JOURNAL SCAN
Do heavier cats need higher dosages of amlodipine to control systemic hypertension ?
Factors Influencing the Relationship Between the Dose of Amlodipine Required for Blood Pressure Control and Change in Blood Pressure in Hypertensive Cats . E . S . Bijsmans et al Journal of Veterinary Internal Medicine , 2016 ( 30 ): 1630-1636 . Summarised by : Dr Wilco Botha BVSc ( Resident Small Animal Medicine )
Why they did it : Systolic hypertension is a common finding that requires therapy in elderly cats , especially those affected by chronic kidney disease . The anti-hypertensive drug , amlodipine , is currently regarded as the first-line choice for the treatment of systemic hypertension in cats . Amlodipine exerts its anti-hypertensive effect by reducing peripheral vascular resistance . Blocking of L-type calcium channels in the vascular smooth muscle mediates a reduction in peripheral resistance and explains the gradual onset of action and slow waning of effect . A long plasma half-life allows once daily dosing . The current recommended dose for cats is 0.125-0.5 mg / kg . The exact patho-mechanism for hypertension in cats is poorly understood . Investigations into the role of RAAS activation are inconsistent . This study served to identify possible factors , such as body weight , influencing the dose of oral amlodipine required to adequately control hypertension in cats and attempted to identify whether individual pharmacokinetics plays into the efficacy of the drug .
What they did : Cats over 9 years of age were diagnosed and treated for systemic hypertension . The data was collected over a 12-year period as part of a study-group screening program of elderly cats at the Royal Veterinary College in the United Kingdom . All cats underwent a standard visit protocol to screen for diseases such as hypertension , chronic kidney disease ( CKD ) and hyperthyroidism and other obvious co-morbities that may influence these conditions . Systemic hypertension was diagnosed when cats had a systolic blood pressure ( SBP ) ≥ 170 mmHg on two consecutive visits or a SBP ≥ 160 mmHg with concurrent evidence of hypertensive retinopathy identified on fundoscopy . Cats diagnosed with hyperthyroidism were excluded from the study unless they were treated with thyroidectomy ≥ 90 days prior to inclusion to allow for stabilisation of the glomerular filtration rate prior to inclusion . Cats with chronic kidney disease were diagnosed when the plasma creatinine was 176.8 µ mol / L either on two visits > 2 weeks apart or in conjunction with a urine specific gravity ( USG ) of < 1.035 but were not excluded for this study .
All cats were started on 0.625 mg amlodipine besylate ( 1 / 8 of a human 5mg formulation tablet ) once daily per os . The dose was doubled on follow-up visits every 1-2 weeks until the target SBP of ≤ 160 mmHg was reached to a maximum dosage of 2.5mg amlodipine per cat , per day . Once adequate SBP control was achieved blood tests to detect renal function changes were performed and follow-up visits were extended to every 8 weeks with blood and urine samples collected every 16 weeks . Only cats which achieved control with dosages of either 0.625mg or 1.25mg were included and analysed for factors which possibly necessitated the higher dosage needed for adequate control .
What they found : One hundred cats , including 50 neutered males and 50 females ( 2 intact ), were identified . Most of the cats ( 73 ) were domestic short hairs . In 59 cats the blood pressure was adequately controlled using 0.625mg / day and in 41 cats using 1.25mg / day . Cats receiving 0.625mg / day and 1.25mg / day were considered adequately controlled after receiving therapy for a median of 14 and 28 days respectively . Most of the cats ( 71 ) were diagnosed with concurrent CKD . The number of cats with CKD as well as cats in IRIS Stage 2 were not significantly different between the low and high dose groups . However , the SBP at the first visit were significantly different between the two groups ( 0.625mg : 182 mmHg and 1.25mg : 207mmHg ) and a comparable post-therapeutic SBP could be achieved ( 0.625mg : 145.6 mmHg and 1.25mg : 146.2 mmHg ). Plasma amlodipine concentration was approximately twice as high in the higher dose groups suggesting negligent effects of inter-individual pharmacokinetic differences or incompliant owners . No significant changes could be detected for age , weight , packed cell volume , plasma albumin , creatinine , urea , phosphate , total calcium , sodium , chloride and cholesterol concentration , and USG . The 1.25mg group had a significantly lower plasma potassium concentration ( 0.3 mEq / L . However , the number of cases of hypokalaemia i . e . < 3.50 mEq / L did not differ significantly between the two groups .
Take-home message Cats with a higher SBP at diagnosis required a higher dose of amlodipine to adequately control systemic hypertension independent of several other factors including body weight . These findings would suggest using a higher dose of amlodipine in cats with a greater SBP at diagnosis . Based on the associated between SBP and the required dose the proposed starting dose for cats with a SBP ≥ 200 mmHg would be 1.25mg daily with follow-up blood pressure monitoring one week after the initiation of therapy .
Issue 06 | DECEMBER 2016 | 33