Compounding For Feline Hypertension
Therapies for feline hypertension have not often been systematically evaluated. Therapies that have been employed and reported include diuretics (furosemide and spironolactone), angiotensin-converting enzyme inhibitors (ACE-I; captopril, enalapril, lisinopril, and benazepril), beta-blockers (propranolol and atenolol), and calcium channel blockers (diltiazem and amlodipine). Littman retrospectively evaluated 24 cats with chronic renal failure (CRF) and found that the most effective antihypertensive therapy was the combination of a beta-blocker and an ACE-I and that there was a poor response to furosemide. Jensen prospectively studied 12 similarly affected cats and found that the response to an ACE-I or beta-blocker alone was poor. A North Carolina State University study retrospectively found amlodipine to lower blood pressure ≥ 20% in 30 of 32 hypertensive cats with 28 of 32 becoming normotensive. Diltiazem and beta-blockers alone or with ACE-I also lowered blood pressure in the majority of cats so treated. The literature and clinical experience would, nevertheless, lead one to appropriately conclude that amlodipine is the single best agent for the management of feline systemic hypertension, and that the adjunct therapies mentioned above may be added if indicated.
To reduce stress to the cardiovascular system of the feline patient and to preserve the owner-pet bond, palatable, non-invasive therapy is mandatory for treatment of feline hypertension. Amlodipine is dosed at 0.3mg – 0.625mg orally once to twice daily, and has also been shown to be effective when applied transdermally at approximately twice the effective oral dose. Amlodipine is only FDA approved for human use and is available in tablet sizes far too large to afford safe and effective therapy in cats. Our compounding pharmacists can compound amlodipine into oral suspensions, capsules, treats, and powders to sprinkle on food, as well as into transdermal gels for application to the pinnae. Diltiazem may also be utilized to lower feline blood pressure and is available in several human-approved dosage forms that are, again, far too large for use in cats. Diltiazem controlled-delivery (Cardizem CD®) is the only dosage form of diltiazem that demonstrates pharmacokinetics to support once daily dosing in cats. Available as a capsule containing a 40/60 mixture of immediate release and sustained release beads of diltiazem, compounding pharmacists can reformulate these capsules into 45mg (total) doses for once daily administration to cats. Diltiazem has not been sufficiently evaluated to determine whether or not transdermal administration is effective; however, there are many anecdotal reports of efficacy. Atenolol may be useful in reducing heart rate in hypertensive cats and is dosed empirically at 6.25mg – 12.5mg per cat orally once daily. Again, our compounding pharmacists can provide palatable dosage forms of atenolol that are voluntarily accepted by feline patients. For feline patients requiring multiple therapies, we can also provide combination therapies in a single dosage form. For example, we can compound a single capsule or treat that contains amlodipine, diltiazem and atenolol, further reducing the stress to both patient and owner. We invite veterinarians wishing to explore palatable and non-invasive therapies for cats with hypertension to consult with our compounding pharmacists.
J Vet Intern Med. 1994 Mar-Apr 1994;8(2):79-86.
J Am Vet Med Assoc. Sep 2000;217(5):695-702.
J Am Anim Hosp Assoc. 2007 May-Jun 2007;43(3):149-156.
Low Dose Anti-platelet Therapies for Feline Arterial Thromboembolism (FATE)
Transdermal Diltiazem for Treatment of Hypertrophic Cardiomyopathy in Cats
J Pharm Biomed Anal. 2005 Jun 1;38(1):60-5. Epub 2004 Dec 25.
International Journal of Pharmaceutical Compounding. Jan/Feb 2008; 12(1):67
Transdermal Atenolol and Feasibility of Transdermal Administration
Oral administration of atenolol at a median dose of 1.1 mg/kg every 12 hours (range, 0.8 to 1.5 mg/kg) in cats induced effective plasma concentrations at 2 hours after treatment in most cats. Transdermal administration provided lower and inconsistent plasma atenolol concentrations. Further studies are needed to find an effective formulation and dosing scheme for transdermal administration of atenolol.
“In theory, the transdermal route of administering medications has many potential advantages. It is noninvasive and not demanding technically, avoids first-pass hepatic metabolism and gastrointestinal breakdown, has potential for sustained release formulations, and can be administered over a large surface area. Transdermal administration of medication has been shown to achieve blood concentrations of drug that are considered to be therapeutic (eg, fentanyl) or efficaciously affect physiologic surrogates (eg, methimazole, nitroglycerine, and lidocaine). Feasibility of transdermal medication varies on a drug-by-drug basis.”
Discussion: In spite of these results, investigators did not conclude that transdermally administered atenolol is not feasible.Because two cats did achieve therapeutic blood concentrations of atenolol after transdermal administration, the authors called for further research to find a transdermal formulation and dosing regimen for atenolol that will consistently result in plasma atenolol concentrations of >260ng/ml.Investigators offered several considerations for future studies. This study utilized a hydrophilic carbomer/propylene glycol/glycerin gel vehicle which has been used in human delivery of transdermal medications. As pluronic lecithin organogel (PLO) is the transdermal vehicle used almost exclusively in veterinary medicine, investigators encouraged future transdermal atenolol research utilizing PLO as the vehicle.Investigators also noted that higher doses of atenolol (3mg/kg) have been reported to consistently result in blood levels providing adequate adrenergic blockade at 12 hours in all cats studied.Since the median atenolol dose administered in this study was 1.1mg/kg, researchers suggest studying transdermal atenolol at the 3.3mg/kg dose.
Because daily oral administration of atenolol to cats is challenging and often results in a lack of compliance, a non-invasive dosage form such as transdermal atenolol will most likely result in better compliance, less stress to the cat, and reveal a positive therapeutic effect.
Am J Vet Res. 2008 Jan;69(1): 39-44.
Enalapril for Cardiomyopathy and CHF
Enalapril has also "been effective in treating cardiomyopathy and CHF in cats and ferrets, and its effects on blood pressure in horses and camels have been studied." Because enalapril is a prodrug and can not be converted to its active form enalaprilat in patients with severe liver dysfunction, captopril or lisinopril might be a better choice in those patients. Renal function should be checked before starting enalapril therapy and at least every two months thereafter. The most common side effects are gastrointestinal, but there have been reports of enalapril-induced cough in dogs and a bird. Hypotension is a major concern if overdose occurs. NSAIDs, including aspirin, may reduce enalapril's effect. The injectable form (enalaprilat) should not be given orally because it is very poorly absorbed.
"The recommended dose for enalapril in dogs is 0.5 mg/kg orally every 12 to 24 hours. The dose for cats is 0.25 to 0.5 mg/kg orally every 12 to 24 hours."
Compendium, Dec. 1999
Amlodipine to Treat Feline Systemic Hypertension
In a study at the Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, amlodipine was shown to be a safe and effective once-daily antihypertensive agent when administered to cats at a dosage of 0.18 +/- 0.03 mg/kg daily as monotherapy. Researchers at the Department of Medical Sciences, University of Wisconsin-Madison, administered amlodipine at an oral daily dosage of 0.625 mg per cat (range = 0.08 to 0.23 mg/kg body weight). Average indirect systolic blood pressure measurements in those 12 cases decreased significantly from 198 to 155 mmHg during amlodipine treatment. Significant changes in body weight and serum creatinine and potassium concentrations were not detected.
Relationship between ocular lesions and hypertension
Am J Vet Res 2002 Jun;63(6):833-9
J Am Vet Med Assoc 2000 Sep 1;217(5):695-702
J Vet Intern Med 1998 May-Jun;12(3):157-62
J Am Anim Hosp Assoc 1997 May-Jun;33(3):226-34
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