nteraction of antihypertensive drugs with anti-inflammatory

drugs.
Polnia J.
Author information

Unidade de Farmacologia Clinica da Faculdade de Medicina do Porto, Portugal.

Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) can induce an increase in blood pressure (BP) and may
potentially reduce the efficacy of several antihypertensive drugs. Probably the main mechanism of action
is inhibition of prostaglandin (PG) synthesis since NSAIDs have higher propensity to increase BP as the
regulation of BP (and renal function) is more PG-dependent and to interact with drugs (diuretics, beta-
blockers and ACE inhibitors) that may act through the increase of PG formation. In contrast, NSAIDs do
not interact with calcium antagonists and central acting drugs which actions are apparently unrelated with
renal/extrarenal production of PG. It has been claimed that inhibition of natriuretic PGs could explain the
pressure effects of NSAIDs in treated hypertensive patients, but sodium retention may be not the single
explanation for such an interaction. We found that despite indomethacin produced sodium retention after
being added either to enalapril or nifedipine-GITS, it only attenuated (by 45%) the antihypertensive effects
of enalapril. In alternative, since PG enhances vasodilatation and attenuates vasoconstrictor influences,
some NSAIDs may counteract the PG-dependent vasodilatory tone in renal and extrarenal vascular beds
that mediate the antihypertensive action of some drugs. Thus, since calcium antagonists are probably not
affected by NSAIDs, they may be preferable to drugs like diuretics, beta-blockers and ACE inhibitors for
the treatment of high blood pressure control in hypertensive patients who are clinically suitable for
NSAIDs therapy.

NSAIDs and Antihypertensive Agents

John R. Horn, PharmD, FCCP, and Philip D. Hansten, PharmD
Published Online: Saturday, April 1, 2006
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It has been estimated that >50% of the US population over age 65 has hypertension. Only
about one third of all hypertensive patients receiving therapy, however, have reached their
goal blood pressure (BP). Whereas there are a number of reasons for this poor response to
antihypertensive therapy, one that can be easily controlled is the risk of potential drug
interactions blunting the effectiveness of antihypertensive drugs. It is the control of BP that
reduces the risk of developing a myocardial infarction, heart failure, stroke, and renal
disease in hypertensive patients. Current hypertension treatment guidelines recommend
starting therapy with a thiazide diuretic and then adding additional drugs as needed to
control BP. An analysis of >12 randomized trials of antihypertensive therapy found that a
20% to 40% reduction in cardiovascular disease required only a 5- to 6-mm-Hg decrease in
diastolic BP.1 This magnitude of BP reduction is typically seen with any single
antihypertensive drug treatment. It is also represents the usual increase in BP seen when
nonsteroidal anti-inflammatory drugs (NSAIDs) interact with antihypertensive drugs.

Hypertensive patients use NSAIDs for a variety of indications. NSAIDs inhibit prostaglandin-
mediated vasodilation and promote salt and water retention. Both of these mechanisms
may contribute to NSAIDs partially reversing the effects of hypotensive drugs, particularly
those agents whose mechanism depends on modulating prostaglandins, renin, or sodium
and water balance. The dose and duration of NSAID therapy will partially determine the
extent of hypotensive therapy reversal. Higher doses of NSAIDs and chronic therapy
extending beyond a week will be more likely to increase BP.

Antihypertensive drugs appear to be affected to variable degrees by NSAIDs. Diuretics,

angiotensin-converting enzyme inhibitors (ACEIs), beta-blockers, and angiotensin II
receptor blockers (ARBs) are most susceptible to the hypotensivenullifying effects of
NSAIDs. Calcium channel blockers and centrally acting antihypertensives seem to be least
affected. For example, one study found that indomethacin reduced the hypotensive effect of
enalapril by nearly 50% while having almost no effect on nifedipine. 2 Similarly, NSAIDs will
demonstrate differing abilities to offset hypotensive response to therapy. Indomethacin has
been the most widely studied and, along with naproxen and piroxicam, appears to produce
the greatest effect. Low-dose aspirin (ie, <250 mg/d) and sulindac have the least
detrimental effect on BP.3,4 Elderly patients and those with heart failure may be more
sensitive to the effects of NSAIDs on their antihypertensive or diuretic therapy.5-7

Based on the evidence for an interaction between NSAIDs and some antihypertensive
agents, the pharmacist should be prepared to offer counseling to patients considering
coadministration of these classes of drugs. The following points should be considered:

Although the absolute increase in BP resulting from NSAID coadministration is

usually limited to <10 mm Hg, it can result in a 50% reduction in the efficacy of an
antihypertensive drug and block the beneficial cardiovascular effects of BP reduction

Short courses of NSAID therapy (ie, less than a week or 2), even with daily NSAID
administration, are unlikely to cause a clinically important increase in a patient's BP

Short courses of NSAIDs may cause exacerbation of heart failure. Patients should
be counseled to report any symptom changes during NSAID administration.

Low-dose aspirin therapy does not appear to affect the efficacy of antihypertensive
drugs or diuretics

Some NSAIDs, such as sulindac, may produce less blunting of hypotensive efficacy
 Diuretics, ACEIs, ARBs, and betablockers are likely to be more affected by NSAIDs
than calcium channel blockers or centrally acting agents. Switching to an
antihypertensive drug not as susceptible to the blunting effects of NSAIDs should be
considered for patients requiring chronic NSAID therapy.

Consider alternative analgesics, such as acetaminophen, tramadol, or narcotic

analgesics, for patients requiring analgesics who are unable to have their
antihypertensive regimen altered

Monitor BP of patients taking NSAIDs for several weeks to determine if they are
candidates for drug regimen adjustments. Also, be alert for signs of fluid retention,
such as weight gain or peripheral edema.

By following these simple guidelines, pharmacists can ensure that patients will receive the
maximum benefit from their antihypertensive drug regimen, even if they require NSAID
therapy.

Drs. Horn and Hansten are both professors of pharmacy at the University of Washington
School of Pharmacy. For an electronic version of this article, including references if any,
visitwww.hanstenandhorn.com.

For a list of references, send a stamped, self-addressed envelope to: References

Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or
send an e-mailrequest to: astahl@ascendmedia.com.

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The effect of nonsteroidal anti-inflammatory drugs on blood pressure

in patients treated with different antihypertensive drugs.
Morgan T1, Anderson A.

Author information

Abstract

Hypertension and arthritis are both common diseases in the older age group and require pharmacologic
treatment. Nonsteroidal anti-inflammatory drugs (NSAIDs) alter renal function if given in high enough
doses, reducing renal blood flow and the glomerular filtration rate and causing sodium retention. In salt
sensitive subjects, this retention of sodium will cause blood pressure to rise. Salt sensitivity is more
common in elderly patients, in diabetics, and in people with renal failure. When most antihypertensive
drugs are used, people become salt sensitive, as shown by the additive effect of salt restriction or
diuretics on blood pressure response. The responses to dihydropyridine and possibly other calcium
channel blocking drugs are not affected to any major extent by sodium intake or by diuretics. Studies are
described which indicate that indomethacin elevates blood pressure in elderly people treated with
enalapril, but not in people whose blood pressure is controlled with amlodipine or felodipine. It is unclear
whether the various NSAIDs have different effects on blood pressure. It is proposed that if the same
analgesic effect is achieved with the same amount of cyclooxygenase inhibition, the response will be
similar. Aspirin, used in a prophylactic dose, does not inhibit to this extent and does not elevate blood
pressure. If elderly people require NSAIDs, it would appear that dihydropyridine calcium channel blocking
drugs are more effective at lowering and maintaining blood pressure control and should be one of the
drugs used. If patients are on other antihypertensive agents, it is important to monitor blood pressure
when a NSAID is added to therapy.