Agriculture Reference
In-Depth Information
A study of the pharmacological activity of the reduced proscillaridins in papillary muscles isolated
from guinea pig heart has shown that hydrogenated products retained the positive inotropic effect of
the parent drug. The compounds bufa-4,20-dienolide, bufa-4,20(22)-dienolide, 2OR-bufo-4-enolide
(Ph4-R), 2OS-bufa-4-enolide (PH4-S), and chola-4-enoate exhibited the fastest onset of action but
lower potency. The concentrations at which half the maximum inotropic effect was observed were
consistently lower for the reduced compounds than the parent drug at less than one-tenth the time
taken by proscillaridins in some cases. A dose of 11.9 mg/kg of bufa-4,20-dienolide was admin-
istered intravenously by bolus injection into guinea pigs and did not cause arrhythmias.
521
If these
effects are reproducible in animals, then the reduced proscillaridins will offer many therapeutic
advantages over other cardiac glycosides.
Clinical Properties —
The drug is indicated for the treatment of all forms of mild-to-medium-
severe heart failure. It is administered both orally and intravenously. Many proprietary preparations
containing the whole herb as tablets and “teas” are available in Europe, as well as preparations
incorporating the pure compound or the processed extract. Semisynthetic derivatives, especially
proscillaridin 4′-methyl ether and methylepoxyproscillaridin, are also used as therapeutic agents. In
an evaluation of the hemodynamic effect of methyl-epoxyproscillaridin on six patients with latent
cardiac insufficiency, it was observed that the compound caused an increase in stroke volume and
the systolic blood pressures both at rest and under ergometer exercise.
522
During physical exercise,
the heart rate decreased significantly, and the cardiac output was increased.
The drug is also used in the preparation of expectorants; in small doses, it causes mild gastric
irritations that initiate a reflex secretion from the bronchioles.
119
Toxicity —
The main side effect of urginea overdose is vomiting. Excessive high doses may
cause cardiac toxicity, but death due to proscillaridin intoxication is not common. The drug is
eliminated rapidly from the body and is unlikely to accumulate to toxic levels without warning
symptoms. In radioimmunoassay determination of proscillaridin given orally to beagle dogs, it was
rapidly absorbed, exhibiting plasma maximum concentrations of 2.06 mg/ml at 20 min. The plasma
level subsequently declined biophysically with half-lives of 0.6 and 25.4 h.
523
ECHINACEA PURPUREA
Botanical Name —
Echinacea purpurea
( L.) Moench.
