Question

why righting reflex is absent after administration of Phenobarbitone​

Answer 1

Answer:

The purpose of this investigation was to develop a method to determine the effect of various diseases on the concentration-pharmacologic activity relationship of phenobarbital (PB) in a manner that excludes or accounts for pharmacokinetic variables affecting drug disposition. Adult female rats (congruent to 180 g) received an i.v. infusion of PB at one of five different rates (0.412-4.12 mg/min) until the animals lost their righting reflex (after 8.0 +/- 0.4 to 62 +/- 10 min of infusion). The total dose, the serum concentration (both total and unbound drug) and the brain concentration of PB at onset of loss of righting reflex (LRR) increased with increasing infusion rate. The PB concentration in cerebrospinal fluid at onset of LRR (mean +/- S.D.: 108 +/- 19 micrograms/ml, n = 29) was not affected by the infusion rate. Concomitant infusion of PB and its p-hydroxy metabolite had no apparent effect on the concentrations of PB at onset of LRR even though the serum concentration of p-hydroxy PB was higher than upon infusion of PB only. The results of this investigation indicate that cerebrospinal fluid, unlike some regions of the brain, equilibrates very rapidly with the biophase of the receptors for PB-induced LRR. Determination of PB concentrations in the cerebrospinal fluid at the onset (rather than offset) of action facilitates assessment of the effect of diseases on the PB concentration-pharmacologic activity relationship by avoiding development of acute tolerance and excluding or minimizing effects due to disease-associated pharmacokinetic variables such as altered plasma protein binding and body distribution of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

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