295chosen, since BBs vary widely in their pharmacological profile [ 24 ]. A recent sys-
tematic review and meta-analysis [ 46 ] endorsed the use of BBs in CKD patients
with heart failure, but did not provide any definitive specific advice on their efficacy
in preventing mortality, cardiovascular outcomes, or renal disease progression in
CKD patients without heart failure [ 24 ].
Notable adverse effects associated with BBs include bradycardia, erectile dys-
function, fatigue, and lipid and glucose abnormalities [ 47 ]. In patients with CKD,
the accumulation of BBs or active metabolites could exacerbate side effects like
bradycardia. Such accumulation occurs with atenolol and bisoprolol, but not with
carvedilol, propranolol, or metoprolol [ 24 ].
BBs have often been combined with diuretics in RCTs and clinical practice.
They can also be combined with ACEIs or ARBs. On the other hand, the combina-
tion of atenolol or bisoprolol with bradycardia-inducing drugs such as nondihydro-
pyridine CCBs is not recommended. The association of lipophilic BBs (e.g.,
propranolol and metoprolol), which cross the blood-brain barrier, with other cen-
trally acting drugs such as clonidine may lead to drowsiness or confusion, particu-
larly in the elderly [ 24 ].
Centrally Acting Alpha-Adrenergic Agonists
Centrally acting alpha-agonists cause vasodilatation by reducing sympathetic out-
flow from the brain. The main agents in use are methyldopa, clonidine, and moxoni-
dine. The use of centrally acting alpha-antagonists is limited by side effects, but
since they interact minimally with other antihypertensives, they are valuable as
adjunct therapy for RH in CKD patients [ 24 ].
Doses of methyldopa or clonidine are not generally reduced in patients with
impaired kidney function. Moxonidine is largely excreted by the kidney, and accord-
ingly it has been recommended that the dosage should be decreased in the presence
of a low GFR [ 24 ].
Combination of alpha-agonists with thiazides may be particularly advantageous
to reduce vasodilatation-induced fluid retention. Because of the side-effect profile,
however, caution is advised when using alpha-agonists in the elderly, in patients
with advanced CKD, and in those taking sedating drugs. Since clonidine can slow
the heart rate, it should be avoided if bradycardia or heart block is present [ 24 ].
Alpha-Blockers
Alpha-adrenergic blockers (e.g., prazosin, doxazosin, and terazosin) selectively act
to reduce BP by causing peripheral vasodilatation. In general, they are not consid-
ered a preferred choice, because of common side effects like postural hypotension,
tachycardia, and headache. These drugs should be started at a low dosage to avoid
18 Treatment of Hypertension in Light of the New Guidelines: Pharmacologic...