692
P A R T 8
Drugs acting on the cardiovascular system
P
hosphodiesterase
inhibitors
The phosphodiesterase inhibitors (Table 44.1) belong to
a second class of drugs that act as cardiotonic (inotropic)
agents. These include milrinone (
Primacor
).
Therapeutic actions and indications
The phosphodiesterase inhibitors block the enzyme
phosphodiesterase. This blocking effect leads to an
increase in myocardial cell cyclic adenosine monophos
phate (cAMP), which increases calcium levels in the
cell (Figure 44.4). Increased cellular calcium causes a
stronger contraction and prolongs the effects of sym
pathetic stimulation, which can lead to vasodilation,
increased oxygen consumption and arrhythmias. These
drugs are indicated for the short-term treatment of
HF that has not responded to digoxin or diuretics alone
or that has had a poor response to digoxin, diuretics
and vasodilators. See Table 44.1 for usual indications
for each drug. Because these drugs have been associated
with the development of potentially fatal ventricular
arrhythmias, their use is limited to severe situations.
Pharmacokinetics
Milrinone is available only for intravenous use. It is
widely distributed after injection, metabolised in the
liver and excreted primarily in the urine.
Contraindications and cautions
Phosphodiesterase inhibitors are contraindicated in the
presence of allergy to either of these drugs or to bisulfites.
They also are contraindicated in the following condi
tions: severe aortic or pulmonic valvular disease,
which
could be exacerbated by increased contraction
; acute
MI,
which could be exacerbated by increased oxygen
consumption and increased force of contraction
; fluid
volume deficit,
which could be made worse by increased
renal perfusion
; and ventricular arrhythmias,
which
could be exacerbated by these drugs.
Caution should be used in the elderly,
who are more
likely to develop adverse effects.
There are no adequate studies about the effects of
these drugs during pregnancy
, and their use should be
reserved for situations in which the benefit to the mother
clearly outweighs the potential risk to the fetus.
It is
not known whether these drugs enter breast milk
, so
caution should be used if the woman is breastfeeding.
Adverse effects
The adverse effects most frequently seen with these
drugs are ventricular arrhythmias (which can progress
to fatal ventricular fibrillation), hypotension and chest
pain. GI effects include nausea, vomiting, anorexia and
abdominal pain. Thrombocytopenia can occur with
milrinone. Hypersensitivity reactions associated with
these drugs include vasculitis, pericarditis, pleuritis and
ascites. Burning at the intravenous injection site is also a
frequent adverse effect.
Clinically important drug–drug interactions
Precipitates form when these drugs are given in solution
with frusemide. Avoid this combination in solution. Use
alternative lines if both of these drugs are being given
intravenously.
• Some of the following adverse effects may occur:
•
Dizziness, drowsiness, headache
: Avoid driving or
performing hazardous tasks or delicate tasks that require
concentration if these occur. Consult your healthcare
provider for an appropriate analgesic if the headache is
a problem.
•
Nausea, gastrointestinal upset, loss of appetite
: Small,
frequent meals may help; monitor your weight loss; if it
becomes severe, consult your healthcare provider.
•
Vision changes, “yellow” halos around objects
: These
effects may pass with time. Take extra care in your
activities for the first few days. If these reactions do not
go away after 3 to 4 days, consult with your healthcare
provider.
• Report any of the following to your healthcare provider:
unusually slow or irregular pulse; rapid weight gain; “yellow
vision”; unusual tiredness or weakness; skin rash or hives;
swelling of the ankles, legs or fingers; difficulty breathing.
• Tell any doctor, nurse, dentist or other healthcare provider
that you are taking this drug.
• Keep this drug, and all medications, out of the reach of
children.
• Avoid the use of over-the-counter medications while
you are taking this drug. If you think that you need one
of these, consult with your healthcare provider for the
best choice. Many of these drugs contain ingredients that
could interfere with your digoxin.
• Consider wearing or carrying a medical identification to
alert any medical personnel who might take care of you in
an emergency that you are taking this drug.
• Schedule regular medical checkups to evaluate the
actions of the drug and to adjust the dose if necessary.
Care considerations for people receiving
phosphodiesterase inhibitors
Assessment: History and examination
■
■
Assess for contraindications or cautions: any
known allergies to these drugs or to bisulfites
