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Pimobendan Injection, which is a drug used to treat cardiovascular diseases and belongs to phosphodiesterase III (PDE3) inhibitors. It exerts positive inotropic and vasodilatory effects by inhibiting the activity of phosphodiesterase III and increasing the concentration of intracellular cyclic adenosine monophosphate (cAMP).
Approval and listing status:
It has different approvals and marketing situations in different countries and regions. In some countries, it has been approved for the treatment of diseases such as congestive heart-failure in dogs. For example, in Europe, it has been approved for the treatment of canine heart-failure since 1999 and quickly accepted by clinical veterinarians for use in the treatment of canine heart-failure.
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Additional information of chemical compound:
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Pimobendan+. COA
Clinical application and indications
Veterinary applications
Canine congestive heart-failure is a serious dsease that threatens the health of canines. Its pathogenesis is complex, and common causes include dilated cardiomyopathy (DCM) and chronic mitral valve insufficiency (CMVI). Dilated cardiomyopathy can lead to decreased myocardial contractility, heart enlargement, and reduced cardiac output; Chronic mitral valve insufficiency can cause blood to reflux during cardiac contraction, increasing the preload on the left ventricle and leading to long-term heart-failure.
Pimobendan injection plays an important role in the treatment of congestive heart-failure in canines. It improves heart funtion through multiple mechanisms. On the one hand, pimobenda can enhance myocardial contractility, mainly by inhibiting phosphodiesterase III (PDE3), reducing the degradation of cyclic adenosine monophosphate (cAMP), increasing the concentration of intracellular cAMP, and activating protein kinase A (PKA), promoting the release of calcium ions in myocardial cells and the uptake of calcium ions by the sarcoplasmic reticulum, increasing the sensitivity of myocardial cells to calcium ions, thereby enhancing myocardial contractility, and this effect of enhancing myocardial contractility does not significantly increase myocardial oxygen consumption.
On the other hand, pimobenda has a vasodilatory effect, which can dilate blod vessels and reduce the pre - and post load on the heart. By dilating veins, reducing the amount of blod returning to the heart, and lowering the end diastolic pressure of the left ventricle; By dilating arteries, reducing peripheral vascular resistance, and alleviating the afterload on the heart.
In clinical practice, the symptoms of canines with congestive heart-failure were significantly improved after treatment. Many affected canines experience reduced breathing difficulties, increased activity tolerance, and decreased edema. Long term use of it can also delay the progression of heart-failure, improve the quality of life of affected canines, and prolong their life expectancy. For example, some canines that were previously unable to walk normally or have lost appetite due to heart-failure can gradually recover a certain level of mobility and improve their mental state after treatment with pimobenda.
Mucous/degenerative mitral valve dsease is one of the common heart dseases in canines, especially in small canines with a high incidence rate. This dsease can cause thickening and curling of the mitral valve leaflets, elongation or rupture of the chordae tendineae, leading to mitral regurgitation. When the mitral valve is not fully closed, during systole, some blod will flow back from the left ventricle to the left atrium, causing an increase in the volume load of the left atrium and left ventricle. Over time, this can lead to left atrial and left ventricular enlargement, ultimately resulting in heart-failure.
It has a good therapeutic effect on canines with mucinous/degenerative mitral valve dsease. It can alleviate left ventricular burden caused by mitral regurgitation. By enhancing myocardial contractility and improving the pumping funtion of the heart, it enables the heart to pump blod more effectively, reducing the accumulation of blod in the heart. Meanwhile, the vasodilatory effect of pimobenda can reduce peripheral vascular resistance, alleviate cardiac afterload, and further improve the pumping function of the heart.
After treatment with it, the symptoms of canines with mucinous/degenerative mitral valve dsease can be significantly relieved. For example, the heart murmur of the affected dog may decrease, and symptoms such as difficulty breathing and coughing may also improve. In addition, It can also delay the progression of the dsease, reduce the risk of heart-failure, and improve the quality of life and prognosis of affected canines.
At present, in addition to the clear indications mentioned above, further research is still exploring the potential applications in other stages of heart dsease. For example, researchers are studying whether pimobenda can be used in the pre heart-failure stage or preclinical heart-failure stage. In the pre heart-failure stage, the dog's heart may have undergone some structural and funtional changes, but no obvious clinical symptoms have yet appeared. At this time, using pimobenda may help delay the progression of heart dsease and prevent the occurrence of heart-failure.
In addition, researchers are also exploring whether the simultaneous use of angiotensin converting enzyme inhibitors (ACEIs) with pimobenda can provide other benefits. ACEI can lower blod pressure, alleviate cardiac afterload, and inhibit myocardial remodeling by inhibiting the renin angiotensin aldosterone system (RAAS). The combination of pimobenda and ACEI may exert effects through different mechanisms, jointly improving cardiac funtion and delaying the progression of heart-failure. Some preliminary research results suggest that this combination therapy may have better therapeutic effects, but further clinical studies are needed to validate it.
Usage and dosage
(1) Dose determination
The usage and dosage of Pimobendan injection should be precisely adjusted according to the weight and condition of the dog. The dosage varies when treating congestive heart-failure caused by different etiologies.
The general daily dose is 0.5mg/kg, divided into 2 doses, administered approximately every 12 hours. This medication regimen can be adjusted appropriately according to the specific condition of the affected dog. For example, for severely ill canines, it may be necessary to increase the dosage appropriately in the initial stage, but it needs to be done while closely monitoring the dog's reactions and adverse reactions.
Dose 0.4-0.6mg/kg, oral, divided into two doses. Oral administration is relatively convenient, but attention should be paid to the absorption and bioavailability of the drug. During the medication process, it is important to ensure that the affected dog can take the medication on time and in the appropriate amount to ensure effective treatment.
Dose of 0.25mg/kg, orally, twice a day. This relatively low dose is suitable for some canines with relatively mild conditions or sensitivity to drugs. During use, it is necessary to closely observe the changes in symptoms and cardiac funtion indicators of the affected dog, and adjust the dosage according to the actual situation.
The dose is 0.1-0.3mg/kg, orally administered once every 12 hours. In emergency situations, this dosing regimen can quickly exert the effects of pimobenda, enhance myocardial contractility, and improve cardiac funtion. However, it should be noted that the follow-up treatment plan after emergency treatment needs to be adjusted according to the specific situation of the affected dog.
(2) Administration method
Usually administered via intravenous or subcutaneous injection.
Intravenous injection: Intravenous injection can quickly reach the peak blod drug concentration and quickly exert its therapeutic effect. Intravenous injection is the preferred method of administration in canines with acute heart-failure attacks or critical conditions. During intravenous injection, it is necessary to strictly follow the operating procedures, select the appropriate venous pathway, control the injection speed, and avoid local tissue damage caused by drug extravasation. Generally speaking, the speed of intravenous injection should be adjusted according to the weight, condition, and tolerance of the affected dog, usually at a slower pace to ensure safe use of the medication.
Subcutaneous injection: Subcutaneous injection is relatively convenient and does not require professional venipuncture techniques. It is suitable for some canines with relatively stable conditions that do not require immediate high blod drug concentrations. After subcutaneous injection, the drug will gradually be absorbed into the bloodstream, and the onset time may be slightly slower than intravenous injection. When performing subcutaneous injection, it is necessary to choose a suitable injection site, such as the neck, back, and other areas with loose skin, to avoid repeated injections in the same area, in order to prevent local tissue inflammation and hardening.
During the administration process, veterinarians need to closely monitor the reactions of the affected dog, including changes in symptoms, heart rate, blood pressure, and other vital signs, as well as whether adverse reactions have occurred. If adverse reactions occur, such as hypotension, arrhythmia, etc., it is necessary to adjust the dosage or stop medication in a timely manner and take corresponding treatment measures. At the same time, it is necessary to regularly perform cardiac funtion tests on the affected canines, such as echocardiography, electrocardiogram, etc., to evaluate the treatment effect and adjust the treatment plan.
Adverse reactions and contraindications
Adverse reactions
Gastrointestinal reactions:
Dogs may experience gastrointestinal reactions such as vomiting and diarrhea after use. This may be related to the stimulation of gastrointestinal mucosa by drugs.
Arrhythmia:
There have been reports of atrial fibrillation or ventricular abnormalities in canines after use, but since cardiomyopathy can also cause arrhythmia, it cannot be fully determined whether this adverse reaction is caused by pimobenda. However, close observation of changes in the dog's heart rhythm is still necessary during use.
Other adverse reactions:
A very small number of affected canines may experience temporary drowsiness, loss of appetite, and other adverse reactions.
Contraindications
Prohibited for specific dseases:
Animals allergic to pimobenda are prohibited, and those with hypertrophic cardiomyopathy, aortic valve stenosis, or any other functional or organic reasons that prevent enhanced cardiac output are prohibited.
Prohibited for special physiological states:
The safety has not been evaluated in the following canines: puppies less than 6 months old, canines with congenital heart defects, canines with diabetes or a series of other metabolic dseases, and female canines used for breeding, pregnancy or lactation.
Arrhythmia should be used with caution:
Uncontrolled arrhythmia should be treated with caution with pimobendan injection.
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