Tip 18 (January 2012)
Effective use of Beta and Alpha Blockers
Although beta blockers are no longer first or second-line agents for management of hypertension, they are still indicated and appropriately prescribed for patients with compelling indications (post MI, atrial fibrillation, heart failure etc). In the absence of compelling indications they are also still commonly used as add-on therapy as part of multi-drug treatment of resistant hypertension.
The most commonly prescribed beta blocker in New Zealand is metoprolol.
Clinical case:
You have a 50 year old European male with hypertension. He has a BMI of 30, abdominal obesity, impaired fasting glucose, and treated dyslipidaemia. Secondary causes of hypertension including Conn’s syndrome and phaeochromocytoma have been excluded on biochemical testing. CT renal angiogram is negative for renal artery stenosis, and the Berlin and Epworth questionnaires indicate a low probability of obstructive sleep apnoea. His medication compliance appears to be excellent.
His current medications are:
Quinapril30mg BD, chlorthalidone 25mg daily, spironolactone 25mg daily, amlodipine 10mg daily and metoprolol CR 190mg daily.
On this regimen his office and home monitored resting blood pressures average 150/90, and heart rate 86BPM
Where to from here?
The three main pathophysiological mechanisms driving hypertension are (1) The renin-angiotensin-aldosterone system (RAAS) , (2) sodium/volume and (3) the sympathetic nervous system (SNS). We tend to forget about the SNS, but SNS-overactivity is probably an important contributor in many cases of difficult hypertension. In this case, the RAAS is well covered with a high dose of ACE-inhibitor ( and the beta blocker should have some rennin-inhibiting effect as well), and the sodium-volume component by the high-dose chlorthalidone-spironolactonecombimation. His resting heart rate of 86BPM suggests that he has untreated sympathetic overactivity (and is not adequately beta-blocked) despite being on a full dose of metoprolol.
Some individuals have poor bioavailability of metoprolol (and carvedilol and labetolol) due high cytochrome P450–mediated first-pass hepatic metabolism. Atenolol is not subject to this effect and in this case a trial of a swap to atenolol is warranted. I would start with 25mg BD and titrate up to 50mg BD dependent on the blood pressure response, and the resting heart rate which one would want to titrate down to about 60BPM. (Remember atenolol needs to be given in a BD dose, daily dosing does not provide adequate 24-hour cover).
If his blood pressure is still not at target, the SNS may still be a factor. SNS-mediated BP reactivity is driven to both β-receptor–mediated increase in cardiac output and heart rate, and by an α-receptor–mediated increase in peripheral resistance, often with one or the other predominating. The lack of effect of β-blocker monotherapy on BP reactivity to stress, although surprising, has been consistently demonstrated. The favorable effect of combined α-/β-blockade on BP reactivity contrasts with the lack of effect on reactivity with beta or alpha blocker monotherapy1. Combined α-/β-blockade may be achieved with labetolol or carvedilol, but because these drugs are variably subject to the samecP450–mediated first-pass hepatic metabolism as atenolol, the most reliable way to achieve it is with a combination of atenolol and doxazosin. Neither of these drugs is subject to that metabolic process. The atenolol dose should be adjusted to achieve an appropriately reduced resting heart rate, and addition of a small dose of doxazosin (1-4mg daily) often has a surprisingly beneficial effect.
1 NICE guideline.2006
2. Mann SJ. Drug therapy for resistant hypertension: a simplified, mechanistic approach. J.Clin.Hypertens.2011(13)