Apakah interaksi tersebut tidak dapat dipungkiri atau tidak?

Apa insidennya

Seberapa penting itu?

Bagaimana itu terjadi?

Dan apa, jika, untuk alternative mencegah interaksi

Nifedipin retart 60 mg/hari CCB

Lisinopril 5 mg/hari ACEI

Simetidin 75 mg/hari H2ra

Aspirin 75 mg/hari OAINS salisilat

Pembengkakan pada wajah seama 6 buan terakhir

Ada papitasi

Sakit kepala

Kemerahan pada wajah

Pasien tidak menyadari adanya peningkatan BB pada dirinya

ACE inhibitors + Aspirin

The antihypertensive efficacy of captopril and enalapril may be reduced by
high-dose
aspirin in about 50% of patients. Low-dose aspirin (less than or equal to 100
mg daily)
appears to have little effect. It is unclear whether aspirin attenuates the
benefits of ACE
inhibitors in coronary artery disease and heart failure. The likelihood of an
interaction
may depend on disease state (more likely with non-ischaemic disease).
For hypertension, no action needed if low-dose aspirin is used. Suspect an
interaction with high-dose aspirin if the ACE inhibitor seems less effective, or
blood pressure control is erratic. Consider an alternative analgesic, but note
that
NSAIDs interact in the same way as high-dose aspirin. For heart failure it is
generally advised that concurrent use is best avoided, unless a specific
indication
(e.g. coronary heart disease, stroke) exists.

C. Effects on renal function

Acute renal failure developed in a woman taking captopril when she started
to take aspirin for arthritis. Renal function improved when both were
stopped.21 However, in a re-analysis of data from the Hypertension Optimal
Treatment (HOT) study, long-term low-dose aspirin 75 mg daily had
no effect on changes in serum creatinine, estimated creatinine clearance or
the number of patients developing renal impairment, when compared with
placebo. Of 18 790 treated hypertensive patients, 41% received an ACE
inhibitor.

Mechanism
Some, but not all the evidence suggests that prostaglandins may be involved
in the hypotensive action of ACE inhibitors, and that aspirin, by inhibiting
prostaglandin synthesis, may partially antagonise the effect of
ACE inhibitors on blood pressure. This effect appears to depend on the dose of aspirin and may
also be dependent on sodium status and plasma
renin, and therefore it does not occur in all patients.
The beneficial effects of ACE inhibitors in heart failure and ischaemic
heart disease are thought to be due, in part, to the inhibition of the breakdown
of kinins, which are important regulators of prostaglandin and nitric
oxide synthesis. Such inhibition promotes vasodilatation and afterload reduction.
Aspirin may block these beneficial effects by inhibiting cyclo-oxygenase
(COX) and thus prostaglandin synthesis, causing
vasoconstriction, decreased cardiac output and worsening heart failure.

ACE inhibitors + NSAIDs

There is evidence that most NSAIDs (including the coxibs) can increase blood
pressure
in patients taking antihypertensives, including ACE inhibitors, although some
studies
have not found the increase to be clinically relevant. Indometacin appears to
have the
most significant effect. The combination of an NSAID and an ACE inhibitor
may
increase the risk of renal impairment, and rarely, hyperkalaemia has been
associated
with the combination.
Only some patients are affected. Consider increasing the frequency of blood
pressure monitoring if an NSAID is started. Monitor renal function and
electrolytes
periodically.

There is evidence that most NSAIDs can increase blood pressure

in patients taking antihypertensives, including ACE inhibitors,
although some studies have not found the increase to be clinically
relevant. Some variation between drugs possibly occurs, with indometacin appearing to
have the most significant effect. The combination
of an NSAID and an ACE inhibitor can increase the risk
of renal impairment and hyperkalaemia.

(B) Effects on renal function

In a retrospective analysis, 3 of 162 patients who had been taking ACE inhibitors
and NSAIDs developed reversible renal failure, compared with
none of 166 patients taking ACE inhibitors alone and none of 2116 patients
taking NSAIDs alone. One patient was taking naproxen or salsalate
and had a progressive decline in renal function over 19 months after
captopril was started. Another man taking unnamed NSAIDs developed
reversible renal failure 4 days after starting to take captopril.41 In another
similar analysis, in patients aged over 75 years, 2 out of 12 patients given
an ACE inhibitor and an NSAID developed acute renal failure (1 died) and
a further 4 showed deterioration in renal function. All of these 6 patients
were also taking ‘diuretics’, (p.21), but of the 6 with unaffected renal function,
only two were taking diuretics.42 A randomised, crossover study in
17 black patients receiving fosinopril with hydrochlorothiazide and
NSAIDs for a month, found that acute renal failure (a decrease in glomerular
filtration rate of greater than or equal to 25%) occurred in 4 of the 17
patients when receiving ibuprofen, 1 of 17 receiving sulindac and 0 of 17
receiving nabumetone.10 In a multivariate analysis, significant renal impairment
was associated with use of two or more of ACE inhibitors or angiotensin
II receptor antagonists with NSAIDs or diuretics.43 In a casecontrol
study, recently starting an NSAID was associated with a 2.2-fold
increased risk of hospitalisation for renal impairment in patients taking
ACE inhibitors.44 In 2002, 28 of 129 reports to the Australian Adverse
Drug Reactions Advisory Committee of acute renal failure were associated
with the combined use of ACE inhibitors (or angiotensin II receptor antagonists),
diuretics, and NSAIDs (including coxibs), and these cases had
a fatality rate of 10%. In patients taking this triple combination, renal failure
appeared to be precipitated by mild stress such as diarrhoea or dehydration.
In other patients, the addition of a third drug (usually an NSAID)
to a stable combination of the other two, resulted in acute renal failure.45
In contrast, another retrospective analysis found no evidence that the adverse
effects of ACE inhibitors on renal function were greater in those takbaseline renal function,
found that indometacin 25 mg three times daily
did not adversely affect renal function when it was given with trandolapril
2 mg daily for 3 weeks.47
(C) Hyperkalaemia
Hyperkalaemia, resulting in marked bradycardia, was attributed to the use
of loxoprofen in an elderly woman taking imidapril.48 A 77-year-old
woman with mild hypertension and normal renal function taking enalapril
2.5 mg daily arrested and died 5 days after starting treatment with
rofecoxib for leg pain. Her potassium was found to be 8.8 mmol/L. Infection
and dehydration could have contributed to the hyperkalaemia in this
patient

Mechanism
Some, but not all the evidence suggests that prostaglandins may be involved
in the hypotensive action of ACE inhibitors, and that NSAIDs, by
inhibiting prostaglandin synthesis, may partially antagonise the effect of
ACE inhibitors. Another suggestion is that NSAIDs promote sodium retention
and so blunt the blood pressure lowering effects of several classes
of antihypertensive drugs, including ACE inhibitors. This interaction may
be dependent on sodium status and on plasma renin, and so drugs that affect
sodium status e.g. diuretics may possibly influence the effect. Therefore,
the interaction does not occur in all patients. It may also depend on
the NSAID, with indometacin being frequently implicated, and sulindac
less so, as well as on the dosing frequency.6
Both NSAIDs and ACE inhibitors alone can cause renal impairment. In
patients whose kidneys are underperfused, they may cause further deterioration
in renal function when used together.51 Impaired renal function is
a risk factor for hyperkalaemia with ACE inhibitors.

ACEI + H2ra

In general, no clinically significant interactions appear to occur

between the H2-receptor antagonists (including cimetidine) and
the ACE inhibitors. However, note that cimetidine modestly reduces
the bioavailability of temocapril.
Clinical evidence, mechanism, importance and management
Cimetidine did not appear to alter the pharmacokinetics or pharmacological
effects of captopril1 or enalapril,2 or the pharmacokinetics of
fosinopril3 or quinapril4 in studies in healthy subjects. The manufacturers
of cilazapril say that no clinically significant interaction occurred with
H2-receptor antagonists (not specifically named)5 and the manufacturers
of moexipril,6,7 ramipril,8 and trandolapril9 say that no important pharmacokinetic
interaction occurred with cimetidine. The manufacturers of
spirapril briefly note in a review that cimetidine did not alter the plasma
concentrations of spirapril or its active metabolite spiraprilat.10 None of
these pairs of drugs appears to interact to a clinically relevant extent, and
no special precautions appear to be necessary.
Preliminary findings suggest that cimetidine 400 mg twice daily had no
effect on the metabolism of temocapril 20 mg daily in 18 healthy subjects,
but the AUC was reduced by 26% on the fifth day of concurrent
use.11 The clinical relevance of this is uncertain, but changes of this magnitude
with other ACE inhibitors have often not been clinically relevant.

Calcium-channel blockers + H2-receptor

antagonists
The plasma levels of diltiazem, isradipine and nifedipine are increased by cimetidine
and it may be necessary to reduce their dosages. High doses of cimetidine may increase
the bioavailability of lercanidipine. Although studies suggest no important interactions
occur between nicardipine or nisoldipine and cimetidine, the manufacturers
advise caution. Plasma felodipine, lacidipine, nimodipine, and nitrendipine levels are
also increased but this does not seem to be clinically significant.
Monitor concurrent use. If adverse effects (such as hypotension, dizziness, flushing
and palpitations) become troublesome decrease the calcium-channel blocker dose.

The plasma levels of diltiazem, isradipine and nifedipine are

increased by cimetidine and it may possibly be necessary to reduce
the dosages of these calcium-channel blockers. High doses of
cimetidine may increase the bioavailability of lercanidipine. Although
studies suggest no important interactions occur between
nicardipine or nisoldipine and cimetidine, the manufacturers advise
caution. Plasma felodipine, lacidipine, nimodipine, andnitrendipine levels are also
increased by cimetidine, but this
seems to be clinically unimportant. Cimetidine does not interact
with amlodipine. It is uncertain whether cimetidine interacts significantly
with verapamil. Ranitidine appears to interact only
minimally with calcium-channel blockers, if at all. Famotidine
does not interact pharmacokinetically with nifedipine.

(h) Nifedipine
Cimetidine 1 g daily for a week increased the AUC of nifedipine 40 mg
daily by about 60% and increased the maximum plasma levels by about
90%. Ranitidine 150 mg twice daily for a week caused an insignificant
rise of about 25% in maximum nifedipine plasma levels and AUC.10 Seven
hypertensive patients had a fall in mean blood pressure from 127 to
109 mmHg after taking nifedipine 40 mg daily for 4 weeks, and a further
fall to 95 mmHg after they also took cimetidine 1 g daily for 3 weeks.
When they took ranitidine 300 mg instead of cimetidine, there was an insignificant
fall in blood pressure.10,11
Other studies clearly confirm that cimetidine causes a very significant
rise in plasma nifedipine levels and an increase in its effects, whereas ranitidine
interacts only minimally.12-18
A study found no pharmacokinetic interaction between nifedipine and
famotidine, but the famotidine reversed the effects of nifedipine on
systolic time intervals and significantly reduced the stroke volume and
cardiac output.19,20 No adverse interaction was seen in 22 patients given
calcium-channel blockers, including nifedipine, with famotidine for 6 to
8 weeks.8

Mechanism
It is believed that cimetidine increases nifedipine levels by inhibiting its
oxidative metabolism by the liver. Like ranitidine, it may also increase the
bioavailability of nifedipine by lowering gastric acidity.14 The mechanisms
of the other interactions are probably similar.

Nifedipin

Mekanisme kerja nifedipin adalah menghambat masuknya ion Ca2+ sehingga menghambat
terjadinya kontraksi otot polos jantung dan otot polos vaskuler. Nifedipin akan menimbulkan
vasodilatasi pada otot polos pembuluh darah sehingga terjadi penurunan tekanan darah.