Veterinary Medicine

Dilated cardiomyopathy in the cat

The aetiology of primary dilated cardiomyopathy in the cat is unknown. Recent work has indicated a close association between dietary taurine deficiency and dilated cardiomyopathy. In the cat, taurine is an essential amino acid which is required for the conjugation of bile acids. The premise that taurine deficiency is one of the causative factors in the pathogenesis of dilated cardiomyopathy is based on the fact that many cats on taurine-deficient diets develop myocardial failure which can be reversed with taurine supplementation.

However, not all cats on taurine-depleted diets develop dilated cardiomyopathy and some which do develop cardiomyopathy fail to respond to taurine supplementation. About 38% of cats with dilated cardiomyopathy in one study failed to respond to taurine supplementation and died within the first 30 days of treatment. Hypothermia and thromboembolism were found to increase the risk of early death.

It is also known that cats on apparently adequate diets can nevertheless become taurine deficient. The minimal concentration of taurine in the diet required to prevent signs of deficiency varies with the type of diet. For example, it has been shown that much higher concentrations (2000-2500 mg taurine / kg dry matter) of taurine are required in canned diets compared to dry cat foods since heating during the canning process produces products which increase the enterohepatic loss of taurine. Low plasma taurine levels have been reported in cats fed a taurine replete but potassium depleted diet containing 0.8% ammonium chloride as a urinary acidifier suggesting a possible association between taurine and potassium balance in cats. Dietary acidification exacerbates potassium depletion in cats by decreasing gastrointestinal absorption of potassium.

It has been suggested therefore that the aetiology of feline dilated cardiomyopathy, like that of dilated cardiomyopathy in dogs, is multifactorial. There is some evidence to show that genetic factors may play a role in feline dilated cardiomyopathy. Burmese, Siamese and Abyssinian cats appear predisposed. The incidence of dilated cardiomyopathy is higher in young to middle-aged cats; the evidence for a sex predilection is equivocal).


Impairment in myocardial contractility leads to systolic dysfunction and increased end-diastolic pressures. Progressive dilatation of the ventricles results in distortion of the atrioventricular valve apparatus and mitral regurgitation which, together with the reduction in myocardial contractility, contributes to the reduction in stroke volume and decreased cardiac output.

Clinical signs of Dilated cardiomyopathy

The clinical signs may be gradual in onset and are often rather vague (lethargy, reduced activity and decreased appetite). Many of the presenting signs are similar to those of hypertrophic cardiomyopathy making differentiation between the two diseases on a clinical basis difficult. Cats which are dyspnocic may be dehydrated and hypothermic with weak femoral pulses. There may be obvious pallor or cyanosis of the mucosae with a prolonged capillary refill time. Increased respiratory crackles in association with a gallop rhythm and systolic murmur are common findings; the presence of a large volume of pleural fluid may result in muffled heart sounds. Less frequently there is also evidence of right-sided failure (jugular distension, and hepatomegaly); ascites is a rare finding.


The electrocardiographic changes do not help differentiate dilated cardiomyopathy from the hypertrophic form of the disease. Some cats remain in a relatively slow sinus rhythm. Tall R waves and wide P waves and QRS complexes may be apparent in Lead II.

Arrhythmias, especially ventricular premature complexes, have been recorded in more than 50% of cases. The mean electrical axis is often within normal limits.

Radiographic findings

Thoracic radiographs typically show evidence of generalized cardiomegaly; enlargement of the-left atrium may be particularly marked. The cardiac silhouette is often obscured by the presence of a bilateral pleural effusion. Pulmonary venous congestion and oedema may be present but these changes are usually mild and are often masked by the presence of fluid in the pleural space. The caudal vena cava is often dilated and there may be evidence of hepatomegaly.


Echocardiography offers the most reliable means of differentiating dilated cardiomyopathy from hypertrophic cardiomyopathy. The interventricular septum and left ventricular free wall appear thin and poorly contractile with a marked reduction in fractional shortening. Both ventricles and the left atrium appear dilated and left ventricular end-diastolic and end-systolic internal dimensions are increased.

Laboratory findings

Normal plasma taurine levels are greater than 60 nmol l-1 ; most cats with dilated cardiomyopathy have plasma taurine concentrations less than 20 nmol l-1 and often less than 10 nmol l-1. Taurine-defielent cats with thromboembolism may have slightly higher plasma taurine concentrations due to reperfusion hyperkalaemia. Whole blood taurine has been reported to be less sensitive to acute changes in taurine intake and provides a better indication of long-term taurine intake. Whole blood taurine concentrations greater than 280 nmol l-1 are considered adequate.

Prerenal azotaemia is a common finding in cats with dilated cardiomyopathy because of reduced renal perfusion. The pleural effusion which develops with feline dilated cardiomyopathy is typically a serosanguineous modified transudate; true chylous effusions have been reported in association with right heart failure.


Non-selective angiocardiography can be used to demonstrate dilatation of all cardiac chambers. The slow circulation time in cats with dilated cardiomyopathy increases the risk of thromboembolus formation during this procedure and decompensated cases should be stabilized beforehand.

Dilated cardiomyopathy: Treatment

Cats which are severely dyspnoeic should be given oxygen, kept warm and placed in a cage. Dyspnoeic animals, particularly those with suspected pleural effusion, should be handled with care and should not be placed in dorsal or lateral recumbency for radiography. A dorsoventral radiograph taken with the animal resting in sternal recumbency is usually sufficient to confirm the presence of pleural fluid. Thoracocentesis should be attempted before a more detailed radiographic examination is performed. Other therapeutic strategics are summarized below.

Digoxin improves myocardial contractility in some but not all cats with dilated cardiomyopathy and it has been suggested that the drug may act synergistically with taurine in this respect.The liquid form of the drug is unpalatable and is generally not well tolerated. There is considerable individual variation in the way in which cats respond to digoxin. The maintenance oral dose is 0.01 mg kg-1 every 48 h for an average 3-4 kg cat which is less than one quarter of a 62.5 μg tablet every other day. Cats with dilated cardiomyopathy are more susceptible to digoxin toxicity and tend to show toxic signs when the plasma concentration of digoxin is approximately 50% of the level which would be considered toxic in a normal healthy cat. Approximately 50% of cats given 0.01 mg kg-1 body weight every 48 h show signs of toxicity.

Other positive inotropic agents such as dopamine and dobutamine must be given by constant slow intravenous infusion and are, therefore, not used as extensively. Both drugs can be given at a rate of 1-5 μg kg-1 body weight min-1 ; with dobutamine, seizures have been reported with infusion rates as low as 5 μg kg-1 min-1 in cats.

Frusemide (initially 1.0 mg kg-1 body weight intravenously twice daily; for maintenance 1-2 mg kg-1 body weight per os once or twice daily)

Mixed arteriovenous vasodilators such as captopril (3.12-6.25 mg kg-1 body weight per os twice or three times daily; this dose equates to approximately one-eighth to one quarter of a 25 mg tablet) or venodilators such as 2% nitroglycerine ointment (1/8-1/4 inch applied three times daily to the inside of the pinna) can be given although the beneficial effects of these drugs have yet to be evaluated fully in cats with dilated cardiomyopathy. They should not be given to cats with cardiogenic shock since they may potentiate the fall in cardiac output especially if used in conjunction with diuretic agents.

Animals which are severely hydrated may require intravenous or subcutaneous fluid therapy, for example 0.45% saline with 2.5% dextrose solution may help combat the effects of circulatory failure. The recommended rate of infusion is 25-35 ml kg-1 body weight day-1 given in two or three divided doses. Care should be taken so that the rate of infusion optimizes cardiac output but minimizes the risk of exacerbating pulmonary oedema or a pleural effusion.

Aspirin (25 mg kg-1 body weight every 72 h).

Taurine supplementation (250-500 mg per os twice daily) may result in a dramatic clinical improvement within 1-2 weeks when dilated cardiomyopathy is associated with taurine deficiency although cehocardiographic evidence of improved cardiac performance is usually not evident until after at least three weeks of treatment.

Sodium restricted diet.


The prognosis for cats which fail to resond to taurine therapy is poor. About 93% of early deaths occur within the first two weeks; few survive longer than one month. Taurine supplementation can eventually be discontinued if adequate taurine intake is provided for in the food.

Veterinary Medicine


Symptomatic bradycardia results from problems of impulse generation in the sinus node and / or its conduction from the atria to the ventricles. Both of these processes are influenced by the autonomic nervous system with the parasympathetic system slowing and the sympathetic system accelerating impulse generation and conduction.

Non-cardiac causes of bradycardia

Sinus bradycardia is often a normal finding in athletic dogs (50 bpm or below) and is rarely associated with clinical signs. Even in dogs showing signs of vague illness, such as lethargy, which demonstrate mild sinus bradycardia, use of drugs which increase the heart rate (for example atropine) does not usually improve their behaviour. Profound symptomatic bradycardia may be caused by a number of factors which do not involve organic cardiac disease, some of which are shown in site. In many cases It is an alteration in the balance between parasympithetic and sympathetic tone to the heart which results in bradycardia so that therapy with antimuscarinic drugs (particularly where vagal tone is raised) or beta-adrenoceptor agonists is indicated to increase heart rate together with supportive therapy such as intravenous fluids and warmth. It is important to consider the underlying cause before using such symptomatic therapy as it may not always be indicated. For example, use of atropine to control bradycardia following the administration of an alpha2-adrenoceptor agonist may potentiate the transient hypertension which results after administration of such drugs to dogs and cats. Administration of beta-adrenoceptor agonists to increase the heart rate in a dog with bradycardia due to digoxin toxicity would increase the potential for ventricular tachycardia to develop. Thus, where possible, specific therapy should be administered based on the diagnosis of the underlying cause. These extrinsic factors should be considered before diagnosing the cause of symptomatic bradycardia as being due to organic disease of the sinoatrial node or of the conducting pathways in the heart.

Symptomatic bradycardia associated with organic cardiac disease

Sick sinus syndrome

This term is used to describe idiopathic disorders of the sinoatrial node, where the animals show signs of intermittent sinus arrest, sinoatrial block or sinus bradycardia. The subsidiary pacemakers fail to generate adequate escape rhythms. Some cases also show intermittent supraventricular tachyarrhythmias which may contribute to the clinical signs. This is a heterogeneous and imprecisely defined group of conditions rather than a single disease. Miniature schnauzers, pugs and dachshunds have been reported as presenting with this syndrome but it has also been seen in mixed breed dogs. In the management of this condition, it is important to manage the bradycardia first before treatment of the tachycardic episodes can be undertaken safely.

Persistent atrial standstill (silent atrium)

In persistent atrial standstill the sinus node fails to generate electrical impulses and the heart rate is governed by supraventricular, functional or ventricular escape beats. This condition is rare in dogs and cats and should be distinguished from the potentially reversible sinoventricular rhythm which accompanies severe and life-threatening hyperkalaemia.

Atrioventricular block

Failure or delay in the conduction of the sinoatrial impulse may be classified as first, second (Mobitz type I and II) or third degree atrioventricular block. In some cases, heart block can be intermittent and therefore more difficult to diagnose without the use of a continuous ambulatory ECG. First degree atrioventricular block and Mobitz type 1 seconddegree atrioventricular block are common in the dog and rarely signify intrinsic disease of the conducting system. They are easily abolished following exercise or atropine administration (0,02-0.04 mg kg-1 i.m. or i.v.). Atropine may cause an initial increase in the severity of the block (by a central action) but within 10-15 min sinus rhythm results. By contrast, in the cat even low-grade heart block is an abnormal finding and warrants further investigation.

Idiopathic persistent high-grade second-degree and complete (third degree) atrioventricular block occur in middle-aged or older dogs and are often associated with clinical signs. These may consist of weakness, exercise intolerance and syncope. Idiopathic third degree atrioventricular black has been reported in the dog in association with acquired myasthenia gravis. If obvious organic heart disease can be identified, the prognosis is much worse than for idiopathic cases where no obvious pathological process can be detected. Drug toxicity (calcium channel blockers, digoxin, beta-adrenoceptor antagonists) or electrolyte disturbances (hyperkalaemia) should be ruled out as possible causes of atrioventricular block.

Medical management of symptomatic bradycardia due to organic heart disease

Pacemaker implantation is the only long-term solution to animals exhibiting high-grade second-degree or complete atrioventricular block, persistent atrial standstill, and many cases of sick sinus syndrome. In an emergency, heart rate can be best increased by using beta-adrenoceptor agonists such as isoprenaline (10 ng kg-1 mm-1) or dopamine (2-10 μg kg-1 min-1), given by continuous intravenous infusion. An oral dose rare of isoprenaline has been described (5-10 mg three to four times daily) but there is less scope for the clinician to control the effects of the drug. Dopamine is the preferred choice since it lacks the profound peripheral vasodilatation in skeletal muscle which occurs following isoprenalinc administration. Although these drugs can be life-saving in severe cases before pacemaker implantation, their use can be associated with the occurrence of ventricular tachyarrhythmias. These should be controlled by stopping the infusion of the drug and not by the administration of drugs which suppress ventricular arrhythmias (for example lignocaine) since such drugs will suppress the escape rhythms which maintain some cardiac output in these animals.

Antimuscarinic drugs often fail to increase the heart rate in animals with heart block and atrial standstill since high vagal tone is not involved in the pathogenesis of these arrhythmias- Junctional escape rhythms may sometimes increase in rate when antimuscarinic drugs are used and some dogs with sick-sinus syndrome can be managed chronically with such drugs. Test doses of atropine will demonstrate those cases where such therapy may be worth trying. Oral preparations of antimuscarinic agents include propantheline bromide (7.5-15 mg three times daily for dogs). In dogs with both bradycardia and tachycardia, administration of antimuscarinic drugs may worsen the episodes of Tachycardia as these drugs increase conduction through the atrioventricular node. In these cases, the bradycardia should be managed by the use of a pacemaker and drugs which suppress the supraventricular tachycardia can then be safely employed. The use of pacemakers to treat symptomatic bradycardias has been extensively covered by others.


Amphotericin B Desoxycholate, Amphotericin B Lipid-Based (Abelcet, Fungizone)


Highlights Of Prescribing Information

Systemic antifungal used for serious mycotic infections

Must be administered IV

Nephrotoxicity is biggest concern, particularly with the deoxycholate form; newer lipid based products are less nephrotoxic & penetrate into tissues better, but are more expensive

Renal function monitoring essential

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based interactions

What Is Amphotericin B Desoxycholate, Amphotericin B Lipid-Based Used For?

Because the potential exists for severe toxicity associated with this drug, it should only be used for progressive, potentially fatal fungal infections. Veterinary use of amphotericin has been primarily in dogs, but other species have been treated successfully. For further information on fungal diseases treated, see the Pharmacology and Dosage sections.

The liposomal form of amphotericin B can be used to treat Leishmaniasis.

Pharmacology / Actions

Amphotericin B is usually fungistatic, but can be fungicidal against some organisms depending on drug concentration. It acts by binding to sterols (primarily ergosterol) in the cell membrane and alters the permeability of the membrane allowing intracellular potassium and other cellular constituents to “leak out.” Because bacteria and rickettsia do not contain sterols, amphotericin B has no activity against those organisms. Mammalian cell membranes do contain sterols (primarily cholesterol) and the drug’s toxicity may be a result of a similar mechanism of action, although amphotericin binds less strongly to cholesterol than ergosterol.

Amphotericin B has in vitro activity against a variety of fungal organisms, including Blastomyces, Aspergillus, Paracoccidioides, Coccidioides, Histoplasma, Cryptococcus, Mucor, and Sporothrix. Zygomycetes is reportedly variable in its response to amphotericin. Aspergillosis in dogs and cats does not tend to respond satisfactorily to amphotericin therapy. Additionally, amphotericin B has in vivo activity against some protozoa species, including Leishmania spp. and Naegleria spp.

It has been reported that amphotericin B has immunoadjuvant properties but further work is necessary to confirm the clinical significance of this effect.


Pharmacokinetic data on veterinary species is apparently unavailable. In humans (and presumably animals), amphotericin B is poorly absorbed from the GI tract and must be given parenterally to achieve sufficient concentrations to treat systemic fungal infections. After intravenous injection, the drug reportedly penetrates well into most tissues but does not penetrate well into the pancreas, muscle, bone, aqueous humor, or pleural, pericardial, synovial, and peritoneal fluids. The drug does enter the pleural cavity and joints when inflamed. CSF levels are approximately 3% of those found in the serum. Approximately 90-95% of amphotericin in the vascular compartment is bound to serum proteins. The newer “lipid” forms of amphotericin B have higher penetration into the lungs, liver and spleen than the conventional form.

The metabolic pathways of amphotericin are not known, but it exhibits biphasic elimination. An initial serum half-life of 24-48 hours, and a longer terminal half-life of about 15 days have been described. Seven weeks after therapy has stopped, amphotericin can still be detected in the urine. Approximately 2-5% of the drug is recovered in the urine in unchanged (biologically active) form.

Before you take Amphotericin B Desoxycholate, Amphotericin B Lipid-Based

Contraindications / Precautions / Warnings

Amphotericin is contraindicated in patients who are hypersensitive to it, unless the infection is life-threatening and no other alternative therapies are available.

Because of the serious nature of the diseases treated with systemic amphotericin, it is not contraindicated in patients with renal disease, but it should be used cautiously with adequate monitoring.

Adverse Effects

Amphotericin B is notorious for its nephrotoxic effects; most canine patients will show some degree of renal toxicity after receiving the drug. The proposed mechanism of nephrotoxicity is via renal vasoconstriction with a subsequent reduction in glomerular filtration rate. The drug may directly act as a toxin to renal epithelial cells. Renal damage may be more common, irreversible and severe in patients who receive higher individual doses or have preexisting renal disease. Usually, renal function will return to normal after treatment is halted, but may require several months to do so.

Newer forms of lipid-complexed and liposome-encapsulated amphotericin B significantly reduce the nephrotoxic qualities of the drug. Because higher dosages may be used, these forms may also have enhanced effectiveness. A study in dogs showed that amphotericin B lipid complex was 8-10 times less nephrotoxic than the conventional form.

The patient’s renal function should be aggressively monitored during therapy. A pre-treatment serum creatinine, BUN (serum urea nitrogen/SUN), serum electrolytes (including magnesium if possible), total plasma protein (TPP), packed cell volume (PCV), body weight, and urinalysis should be done prior to starting therapy. BUN, creatinine, PCV, TPP, and body weight are rechecked before each dose is administered. Electrolytes and urinalysis should be monitored at least weekly during the course of treatment. Several different recommendations regarding the stoppage of therapy when a certain BUN is reached have been made. Most clinicians recommend stopping, at least temporarily, amphotericin treatment if the BUN reaches 30-40 mg/dL, serum creatinine >3 mg/dL or if other clinical signs of systemic toxicity develop such as serious depression or vomiting.

At least two regimens have been used in the attempt to reduce nephrotoxicity in dogs treated with amphotericin desoxycholate. Mannitol (12.5 grams or 0.5-1 g/kg) given concurrently with amphotericin B (slow IV infusion) to dogs may reduce nephrotoxicity, but may also reduce the efficacy of the therapy, particularly in blasto-mycosis. Mannitol treatment also increases the total cost of therapy. Sodium loading prior to treating has garnered considerable support in recent years. A tubuloglomerular feedback mechanism that induces vasoconstriction and decreased GFR has been postulated for amphotericin B toxicity; increased sodium load at the glomerulus may help prevent that feedback. One clinician (Foil 1986), uses 5 mL/kg of normal saline given in two portions, before and after amphotericin B dosing and states that is has been “… helpful in averting renal insufficiency….”

Cats are apparently more sensitive to the nephrotoxic aspects of amphotericin B, and many clinicians recommend using reduced dosages in this species (see Dosage section).

Adverse effects reported in horses include: tachycardia, tachyp-nea, lethargy, fever, restlessness, anorexia, anemia, phlebitis, polyuria and collapse.

Other adverse effects that have been reported with amphotericin B include: anorexia, vomiting, hypokalemia, distal renal tubular aci-dosis, hypomagnesemia, phlebitis, cardiac arrhythmias, non-regenerative anemia and fever (may be reduced with pretreatment with NSAIDs or a low dosage of steroids). Calcinosis cutis has been reported in dogs treated with amphotericin B. Amphotericin B can increase creatine kinase levels.

Reproductive / Nursing Safety

The safety of amphotericin B during pregnancy has not been established, but there are apparently no reports of teratogenicity associated with the drug. The risks of therapy should be weighed against the potential benefits. In humans, the FDA categorizes this drug as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, hut there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, hut adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters.) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: A (Prohahly safe. Although specific studies may not have proved the safety of all drugs in dogs and cats, there are no reports of adverse effects in laboratory animals or women.)

Overdosage / Acute Toxicity

No case reports were located regarding acute intravenous overdose of amphotericin B. Because of the toxicity of the drug, dosage calculations and solution preparation procedures should be double-checked. If an accidental overdose is administered, renal toxicity maybe minimized by administering fluids and mannitol as outlined above in the Adverse Effects section.

How to use Amphotericin B Desoxycholate, Amphotericin B Lipid-Based

All dosages are for amphotericin B desoxycholate (regular amphotericin B) unless specifically noted for the lipid-based products.

Note: Some clinicians have recommended administering a 1 mg test dose (less in small dogs or cats) IV over anywhere from 20 minutes to 4 hours and monitoring pulse, respiration rates, temperature, and if possible, blood pressure. If a febrile reaction occurs some clinicians recommend adding a glucocorticoid to the IV infusion solution or using an antipyretic prior to treating, but these practices are controversial.

A published study () demonstrated less renal impairment and systemic adverse effects in dogs who received amphotericin BIV slowly over 5 hours in 1 L of D5W than in dogs who received the drug IV in 25 mL of D5W over 3 minutes.

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based dosage for dogs:

For treatment of susceptible systemic fungal infections:

a) Two regimens can be used; after diluting vial (as outlined below in preparation of solution section), either:

1) Rapid-Infusion Technique: Dilute quantity of stock solution to equal 0.25 mg/kg in 30 mL of 5% dextrose. Using butterfly catheter, flush with 10 mL of D5W. Infuse amphotericin B solution IV over 5 minutes. Flush catheter with 10 mL of D5W and remove catheter. Repeat above steps using 0.5 mg/kg 3 times a week until 9-12 mg/kg accumulated dosage is given.

2) Slow IV Infusion Technique: Dilute quantity of stock solution to equal 0.25 mg/kg in 250-500 mL of D5W. Place indwelling catheter in peripheral vein and give total volume over 4-6 hours. Flush catheter with 10 mL of D5W and remove catheter. Repeat above steps using 0.5 mg/kg 3 times a week until 9-12 mg/kg accumulated dosage is given. ()

b) In dehydrated, sodium-depleted animals, must rehydrate before administration. Dosage is 0.5 mg/kg diluted in D5W. In dogs with normal renal function, may dilute in 60-120 mL of D5W and give by slow IV over 15 minutes. In dogs with compromised renal function, dilute in 500 mL or 1 liter of D5W and give over slowly IV over 3-6 hours. Re-administer every other day if BUN remains below 50 mg/dl. If BUN exceeds 50 mg/dl, discontinue until BUN decreases to at least 35 mg/dl. Cumulative dose of 8 -10 mg/kg is required to cure blastomycosis or histoplasmosis. Coccidioidomycosis, aspergillosis and other fungal diseases require a greater cumulative dosage. ()

c) For treating systemic mycoses using the lipid-based products: AmBisome, Amphocil or Abelcet Give test dose of 0.5 mg/ kg; then 1-2.5 mg/kg IV q48h (or Monday, Wednesday, Friday) for 4 weeks or until the total cumulative dose is reached. Use 1 mg/kg dose for susceptible yeast and dimorphic fungi until a cumulative dose of 12 mg/kg is reached; for more resistant filamentous fungal infections (e.g., pythiosis) use the higher dose 2-2.5 mg/kg until a cumulative dose of 24-30 mg/kg is reached. ()

d) For treating systemic mycoses using the amphotericin B lipid complex (ABLC; Abelcet) product: 2-3 mg/kg IV three days per week for a total of 9-12 treatments (cumulative dose of 24-27 mg). Dilute to a concentration of 1 mg/mL in dextrose 5% (D5W) and infuse over 1-2 hours ()

e) For systemic mycoses using amphotericin B lipid complex (Abelcet): Dilute in 5% dextrose to a final concentration of 1 mg/mL and administer at a dosage of 2-3 mg/kg three times per week for 9-12 treatments or a cumulative dosage of 24-27 mg/kg ()

For blastomycosis (see general dosage guidelines above):

a) Amphotericin B 0.5 mg/kg 3 times weekly until a total dose of 6 mg/kg is given, with ketoconazole at 10-20 mg/kg (30 mg/kg for CNS, bone or eye involvement) divided for 3-6 months ()

b) Amphotericin B 0.15-0.5 mg/kg IV 3 times a week with ketoconazole 20 mg/day PO once daily or divided twice daily; 40 mg/kg divided twice daily for ocular or CNS involvement (for at least 2-3 months or until remission then start maintenance). When a total dose of amphotericin B reaches 4-6 mg/kg start maintenance dosage of amphotericin B at 0.15-0.25 mg/kg IV once a month or use ketoconazole at 10 mg/kg PO either once daily, divided twice daily or ketoconazole at 2.5-5 mg/kg PO once daily. If CNS/ocular involvement use ketoconazole at 20-40 mg/kg PO divided twice daily ()

c) For severe cases, using amphotericin B lipid complex (Abelcet): 1-2 mg/kg IV three times a week (or every other day) to a cumulative dose of 12-24 mg/kg ()

For cryptococcosis (see general dosage guidelines above):

a) Amphotericin B 0.5 – 0.8 mg/kg SC 2 – 3 times per week. Dose is diluted in 0.45% NaCl with 2.5% dextrose (400 mL for cats, 500 mL for dogs less than 20 kg and 1000 mL for dogs greater than 20 kg). Concentrations greater than 20 mg/L result in local irritation and sterile abscess formation. May combine with flucytosine or the azole antifungals. ()

For histoplasmosis (see general dosage guidelines above):

a) Amphotericin B 0.15 – 0.5 mg/kg IV 3 times a week with ketoconazole 10-20 mg/day PO once daily or divided twice daily (for at least 2-3 months or until remission then start maintenance). When a total dose of amphotericin B reaches 2-4 mg/kg, start maintenance dosage of amphotericin B at 0.15-0.25 mg/kg IV once a month or use ketoconazole at 10 mg/kg PO either once daily, divided twice daily or at 2.5-5 mg/kg PO once daily ()

b) As an alternative to ketoconazole treatment: 0.5 mg/kg IV given over 6-8 hours. If dose is tolerated, increase to 1 mg/ kg given on alternate days until total dose of 7.5-8.5 mg/kg cumulative dose is achieved ()

For Leishmaniasis:

a) Using the liposomal form of Amphotericin B: 3-3.3 mg/kg IV 3 times weekly for 3-5 treatments)

b) Using AmBisome (lipid-based product): Give initial test dose of 0.5 mg/kg, then 3-3.3 mg/kg IV every 72-96 hours until a cumulative dose of 15 mg/kg is reached. May be possible to give the same cumulative dose with a lower level every 48 hours. ()

For gastrointestinal pythiosis:

a) Resect lesions that are surgically removable to obtain 5 – 6 cm margins. Follow-up medical therapy using the amphotericin B lipid complex (ABLC; Abelcet) product: 1-2 mg/kg IV three times weekly for 4 weeks (cumulative dose 12-24 mg). May alternatively use itraconazole at 10 mg/kg PO once daily for 4-6 months. ()

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based dosage for cats:

For treatment of susceptible systemic fungal infections: a) Rapid-Infusion Technique: After diluting vial (as outlined below in preparation of solution section), dilute quantity of stock solution to equal 0.25 mg/kg in 30 mL of 5% dextrose. Using butterfly catheter, flush with 10 mL of D5W Infuse amphotericin B solution IV over 5 minutes. Flush catheter with 10 mL of D5W and remove catheter. Repeat above steps using 0.25 mg/kg 3 times a week until 9-12 mg/kg accumulated dosage is given. ()

For cryptococcosis (see general dosage guidelines above):

a) As an alternative therapy to ketoconazole: Amphotericin B: 0.25 mg/kg in 30 mL D5WIV over 15 minutes q48h with flucytosine at 200 mg/kg/day divided q6h PO. Continue therapy for 3-4 weeks after clinical signs have resolved or until BUN >50 mg/dl. (Legendre 1989)

b) Amphotericin B 0.15-0.4 mg/kg IV 3 times a week with flucytosine 125-250 mg/day PO divided two to four times a day. When a total dose of amphotericin B reaches 4-6 mg/ kg, start maintenance dosage of amphotericin B at 0.15-0.25 mg/kg IV once a month with flucytosine at dosage above or with ketoconazole at 10 mg/kg PO once daily or divided twice daily ()

c) Amphotericin B 0.5-0.8 mg/kg SC 2-3 times per week. Dose is diluted in 0.45% NaCl with 2.5% dextrose (400 mL for cats, 500 mL for dogs less than 20 kg and 1000 mL for dogs greater than 20 kg). Concentrations greater than 20 mg/L result in local irritation and sterile abscess formation. May combine with flucytosine or the azole antifungals. ()

d) For treating systemic mycoses using the amphotericin B lipid complex (ABLC; Abelcet) product: 1 mg/kg IV three days per week for a total of 12 treatments (cumulative dose of 12 mg). Dilute to a concentration of 1 mg/mL in dextrose 5% (D5W) and infuse over 1-2 hours ()

For histoplasmosis (see general dosage guidelines above):

a) Amphotericin B: 0.25 mg/kg in 30 mL D5WIV over 15 minutes q48h with ketoconazole at 10 mg/kg q12h PO. Continue therapy for 4-8 weeks or until BUN >50 mg/dl. If BUN increases greater than 50 mg/dl, continue ketoconazole alone. Ketoconazole is used long-term (at least 6 months of duration. ()

b) Amphotericin B 0.15-0.5 mg/kg IV 3 times a week with ketoconazole 10 mg/day PO once daily or divided twice daily (for at least 2-3 months or until remission, then start maintenance). When a total dose of amphotericin B reaches 2-4 mg/ kg, start maintenance dosage of amphotericin B at 0.15-0.25 mg/kg IV once a month or use ketoconazole at 10 mg/kg PO either once daily, divided twice daily or at 2.5-5 mg/kg PO once daily ()

For blastomycosis (see general dosage guidelines above):

a) Amphotericin B: 0.25 mg/kg in 30 mL D5WIV over 15 minutes q48h with ketoconazole: 10 mg/kg q12h PO (for at least 60 days). Continue amphotericin B therapy until a cumulative dose of 4 mg/kg is given or until BUN >50 mg/dl. If renal toxicity does not develop, may increase dose to 0.5 mg/ kg of amphotericin B. ()

b) Amphotericin B 0.15-0.5 mg/kg IV 3 times a week with ketoconazole 10 mg/day PO once daily or divided twice daily (for at least 2-3 months or until remission then start maintenance). When a total dose of amphotericin B reaches 4-6 mg/ kg start maintenance dosage of amphotericin B at 0.15-0.25 mg/kg IV once a month or use ketoconazole at 10 mg/kg PO either once daily, divided twice daily or ketoconazole at 2.5 – 5 mg/kg PO once daily. If CNS/ocular involvement, use ketoconazole at 20-40 mg/kg PO divided twice daily. ()

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based dosage for rabbits, rodents, and small mammals:

a) Rabbits: 1 mg/kg/day IV ()

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based dosage for horses:

For treatment of susceptible systemic fungal infections:

a) For fungal pneumonia: Day 1: 0.3 mg/kg IV; Day 2: 0.4 mg/kg IV; Day 3: 0.6 mg/kg IV; days 4-7: no treatment; then every other day until a total cumulative dose of 6.75 mg/kg has been administered ()

b) For phycomycoses and pulmonary mycoses: After reconstitution (see below) transfer appropriate amount of drug to 1L of D5W and administer using a 16 g needle IV at a rate of 1 L/ hr. Dosage schedule follows: Day 1: 0.3 mg/kg IV; Day 2: 0.45 mg/kg IV; Day 3: 0.6 mg/kg IV; then every other day for 3 days per week (MWF or TTHSa) until clinical signs of either improvement or toxicity occur. If toxicity occurs, a dose may be skipped, dosage reduced or dosage interval lengthened. Administration may extend from 10-80 days. ()

For intrauterine infusion: 200-250 mg. Little science is available for recommending doses, volume infused, frequency, diluents, etc. Most intrauterine treatments are commonly performed every day or every other day for 3-7 days. ()

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based dosage for Llamas:

For treatment of susceptible systemic fungal infections: a) A single case report. Llama received 1 mg test dose, then initially at 0.3 mg/kg IV over 4 hours, followed by 3 L of LRS with 1.5 mL of B-Complex and 20 mEq of KC1 added. Subsequent doses were increased by 10 mg and given every 48 hours until reaching 1 mg/kg q48h IV for 6 weeks. Animal tolerated therapy well, but treatment was ultimately unsuccessful (Coccidioidomycosis). ()

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based dosage for birds:

For treatment of susceptible systemic fungal infections:

a) For raptors and psittacines with aspergillosis: 1.5 mg/kg IV three times daily for 3 days with flucytosine or follow with flucytosine. May also use intratracheally at 1 mg/kg diluted in sterile water once to 3 times daily for 3 days in conjunction with flucytosine or nebulized (1 mg/mL of saline) for 15 minutes twice daily. Potentially nephrotoxic and may cause bone marrow suppression. ()

b) 1.5 mg/kg IV q12h for 3-5 days; topically in the trachea at 1 mg/kg q12h; 0.3-1 mg/mL nebulized for 15 minutes 2-4 times daily ()

Amphotericin B Desoxycholate, Amphotericin B Lipid-Based dosage for reptiles:

For susceptible fungal respiratory infections: a) For most species: 1 mg/kg diluted in saline and given intratracheally once daily for 14-28 treatments ()

Client Information

■ Clients should be informed of the potential seriousness of toxic effects that can occur with amphotericin B therapy

■ The costs associated with therapy

Chemistry / Synonyms

A polyene macrolide antifungal agent produced by Streptomyces nodosus, amphotericin B occurs as a yellow to orange, odorless or practically odorless powder. It is insoluble in water and anhydrous alcohol. Amphotericin B is amphoteric and can form salts in acidic or basic media. These salts are more water soluble but possess less antifungal activity than the parent compound. Each mg of amphotericin B must contain not less than 750 micrograms of anhydrous drug. Amphotericin A may be found as a contaminant in concentrations not exceeding 5%. The commercially available powder for injection contains sodium desoxycholate as a solubilizing agent.

Newer lipid-based amphotericin B products are available that have less toxicity than the conventional desoxycholate form. These include amphotericin B cholesteryl sulfate complex (amphotericin B colloidal dispersion, ABCD, Amphotec), amphotericin B lipid complex (ABLC, Abelcet), and amphotericin B liposomal (ABL, L-AMB, Ambisome).

Amphotericin B may also be known as: amphotericin; amphotericin B cholesteryl sulfate complex, amphotericin B lipid complex, amphotericin B liposome, amphotericin B phospholipid complex, amphotericin B-Sodium cholesteryl sulfate complex, anfotericina B, or liposomal amphotericin B; many trade names are available.

Storage / Stability / Compatibility

Vials of amphotericin B powder for injection should be stored in the refrigerator (2-8°C), protected from light and moisture. Reconstitution of the powder must be done with sterile water for injection (no preservatives — see directions for preparation in the Dosage Form section below).

After reconstitution, if protected from light, the solution is stable for 24 hours at room temperature and for 1 week if kept refrigerated. After diluting with D5W (must have pH >4.3) for IV use, the manufacturer recommends continuing to protect the solution from light during administration. Additional studies however, have shown that potency remains largely unaffected if the solution is exposed to light for 8-24 hours.

Amphotericin B deoxycholate is reportedly compatible with the following solutions and drugs: D5W, D5W in sodium chloride 0.2%, heparin sodium, heparin sodium with hydrocortisone sodium phosphate, hydrocortisone sodium phosphate/succinate and sodium bicarbonate.

Amphotericin B deoxycholate is reportedly incompatible with the following solutions and drugs: normal saline, lactated Ringer’s, D5-normal saline, Ds-lactated Ringer’s, amino acids 4.25%-dextrose 25%, amikacin, calcium chloride/gluconate, carbenicillin disodium, chlorpromazine HCL, cimetidine HCL, diphenhydramine HCL, dopamine HCL, edetate calcium disodium (Ca EDTA), gentamicin sulfate, kanamycin sulfate, lidocaine HCL, metaraminol bitartrate, methyldopate HCL, nitrofurantoin sodium, oxytetracycline HCL, penicillin G potassium/sodium, polymyxin B sulfate, potassium chloride, prochlorperazine mesylate, streptomycin sulfate, tetracycline HCL, and verapamil HCL. Compatibility is dependent upon factors such as pH, concentration, temperature and diluent used; consult specialized references or a hospital pharmacist for more specific information.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

Human-Labeled Products:

Amphotericin B Desoxycholate Powder for Injection: 50 mg in vials; Amphocin (Gensia Sicor); Fungizone Intravenous (Apothecon); generic (Pharma-Tek); (Rx)

Directions for reconstitution/administration: Using strict aseptic technique and a 20 gauge or larger needle, rapidly inject 10 mL of sterile water for injection (without a bacteriostatic agent) directly into the lyophilized cake; immediately shake well until solution is clear. A 5 mg/mL colloidal solution results. Further dilute (1:50) for administration to a concentration of 0.1 mg/mL with 5% dextrose in water (pH >4.2). An in-line filter may be used during administration, but must have a pore diameter >1 micron.

Amphotericin B Lipid-Based Suspension for Injection: 100 mg/20 mL (as lipid complex) in 10 mL & 20 mL vials with 5 micron filter needles: Abelcet (Enzon); (Rx)

Amphotericin B Lipid-Based Powder for Injection: 50 mg/vial (as cholesteryl) in 20 mL vials; 100 mg (as cholesteryl) in 50 mL vials; Amphotec (Sequus Pharmaceuticals); 50 mg (as liposomal) in single-dose vials with 5-micron filter; AmBisome (Fujisawa; (Rx)

Amphotericin B is also available in topical formulations: Fungizone (Apothecon); (Rx)


Aminophylline Theophylline

Phosphodiesterase Inhibitor Bronchodilator

Highlights Of Prescribing Information

Bronchodilator drug with diuretic activity; used for bronchospasm & cardiogenic pulmonary edema

Narrow therapeutic index in humans, but dogs appear to be less susceptible to toxic effects at higher plasma levels

Therapeutic drug monitoring recommended

Many drug interactions

What Is Aminophylline Theophylline Used For?

The theophyllines are used primarily for their broncho dilatory effects, often in patients with myocardial failure and/or pulmonary edema. While they are still routinely used, the methylxanthines must be used cautiously due to their adverse effects and toxicity.


The theophyllines competitively inhibit phosphodiesterase thereby increasing amounts of cyclic AMP which then increase the release of endogenous epinephrine. The elevated levels of cAMP may also inhibit the release of histamine and slow reacting substance of anaphylaxis (SRS-A). The myocardial and neuromuscular transmission effects that the theophyllines possess maybe a result of translocating intracellular ionized calcium.

The theophyllines directly relax smooth muscles in the bronchi and pulmonary vasculature, induce diuresis, increase gastric acid secretion and inhibit uterine contractions. They have weak chronotropic and inotropic action, stimulate the CNS and can cause respiratory stimulation (centrally-mediated).


The pharmacokinetics of theophylline have been studied in several domestic species. After oral administration, the rate of absorption of the theophyllines is limited primarily by the dissolution of the dosage form in the gut. In studies in cats, dogs, and horses, bioavail-abilities after oral administration are nearly 100% when non-sustained release products are used. One study in dogs that compared various sustained-release products (), found bioavailabilities ranging from approximately 30-76% depending on the product used.

Theophylline is distributed throughout the extracellular fluids and body tissues. It crosses the placenta and is distributed into milk (70% of serum levels). In dogs, at therapeutic serum levels only about 7-14% is bound to plasma proteins. The volume of distribution of theophylline for dogs has been reported to be 0.82 L/kg. The volume of distribution in cats is reported to be 0.46 L/kg, and in horses, 0.85-1.02 L/kg. Because of the low volumes of distribution and theophylline’s low lipid solubility, obese patients should be dosed on a lean body weight basis.

Theophylline is metabolized primarily in the liver (in humans) to 3-methylxanthine which has weakbronchodilitory activity. Renal clearance contributes only about 10% to the overall plasma clearance of theophylline. The reported elimination half-lives (mean values) in various species are: dogs = 5.7 hours; cats = 7.8 hours, pigs = 11 hours; and horses = 11.9 to 17 hours. In humans, there are very wide interpatient variations in serum half-lives and resultant serum levels. It could be expected that similar variability exists in veterinary patients, particularly those with concurrent illnesses.

Before you take Aminophylline Theophylline

Contraindications / Precautions / Warnings

The theophyllines are contraindicated in patients who are hypersensitive to any of the xanthines, including theobromine or caffeine. Patients who are hypersensitive to ethylenediamine should not take aminophylline.

The theophyllines should be administered with caution in patients with severe cardiac disease, seizure disorders, gastric ulcers, hyperthyroidism, renal or hepatic disease, severe hypoxia, or severe hypertension. Because it may cause or worsen preexisting arrhythmias, patients with cardiac arrhythmias should receive theophylline only with caution and enhanced monitoring. Neonatal and geriatric patients may have decreased clearances of theophylline and be more sensitive to its toxic effects. Patients with CHF may have prolonged serum half-lives of theophylline.

Adverse Effects

The theophyllines can produce CNS stimulation and gastrointestinal irritation after administration by any route. Most adverse effects are related to the serum level of the drug and may be symptomatic of toxic blood levels; dogs appear to tolerate levels that may be very toxic to humans. Some mild CNS excitement and GI disturbances are not uncommon when starting therapy and generally resolve with chronic administration in conjunction with monitoring and dosage adjustments.

Dogs and cats can exhibit clinical signs of nausea and vomiting, insomnia, increased gastric acid secretion, diarrhea, polyphagia, polydipsia, and polyuria. Side effects in horses are generally dose related and may include: nervousness, excitability (auditory, tactile, and visual), tremors, diaphoresis, tachycardia, and ataxia. Seizures or cardiac dysrhythmias may occur in severe intoxications.

Reproductive / Nursing Safety

In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, hut there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans.)

Overdosage / Acute Toxicity

Clinical signs of toxicity (see above) are usually associated with levels greater than 20 mcg/mL in humans and become more severe as the serum level exceeds that value. Tachycardias, arrhythmias, and CNS effects (seizures, hyperthermia) are considered the most life-threatening aspects of toxicity. Dogs appear to tolerate serum levels higher than 20 mcg/mL.

Treatment of theophylline toxicity is supportive. After an oral ingestion, the gut should be emptied, charcoal and a cathartic administered using the standardized methods and cautions associated with these practices. Patients suffering from seizures should have an adequate airway maintained and treated with IV diazepam. The patient should be constantly monitored for cardiac arrhythmias and tachycardia. Fluid and electrolytes should be monitored and corrected as necessary. Hyperthermia may be treated with phenothiazines and tachycardia treated with propranolol if either condition is considered life threatening.

How to use Aminophylline Theophylline

Note: Theophyllines have a low therapeutic index; determine dosage carefully. Because of aminophylline/theophylline’s pharmacokinet-ic characteristics, it should be dosed on a lean body weight basis in obese patients. Dosage conversions between aminophylline and theophylline can be easily performed using the information found in the Chemistry section below. Aminophylline causes intense local pain when administered IM and is rarely used or recommended via this route.

Aminophylline Theophylline dosage for dogs:

a) Using Theochron Extended-Release Tablets or Theo-Cap Extended-Release Capsules: Give 10 mg/kg PO every 12 hours initially, if no adverse effects are observed and the desired clinical effect is not achieved, give 15 mg/kg PO q12h while monitoring for adverse effects. ()

b) For adjunctive medical therapy for mild clinical signs associated with tracheal collapse (<50% collapse): aminophylline: 11 mg/kg PO, IM or IV three times daily. ()

c) For adjunctive therapy of severe, acute pulmonary edema and bronchoconstriction: Aminophylline 4-8 mg/kg IV or IM, or 6-10 mg/kg PO every 8 hours. Long-term use is not recommended. ()

d) For cough: Aminophylline: 10 mg/kg PO, IV three times daily ()

e) As a broncho dilator tor collapsing trachea: 11 mg/kg PO or IV q6- 12h ()

Aminophylline Theophylline dosage for cats:

a) Using Theo-Dur 20 mg/kg PO once daily in the PM; using Slo-Bid 25 mg/kg PO once daily in the PM (Johnson 2000) [Note: The products Theo-Dur and Slo-Bid mentioned in this reference are no longer available in the USA. Although hard data is not presently available to support their use in cats, a reasonable alternative would be to cautiously use the dog dose and products mentioned above in the reference by Bach et al — Plumb]

b) Using aminophylline tablets: 6.6. mg/kg PO twice daily; using sustained release tablets (Theo-Dur): 25-50 mg (total dose) per cat PO in the evening ()

c) For adjunctive medical therapy for mild clinical signs associated with tracheal collapse (<50% collapse): aminophylline: 5 mg/kg PO, two times daily. ()

d) For adjunctive therapy for bronchoconstriction associated with fulminant CHF: Aminophylline 4-8 mg/kg SC, IM, IV q8-12h. ()

e) For cough: Aminophylline: 5 mg/kg PO twice daily ()

Aminophylline Theophylline dosage for ferrets:

a) 4.25 mg/kg PO 2-3 times a day ()

Aminophylline Theophylline dosage for horses:

(Note: ARCI UCGFS Class 3 Aminophylline Theophylline)

NOTE: Intravenous aminophylline should be diluted in at least 100 mL of D5W or normal saline and administered slowly (not >25 mg/min). For adjunctive treatment of pulmonary edema:

a) Aminophylline 2-7 mg/kg IV q6- 12h; Theophylline 5-15 mg/kg PO q12h ()

b) 11 mg/kg PO or IV q8-12h. To “load” may either double the initial dose or give both the oral and IV dose at the same time. IV infusion should be in approximately 1 liter of IV fluids and given over 20-60 minutes. Recommend monitoring serum levels. ()

For adjunctive treatment for heaves (RAO):

a) Aminophylline: 5-10 mg/kg PO or IV twice daily. ()

b) Aminophylline: 4-6 mg/kg PO three times a day. ()


■ Therapeutic efficacy and clinical signs of toxicity

■ Serum levels at steady state. The therapeutic serum levels of theophylline in humans are generally described to be between 10-20 micrograms/mL. In small animals, one recommendation for monitoring serum levels is to measure trough concentration; level should be at least above 8-10 mcg/mL (Note: Some recommend not exceeding 15 micrograms/mL in horses).

Client Information

■ Give dosage as prescribed by veterinarian to maximize the drug’s benefit

Chemistry / Synonyms

Xanthine derivatives, aminophylline and theophylline are considered to be respiratory smooth muscle relaxants but, they also have other pharmacologic actions. Aminophylline differs from theophylline only by the addition of ethylenediamine to its structure and may have different amounts of molecules of water of hydration. 100 mg of aminophylline (hydrous) contains approximately 79 mg of theophylline (anhydrous); 100 mg of aminophylline (anhydrous) contains approximately 86 mg theophylline (anhydrous). Conversely, 100 mg of theophylline (anhydrous) is equivalent to 116 mg of aminophylline (anhydrous) and 127 mg aminophylline (hydrous).

Aminophylline occurs as bitter-tasting, white or slightly yellow granules or powder with a slight ammoniacal odor and a pKa of 5. Aminophylline is soluble in water and insoluble in alcohol.

Theophylline occurs as bitter-tasting, odorless, white, crystalline powder with a melting point between 270-274°C. It is sparingly soluble in alcohol and only slightly soluble in water at a pH of 7, but solubility increases with increasing pH.

Aminophylline may also be known as: aminofilina, aminophyllinum, euphyllinum, metaphyllin, theophyllaminum, theophylline and ethylenediamine, theophylline ethylenediamine compound, or theophyllinum ethylenediaminum; many trade names are available.

Theophylline may also be known as: anhydrous theophylline, teofillina, or theophyllinum; many trade names are available.

Storage / Stability/Compatibility

Unless otherwise specified by the manufacturer, store aminophylline and theophylline oral products in tight, light-resistant containers at room temperature. Do not crush or split sustained-release oral products unless label states it is permissible.

Aminophylline for injection should be stored in single-use containers in which carbon dioxide has been removed. It should also be stored at temperatures below 30°C and protected from freezing and light. Upon exposure to air (carbon dioxide), aminophylline will absorb carbon dioxide, lose ethylenediamine and liberate free theophylline that can precipitate out of solution. Do not inject aminophylline solutions that contain either a precipitate or visible crystals.

Aminophylline for injection is reportedly compatible when mixed with all commonly used IV solutions, but may be incompatible with 10% fructose or invert sugar solutions.

Aminophylline is reportedly compatible when mixed with the following drugs: amobarbital sodium, bretylium tosylate, calcium gluconate, chloramphenicol sodium succinate, dexamethasone sodium phosphate, dopamine HCL, erythromycin lactobionate, heparin sodium, hydro cortisone sodium succinate, lidocaine HCL, mephentermine sulfate, methicillin sodium, methyldopate HCL, metronidazole with sodium bicarbonate, pentobarbital sodium, phenobarbital sodium, potassium chloride, secobarbital sodium, sodium bicarbonate, sodium iodide, terbutaline sulfate, thiopental sodium, and verapamil HCL

Aminophylline is reportedly incompatible (or data conflicts) with the following drugs: amikacin sulfate, ascorbic acid injection, bleomycin sulfate, cephalothin sodium, cephapirin sodium, clindamycin phosphate, codeine phosphate, corticotropin, dimenhydrinate, dobutamine HCL, doxorubicin HCL, epinephrine HCL, erythromycin gluceptate, hydralazine HCL, hydroxyzine HCL, insulin (regular), isoproterenol HCL, levorphanol bitartrate, meperidine HCL, methadone HCL, methylprednisolone sodium succinate, morphine sulfate, nafcillin sodium, norepinephrine bitartrate, oxytetracycline, penicillin G potassium, pentazocine lactate, procaine HCL, prochlorperazine edisylate or mesylate, promazine HCL, promethazine HCL, sulfisoxazole diolamine, tetracycline HCL, vancomycin HCL, and vitamin B complex with C. Compatibility is dependent upon factors such as pH, concentration, temperature, and diluent used and it is suggested to consult specialized references for more specific information.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information.

Human-Labeled Products:

The listing below is a sampling of products and sizes available; consult specialized references for a more complete listing.

Aminophylline Tablets: 100 mg (79 mg theophylline) & 200 mg (158 mg theophylline); generic; (Rx)

Aminophylline Injection: 250 mg (equiv. to 197 mg theophylline) mL in 10 mL & 20 mL vials, amps and syringes; generic; (Rx)

Theophylline Time Released Capsules and Tablets: 100 mg, 125 mg 200 mg, 300 mg, 400 mg, 450 mg, & 600 mg. (Note: Different products have different claimed release rates which may or may not correspond to actual times in veterinary patients; Theophylline Extended-Release (Dey); Theo-24 (UCB Pharma); Theophylline SR (various); Theochron (Forest, various); Theophylline (Able); Theocron (Inwood); Uniphyl (Purdue Frederick); generic; (Rx)

Theophylline Tablets and Capsules: 100 mg, 200 mg, & 300 mg; Bronkodyl (Winthrop); Elixophyllin (Forest); generic; (Rx)

Theophylline Elixir: 80 mg/15 mL (26.7 mg/5 mL) in pt, gal, UD 15 and 30 mL, Asmalix (Century); Elixophyllin (Forest); Lanophyllin (Lannett); generic; (Rx)

Theophylline & Dextrose Injection: 200 mg/container in 50 mL (4 mg/mL) & 100 mL (2 mg/mL); 400 mg/container in 100 mL (4 mg/ mL), 250 mL (1.6 mg/mL), 500 mL (0.8 mg/mL) & 1000 mL (0.4 mg/mL); 800 mg/container in 250 mL (3.2 mg/mL), 500 mL (1.6 mg/mL) & 1000 mL (0.8 mg/mL); Theophylline & 5% Dextrose (Abbott & Baxter); (Rx)


Amantadine HCL (Symmetrel)

Antiviral (Influenza A); Nmda Antagonist

Highlights Of Prescribing Information

Antiviral drug with NMDA antagonist properties; may be useful in adjunctive therapy of chronic pain in small animals & treatment of equine influenza in horses

Very limited clinical experience; dogs may exhibit agitation & GI effects, especially early in therapy

Large interpatient variations of pharmacokinetics in horses limit its therapeutic usefulness

Overdoses are potentially very serious; fairly narrow therapeutic index in dogs & cats; may need to be compounded

Extra-label use prohibited (by FDA) in chickens, turkeys & ducks

What Is Amantadine HCL Used For?

While amantadine may have efficacy and clinical usefulness against some veterinary viral diseases, presently the greatest interest for its use in small animals is as a NMDA antagonist in the adjunctive treatment of chronic pain, particularly those tolerant to opioids.

Amantadine has also been investigated for treatment of equine-2 influenza virus in the horse. However, because of expense, interpatient variability in oral absorption and other pharmacokinetic parameters, and the potential for causing seizures after intravenous dosing, it is not commonly used for treatment.

In humans, amantadine is used for treatment and prophylaxis of influenza A, parkinsonian syndrome, and drug-induced extrapyramidal effects. As in veterinary medicine, amantadine’s effect on NMDA receptors in humans are of active interest, particularly its use as a co-analgesic with opiates and in the reduction of opiate tolerance development.


Like ketamine, dextromethorphan and memantine, amantadine antagonizes the N-methyl-D-aspartate (NMDA) receptor. Within the central nervous system, chronic pain can be maintained or exacerbated when glutamate or aspartate bind to this receptor. It is believed that this receptor is particularly important in allodynia (sensation of pain resulting from a normally non-noxious stimulus). Amantadine alone is not a particularly good analgesic, but in combination with other analgesics (e.g., opiates, NSAIDs), it is thought that it may help alleviate chronic pain.

Amantadine’s antiviral activity is primarily limited to strains of influenza A. While its complete mechanism of action is unknown, it does inhibit viral replication by interfering with influenza A virus M2 protein.

Amantadine’s antiparkinsonian activity is not well understood. The drug does appear to have potentiating effects on dopaminergic neurotransmission in the CNS and anticholinergic activity.


The pharmacokinetics of this drug have apparently not been described in dogs or cats. In horses, amantadine has a very wide interpatient variability of absorption after oral dosing; bioavailability ranges from 40-60%. The elimination half-life in horses is about 3.5 hours and the steady state volume of distribution is approximately 5 L/kg.

In humans, the drug is well absorbed after oral administration with peak plasma concentrations occurring about 3 hours after dosing. Volume of distribution is 3-8 L/kg. Amantadine is primarily eliminated via renal mechanisms. Oral clearance is approximately 0.28 L/hr/kg; half-life is around 17 hours.

Before you take Amantadine HCL

Contraindications / Precautions / Warnings

In humans, amantadine is contraindicated in patients with known hypersensitivity to it or rimantadine, and in patients with untreated angle-closure glaucoma. It should be used with caution in patients with liver disease, renal disease (dosage adjustment may be required), congestive heart failure, active psychoses, eczematoid dermatitis or seizure disorders. In veterinary patients with similar conditions, it is advised to use the drug with caution until more information on its safety becomes available.

In 2006, the FDA banned the use of amantadine and other influenza antivirals in chickens, turkeys and ducks.

Adverse Effects

There is very limited experience in domestic animals with amantadine and its adverse effect profile is not well described. It has been reported that dogs given amantadine occasionally develop agitation, loose stools, flatulence or diarrhea, particularly early in therapy. Experience in cats is limited; an adverse effect profile has yet to be fully elucidated, but the safety margin appears to be narrow.

Reproductive / Nursing Safety

In humans, the FDA categorizes amantadine as a category C drug for use during pregnancy (Animal studies have shown an adverse effect on the fetus, hut there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans). High dosages in rats demonstrated some teratogenic effects.

Amantadine does enter maternal milk. The manufacturer does not recommend its use in women who are nursing. Veterinary significance is unclear.

Overdosage / Acute Toxicity

Toxic dose reported for cats is 30 mg/kg and behavioral effects may be noted at 15 mg/kg in dogs and cats.

In humans, overdoses as low as 2 grams have been associated with fatalities. Cardiac dysfunction (arrhythmias, hypertension, tachycardia), pulmonary edema, CNS toxicity (tremors, seizures, psychosis, agitation, coma), hyperthermia, renal dysfunction and respiratory distress syndrome have all been documented. There is no known specific antidote for amantadine overdose. Treatment should consist of gut emptying, if possible, intensive monitoring and supportive therapy. Forced urine acidifying diuresis may increase renal excretion of amantadine. Physostigmine has been suggested for cautious use in treating CNS effects.

How to use Amantadine HCL

Amantadine HCL dosage for dogs:

As adjunctive therapy for chronic pain:

a) 1.25-4 mg/kg PO ql2-24h. Usually use 3 mg/kg PO once daily as an adjunct with a NSAID May require 5-7 days to have a positive effect. ()

b) Approximate dose is 3-5 mg/kg PO once daily. ()

c) To decrease wind-up: 3-5 mg/kg PO once daily for one week ()

Amantadine HCL dosage for cats:

As adjunctive therapy for chronic pain:

a) 3 mg/kg PO once daily. May be useful addition to NSAIDs; not been evaluated for toxicity. May need to be compounded. ()

b) Approximate dose is 3-5 mg/kg PO once daily. ()

c) 3 mg/kg PO once daily. ()

Amantadine HCL dosage for horses:

For acute treatment of equine-2 influenza: a) 5 mg/kg IV q4h ()


■ Adverse effects (GI, agitation)

■ Efficacy

Client Information

■ When used in small animals, the drug must be given as prescribed to be effective and may take a week or so to show effect.

■ Gastrointestinal effects (loose stools, gas, diarrhea) or some agitation may occur, particularly early in treatment. Contact the veterinarian if these become serious or persist.

■ Overdoses with this medication can be serious; keep well out of reach of children and pets.

Chemistry / Synonyms

An adamantane-class antiviral agent with NMDA antagonist properties, amantadine HCL occurs as a white to practically white, bitter tasting, crystalline powder with a pKa of 9. Approximately 400 mg are soluble in 1 mL of water; 200 mg are soluble in 1 mL of alcohol.

Amantadine HCL may also be known as: adamantanamine HCL, Adekin, Amanta, Amantagamma, Amantan, Amantrel, Amixx, Antadine, Antiflu-DES, Atarin, Atenegine, Cerehramed, Endantadine, Infectoflu, Influ-A, Lysovir, Mantadine, Mantadix, Mantidan, Padiken, Symadine, Symmetrel, Viroifral and Virucid.

Storage / Stability

Tablets, capsules and the oral solution should be stored in tight containers at room temperature. Limited exposures to temperatures as low as 15°C and as high as 30°C are permitted. Avoid freezing the liquid.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

Human-Labeled Products:

Amantadine HCL Tablets & Capsules: 100 mg; Symmetrel (Endo); generic; (Rx)

Amantadine HCL Syrup: 10 mg/mL in 480 mL; Symmetrel (Endo); generic; (Rx)

In 2006, the FDA banned the extra-label use of amantadine and other influenza antivirals in chickens, turkeys and ducks.


Dilated Cardiomyopathy: Acute Therapy

Treatment Goals

The treatment goals depend on the type and severity of the clinical signs. If severely dyspneic the initial goal is to make it easier for the cat to breathe by removing pleural effusion, by reducing pulmonary edema pharmacologically, or by administering oxygen. If the primary problem is a marked reduction in perfusion leading to hypothermia, the goal is to increase cardiac output, if possible, via the administration of an intravenous positive inotropic agent, such as dobutamine, and possibly the judicious use of intravenous fluid administration, especially if the cat is severely dehydrated.


Pleurocentesis is often life saving in the severely dyspneic cat that has a large amount of pleural effusion. Thoracocentesis is described in posts.

Diuretic Therapy

Diuretic administration is the only reliable way to reduce pulmonary edema formation in a cat with severe dilated cardiomyopathy. Furosemide is used almost exclusively. The dose depends on the severity of the pulmonary edema, on whether the cat is currendy on furosemide for heart failure, and whether the situation is acute or chronic Cats in severe respiratory distress may need an initial dose as high as 2 mg/lb parenterally. Intravenous administration is preferred, but the drug should be administered intramuscularly if restraint for intravenous administration produces stress. Absorption half-life after intramuscular administration is around 5 minutes, so the entire dose is fully absorbed within 20 to 25 minutes. The duration of effect of furosemide after parenteral administration is probably 1 to 2 hours in a cat in heart failure. Consequently, another dose should be administered within that period if the cat is still in respiratory distress and is not severely dehydrated. A cat with a lesser amount of pulmonary edema and less respiratory distress needs a smaller dose of furosemide parenterally in the acute setting. Respiratory rate and character should be monitored carefully after diuretic administration with the cat in an oxygen-enriched environment.


Increasing the percent concentration of oxygen delivered to the alveoli is critical in cats in respiratory distress. This can be accomplished using a face mask, standard oxygen cage, a pediatric incubator, or nasal insufflation. Generally the goal is to increase fraction of inspired oxygen (FIO2) to at least 40% (normal is 21%). If the cat resists a face mask, it should not be used. When placed in a confined space, especially a small space like an incubator, it is mandatory to keep the environmental temperature and the carbon dioxide concentration within reasonable levels. Failure to do so can cause death. A canister containing sodium lime or barium hydroxide lime controls carbon dioxide level in an oxygen cage, and a refrigeration unit controls temperature. Carbon dioxide concentration is usually controlled in an incubator by maximizing the flow rate of oxygen (and therefore flushing out the carbon dioxide).

Inotropic Support

Beta-adrenergic agonists, usually dobutamine or dopamine, can be used for acute inotropic support in a cat widi severe dilated cardiomyopathy and severe heart failure. However, conscious cats have more side effects with these drugs than do dogs. They often appear agitated and may even seizure. The half-life of these drugs is around 1 minute, so stopping the drug infusion results in rapid cessation of adverse effects. The infusion rate for dobutamine and dopamine in a cat is less than that used in a dog and is generally in the range of 1 to 2.5 Mg/lb/min.


Nitroprusside is a potent dilator (i.e., smooth muscle relaxant) of systemic arterioles and systemic veins. It can only be used in cats with dilated cardiomyopathy that are not in cardiogenic shock (systolic systemic arterial blood pressure over 100 mm Hg). If systemic pressure is adequate, the drug can be used in one of two ways: (1) empirically at a dose of 2 µg/lb/min or (2) titrated using blood pressure starting at a dose of 1 ug/lb/min and increased until the systolic pressure has decreased by at least 10 to 15 mm Hg. ()

General Supportive Measures

Although dogs commonly start to drink water and eat once they are no longer in respiratory distress, cats may not. Dehydration is a common side effect of aggressive diuretic therapy, and some cats are dehydrated at presentation. Generally cats do better if they are sent home as soon as possible. However, if hospitalization is required after the edema and effusion are controlled, judicious use of fluid therapy may be needed. Electrolyte disturbances, most commonly hyponatremia, hypokalemia, and hypochloremia, are also more frequent in cats than in dogs in this acute setting. Consequendy, serum electrolyte concentrations should be monitored.


Acyclovir (Zovirax)

Antiviral (Herpes)

Highlights Of Prescribing Information

Used primarily in birds for Pacheco’s disease; may be useful in cats for Herpes infection

If given rapidly IV, may be nephrotoxic

Oral use may cause GI distress

Reduce dosage with renal insufficiency

May be fetotoxic at high dosages

What Is Acyclovir Used For?

Acyclovir may be useful in treating herpes infections in a variety of avian species and in cats with corneal or conjunctival herpes infections. Its use in veterinary medicine is not well established, however, and it should be used with caution. Acyclovir has relatively mild activity against Feline Herpesvirus-1 when compared to some of the newer antiviral agents (e.g., ganciclovir, cidofovir, or penciclovir).

Acyclovir is being investigated as a treatment for equine herpes virus type-1 myeloencephalopathy in horses, but clinical efficacy has not yet been proven and the drug’s poor oral bioavailability is problematic. There continues to be interest in finding a dosing regimen that can achieve therapeutic levels and be economically viable, particularly since the drug’s use during a recent outbreak appeared to have some efficacy in reducing morbidity and mortality (not statistically proven). Also, intravenous acyclovir may be economically feasible to treat some neonatal foals.


Acyclovir has antiviral activity against a variety of viruses including herpes simplex (types I and II), cytomegalovirus, Epstein-Barr, and varicella-Zoster. It is preferentially taken up by these viruses, and converted into the active triphosphate form where it inhibits viral DNA replication.


In dogs, acyclovir bioavailability varies with the dose. At doses of 20 mg/kg and below, bioavailability is about 80%, but declines to about 50% at 50 mg/kg. Bioavailability in horses after oral administration is very low (<4%) and oral doses of up to 20 mg/kg may not yield sufficient levels to treat equine herpes virus. Elimination half-lives in dogs, cats and horses are approximately 3 hours, 2.6 hours, and 10 hours, respectively.

In humans, acyclovir is poorly absorbed after oral administration (approx. 20%) and absorption is not significantly affected by the presence of food. It is widely distributed throughout body tissues and fluids including the brain, semen, and CSE It has low protein binding and crosses the placenta. Acyclovir is primarily hepatically metabolized and has a half-life of about 3 hours in humans. Renal disease does not significantly alter half-life unless anuria is present.

Before you take Acyclovir

Contraindications / Precautions / Warnings

Acyclovir is potentially contraindicated (assess risk vs. benefit) during dehydrated states, pre-existing renal function impairment, hypersensitivity to it or other related antivirals, neurologic deficits, or previous neurologic reactions to other cytotoxic drugs.

Adverse Effects

With parenteral therapy potential adverse effects include thrombophlebitis, acute renal failure, and ecephalopathologic changes (rare). GI disturbances may occur with either oral or parenteral therapy.

Preliminary effects noted in cats, include leukopenia and anemias, which are apparently reversible with discontinuation of therapy.

Reproductive / Nursing Safety

Acyclovir crosses the placenta, but rodent studies have not demonstrated any teratogenic effects thus far. Acyclovir crosses into maternal milk but associated adverse effects have not been noted. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, but there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans.)

Acyclovir concentrations in milk of women following oral administration have ranged from 0.6 to 4.1 times those found in plasma. These concentrations would potentially expose the breastfeeding infant to a dose of acyclovir up to 0.3 mg/kg/day. Data for animals was not located. Use caution when administering to a nursing patient.

Overdosage / Acute Toxicity

Oral overdose is unlikely to cause significant toxicity. In a review of 105 dogs ingesting acyclovir (Richardson 2000), 10 animals were considered cases of acyclovir toxicosis. Adverse effects included vomiting, anorexia, diarrhea and lethargy. One dog developed polyuria/ polydipsia and another dog developed a mildly elevated BUN and serum creatinine 24 hours after ingesting 2068 mg/kg of acyclovir. Per the APCC database, acute renal injury was reported in one dog at a dose of 250 mg/kg. Treatment consists of standard decontamination procedures and supportive therapy. Contact an animal poison control center for further information, if necessary.

There were 92 exposures to acyclovir reported to the ASPCA Animal Poison Control Center (APCC; during 2005-2006. In these cases 90 were dogs with 7 showing clinical signs; the remaining 2 cases were cats that showed no clinical signs. Common findings recorded in decreasing frequency included vomiting, diarrhea, lethargy, anorexia, and crystalluria.

How to use Acyclovir

Acyclovir dosage for birds:

For treatment of Pacheco’s Disease:

a) 80 mg/kg PO q8h or 40 mg/kg q8h IM (do not use parenterally for more than 72 hours as it can cause tissue necrosis at site of injection) ()

b) 80 mg/kg in oral suspension once daily PO; mix suspension with peanut butter or add to drinking water 50 mg in 4 oz of water for 7-14 days ()

c) When birds are being individually treated: 80 mg/kg PO or IM twice daily ()

d) For prophylaxis: Exposed birds are given 25 mg/kg IM once (give IM with caution as it is very irritating), and then acyclovir is added to drinking water at 1 mg/mL and to the food at 400 mg/quart of seed for a minimum of 7 days. Quaker parrots have been treated with a gavage of acyclovir at 80 mg/ kg q8h for 7 days. ()

Acyclovir dosage for cats:

For Herpesvirus-1 infections:

a) 10-25 mg/kg PO twice daily. Never begin therapy until diagnostic evaluation is completed. Maybe toxic in cats; monitor CBC every 2- 3 weeks. ()

Acyclovir dosage for horses:

a) Although efficacy is undetermined, anecdotal use of acyclovir orally at 10 mg/kg PO 5 times daily or 20 mg/kg PO q8h may have had some efficacy in preventing or treating horses during EHV-1 outbreaks.


■ Renal function tests (BUN, Serum Cr) with prolonged or IV therapy

■ Cats: CBC

Chemistry / Synonyms

An antiviral agent, acyclovir (also known as ACV or acycloguanosine), occurs as a white, crystalline powder. 1.3 mg are soluble in one mL of water. Acyclovir sodium has a solubility of greater than 100 mg/mL in water. However, at a pH of 7.4 at 37°C it is practically all unionized and has a solubility of only 2.5 mg/mL in water. There is 4.2 mEq of sodium in each gram of acyclovir sodium.

Acyclovir may be known as: aciclovirum, acycloguanosine, acyclovir, BW-248U, Zovirax, Acic, Aciclobene, Aciclotyrol, Acivir, Acyrax, Cicloviral, Geavir, Geavir, Herpotern, Isavir, Nycovir, Supraviran, Viclovir, Virherpes, Viroxy, Xorox, or Zovirax.

Storage / Stability/Compatibility

Acyclovir capsules and tablets should be stored in tight, light resistant containers at room temperature. Acyclovir suspension and sodium sterile powder should be stored at room temperature.

When reconstituting acyclovir sodium do not use bacteriostatic water with parabens as precipitation may occur. The manufacturer does not recommend using bacteriostatic water for injection with benzyl alcohol because of the potential toxicity in neonates. After reconstitution with 50-100 mL of a standard electrolyte or dextrose solution, the resulting solution is stable at 25°C for 24 hours. Acyclovir is reportedly incompatible with biologic or colloidial products (e.g., blood products or protein containing solutions). It is also incompatible with dopamine HC1, dobutamine, fludarabine phosphate, foscarnet sodium, meperidine and morphine sulfate. Many other drugs have been shown to be compatible in specific situations. Compatibility is dependent upon factors such as pH, concentration, temperature and diluent used; consult specialized references or a hospital pharmacist for more specific information.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

Human-Labeled Products:

Acyclovir Tablets: 400 mg & 800 mg; Zovirax (GlaxoWellcome); generic; (Rx)

Acyclovir Capsules: 200 mg; Zovirax (GlaxoWellcome); generic; (Rx)

Acyclovir Suspension: 200 mg/5 mL in 473 mL; Zovirax (GlaxoWellcome); generic; (Rx)

Acyclovir Sodium Injection (for IV infusion only): 50 mg/mL (as sodium): generic; (Rx)

Acyclovir Powder for Injection: 500 mg/vial (as sodium) in 10 mL vials; 1000 mg/vial (as sodium) in 20 mL vials; 500 mg/vial Lyophilized in 10 mL vials; Zovirax (GlaxoWellcome); generic; (Rx)

Acyclovir Ointment: 5% (50 mg/g) in 15 g; Zovirax (Biovail); (Rx)

Acyclovir Cream: 5% (50 mg/g) in 2g tubes; Zovirax (Biovail); (Rx)


Hemolytic Anemia

Hemolytic anemia is a pathologic condition that results from accelerated erythrocyte removal and can be intravascular and extravascular. Intravascular hemolysis occurs when erythrocytes are destroyed within the vascular space. Clinical signs associated with intravascular hemolysis are typically acute in onset and classically include icterus and red- to port-wine-colored urine. Extravascular hemolysis results from accelerated erythrocyte removal by macrophages in the spleen or liver and is characterized by icterus without hemoglobinuria.

Diseases That Primarily Cause Intravascular Hemolysis

Oxidative Erythrocyte Damage

Oxidant damage to erythrocytes can develop following exposure to a variety of oxidizing agents such as phenothiazines, onions, or wilted red maple (Acer rubrum) leaves. The latter cause is by far the most common. The oxidizing agent causes hemoglobin to become denatured with subsequent disulfide bond formation. Oxidized hemoglobin forms precipitates referred to as Heinz bodies that are visible with Romanowsky’s-stained blood smears. These cell changes result in increased fragility of cells with subsequent intravascular hemolysis and enhanced removal by the mononuclear phagocytic system in the spleen and liver. In addition, oxidative damage causes increased permeability of the membrane, thereby altering ion transport mechanisms and osmotic gradients. Due to these changes, erythrocytes may rupture within the vascular lumen, thus resulting in intravascular hemolysis and microangiopathy. In contrast to oxidative damage that leads to erythrocyte destruction, altered oxygen carrying capacity results when hemoglobin is oxidized and forms methemoglobin. Methemoglobinemia occurs when more than 1.77% of the hemoglobin is oxidized from the ferrous (Fe2+) to the ferric (Fe3+) state by oxidizing agents.

Because A. rubrum is a common tree in the eastern United States, toxicity associated with red maple leaf ingestion is a fairly common clinical disease in that region. Although the specific toxic agent in the plant has not been identified, a seasonal trend appears to exist for the development of disease because more cases are associated with ingestion of wilted or dried leaves in the fall than for leaves ingested in the spring.

Clinical Signs and Diagnosis

In cases of red maple toxicity, a combination of intravascular and extravascular hemolysis develops over a variable period of 2 to 6 days. In severe cases, clinical signs of hemolytic anemia and tissue hypoxia secondary to methemoglobinemia may develop more rapidly. The prognosis for horses suffering from red maple toxicity is guarded; the approximate survival rate is 60% to 70%. Clinical signs result from the combined effects of tissue hypoxia and hemolysis that results in fever, tachycardia, tachypnea, lethargy, intense icterus, and hemoglobinuria, with characteristic brown coloration of skin, mucous membranes, and — if methemoglobinemia is present — blood. Hematologic abnormalities include anemia, increased mean corpuscular hemoglobin concentration and mean corpuscular hemoglobin, free plasma hemoglobin, anisocytosis, poikilocytosis, eccentrocytes, lysed erythrocytes that produce fragments or membrane ghosts, agglutination, increased red blood cell fragility, variable presence of Heinz bodies, and neutrophilia. Serum chemistry abnormalities include increased total and indirect bilirubin, serum creatinine, and serum urea nitrogen concentrations, reduced red blood cell glutathione and increased aspartate aminotransferase, sorbitol dehydrogenase, creatinine phosphokinase, and gamma-glutamyl transpeptidase activities.

Additional abnormalities may include hypercalcemia and hyperglycemia, with a variable degree of metabolic acidosis. Urinalysis findings could include any combination of the following: hemoglobinuria, methemoglobinuria, proteinuria, bilirubinuria, and urobilinogenuria. Methemoglobin can be quantified spectrophotometrically. Red maple leaf, wild onion, or phenothiazine toxicosis would be strongly suspected if a history of exposure or opportunity for exposure exists. Diagnosis is based on clinical signs of an acute onset primarily of intravascular hemolytic crisis supported by laboratory evidence of oxidative damage — that is, Heinz bodies or methemoglobinemia. Additional differential diagnoses for methemoglobinemia should include familial methemoglobinemia and nitrate toxicity, both of which are exceptionally rare in the horse.


Treatment for oxidative injury involves reducing the fragility of erythrocytes, maximizing tissue oxygenation, maintaining renal perfusion, and providing supportive care. The horse needs to be removed from the environmental source of the toxin and treated with activated charcoal (8-24 mg/kg up to 2.2 kg PO) via nasogastric tube to reduce further absorption of red maple toxin. Dexamethasone (0.05-0.1 mg/kg IV ql2-24h) may be helpful to stabilize cellular membranes and reduce extravascular removal of erythrocytes by phagocytes. Ascorbic acid (10-20 g PO q24h) is often used to maintain cellular α-tocopherol in the reduced form and as a scavenger of free radicals. No data support the use of methylene blue as a reducing agent in horses; in fact, it may exacerbate oxida-tive damage. Oxygen insufflation may be required for horses that suffer from severe hypoxia. Whole blood transfusion from a compatible donor should be considered in those horses that demonstrate severe hemolytic disease. These signs include a severe reduction in venous oxygen tension (PVo2) and increased anion gap or packed cell volume (packed cell volume) 10% to 12% with evidence of cardiovascular and respiratory distress. In cases of severe hemolysis, pigmentary nephropathy — induced by the combination of excess filtration of hemoglobulin and hypoxemia — may be a complication. Renal function should therefore be monitored during the course of treatment. Intravenous fluids are administered as needed, but hemodilution in anemic patients should be avoided. If acute renal failure develops, diuretic agents such as dopamine, furosemide, or mannitol may be indicated. In high-risk patients, drug therapy should be designed to avoid additional potentially nephrotoxic agents such as aminoglycosides and non-steroidal antiinflammatory drug (NSAID) agents.


Complications are a major component of morbidity following severe hemolysis. Poor tissue oxygenation may lead to cerebral anoxia and altered mentation, renal failure, and myocarditis. Blood transfusion may result in colic secondary to reperfusion of hypoperfused bowel. Laminitis is always a concern in horses with severe illness and may be compounded by the use of corticosteroids. Disseminated intravascular coagulopathy may develop secondary to severe hemolysis.

In conclusion, horses should not be housed in areas with access to red maple trees or other potential oxi-dants. Good quality forage should be available at all times to reduce the likelihood of horses ingesting leaves as they fall or blow into pastures. Other maple varieties of trees should be considered potentially dangerous; reports have suggested clinical signs consistent with red maple toxicity when affected animals were exposed to red maple hybrids.

Additional Causes of Intravascular Hemolysis

Microangiopathic hemolysis may be associated with vessel thrombosis. Hemolysis is secondary to intravascular fibrin accumulation and may be characterized by the presence of schizocytes. This is a potential complication that is characteristic of chronic disseminated intravascular coagulation (DIC) in horses. Fulminant liver failure also carries the potential complication of hemolysis. Clinical evidence is consistent with intravascular hemolysis that includes icterus and hemoglobinuria. The severity of hemolysis contributes to mortality in most cases. Lesions at necropsy are consistent with DIC. It has been proposed that alterations in exchangeable red blood cell lipoprotein are affected by increased bile acids, thus contributing to altered metabolism of red cells resulting in hemolysis.

Toxin exposure may result in acute intravascular hemolysis. Snakebites that result in envenomation with potential hemolysis include: rattlesnakes (Crotalus spp.), pigmy rattlesnakes (Sistrurus spp.), copperhead (Agk-istrodon spp.), cottonmouth (Agkistrodon piscivorus), or water moccasins. Snake toxins comprise more than 90% proteins that include proteolytic and phospholipase enzymes. These toxins are well known to induce episodes of severe hemolysis and altered coagulation mechanisms. Bacterial exotoxins produced from Clostridium spp. and some staphylococcal pathogens carry the potential of inducing severe intravascular hemolysis, which is especially apparent in septic neonatal foals. Although rare in horses, infection by Leptospira pomona and Leptospira icterohaemorrhagiae serotypes have been reported to cause acute intravascular hemolysis in several large animal species. Intravenous iatrogenic administration of hypotonic fluids or undiluted dimethyl sulfoxide (DMSO) or excessive administration of water enemas to neonates may result in hemolysis. Although rare, heavy metal intoxication may also cause hemolysis.

Diseases That Primarily Cause Extravascular Hemolysis


Pharmacologic Induction Of Estrus

It is clear that use of artificial lighting is the most successful and most widely employed method for jump-starting the breeding season. However, is there hope for a pharmacologic approach that does not require rewiring the farm? The short answer is that there is hope — but not necessarily promise.

Careful study of Table Physiologic Events of Vernal Transition in Chronologic Order reveals the problem to be surmounted in order for a mare to reinitiate estrous cyclicity. Luteinizing hormone (LH) secretion from the pituitary is, for all practical purposes, limiting throughout anestrus and vernal transition. These authors have shown that the gene for production of the LH subunits is not detectable in the pituitaries of anestrus mares. It is this reduction or outright lack of LH that appears to be responsible for the anovulatory vernal transition follicles. The reduction in pituitary LH appears to continue even after hypothalamic gonadotropin-releasing hormone (GnRH) secretion is renewed. That may explain the mixed results when GnRH is administered to mares in vernal transition in attempts to stimulate ovulation. Studies that employed this strategy several years ago were promising, but positive results likely reflected treatment given to mares further along in vernal transition. Similarly, studies using synthetic progestins to “stimulate” early onset of estrous cyclicity may have employed mares further along in vernal transition.

Dopamine Antagonist and Seasonality in Horses

In species such as sheep, evidence indicates that dopamine plays an inhibitory role on the hypothalamic-pituitary axis (HPA) during the nonbreeding season. Specifically, gonad-otropin secretion decreases during the nonbreeding season because of a neuronal inhibition of GnRH secretion via dopaminergic input. The inhibition of the HPA occurs only during anestrous and is estrogen-dependent.

Although a direct relationship between dopamine secretion and suppression of the equine HPA has not been demonstrated to date, dopamine concentrations in cerebrospinal fluid are highest in mares during anestrus. Thus recent interest in studying the effects of various dopamine antagonists on the equine hypothalamic-pituitary-gonadal axis and their subsequent effects on the timing of the breeding season in mares has been considerable.

The first dopamine antagonist to be tested was sulpiride at a dose of 0.5 mg/kg, orally every 12 hours. This dose caused a significant advance of the onset of the breeding season. Similarly, when domperidone (1.1 mg/kg once daily orally), another dopamine antagonist, was administered to horses during early vernal transition, it resulted in a significant advance of the onset of the breeding season over that in control mares. The primary difference between sulpiride and domperidone is that sulpiride crosses the blood-brain barrier, whereas domperidone does not.

The reported effect of dopamine antagonist on accelerating the onset of the breeding season in mares has been further evaluated to determine what effect, if any, the antagonist has on the hypothalamic-pituitary axis. Brendemuehl and Cross (2000) treated anestrous mares with domperidone beginning on January 15 and reported no effect on FSH, LH, nor estradiol secretion. However, Brendemuehl and Cross (see readings list) reported a significant advance in the onset of the breeding season in those mares treated with domperidone (51 days versus 130 days). Similarly, unpublished data from laboratory of the authors of this chapter reported that anestrous pony mares treated with sulpiride twice daily for 2 weeks during winter anestrus were not different from control mares with respect to LH and GnRH secretion. Therefore the data suggest that dopamine antagonist may accelerate the onset of the breeding season in vernal transition mares but not through activation of the hypothalamic-pituitary axis. Recent work by Daels and colleagues (2000) reported that treatment of anestrous mares with daily sulpiride plus extended photoperiod and ambient temperature resulted in an advance of the onset of the breeding season. However, when mares were treated with sulpiride alone and maintained under natural photoperiod and natural temperatures, no difference in date of the first ovulation of the year was found. It is important to note that no data on the fertility of the reported “early” ovulations exist.

Although the current evidence that suggests that dopamine antagonist may be helpful in manipulating the timing of the first ovulation of the year in mares is promising, variation in results may again suggest that treatment efficacy depends to some extent on the photic status of the mare. As in many experimental treatments, timing of treatment may be critical relative to photic exposure (anestrous versus vernal transition). These authors have proposed the idea of a “photic gate,” which means that some neural mechanism(s) require exposure to stimulatory photoperiods before pharmacologic initiation of estrous cyclicity can be accomplished.


Heart Failure: Treatment Strategies

Management of Acute Decompensated Congestive Heart Failure

Dogs with dilated cardiomyopathy or mitral regurgitation often present with acute onset of coughing, dyspnea, restlessness, orthopnea, and weakness subsequent to the development of severe pulmonary edema and/or low cardiac output. The immediate priorities in these patients are resolution of the pulmonary edema, maintenance of adequate tissue perfusion pressure, and adequate delivery of blood flow to vital tissues. These goals must be achieved quickly, therefore it is important that the practitioner use drugs with proven hemodynamic benefits and a rapid onset of action.

Oxygen Supplementation

As left atrial and pulmonary capillary pressures increase and the lymphatics’ capacity to remove fluid is overwhelmed, the interstitial space and alveoli become flooded. Because these flooded alveoli lack ventilation and represent areas of functional shunting, oxygen administration must be combined with agents that effectively lower pulmonary venous pressure. Oxygen can easily be administered to compromised patients by provision of an oxygen-enriched environment (i.e., oxygen cage) or by use of nasal insufflation, achieving maximal inspired oxygen concentrations of 40% to 90%, respectively.

Reduction of Pulmonary Venous Pressure

Rapid reduction of pulmonary venous pressure is most readily achieved through use of a combination of intravenous (IV) drugs that lower the circulating plasma volume and redistribute the intravascular volume. Intravenous furosemide (2 to 8 mg/kg) should be administered to dogs with severe pulmonary edema to promote natriuresis and diuresis quickly. These large doses may be repeated (initially every 1 to 2 hours) until the respiratory rate and dyspnea start to decline. After stabilization, the dose should be reduced (2 to 4 mg/kg every 8 to 12 hours), because excessive administration may lead to profound dehydration, electrolyte depletion, renal failure, low cardiac output, and circulatory collapse.

Drugs that decrease preload (to combat congestion) and afterload (to decrease myocardial work) are administered concurrently with furosemide. Intravenous sodium nitroprusside is a potent, ultrarapid, balanced vasodilator that seems to reduce pulmonary venous pressure quickly and effectively. When used in animals with congestive heart failure, nitroprusside decreases right atrial and pulmonary capillary wedge pressures and systemic vascular resistance and increases cardiac output. Although hypotension and tachycardia are reported side effects, the reduction in systemic vascular resistance (SVR) is theoretically associated with an increase in cardiac output (CO) that serves to maintain systemic arterial blood pressure (BP = SVR. x CO). Nausea, vomiting, and cyanide toxicity during prolonged administration are other reported side effects. Because of its short half-life, nitroprusside, mixed with 5% dextrose, must be administered by constant-rate infusion (CRI). After institution of an initial dose of 1 µg/kg/min, the rate is slowly titrated upward while the blood pressure is monitored. An infusion rate of 2 to 5 µg/kg/min usually is sufficient to decrease afterload, although rarely doses as high as 10 µg/kg/min may be required. If significant hypotension is encountered after administration of nitroprusside, slowing the infusion rate generally is effective at raising the blood pressure to acceptable levels.

Sodium nitroprusside Nitroprusside is an intravenous preparation with potent arteriolar and venous vasodilative properties mediated by the formation of nitric oxide and subsequently the second messenger cyclic guanosine monophosphate (cGMP). To some degree, the combination of nitroprusside and dobutamine can be considered short-term “cardiac life support,” used primarily during an attempt to rescue dogs with severe, life-threatening pulmonary edema subsequent to dilated cardiomyopathy. This drug combination’s ability to reduce afterload quickly appears to be beneficial also in patients with chronic degenerative valvular disease and pulmonary edema, although management of these cases often can be accomplished less intensively.

Unfortunately, the beneficial hemodynamic profile of nitroprusside is accompanied by a difficult administration protocol that requires intensive monitoring. Because nitroprusside produces an almost immediate and often profound reduction in systemic vascular resistance, continuous blood pressure monitoring throughout administration is recommended. The drug is light sensitive, is given by constant-rate infusion (typically 2 to 5 µg/kg/min), and should not be infused with another agent, which necessitates placement of a second intravenous catheter for administration of dobutamine. These stringent requirements may provide cause for more frequent use of intravenous bipyridines to combat life-threatening heart failure, at least until studies are able to elucidate whether either method produces better results.

If nitroprusside is unavailable, balanced vasodilatation may be attempted through administration of an arterial vasodilator (hydralazine, 0.5 to 2 mg/kg given orally) in combination with a venodilator (nitroglycerin ointment, ¼ to ¾ -inch applied cutaneously every 8 to 12 hours; or isosorbide dinitrate, 0.5 to 2 mg/kg given orally every 8 hours). Although easier to administer, this therapy seems to be less effective at quickly reducing pulmonary venous pressure compared with nitroprusside.

Potent afterload reduction in patients with severe mitral insufficiency and large regurgitant volumes serves to decrease the left ventricular to left atrial pressure gradient and hence the volume of insufficiency. Nitroprusside, or possibly hydralazine, can effectively decrease the volume of mitral regurgitation and lower left atrial pressure in cases of severe congestive heart failure subsequent to rupture of the chordae tendineae or the onset of atrial fibrillation. Despite this obvious theoretical advantage, a recent human study showed that mitral regurgitation worsened in four of nine patients with mitral valve prolapse during nitroprusside infusion. This finding highlights the point that adjustments in the therapeutic regimen may be required and should be based on patient response rather than physiologic principles.

Augmentation of Systolic Performance

Preload reducing agents, such as furosemide, cannot enhance systolic function and in fact at high doses serve only to decrease cardiac output. Therefore the use of a rapid-acting, intravenous inotropic agent is vital to the management of acute decompensated congestive heart failure in dogs with dilated cardiomyopathy. Although there is debate over whether dogs with mitral valve insufficiency have systolic dysfunction, acutely positive inotropic agents may serve to decrease the regurgitant orifice area and hence the volume of insufficiency.

The short-acting, positive inotropic agents most commonly used to manage decompensated heart failure increase cyclic adenosine monophosphate (cAMP). Dobutamine and dopamine are sympathomimetic agents that bind to beta, receptors, thereby stimulating adenylyl cyclase activity and production of cAMP. The bipyridines amrinone and milrinone increase cyclic adenosine monophosphate by preventing its degradation by phosphodiesterase. Both drug classes are capable of rapidly augmenting systolic function during constant-rate intravenous infusions. By increasing cytosolic cAMP, these agents enhance (1) calcium entry into the cell, promoting ventricular contraction; (2) diastolic calcium uptake by the sarcoplasmic reticulum, promoting ventricular relaxation; and (3) peripheral vasodilatation, reducing after-load. It should be remembered that the sympathomimetics also have alpha-agonistic properties that promote vasoconstriction. Unfortunately, both the sympathomimetics and the bipyridines may promote tachycardia and undesirable ventricular arrhythmias. Therefore careful electrocardiographs (ECG) monitoring is required during administration of these drugs, and significant or worsening ventricular arrhythmias may warrant discontinuation of the infusion and institution of antiarrhythmic therapy.

Sympathomimetics The sympathomimetics enhance cardiac contractility by complexing with myocardial beta receptors. After substrate binding to an unoccupied beta receptor, a coupled G-protein stimulates the enzyme cyclase to produce cAMP. This second-messenger “effector” system acts by means of protein kinase A to phosphorylate intracellular proteins, including the L-type calcium channel, phospholamban, and troponin I, thereby enhancing ventricular contraction and relaxation. Despite the sympathomimetics’ ability to increase cardiac contractility approximately 100% above baseline, not all drugs in this class are suitable for the management of heart failure. The specificity for beta receptor binding depends on the specific agent and dose administered. Sympathomimetics inappropriate for the management of heart failure include the pure beta agonist isoproterenol and the naturally occurring catecholamines norepinephrine and epinephrine. These agents tend to promote tachycardia, arrhythmias, and untoward alterations in systemic vascular resistance

Dobutamine and dopamine are more appropriate sympathomimetics for the management of heart failure. Although both drugs can enhance cardiac contractility, several drawbacks discourage long-term use: (1) they must be given intravenously, because successful oral administration is precluded by extensive first-pass hepatic metabolism; (2) because of their extremely short half-lives (approximately 1 to 2 minutes), they must be administered by constant-rate infusion; (3) almost any positive inotropic response tends to increase myocardial work and thus the propensity for ventricular arrhythmias; and (4) after 24 to 48 hours of constant-rate infusion, their positive inotropic response is limited by beta receptor downregulation and uncoupling. The tendency for long-term sympathomimetic administration to increase mortality, as documented in humans, appears to relegate these agents to short-term management of acute, life-threatening heart failure.

Dobutamine Dobutamine is a synthetic analog of dopamine that displays predominately betaj receptor binding (beta1 > beta2 > alpha). Dobutamine is able to increase cardiac contractility and thus cardiac output without causing a profound, concomitant increase in the heart rate. The mechanism underlying the lack of a positive chronotropic response is not well understood, but this characteristic tends to make dobutamine the most appropriate agent for short-term treatment of heart failure. It appears that complexing with vasodilative beta receptors and vasoconstrictive alpha receptors, combined with an increase in cardiac output, maintains arterial blood pressure at near baseline values. If the systolic blood pressure is normal to elevated, dobutamine infusion (slow titration up to 5 to 15 µg/kg/min in 5% dextrose) can be combined with the potent vasodilator nitroprusside in an attempt to decrease internal cardiac work and further enhance forward blood flow. Continuous ECG and blood pressure monitoring is recommended during this treatment regimen, and exacerbation of tachycardia or ventricular arrhythmias may necessitate discontinuation of dobutamine.

Dopamine A precursor of norepinephrine, dopamine can bind myocardial beta receptors in addition to peripherally located dopaminergic, beta2, and alpha receptors. Within the renal, mesenteric, coronary, and cerebral vascular beds, these dopaminergic DA2 receptors are able to promote vasodilata-tion at low infusion rates of dopamine (1 to 2 µg/kg/min). However, at higher infusion rates (10 to 20 µg/kg/min), these vasodilative properties are over-ridden by an undesirable, alpha-mediated vasoconstrictive response. Also, high doses are accompanied by increases in the heart rate, the likelihood of arrhythmogenesis, the release of norepinephrine, and the myocardial oxygen demand. Dopamine (slow titration up to 1 to 10 µg/kg/min) may be used in situations similar to those in which dobutamine is appropriate (e.g., profound myocardial failure) and may further enhance renal blood flow. For the authors, an increased propensity for the development of tachycardia relegates dopamine to the role of second-choice drug. As with dobutamine, careful ECG and blood pressure monitoring is indicated during dopamine administration.

Bipyridines Similar to the sympathomimetics, the bipyridines promote an increase in cardiac contractility by increasing cytosolic cyclic adenosine monophosphate levels. However, rather than directly enhancing the production of cAMP, they increase circulating levels by inhibiting phosphodiesterase III, the enzyme responsible for cyclic adenosine monophosphate inactivation. Unlike the sympathomimetics, the bipyridines do not rely on beta-adrenergic receptors and therefore are less affected by downregulation and uncoupling. Furthermore, because phosphodiesterase inhibitors increase vascular smooth muscle cyclic adenosine monophosphate without displaying affinity for alpha receptors, they are also vasodilators. Because of the bipyridines’ combination of positive inotropic and vasodilative properties, the term inodilators has come into use for these agents. Because they increase cytosolic calcium and myocardial work, they inherently carry the caveats of tachycardia and ventricular arrhythmias. In fact, the 28% increase in all-cause mortality identified in humans randomized to oral milrinone versus placebo has severely limited further attempts to evaluate agents that act via cAMP-dependent mechanisms.

Milrinone The phosphodiesterase inhibitor milrinone is substantially more potent than amrinone and is available in an intravenous preparation. Because of its combined positive inotropic and vasodilative properties, milrinone may be used as a substitute for the dobutamine/nitroprusside combination in the management of acute life-threatening heart failure. Despite milrinone’s ability to increase measures of fractional shortening after oral administration in dogs, this formulation is no longer available for prescription.”

There are no published reports regarding the hemodynamic effects of intravenous milrinone administered to dogs with acute myocardial failure. When administered to normal dogs at an infusion rate of 1 to 10 µg/kg/min, milrinone increased cardiac contractility 50% to 140%. Whether similar doses are efficacious in dogs with heart failure is uncertain, and dosing recommendations currently are difficult to propose. Because CRI milrinone requires 10 to 30 minutes to reach maximal peak effects in normal dogs, it may be prudent to administer a loading dose, followed by constant-rate infusion. Theoretical administration guidelines after the bolus would be to titrate the infusion rate upward slowly while monitoring the systemic blood pressure and a continuous electrocardiogram. Efficacy may be monitored clinically (e.g., reduction in the respiratory rate, alleviation of orthopnea) or echocardiographically with periodic measures of systolic function.

Amrinone The effects of amrinone are almost identical to those of milrinone except that it does not appear to be as potent. Although there are no reports of its large-scale use in the management of acute decompensated congestive heart failure, treatment recommendations have been extrapolated from studies of normal dogs. Constant-rate infusions of 10 to 100 µg/kg/min appear to be capable of increasing cardiac contractility by 10% to 80% in awake, normal dogs. Anesthetized dogs showed a 15% increase in the heart rate at an infusion rate of 30 µg/kg/min and a 20% increase at 100 µg/kg/min. This tachycardia may have been induced either directly, through cyclic adenosine monophosphate stimulation, or indirecdy, in response to a decrease in blood pressure. The 30 µg/kg/min infusion rate was associated with a 10% decrease in blood pressure, whereas the 100 µg/kg/min rate reduced blood pressure by 30%.I After institution of a CRI, amrinone requires approximately 45 minutes to reach peak effect. Therefore, similar to milrinone, it appears most appropriate to administer a slow IV bolus of 1 to 3 mg/kg, followed by a slowly up-titrated CRI of 10 to 100 µg/kg/min. Continuous ECG monitoring should be instituted to allow evaluation for excessive tachycardia or arrhythmogenesis, and the systemic blood pressure should be monitored to avoid hypotension.

Management of Acute Heart Failure Secondary to Diastolic Dysfunction

Cats with hypertrophic cardiomyopathy (HCM) often present with signs of respiratory distress subsequent to the development of pulmonary edema or pleural effusion. Impaired ventricular relaxation produces elevated atrial and venous pressures, with eventual fluid exudation into the alveoli or pleural space. The treatment goals for cats with HCM and heart failure focus on relieving congestion through preload reduction rather than augmenting systolic function or decreasing afterload.