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→Pharmacologic Activity
Barbituates act by depressing the central nervous system (CNS) by acting at the Gamma Aminobutyric Acid A receptors (GABAa). They mimic and enhance GABA, which is the principle inhibitory neurotransmitter in the CNS. Once bound to the GABAa receptor they reduce the rate of GABA dissocation and thereby increase chloride conductance is maintained resulting in hyperpolarisation of the membrane and reduced neuronal excitability. However, as the concentration of barbituate increases, it starts to have a direct effect on the chloride conductance and it is this that is thought to bring about the anaesthetic effects, while the GABA related increases causes a sedative effect. They act to depress the motor centres allowing there use as an anticonvulsant agent, as well as depressing the sensory centres and inducing an anesthetised state.
Barbituates act by depressing the central nervous system (CNS) by acting at the Gamma Aminobutyric Acid A receptors (GABAa). They mimic and enhance GABA, which is the principle inhibitory neurotransmitter in the CNS. Once bound to the GABAa receptor they reduce the rate of GABA dissocation and thereby increase chloride conductance is maintained resulting in hyperpolarisation of the membrane and reduced neuronal excitability. However, as the concentration of barbituate increases, it starts to have a direct effect on the chloride conductance and it is this that is thought to bring about the anaesthetic effects, while the GABA related increases causes a sedative effect. They act to depress the motor centres allowing there use as an anticonvulsant agent, as well as depressing the sensory centres and inducing an anesthetised state.
==Pharmacologic Activity==
==Pharmacologic Considerations==
In humans, approximately 60-90% of an oral does of primidone is rapidly absorbed from the GI tract, with a peak serum level being obtained in about 3 hours. in animals, primidone is oxidised to phenobarbital and cleaved to PEMA (C2). Although all three compounds have anticonvulsant activity, most of primidone's anticonvulsant activity in dogs results from phenobarbital: as the compounf with the longest half-life, it accumulates to the highest concentrations. The potency of primidone and PEMA is 1/30 that of phenobarbital. The efficacy of primidone generally is equal to or less that that or phenobarbital, and anticonvulsant acitivity can be correlated to serum phenobarbital levels. Because of this relationship. serum phenobarbital concentrats can and should be used to guide design of primidone dosing regimens. Target therapetic ranges are teh same as for phenobarbital. Primidone continues to be used in patients which have proven refractory to phenobarbital at the maximum therapeutic drug concentration. Note that its efficacy in the scenario has not been proven. efficacy may simply reflect improced conversion to phenobarbital (i.e. animals that are induced may metabolise the drug to greater concentrations of phenobarbital that those generated from administration of phenobarbital alone). There is no advantage in useing primisone rather than phenobarbital for control of epilepsy in most dogs.
In humans, approximately 60-90% of an oral does of primidone is rapidly absorbed from the GI tract, with a peak serum level being obtained in about 3 hours. in animals, primidone is oxidised to phenobarbital and cleaved to PEMA (C2). Although all three compounds have anticonvulsant activity, most of primidone's anticonvulsant activity in dogs results from phenobarbital: as the compounf with the longest half-life, it accumulates to the highest concentrations. The potency of primidone and PEMA is 1/30 that of phenobarbital. The efficacy of primidone generally is equal to or less that that or phenobarbital, and anticonvulsant acitivity can be correlated to serum phenobarbital levels. Because of this relationship. serum phenobarbital concentrats can and should be used to guide design of primidone dosing regimens. Target therapetic ranges are teh same as for phenobarbital. Primidone continues to be used in patients which have proven refractory to phenobarbital at the maximum therapeutic drug concentration. Note that its efficacy in the scenario has not been proven. efficacy may simply reflect improced conversion to phenobarbital (i.e. animals that are induced may metabolise the drug to greater concentrations of phenobarbital that those generated from administration of phenobarbital alone). There is no advantage in useing primisone rather than phenobarbital for control of epilepsy in most dogs.