DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

(Parving et al., 2008). The long- term ALTITUDE study (Aliskiren
Trial in Type 2 Diabetes Using Cardio- Renal Endpoints) is in
progress to assess if aliskiren will reduce cardiovascular and renal
morbidity and mortality when added to ACE inhibitors and ARBs.
The study is expected to end in 2011 (Parving et al., 2009).
Aliskiren is an effective antihypertensive agent
that is well tolerated in monotherapy and combination
therapy. It has cardioprotective and renoprotective
effects in combination therapy; however, long- term
advantages still need to be established. Aliskiren is recommended
in patients who are intolerant to other antihypertensive
therapies or for use in combination with
other drugs for further blood pressure control.
Adverse Events. Aliskiren is well tolerated, and adverse events are
mild or comparable to placebo with no gender difference. Adverse
effects include mild gastrointestinal symptoms such as diarrhea
observed at high doses (600 mg daily), abdominal pain, dyspepsia,
and gastroesophageal reflux; headache; nasopharyngitis; dizziness;
fatigue; upper- respiratory tract infection; back pain; angiodema; and
cough (cough was much less common than with ACE inhibitors).
Other adverse effects reported for aliskiren that were slightly
increased compared with placebo include rash, hypotension, hyperkalemia
in diabetics on combination therapy, elevated uric acid, renal
stones, and gout. Like other RAS inhibitors, aliskiren is not recommended
in pregnancy.
Drug Interactions. Aliskiren does not interact with drugs that interact
with CYPs. Aliskiren reduces absorption of furosemide by 50%.
Irbesartan reduces the C max
of aliskiren by 50%. Aliskiren plasma
levels are increased by drugs, such as ketoconazole, atorvastatin, and
cyclosporine, that inhibit P- glycoprotein.
Pharmacological Lowering of Blood
Pressures Alters Components of the RAS
The renin-angiotensin system responds to alterations in blood pressure
with compensatory changes (Figure 26-2). Thus, pharmacological
agents that lower blood pressure will alter the feedback
loops that regulate the RAS and cause changes in the levels and
activities of the system’s components. These changes are summarized
in Table 26-1.
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CHAPTER 26
RENIN AND ANGIOTENSIN