Angiotensin II receptor antagonists (ARBs) are administered primarily to treat hypertension and proteinuria in cats and dogs.
While angiotensin-converting enzyme (ACE) inhibitors and ARBs both affect the renin angiotensin system, they have different mechanisms of action. ARBs selectively block the binding of angiotensin II to the angiotensin type I receptor, further blocking the effects of angiotensin II. (See the ACE inhibitors section for a review on the actions of angiotensin II.)
The mechanism by which ARBs decrease proteinuria remains unclear. It is suspected that renal impairment leads to proteinuria, which stimulates the renin-angiotensin-aldosterone system (RAAS) to drive hyperfiltration, resulting in worsening proteinuria. Therefore, blunting RAAS may counteract this effect.
Preparations and Disposition of Angiotensin II Receptor Antagonists in Animals
The most commonly administered ARB in veterinary medicine is telmisartan, which is available in a 10 mg/mL oral form. Telmisartan is approved in the United States for oral use for treatment of systemic hypertension in cats. After oral administration, the medication is rapidly absorbed.
In humans, bioavailability decreases by roughly 20% when administered with food. In cats, bioavailability after oral administration is approximately 30% and is not affected by food. Plasma concentrations peak at 20 to 30 minutes and the half-life is roughly 8 hours. In dogs, plasma concentrations peak at 45 minutes, and half-life is roughly 5.4 hours. In dogs, telmisartan is lipophilic and highly protein bound (98%). Telmisartan is metabolized via glucuronidation and is excreted largely via bile into the feces unchanged.
Drug Interactions and Toxicity of Angiotensin II Receptor Antagonists in Animals
Limited data are available regarding interactions between telmisartan and other medications. Coadministration of telmisartan with digoxin in humans results in increased plasma digoxin concentrations.
Administration of telmisartan with other medications that lower blood pressure (amlodipine) or interfere with RAAS (ACE inhibitors) has not been thoroughly evaluated. However, the combination of telmisartan with such medications may alter renal function or lead to hypotension and should be administered with caution.
In studies evaluating telmisartan in cats with hypertension and proteinuria, chronic oral daily doses of 2 mg/kg q 24 hrs are well tolerated and efficacious for reduction in systolic blood pressure and reduction in proteinuria respectively.(1, 2, 3)
Clinical Use of Angiotensin II Receptor Antagonists in Animals
Telmisartan is administered primarily to treat systemic hypertension and proteinuria in cats and dogs.
In cats, systemic hypertension is a common disease with a variety of causes and, left uncontrolled, may lead to hypertensive target organ damage. Consequently, early intervention in the management of systemic hypertension is necessary to minimize these adverse effects.
The initial dose of telmisartan in cats is 1.5 mg/kg, PO, every 12 hours for 14 days, followed by 2 mg/kg, PO, every 24 hours. In cats, GI clinical signs include vomiting, regurgitation, diarrhea, and soft stool.
To treat proteinuria associated with chronic kidney disease in cats, the dose is 1 mg/kg, PO, every 24 hours. For the management of proteinuria in dogs with glomerular disease, the dose is 1 mg/kg, PO, every 24 hours, which can be increased by 0.5 mg/kg, every 24 hours, up to 2 mg/kg, every 24 hours.
References
Glaus TM, Elliott J, Herberich E, Zimmering T, Albrecht B. Efficacy of long-term oral telmisartan treatment in cats with hypertension: Results of a prospective European clinical trial. J Vet Intern Med. 2019;33(2):413–422. doi: 10.1111/jvim.15394. Epub 2018 Dec 18. PMID: 30561059; PMCID: PMC6430888.
Coleman AE, Brown SA, Traas AM, Bryson L, Zimmering T, Zimmerman A. Safety and efficacy of orally administered telmisartan for the treatment of systemic hypertension in cats: Results of a double-blind, placebo-controlled, randomized clinical trial. J Vet Intern Med. 2019;33(2):478–488. doi: 10.1111/jvim.15429. Epub 2019 Mar 9. PMID: 30851066; PMCID: PMC6430933.
Sent U, Gössl R, Elliott J, Syme HM, Zimmering T. Comparison of Efficacy of Long-term Oral Treatment with Telmisartan and Benazepril in Cats with Chronic Kidney Disease. J Vet Intern Med. 2015;29(6):1479–1487. doi: 10.1111/jvim.13639. Epub 2015 Oct 16. Erratum in: J Vet Intern Med. 2016;30(2):689. PMID: 26474314; PMCID: PMC4895689.
