| dc.description.abstract | There is no information available about the antagonism of xylazine by 4- aminopyridine and yohimbine
in goats. This study was therefore designed to determine the optimal dose regimes of 4-
aminopyridine and yohimbine for the antagonism ofxylazine in goats and to evaluate these drugs as
reversal agents for xylazine in goats.
The study was carried out in four experimental parts. Part one of the study determined the optimal
dosages of 4- aminopyridine and yohimbine for the reversal of xylazine in goats. Five groups, each
offive non-sedated animals were used to determine the optimal dosage of each drug. Each group
received one dose level. The dosages were considered optimal when treated goats manifested
clinical signs of mild excitement, as evidenced by trembling and muscle twitching, without causing
convulsions. Yohimbine, even at the highest dose level, did not produce any apparent effect. Thus,
four more groups, each offive non-sedated goats were given additional doses of yohimbine, with an
increment factor of 0.025 mg/kg. Each group received one dose level. Yohimbine produced sedation
and not central nervous system stimulation as expected. The dosage of yohimbine was therefore
considered optimal when it produced mild uneasiness as evidenced by increased head and tail
movements, without causing marked sedation.
Parts two and three were designed to evaluate 4- aminopyridine, yohimbine and the combination of
both drugs as reversal agents ofa routine clinical dosage (0.22 mg/kg body weight), and twice the
clinical dosage (0.44 mg/kg body weight) ofxylazine, respectively. In both experiments, four groups
of six animals each were used, in which one was the control group which was given water for
injection. In the fourth part of the experiment, the combination of 4- arninopyridine and yohimbine
which was determined as the best for the reversal of xylazine in parts two and three, was used to
reverse a four times the clinical dosage ofxylazine (i.e. 0.88 mg/kg body weigh). Only six animals
were used in this case. The drugs were given at the same dose rates and concentrations as in parts
two and three. Control animals were not used because ofthe xylazine overdose.
Xylazine was administered intramuscularly, into the gluteal muscles. Water for injection and the
reversal drugs were administered intravenously into the jugular vein, at the time of maximum sedation.
An interval of one week was allowed between experiments to avoid the development of drug
tolerance.
Treatment effects were assessed by determination of changes in the heart rates, respiratory rates,
and rates of rumina Imovements and the reappearances of pain sensation, as well as the pedal and
palpebral reflexes. These were recorded 10 minutes before xylazine administration, at the time of
maximum sedation, and at 5, 10, 15,20,30,40, and 50 minutes after water of injection or the
reversal agents. The standing and total recovery times as well as the recovery phenomena [recorded
as smooth, fairly smooth, fairly rough and rough], were also observed and recorded.
The optimum dosages of.4- aminopyridine and yohimbine determined were 0.4 and 0.25 mg/kg
body weight respectively.
The antagonists alone and in combination, reversed all the effects of xylazine, namely bradycardia,
depression on the respiratory rates and ruminal atony. In part two ofthe experiment, bradycardia
and ruminal atony were significantly reversed by the three treatments, while only 4-aminopyridine
significantly reversed the depression on the respiratory rates. In the third part ofthe experiment, the
depression on the respiratory rates and ruminal atony were significantly reversed by the three treatments.
However, only 4-aminopyridine and the combination significantly reversed the bradycardia
in this part of the experiment. In addition, the antagonists alone and in combination rapidly restored
the pedal as well as the palpebral reflexes. The sensation to pain was also rapidly restored.
After administration of the reversal drugs, the goats regained awareness and would stand sooner
than control animals, hence reduced total recovery (TR) and standing times (ST). The reduction of
the mean standing time (MST) was significant in all treatment groups in both experiments two and
three. The antagonists' combination produced the greatest reduction of the MST, and its value was
significantly less than for the yohimbine treatment groups in both experiments. The MST for the
combination and the 4-arninopyridine treatment groups in both experiments were not significantly
different.
Yohimbine produced a non-significant reduction of the mean total recovery times (MTRT), while the
other treatments produced a significant reduction. The combination produced the greatest reduction.
In part two of the experiment, the MTRT for the combination was significantly less than for the
other treatment groups. In the third part of the experiment, the MTRT for the combination was
significantly less than for the yohimbine treatment group.
The 4- aminopyridine/yohimbine combination and yohimbine, had more desirable recovery phenomena
in part two of the experiment, as demonstrated by co-ordinated attempts to rise and rising
on the first attempt. They were recorded as smooth in most animals in both groups. The drug 4-
aminopyridine produced difficult recovery that was recorded as rough. The animals in this group .
made several attempts to rise, rolled and kicked when attempting to rise, while others fell back
down after standing. In part three of the experiment, only yohimbine had a desirable recovery
phenomenon that was recorded as smooth. The attempts to rise in these animals were co-ordinated,
and they stood on the first attempt. The combination produced a fairly rough recovery phenomenon
this time. The animals rolled before standing, and some could not stand on the first attempt. Some
animals also manifested ataxia and hyperesthesia lasting five to ten minutes. The reccovery phenomenon
was rough in the group given 4- aminopyridine. The animals in this group rolled and kicked
when standing. There was repeated attempts to rise in some animals, and others showed some
trembling lasting 10 to 15 minutes.
The animals did not relapse into marked sedation after the treatments, although some degree of
sedation persisted for a variable period of time. However, the animals could be easily aroused to
walk, eat or even to drink. Thus, the duration of the effects of the antagonists proved adequate to
prevent a relapse into marked sedation.
Yohimbine, 4-aminopyridine and the 4-aminopyridine/yohimbine combination, reversed the effects
of xylazine at the three dose levels and also reduced the standing as well as the total recovery times.
The 4-aminopyridine/ yohimbine combination produced better responses compared with the other
treatments. Thus, the results indicate that the combination of 4-aminopyridine and yohimbine may
be useful in veterinary clinical practice for reversal of sedation caused by standard doses and overdoses
of xylazine in the Small East Afiican goats. Yohimbine and 4-aminopyridine may be useful for
this purpose but produce prolonged recoveries compared to the combination. | en |
