Page 1017 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Toxicity of Yew (Taxus spp.) Alkaloids Chapter | 66 949

VetBooks.ir H 3 C R 2 O OR 3 H
H

O H 3 C N CH 3
CH 3
O
CH 3
O
H

CH 2
R 1
OR 4

Taxine alkaloids R 1 R 2 R 3 R 4
Taxine B OH Ac H H

Isotaxine B OH H Ac H
1-Deoxytaxine B H Ac H H
1-Deoxyisotaxine B H H Ac H

FIGURE 66.2 Structural formulas for taxines B.

PHYSIOLOGY/MECHANISM OF ACTION by taxine extracts was not mediated via the sympathetic
or parasympathetic nervous systems but, rather, by a
Due to their instability and the lack of highly purified
direct action on myocardium (Vohora, 1972).
taxines A and B for experimental use, research delving
Significant differences in the cardiotoxicity of taxine
into the mechanism of action of taxines frequently
A and taxine B have been reported (Bauereis and Steiert,
involved the use of crude extracts of taxines from yew.
1959; Alloatti et al., 1996). Through administration of
The earliest investigations were published in 1921 and
taxine B either in vivo or in vitro, it was shown that
described cardiovascular effects upon administration of
taxine B is more cardiotoxic than taxine A, causing ino-
crude extracts of yew. When administered by intraperito-
tropic effects while eliciting marked changes in atrioven-
neal or intravenous routes in rabbits and dogs, hypoten-
tricular conduction. In isolated, perfused guinea pig
sion and cardiac arrest occurred in both species
hearts, a 5 μM concentration of taxine B markedly
(Bryan-Brown, 1932). In addition, when toxicity was
increased atrioventricular conduction time and widening
severe enough to result in cardiac abnormalities, it was
of the QRS interval, whereas a 1 μM concentration (the
noted that peristaltic contractions in the gastrointestinal
lowest concentration used) significantly reduced heart rate
tract ceased. Electrocardiographs conducted on isolated,
(Alloatti et al., 1996). These changes led to atrioventricu-
perfused hearts from rabbits and frogs revealed that crude
lar conduction blocks and complete diastolic cardiac
taxine extracts gradually induced bradycardia, resulting in
arrest. The marked increase in QRS duration has also
diastolic cardiac arrest. Further investigations have indi-
been reported one human case of yew poisoning and also
cated that taxines depress atrioventricular conduction in a
in intravenous administrations of yew extracts to pigs
dose-dependent manner in isolated frog heart, having the
(Matthew et al., 1993; Ruha et al., 2002). Taxine B has
greatest effect on ventricular rate (Smythies et al., 1975;
been shown to cause a marked reduction in the maximum
Tekol and Kameyama, 1987). In those studies, the cardio-
rate of depolarization of the action potential in isolated
toxic effect could not be inhibited by the administration
papillary muscle, which thus resembles the action of class
of atropine, performing a vagotomy, or through gangli-
I antiarrhythmic drugs (e.g., flecainide, procainamide, and
onic/adrenergic blockade (Bryan-Brown, 1932; Vohora,
quinidine) (Bauereis and Steiert, 1959; Tekol, 1985;
1972). It was thus concluded that the hypotension induced
Alloatti et al., 1996). In contrast, taxine A had a minimal