
/hypoalbuminemia
Hypoalbuminemia
Hypoalbuminemia is a medical condition where levels of albumin in blood serum are abnormally low. It is a specific form of hypoproteinemia.Albumin is a major protein in the human body, making up about 60% of total human plasma protein by mass...
) and with patients that are on concurrent therapies that are also highly protein bound.
Combinations
Pimobendan is often used in combination with three other drugs to palliate dogs with heart disease and reduce clinical signs of disease. These are:- FurosemideFurosemideFurosemide or frusemide is a loop diuretic used in the treatment of congestive heart failure and edema. It is most commonly marketed by Sanofi-Aventis under the brand name Lasix...
, a diuretic, to reduce pulmonary edemaPulmonary edemaPulmonary edema , or oedema , is fluid accumulation in the air spaces and parenchyma of the lungs. It leads to impaired gas exchange and may cause respiratory failure...
. This can be given intravenously if the animal is in respiratory distress (6–8 mg/kg), and then titrated down to the minimum dose required orally. - SpironolactoneSpironolactoneSpironolactone , commonly referred to as simply spiro, is a diuretic and is used as an antiandrogen.It is a synthetic 17-lactone drug that is a renal competitive aldosterone antagonist in a class of pharmaceuticals called...
, an aldosterone antagonistAldosterone antagonistAldosterone antagonist refers to diuretic drugs which antagonize the action of aldosterone at mineralocorticoid receptors. This group of drugs is often used as adjunctive therapy, in combination with other drugs, for the management of chronic heart failure...
. This has two actions, firstly, as a potassium-sparing diureticPotassium-sparing diureticPotassium-sparing diuretics are diuretic drugs that do not promote the secretion of potassium into the urine.They are used as adjunctive therapy, together with other drugs, in the treatment of hypertension and management of congestive heart failure....
, although its diuretic properties are small compared with those of furosemide. Secondly, it reduces aldosterone-mediated myocardial remodelling and fibrosis, slowing the progression of heart disease. - An ACE inhibitorACE inhibitorACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...
, often enalaprilEnalaprilEnalapril is an angiotensin converting enzyme inhibitor used in the treatment of hypertension and some types of chronic heart failure. ACE raises blood pressure by constricting blood vessels. ACE inhibitors like enalapril prevent this effect. Enalapril has been shown to lower the death rate in...
(trade name Enacard) or benazeprilBenazeprilBenazepril, brand name Lotensin, is a medication used to treat high blood pressure , congestive heart failure, and chronic renal failure...
(Fortekor). These drugs inhibit the action of angiotensin-converting enzymeAngiotensin-converting enzymeAngiotensin I-converting enzyme , an exopeptidase, is a circulating enzyme that participates in the body's renin-angiotensin system , which mediates extracellular volume , and arterial vasoconstriction...
, producing a balanced vasodilation, along with other favourable effects.
Other drugs may also be used as required to manage certain arrhythmias that are often associated with heart disease.
Chemistry
Pimobendan can be synthesized beginning with anisoyl chlorideAnisoyl chloride
Anisoyl chloride is an acyl halide, specifically an aromatic acyl chloride, and may be formed from anisic acid by replacing a hydroxyl group with a chloride group. There are three isomers, the ortho-, meta-, and para- forms....
:
External links
- Official Vetmedin Product Website
- UK Product Website
- Australia Product Website
- Website about the QUEST study (reference 2) (http://www.questtrial.com)
- A Few Words About Pimobendan