pharmacology help! benzo/barbituate/non-barbituate..??

Daytonite, BSN, RN · Jun 28, 2009

while the nonbarbiturates (a handful of miscellaneous drugs and the benzodiazepines) are used as sedatives and hypnotics they are also classified as antianxiety drugs. in the pharmacology book that i have, i found the mechanism of action of benzodiazepines clearly delineated in the chapter on anxiety agents and not where they were spoken about as sedative/hypnotics.

(from page 120,

pharmacology: an introduction

, 5th edition, by henry hitner and barbara nagle)

barbiturate sedatives and hypnotics. . .mechanism of action

"barbiturates are believed to have two mechanisms of action. at lower doses, barbiturates increase the inhibitory actions of gamma-aminobutyrin acid (gaba). gaba is an inhibitory neurotransmitter in the cns that reduces neuronal excitability, especially in the reticular activating system. increasing the effects of gaba reduces brain activity and promotes sleep.

at higher doses, barbiturates also cause a general depression of the entire cns that is similar to the actions of the general anesthetics. this action of the barbiturates is not well understood but may be related to the ability of the barbiturates to dissolve in the neuronal membranes, where they interfere with the normal function and movement of ions that regulate neuronal excitability and the release of excitatory neurotransmitters.

the main sites of action of the barbiturates for sedation and hypnosis are the reticular formation and the cerebral cortex. inhibition of the reticular activating system reduces excitatory stimulation of the cerebral cortex. as a result, individuals become sedated and, with further cns depression, become sleepy. the dose of barbiturate required to produce hypnosis is usually two to three times greater than the dose required to produce sedation.

barbiturates usually increase stage 2 sleep but decrease slow-wave sleep (stages 3 ands 4). in addition, barbiturates suppress rem sleep. when barbiturates are discontinued, patients often spend excess time in rem sleep during the next night or two as to make up for the lost rem sleep (rem rebound effect). during the rebound period, there is increased dreaming that may cause restlessness, anxiety and nightmares."

all that is said about the mechanism of benzodiazepines in this chapter is on page 123: "the benzodiazepines produce sedative and hypnotic effects by increasing the inhibitory activity of gamma-aminobutyrin acid (gaba), a neurotransmitter in the cns. when gaba is released by certain neurons, it binds to gaba receptors and this leads to a reduction in neuronal excitability. the benzodiazepines bind to receptor sites (names benzodiazepine receptors) that are in close relationship to the gaba receptors.

when benzodiazepines bind to their receptors, there appears to be an additional increase in the inhibitory activity of gaba, which further decreases neuronal excitability.

in the reticular activating system, this depression produces sedation or hypnosis, depending on the dose of drug administered."

(from page 137,

pharmacology: an introduction

, 5th edition, by henry hitner and barbara nagle)

benzodiazepines. . .mechanism of action

"the benzodiazepines decrease the excitability and functional activity of specific areas of the brain and spinal cord. gamma-aminobutyrin acid (gaba) is an inhibitory neurotransmitter in the cns that, when released from nerve endings, binds to receptors (called gaba receptors) located on the membranes of other neurons.

gaba appears to allow more chloride ions to pass into the neurons which makes the inside of the neuron more negatively charged (hyperpolarization). hyperpolarization of the neuron reduces neuronal excitability and consequently produces a depressant effect on those neurons

.

the benzodiazepine drugs also bind to neuronal membranes at receptor sites (referred to as the benzodiazepine receptors) that are actually a part of the gaba receptors.

when both the gaba and a benzodiazepine drug are bound to their receptors, more chloride ions pass into the neuron than when only gaba is bound alone. consequently, a greater degree of hyperpolarization and neuronal depression is produced.

simply stated, benzodiazepines are believed to increase the inhibitory actions of gaba, which results in reduced (depression) of specific areas of the cns."

from a pharmacy school website (this is really advanced information) http://www.pharmacology2000.com/central/sedhyp/shobj1.htm#stages%20of%20central%20nervous%20system%20depression:

possible biochemical mechanism of action of anxiolytics, sedatives and hypnotics especially barbiturates and benzodiazepines:

benzodiazepines
- benzodiazepines act on gabaa receptors
  - gaba receptor: a pentameric protein, consists of several subunits designated alpha (mainly responsible for the pharmacology of the receptor), beta and gamma which is required for high affinity benzodiazepine binding.
    - electrophysiological effects: benzodiazepines enhance gaba-activated hyperpolarizing chloride currents.
[*]
barbiturates
- mechanism of action
  - molecular: barbiturates activate inhibitory gabaa while inhibiting excitatory ampa receptors.
  - ampa receptors are the subtype of glutamate receptors sensitive to kainate or quisqualate.
  - barbiturates interact differently than benzodiazepines at gaba receptors. for example, the gamma subunit is not required for barbiturate activity.
  - the combination of these receptor effects may result in the profound cns depression that occurs with higher barbiturate doses.