This blocks sustained high frequency repetitive firing of action potentials. The mechanism of action is not completely known, but it is thought to involve stabilization of neuronal membranes at the cell body, axon, and synapse and limitation of the spread of neuronal or seizure activity. Phenytoin controls partial seizures and generalized tonicclonic seizures. Pentobarbital increased the uptake of gaba twofold and only slightly increased the. Paracetamol is the most widely used overthecounter medication in the world. Sander ucl institute of neurology, university college london, national hospital for neurology and neurosurgery, queen square, london, and epilepsy society, chalfont st peter, buckinghamshire established antiepileptic drugs aeds are those which were licensed before 2000. Also, molindone contains calcium ions, which interfere with the absorption of phenytoin.
Phenobarbital n h h n o o n o nh2 hn n h o o o phenytoin dilantin carbamazapine phenobarbital. Mechanisms of action of antiepileptic drugs sciencedirect. However, intravenous phenytoin has three major disadvantages. Davies department of pharmacology and therapeutics, university of wales college of medicine, heath park, cardiff, uk depending on their mechanism of action, anticonvulsant drugs in clinical use may be divided into three groups.
Mechanism of action action of phenytoin on na channel aresting state in which na channel activation gate a is closed b arrival of an action potential causes depolarization and opening of activation gate a and na flows into the cell. Possibly by promoting sodium efflux from neurons, phenytoin tends to stabilize the threshold. Phenytoin was originally approved by the fda in 1939. Posttetanic potentiation at synaptic junctions are blocked which alters synaptic transmission. Neuropharmacology iii anticonvulsants mit opencourseware. Mechanisms of action antiseizure drugs are typically grouped by their principal mode of action, although for many drugs, the precise mechanism of action is not known or multiple actions are suspected. Fosphenytoin is a prodrug of phenytoin and accordingly, its anticonvulsant effects are attributable to phenytoin. Phenytoin inhibits the spread of seizure activity in the motor cortex. Dilantin clinical pharmacology mechanism of action. Action potentials are caused by an exchange of ions across the neuron membrane. Clinical pharmacokinetics of phenytoin springerlink. Phenytoin is an antiepileptic drug which can be useful in the treatment of epilepsy. Hyperpolarizing this postsynaptic membrane leads to a decrease in the general excitatory aspects of the postsynaptic neuron. Pdf phenytoin is an established drug in the treatment of acute repetitive seizures and status epilepticus.
Tricyclic, antidepressant bipolar 3d conformation similar to phenytoin. The finding of increased risk with aeds of varying mechanisms of action and. Phenytoin 100mg filmcoated tablets summary of product. Phenytoin is an anticonvulsant which also has class 1b antiarrhythmic activity. Bioavailability is dependent upon particle size and problems of generic inequivalence have therefore arisen, particularly in scandinavia. Nonsynaptic effects to reduce sodium conductance, enhance active sodium extrusion, block repetitive. Summary of antiepileptic drugs proposed mechanisms of action. Q3 describe the pharmacology of phenytoin march 2012. Gammaaminobutyric acid gaba, one of the main inhibitory neurotransmitters in the brain, interacts with three types of receptors for gabagabaa, gabab and gabac. Several mechanisms are involved in the development of gingival overgrowth.
Additive cns depression with other cnsdepressants, including alcohol, antihis tamines, antidepressants, opioids, and sedativehypnotics. Clinically important displacement can be caused by. Clinical pharmacology mechanism of action phenytoin is an anticonvulsant which may be useful in the treatment of generalized tonic. The mechanism of action is complex and includes the effects of both the peripheral cox inhibition, and central cox, serotonergic descending neuronal pathway. Route onset peak duration phenytoin itoyn po 224hr1wk. C when depolarization continues,an inactivation gate b moves into the cell.
Other mechanisms of action that may contribute to the drugs efficacy and selectivity are also discussed. Other mechanisms possibly contributing to its anticonvulsant properties are. Benzodiazepine pharmacology and central nervous system ncbi. Chapter 43 n mechanisms of action of antiepileptic. Phenytoin dilantin mechanism of action, indication, and. Pathogenesis of phenytoin induced gingival overgrowth.
The exact mechanism of action is not known, phenytoin may work by reducing the sensitivity of nerves in the brain to excessive stimulation and reducing transmission of impulses between nerves. The drug has a moderately large volume of distribution and is approximately 90% bound to plasma proteins. Phenytoin sodium is related to the barbiturates in chemical structure, but has a fivemembered ring. A 44yearold first nations man presented to the emergency department with headache, nystagmus. The mechanism of action of its analgesic effect was often considered as based on. Through its action on gaba a receptors, phenobarbital increases the flow of chloride ions into the neuron which decreases the excitability of the postsynaptic neuron.
Inhibition of the neuronal action potential is typically focused on the activation of voltagegated channels involved in the electrical propagation of the seizure. Because of its dosedependent clearance, drugs taken concomitantly that either inhibit or induce cyp 2c9 or 2c19 can cause large changes in phenytoin plasma levels. The older formulation phenytoin in a basic solution including ethylene glycol is still used because its cost is substantially lower. Dosage increases of the tricyclic antidepressant may be required to produce improvement of the depressed state. The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited.
Microsoft word q3 describe the pharmacology of phenytoin march 2012. Mechanism of action overview sodium channel blockers. Dilantin fda prescribing information, side effects and uses. Because there are many more sodium ions on the outside, and the inside of the neuron is negative relative to the outside, sodium ions rush into the neuron. Mechanism of action effect on neuronal transmission firstgeneration aeds secondthirdgeneration aeds aeds under development sodium channel blockade fast inactivation slowed recovery from inactivated state phenytoin carbamazepine valproate topiramate zonisamide. Other measures, including concomitant administration of an iv benzodiazepine such as diazepam, or an iv shortacting barbiturate, will usually be necessary for rapid control of seizures because of the. The molecular mechanism for this is a voltagedependent blockade of membrane sodium channels responsible for the action potential. Pharm hons, m clin pharm department of pharmacy, singapore general hospital, singapore abstr act therapeutic drug monitoring of phenytoin is carried out to. Competition for protein binding sites leads to many drug interactions. Iv phenytoin and dopaminemay cause additive hypotension. Phenytoin is an effective anticonvulsant against tonicclonic and partial seizures and an important pharmacologic tool that has increased understanding of the underlying mechanisms responsible for epileptic syndromes. A longer time is required to achieve therapeutic levels. The mechanisms by which amlodipine relieves angina are.
Mechanisms of action of existing agents sodium channels. Both pentobarbital and phenytoin inhibited the uptake of norepinephrine. Amlodipine, sold under the brand name norvasc among others, is a medication used to treat. Mechanisms of action of antiepileptic drugs 3 receive ethosuximide are more likely than those who receive valproic acid to achieve longterm remission is consistent with the diseasemodifying actions observed in animal studies 21. Amlodipine has additionally been found to act as an antagonist of the.
Domperidone is a dopamine antagonist blocking both d1 and. Sodium channels are integral to the action potential and neuronal depolarization. Parenteral phenytoin sodium injection, usp warning. In the hospital, it can be given through a vein to quickly bring a. In neurons, phenytoin decreases sodium and calcium ion influx by prolonging channel inactivation time during generation of nerve impulses. At the cellular level, the mechanism of action for phenytoin appears related to its ability to prolong the inactivation of voltageactivated sodium ion channels and reduction of the ability of neurons to fire at high frequencies. The effect of pentobarbital and phenytoin on the highaffinity uptake of the putative neurotransmitters gammaaminobutyric acid gaba, glutamate, and norepinephrine was examined in synaptosomes prepared from rat brain. Gabaa receptors, associated with binding sites for benzodiazepines and. It binds and blocks sodium influx, stabilising the neuronal threshold against excitability caused by excessive stimulation. Blockade of voltagegated sodium channels is the most common mechanism of action among currently available aeds.
The precise mechanism by which phenytoin exerts its therapeutic effect has not been established but is thought to involve the voltagedependent blockade of membrane sodium channels resulting in a reduction in sustained highfrequency neuronal discharges. Phenytoin is a major anticonvulsant drug that is very effective in controlling a wide variety of seizure disorders while impairing neurological function little, if at all. Avoid using phenytoin or fosphenytoin as alternatives to carbamazepine for patients who test positive. Through this action, phenytoin obstructs the positive feedback that underlies the development of maximal seizure activity, while normal brain activity, proceeding at lower neuronal firing rates, is spared its depressant action. Register for one of our web classes at the link below. To report a case of phenytoin toxicity potentially associated with concurrent diazepam therapy. If less serious skin eruptions measleslike or scarlatiniform occur, phenytoin may be resumed after complete clearing of the rash. To some degree, the cellular effects of antiseizure drugs are linked with the types of seizures against which they are most effective. A guide to therapeutic drug monitoring melissa faye wu, bsc pharm hons, wai hing lim, b. Phenytoin is an antiepileptic drug which can be used in the treatment of epilepsy. The established agents phenytoin and carbamazepine are archetypal sodium channel blockers, a mechanism they share with the. The precise mechanisms by which amlodipine relieves angina have not been fully delineated, but are thought to include.
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