Kathryn Primm, DVM
A recent study suggests that cats presenting with higher blood pressure when diagnosed with hypertension could benefit from greater doses of amlodipine.
fantom_rd/Shutterstock.comHypertension is common in older cats (especially those with chronic kidney disease), and amlodipine besylate is the primary treatment of choice. It acts by blocking L-type calcium channels in vascular smooth muscle and is classified as a second-generation dihydropyridine. Current guidelines suggest a daily dose of 0.125 to 0.5 mg/kg (though cats with higher body weights may require higher doses) with regular blood pressure screenings and appropriate dose adjustments.
The mechanism for high blood pressure in cats is still poorly understood, but we do know that cats suffering from chronic kidney disease are at a greater risk of developing hypertension, and even an increase in plasma creatinine concentration alone has been found to be an independent risk.1 To date, no consistent link has been found between high blood pressure and the renin-angiotensin-aldosterone system.2
A recent study set out to answer two questions:
Do individual cat factors (such as age, weight, heart rate, systolic blood pressure (SBP), creatinine, urea, sodium and potassium) influence the amount of amlodipine a cat needs to control its blood pressure?
Other than the drug dose, are there other factors that affect plasma amlodipine concentrations?
One hundred cats, all 9 years or older and all previously diagnosed with and treated for systemic hypertension, were included in the study. Using a noninvasive Doppler technique, all of the cats had their SBP measured. If a cat's average reading was ≥ 160 mm Hg, one drop of tropicamide 1% was added to both of its eyes before undergoing an indirect fundoscopy in order to ascertain the presence of hypertensive retinopathy.
A diagnosis of systemic hypertension was declared when the cats had SBP measurements that were ≥ 170 mm Hg at two consecutive checks. Cats with SBP ≥ 160 mm Hg that also showed signs of hypertensive retinopathy on the fundoscopy received the same diagnosis. Cats were further classified by the presence of chronic renal disease if their creatinine concentrations were ≥ 2 mg/dl twice in a row less than two weeks apart or if their urine specific gravity was less than 1.035.
The study cats were given 0.625 mg amlodipine besylate orally once a day, and blood pressure readings were taken one to two weeks later. As the target SBP was determined to be < 160 mm Hg, cats with higher measurements had their amlodipine doses doubled on follow-up visits (up to 2.5 mg per day).
Once a patient reached an SBP measurement < 160 mm Hg, its blood was drawn in order to see if the antihypertensive treatment had had any effect on kidney function. Blood and urine samples were taken every 16 weeks. Only those cats that achieved blood pressure control at 0.625 mg and 1.25 mg were included in the analysis, and only those blood samples taken at the time of the adequately controlled SBP reading were used to measure amlodipine concentrations.
The researchers used liquid chromatography to evaluate amlodipine concentrations in the plasma of each cat. Cats that were not given amlodipine and cats receiving various other feline medications served as controls.
Cats that presented with a higher SBP needed higher doses of amlodipine to achieve control, and proportionately higher levels of amlodipine were observed in the plasma of cats that had received higher doses of the drug. This suggests that an individual cat's response to the drug cannot be explained by its amlodipine pharmacokinetics or by owner compliance, though it's worth noting that the study only included cats that hit the target SBP.
Based on the findings in this study, 1.25-mg doses of amlodipine could be considered for cats with systemic hypertension that have an SBP ≥ 200 mm Hg. However, the patient's blood pressure should be closely monitored after one week of treatment because there are case reports of people developing severe hypotension after an amlodipine overdose.3 Ultimately, more studies are needed to better understand the the relationship between SBP and plasma amlodipine concentration.
Bijsmans ES, Doig M, Jepson RE, et al. Factors influencing the relationship between the dose of amlodipine required for blood pressure control and change in blood pressure in hypertensive cats. J Vet Intern Med 2016;30:1630-1636.
Link to full study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5032874/
1. Bijsmans ES, Jepson RE, Chang YM, et al. Changes in systolic blood pressure over time in healthy cats and cats with chronic kidney disease. J Vet Intern Med 2015;29:855-861.
2. Jepson RE, Syme HM, Elliott J. Plasma renin activity and aldosterone concentrations in hypertensive cats with and without azotemia and in response to treatment with amlodipine besylate. J Vet Intern Med 2014;28:144-153.
3. Rasmussen L, Husted SE, Johnsen SP. Severe intoxication after an intentional overdose of amlodipine. Acta Anaesthesiol Scand 2003;47:1038-1040.