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Owned and operated by the City Government of Urdaneta NAME/S: Nava JE ., Nietes F ., Ogoy DC ., Ordonio JA ., Perez XK. DATE SUBMITTED: 5/24/ COURSE AND YEAR: BS PHARMACY II ANTI-CONVULSANTS GENERIC NAME BRAND NAME MECHANISM OF ACTION Phenytoin Dilanti ®, Phenytek® Phenytoin is often described as a non-specific sodium channel blocker and targets almost all voltage-gated sodium channel subtypes. Phenytoin prevents seizures by inhibiting the positive feedback loop that results in neuronal propagation of high frequency action potentials. Phenobarbital Donnatal®, Luminal®, Phenobar ®, Phenohytro ® Phenobarbital acts on GABAA receptors, increasing synaptic inhibition. This has the effect of elevating seizure threshold and reducing the spread of seizure activity from a seizure focus. Phenobarbital may also inhibit calcium channels, resulting in a decrease in excitatory transmitter release. The sedative-hypnotic effects of phenobarbital are likely the result of its effect on the polysynaptic midbrain reticular formation, which controls CNS arousal. Carbamazepine Carbatrol®, Carnexiv®, Epitol®, Equetro®, Tegretol® Carbamazepine exerts its effects by lowering polysynaptic nerve response and inhibiting post-tetanic potentiation. In both cats and rats, carbamazepine was shown to decrease pain caused by infraorbital nerve stimulation. Carbamazepine decreases the action potential in the nucleus ventralis of the thalamus in the brain and inhibition of the lingual mandibular reflex by binding to voltage-dependent sodium channels and preventing action potentials, which normally lead to stimulatory effects on nerves. In bipolar disorder, carbamazepine is thought to increase dopamine turnover and increase GABA transmission, treating manic and depressive symptoms. Ethosuximide Zarontin® Binds to T-type voltage sensitive calcium channels. Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. Gabapentin Gralise®, Neurontin® Gabapentin appears to inhibit the action of α 2 δ-1 subunits, thus decreasing the
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Owned and operated by the City Government of Urdaneta density of pre-synaptic voltage-gated calcium channels and subsequent release of excitatory neurotransmitters. It is likely that this inhibition is also responsible for the anti-epileptic action of gabapentin. There is some evidence that gabapentin also acts on adenosine receptors and voltage-gated potassium channels, though the clinical relevance of its action at these sites is unclear. Pregabalin Lyrica® By binding presynaptically to the alpha2-delta subunit of voltage-gated calcium channels in the central nervous system, pregabalin modulates the release of several excitatory neurotransmitters including glutamate, substance-P, norepinephrine, and calcitonin gene related peptide. In addition, pregabalin prevents the alpha2-delta subunit from being trafficked from the dorsal root ganglia to the spinal dorsal horn, which may also contribute to the mechanism of action. Vigabatrin Sabril®, Vigadrone® Vigabatrin increases concentrations of GABA in the central nervous system by irreversibly inhibiting the enzymes responsible for its metabolism to succinic semialdehyde: gamma-aminobutyric acid transaminase (GABA-T) Valproic acid/Sodium Valproate Depakene®, Depakote®, Epival® Valproate is known to inhibit succinic semialdehyde dehydrogenase. This inhibition results in an increase in succinic semialdehyde which acts as an inhibitor of GABA transaminase ultimately reducing GABA metabolism and increasing GABAergic neurotransmission. Lamotrigine Lamictal® Lamotrigine likely acts by inhibiting sodium currents by selective binding to the inactive sodium channel, suppressing the release of the excitatory amino acid, glutamate. The mechanism of action of lamotrigine in reducing anticonvulsant activity is likely the same in managing bipolar disorder. Topiramate Qsymia®, Qudexy®, Topamax®, Trokendi® Topiramate stimulates GABA-A receptor activity at brain non-benzodiazepine receptor sites and reduces glutamate activity at both AMPA and kainate receptors. Normally, GABA-A receptors are inhibitory and glutaminergic receptors are stimulatory for neuronal activity. By increasing GABA activity and inhibiting glutamate activity, topiramate blocks neuronal excitability, preventing seizures and migraines. Additionally, it blocks the voltage-dependent sodium channels, further blocking seizure activity. Topiramate has been shown to inhibit various carbonic anhydrase isozymes, but the clinical significance of this is unknown at this time.
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Owned and operated by the City Government of Urdaneta 15 – 30 min. the effects of GABA by increasing GABA affinity for the GABA(a) receptor, which ultimately enhances GABA ligand binding at the receptors. This enhancedligand binding of the inhibitory neurotransmitter GABA to the receptors increases the aforementioned chloride ion conduction (perhaps reportedly via an increase in the frequency of the chloride channel opening), resulting in a hyperpolarized cell membrane that prevents further excitation of the associated neuron cells Estazolam Prosom ® Benzodiazepines bind nonspecifically to benzodiazepine receptors, which affects affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell. Long-acting Benzodiazepines Diazepam Diastat®, Valium®, Valtoco 5 Mg Dose Kit Diazepam is a benzodiazepine tranquilliser with anticonvulsant, sedative, muscle relaxant and amnesic properties. Benzodiazepines, such as diazepam, bind to receptors in various regions of the brain and spinal cord. This binding increases the inhibitory effects of gamma-aminobutyric acid (GABA). GABAs functions include CNS involvement in sleep induction. Also involved in the control of hypnosis, memory, anxiety, epilepsy and neuronal excitability 1-5mins (IV) 15-30mins (IM) 30 – 60 min. Flurazepam Dalmane® Flurazepam binds to an allosteric site on GABA-A receptors. Binding potentiates the action of GABA on GABA-A receptors by opening the chloride channel within the receptor, causing chloride influx and hyperpolarization. Chlordiazepoxide Chlorax®, Librax® Chlordiazepoxide binds to stereospecific benzodiazepine (BZD) binding sites on GABA (A) receptor complexes at
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Owned and operated by the City Government of Urdaneta 1-5 min (IV) 20 – 45 min. 1-2 hr. several sites within the central nervous system, including the limbic system and reticular formation. This results in an increased binding of the inhibitory neurotransmitter GABA to the GABA(A) receptor. BZDs, therefore, enhance GABA- mediated chloride influx through GABA receptor channels, causing membrane hyperpolarization. The net neuro- inhibitory effects result in the observed sedative, hypnotic, anxiolytic, and muscle relaxant properties. Quazepam Doral® Used to treat insomnia. With our commercial data, access important information on dangerous risks, contraindications, and adverse effects. Quazepam is a benzodiazepine derivative. The main pharmacological action of quazepam is the enhancement of the neurotransmitter GABA at the GABAA receptor. Clorezepate Tranxene® Benzodiazepines bind nonspecifically to benzodiazepine receptors BNZ1, which mediates sleep, and BNZ2, which affects affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.. Barbiturates Ultra-Short acting Barbiturates Generic Name Brand Name Mechanism of action Onset of action (mins) Thiopental Pentothal ® Thiopental binds at a distinct binding site associated with a Cl- ionopore at the GABAA receptor, increasing the duration of time for which the Cl- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged. 15 – 40 min. Methohexital Brevital ® Methohexital binds at a distinct binding site associated with Intramuscular Route After intramuscular injection to pediatric
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Owned and operated by the City Government of Urdaneta input resistance, depresses burst and tonic firing, especially in ventrobasal and intralaminar neurons, while at the same time increasing burst duration and mean conductance at individual chloride channels; this increases both the amplitude and decay time of inhibitory postsynaptic currents. In addition to this GABA-ergic effect, barbiturates also block the AMPA receptor, a subtype of glutamate receptor. Glutamate is the principal excitatory neurotransmitter in the mammalian CNS. Amobarbital also appears to bind neuronal nicotinic acetylcholine receptors. Butabarbital Butisol Sodium ® Barbiturates like butabarbital potentiate GABA-A receptors and inhibit receptors for neuronal acetylcholine, and kainate.8,10 GABA-A receptors are predominantly on the post-synaptic membrane, and upon activation, open chloride channels to hyperpolarize the neuron and decreased firing rate.9 Potentiation of GABAergic neurons produces sedation.9 Inhibition of neuronal acetylcholine receptors and glutamate receptors of the kainate subtype desensitize their respective neurons, producing sedation. 45-60 mins. Long-acting Barbiturates Phenobarbital Donnatal ® , Luminal ® , Phenobarb ® , Phenohytro ® Phenobarbital acts on GABAA receptors, increasing synaptic inhibition. This has the effect of elevating seizure threshold and reducing the spread of seizure activity from a seizure focus. Phenobarbital may also inhibit calcium channels, resulting in a decrease in excitatory transmitter release. The sedative-hypnotic effects of phenobarbital are likely the result of its effect on the polysynaptic midbrain reticular formation, which controls CNS arousal. Oral: ≥ 60 minutes; IV: 5 minutes; Peak effect: IV: CNS depression: ≥ 15 minutes.
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Owned and operated by the City Government of Urdaneta (^) Newer Hypnotics Generic Name Brand Name Mechanism of Action Eszopiclone Lunesta® The precise mechanism of action of eszopiclone as a hypnotic is unknown, but its effect is believed to result from its interaction with GABA receptor complexes at binding domains located close to or allosterically coupled to benzodiazepine receptors. Zaleplon Sonata® Zaleplon is a nonbenzodiazepine from the pyrazolopyrimidine class with hypnotic, sedative, anxiolytic, and muscle relaxant properties. Zaleplon interacts with the gamma-aminobutyric acid (GABA) -A receptor, thereby affecting the chloride channel ionophore complex and potentiating the inhibitory effects of GABA. Zolpidem Ambien® Zolpidem, a non-benzodiazepine hypnotic agent, works as a GABAa receptor chloride channel modulator/agonist that increases GABA inhibitory effects leading to sedation. It also has anticonvulsant, anxiolytic, and minor myorelaxant properties.
