Zonisamide for partial seizuresZonisamide for partial seizures let us discuss Jonisamide. Jonisamide is one of the antiepleptic drug commonly known as AED. And particularly, Jonisimide is one of the atypical antiepleptic drug that acts by multiple mechanisms. And this drug can be used as an adjuvant th in the partial onset seizures.
And structurally, this drug is a sulfonamide. So it can produce some allergic reactions. But because of multiple mechanism of actions, this drug can be used in the management of partial onset seizures. This drug is having some additional activity on carbonic and hydrazengine. Just like diuretics, this drug can inhibit carbonic and hydrazengome activity, which should be considered when this drug is given along with other diuretics.
Similarly, this drug should not be prescribed for children age less than 16 years because the safety is not completely established. So genesimide is only indicated in the adults and adolescents with age greater than 16 years. Today, in this , let us discuss how this drug acts. What is its chemical nature, what are the important precautions, side effects, doses? All these things we will discuss in this.
Zonisamide for partial seizures
First of all, let us see the chemical nature of this drug. So, this is the structure of Jonisamide. Here we can observe one of the moiti. This is nothing but sulfonamide. So Jonisamide is a sulfonamide derivative.
Because of sulfonide moiety, within the structure, this drug can produce some allergic reactions which are commonly observed with sulfonamides. Many of the sulfonamides are used as antibacterial agents which can produce allergic and hypersensitive reactions. Similarly, Junisamide can also show some allergic reactions. And if we write the IUPAC name of this drug, simply this is a methane sulfonamide derivative. So we can write the suffix as methane sulfonamide.
To this methane sulfonamide, one of the heterocyclic ring system is attached with oxygen at first portion and nitrogen at second portion. So this is nothing but one, two, benjo oxygeol three, IEL. It is attached by third portion. So that is a simple name of Jonisamide. Now, let us see how this drug acts.
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Within the CNS exhibited neurons can store the glutamate, which is one of the exudatory amino acid neurotransmitter. The release of glutamate is controlled by calcium mediated exocytosis and the action potentially is transmitted to the nervous through the voltage gated sodium channels. So both sodium as well as calcium is required for release of glutamate. Now, this glutamate can act on the postsynaptic neurons which are equipped with glutamate receptors such as AMPA. This AMPA is a iotropic receptor which is coupled with fast acting sodium channels.
Now, when sodium enters through the voltage gated sodium channels, it can activate the neuroteminal, resulting in the stimulation of voltage gated calcium channels. These calcium channels are ttype calcium channels which can allow the calcium. So, by entry of calcium, exocytosis is going to take place, resulting in the release of glutamate. This glutamate acts on the Amp receptors on the postsynaptic neurons. Since these are the inotropic receptors they can allow the sodium ions which produce fast synaptic action potential.
In this way, within the CNS, neurons are excited, resulting in the increased neuronal activity, leading to induction of seizures. Similarly, on the postynaptic neurons, GABA air receptors are also present, which are inhibitory in nature, which can reduce the neuronal activity. Now, Joonis mite is one of the anti epileptic agent, which acts by multiple mechanisms. Even the exact mechanism of action is unknown. But this drug can block the voltage gated sodium channels, resulting in the decreased activation of neurons.
It can also block the ttype calcium channels, resulting in the decreased release of glutamate. In this, it can reduce the neuronal activity by inhibition of glutamate release. And this drug is having some possible effect on the GABA. Even it is not directly binding to this receptor. But it can increase the transmission of GABA, resulting in the hyperpolarization and inhibition of neuronal activity.
All these mechanisms may result in the antiepleptic action produced by Zonissamide. Now, let us the precautions of this drug. One of the important precautions of Zonissamide is that this drug can produce some hypersensitive reactions. Since this drug is a sulfuramide, it can produce few of the skin rashes. Even it can produce serious skin rashes like Stevens Johnson syndrome.
So, whenever these hypersensitive reactions are developed, this drug should not be used and it should be replaced with alternative agent. Similarly, this drug can induce acute myopia. So, this drug can result in loss of vision of foreign objects. Even it can produce some swelling of anterior chamber of the eye and hyperemia redness of the eye genesimide can also increase the intraocular pressure, which can increase the risk of angle closure glaucoma. So, in the patients with any history of angle closure glaucoma, this drug should not be given.
And on long term use at a high dose, particularly above 300 mg, this drug may produce some vision changes which should be closely monitored. And the important is activities on the renal tubules. Within the proximal convoluted tubule, sodium as well as bicarbonate are reabsorbed. Sodium can enter into the renal tubular membrane for exchange of proton. This proton can be combined with Bicarbonate to produce the carbonic acid.
This carbonic acid can split into water and carbon dioxide by one of the enzyme carbonic and hydrazengine. Now, this water and carbon dioxide can travel through the membrane and again they can be converted into carbonic acid by the same enzyme carbonic and hydrates. This carbonic acid is splitted into proton and bicarbonate. In this way, sodium and bicarbonate are going to be absorbed into the tubular membrane. Now, on the basilateral membrane, sodium and bicarbonate can be absorbed into the systemic circulation.
In this way, sodium bicarbonate is reabsorbed within the Pct. Now, Zunissamide can inhibit the active of carbonic and hydrazen gem activity, which results in the decreased reabsorption of sodium as well as bicarbonate. So, Bicarbonate is more excreted within the urine, which increase the acidic levels within the systemic circulation. In this way, jonisamide can produce some metabolic acidosis. So drugs like estrogelamide can also produce metabolic acidosis.
Therefore, along with jonisamide, any other drugs which increase the estosis should not be combined. Similarly, Jonisomide is one of the teratogenic agents, so it should not be given to the pregnant woman. And this drug can also increase the oligohydrosis, resulting in the decreased sweating and increased body temperature. That’s why this drug should not be given in the children with age less than 16 years because of hyperthermia produced by jonisamide. Now let us see the side effects.
The important side effects are related with the central nervous system. So jonisamide can produce somnolence some sleepiness in the patients, loss of peptide diziness, some drowsiness can be observed ataxia, loss of balance, agitation and irritability can be observed within the patients. Genesement can produce some impairment of memory.
It can reduce the ability of concentration, dyspepsia, indigestion, constipation, skin rashes, rhinitis or the other side effects produced by Jonisamide. How it is given this drug is available as tablet as well as capsule.
It is also available as oral suspension. The initial dose is started at 100 mg per day. It can be given either in a single dose or divided doses. It can be given either with food or without food. The dose can be slowly escalated after two weeks of the treatment with an increment of 100 mg.
And the dose can be slowly achieved up to 400 mg per day, which is the tolerable dose in many of the patients. In very rare conditions, the dose may be further increased to the maximum dose of 600 mg per day above 600 mg. This drug should not be given. So that’s about this drug jonisamide, which is a atypical antieptic agent which acts by multiple mechanisms. It blocks voltage gated, sodium channels, voltage gated, ttype, calcium channels.
It also increases the carbagic transmission. By all of these, it can reduce the neuronal activity. That’s why it can be used in the management of partial onset seizures. But this drug can be given along with other agents as this drug can produce oligohydrosis resulting in hyperthemia. And this drug should not be given in the children with age less than 16 years.
