PHOSPHODIESTERASE INHIBITORS
Inamrinone, dipyridamole, enoximone, milrinone, pimobendan,
vesnarinone. The important examples are discussed here.
As of April 2000, the name of amrinone was changed to
“inamrinone” to reduce the number of accidental injuries and deaths associated
with the cardiac drug names inamrinone and amiodarone.
Inamrinone, a bipyridine derivative is a noncatecholamine
cardiotonic agent with positive inotropic effects and vasodila-tory properties.
Treatment of
·
Refractory congestive heart failure.
·
Pulmonary hypertension.
·
Post-operative heart failure.
namrinone is usually administered intravenously. Oral
inam-rinone was discontinued due to reports of a higher incidence of
gastrointestinal adverse effects when compared to the intra- venous form.
Plasma half-life varies from 2.6 to 3.6 hours.
Volume of distribution is 1.2 litres/kg. 10 to 40% of the
drug is excreted unchanged. Several metabolites have been identified in the
urine, and include N-glycolate (8%), N-acetate (5%), and O-glucuronide and
N-glucuronide (less than 5% each).
Elimination half-life is 3.6 hours in normal subjects; 5.8
hours in patients with congestive heart failure.
The
inotropic action of inamrinone is due to selective inhibition of
phosphodiesterase III, with subsequent increase in cardiac cyclic AMP
concentration.
Inamrinone
does not inhibit the cardiac Na+-K+-dependant ATP.
The
recommended adult dosage for inamrinone is an initial intravenous loading dose
of 0.75 ml/kg over 2 to 3 minutes followed by a continuous infusion of 5 to 10
mcg/kg/min, with the total daily dosage not to exceed 10 ml/kg/day.
■■ Headache,
nausea, vomiting, diarrhoea, and abdominal pain occur occasionally.
■■ Reduced
tear secretion and dysosmia have been reported with inamrinone.
■■ Bright
yellow discolouration of nails has been described following therapeutic use.
■■ Thrombocytopenia
can occur in upto 34% of patients taking the drug on a long-term basis.
Pancytopenia has been reported following short-term, high-dose IV therapy.
■■ Intravenous
use is also associated with hypotension, ventricular arrhythmias,
hepatotoxicity, metabolic acidosis, and GIT disturbances (vomiting, diarrhoea,
abdominal pain).
■■ The
commercial preparation of inamrinone contains sodium metabisulfite which can
cause allergic reactions in suscep-tible patients (e.g. asthmatics).
·
Additive inotropic effects are seen
with cardiac glycosides.
·
Severe hypotension may occur when
disopyramide isadministered together with inamrinone.
·
Dextrose must not be used when administering
inamrinone, since chemical interaction and precipitation can occur.
The
following manifestations have been reported in inamrinone overdose: severe
hypotension, ventricular arrhythmias, throm-bocytopenia, hepatotoxicity,
metabolic acidosis, oliguria, and cardiac arrest.
· Admit patient to cardiac intensive
care unit. Monitor vital signs and cardiac parameters continuously.
· Treat hypotension with IV fluids and
pressor agents as required. Infuse 10 to 20 ml/kg of isotonic fluid and place
in Trendelenburg position. If hypotension persists, administer dopamine or
noradrenaline. Consider central venous pressure monitoring to guide further
fluid therapy.
· For arrhythmias: Obtain an ECG,
institute continuous cardiac monitoring and administer oxygen. Evaluate for
hypoxia, acidosis, and electrolyte disorders (particularly hypokalaemia,
hypocalcaemia, and hypomagnesaemia). Lignocaine and amiodarone are generally
first line agents for stable monomorphic ventricular tachycardia, particularly
in patients with underlying impaired cardiac function. Sotalol is an
alternative for stable monomorphic ventricular tachycardia. Amiodarone and
sotalol should be used with caution. Unstable rhythms require cardio-version.
Atropine may be used when severe bradycardia is present and PVCs are thought to
represent an escape complex.
·
Particular attention must be paid to ventilatory support,
oxygen administration, electrolyte studies (especially potas-sium levels),
complete blood count, and hepatic and renal function tests.
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