School Work

Pharmacoresistance in Epilepsy by Ishwarya Sivakumar

Description
A grade AS level Coursework by Ishwarya Sivakumar
Categories
Published
of 13
All materials on our website are shared by users. If you have any questions about copyright issues, please report us to resolve them. We are always happy to assist you.
Related Documents
Share
Transcript
    SHOULD CANNABIS OIL BE USED FOR TREATMENT - RESISTANT EPILEPSY?    Name: Ishwarya Sivakumar   1 Contents   The Problem ……………………………………………………………………………………...……..2   Possible Solution…………………………………………………………………………………….….2  Ethical, Economic and Social Issues…………………………………………………………….. . …….5   Benefits and Risks…………………………………………………………………………………….. ..7 Alternative Solutions…………………………………………………………………………… ..... ….. 8 Evaluation………………………………………………………………………………………….… .10 Bibliography…………………………………………………………………………………………..11     2 Fig.1: Structure of P-gp that causes anti-epileptic drug efflux by re-distribution or direct transport.  Should Cannabis Oil be used for Treatment - Resistant Epilepsy?   The Problem Around one third of people with epilepsy are resistant to the current treatment - antiepileptic drugs (AEDs). [1] At some point of their condition, 20% of patients with generalized epilepsy and up to 60% of patients with partial epilepsy can develop resistance to drug therapy. Currently mechanisms underlying the drug-resistance are not fully understood. The cause is thought to be an increased number of P-glycoprotein (P-gp) pumps in the blood-brain barrier which move AEDs out of the brain to maintain a steady concentration; more of these pumps means that larger amounts of AEDs are transported out of the brain than usual making them ineffective (see fig.1). [17] Resistance to AEDs results in debilitating, long-lasting and consecutive seizures, [2] causing cognitive and psychological dysfunction. There is a large amount of electrical abnormality in the brain during a seizure. Normal cell function is disrupted leading to cell death. [3]  Resistance to treatment is also associated with a lower quality of life, social impairment and sudden unexpected death (SUDEP). So what is the solution to this unmet clinical need? Possible Solution: Cannabis oil Cannabis oil is being proposed by GW  pharmaceuticals as the most effective treatment for treatment-resistant epilepsy. [29] It is known to significantly increase the life expectancy of patients with uncontrollable seizures [23]  In rodent seizure models, 1, 10 and 100mg/kg CBD significantly lowered mortality and the percentage of animals experiencing tonic-clonic seizures. Numerous  patients claimed that they are experiencing over 75% reductions in seizures after taking high CBD infusions and oils orally everyday. [36] Unfortunately, it induces some side effects. The plant is bred so that it predominantly contains the non-psychoactive component „ Cannabidiol ‟  (CBD) which has seizure-fighting properties and is low in Tetrahydrocannabinol (THC) - the psychoactive component of Cannabis. CBD is hydrophobic and lipophilic which makes it lipid-soluble so it is mixed with olive oil for people to consume. [9, 14] Fig.2   3 Currently, little is known about the molecular mechanisms of CBD. There are two plausible theories which explain how CBD controls seizures via another route. One theory states that CBD works by reducing the Ca 2+  oscillations under high- excitability in the hippocampal neurons adjusting the brain‟s exchange of information; this in turn reduces the seizures. The other theory involves the protective effect of cannabinoids through receptor proteins known as NMDA which play a key role in memory and learning, cannabinoids can have a „special‟ site of interaction on these receptors too. [15-16, 31]  There is some evidence that CBD has controlled seizures in cases where AEDs have been ineffective (see fig.3).   To see just how effective CBD were, a parent survey of 19 patients was carried out on the use of cannabidiol-enriched use in pediatric treatment-resistant epilepsy for children with Dravet syndrome, Doose syndrome, Lennox-Gastaut syndrome and idiopathic early-onset epilepsy. [18] The survey consisted of children aged 2-16 years. All children aged above 2 years experienced no less than 3 years of treatment-resistant epilepsy before taking cannabidiol-enriched cannabis. Parents reported that the dosage of CBD-enriched cannabis given to their children ranged from 0.5 to 28.6 mg/kg/day. This cannabis only contained a range of 0-0.7 mg/kg/day of the psychoactive component.   According to two parents, their child became completely seizure-free after 4 months of CBD-enriched cannabis use. 84% of the 19 parents claimed that their child‟s reduction frequency was minimized. As stated in the table, before CBD was given, the occurrence of seizures varied from 2/week to 250/day whereas after CBD was given the occurrence of seizures dropped to 0/week to 10/day. This data clearly signifies that CBD definitely prevents or greatly reduces the occurrence of epileptic seizures  plus CBD is shown to be more effective and favourable over AEDs. An average number of 12 seizures (211/18=11.7) were noted before CBD administration. The average percentage decrease in seizure frequency after CBD was administered is 54.7%. Other accounts of cannabidiol and seizure reduction support these results which makes the information about CBD both valid and reliable. [21] Data was collected by the Scientific Committee of ACT (Associazone Cannabis Terapeutica- Italy) in which children with drug-resistant seizures were given a 2.5% corn oil solution of CBD. The outcome of the CBD treatment was encouragingly  positive. In 2001, only four of the 16 parents dropped the CBD treatment for their children and this was due to the treatment‟s expensiveness. Nevertheless, they were very pleased about their child‟s reduced seizures. Fig.3: Summary of the responses obtained from the parent survey.
Search
Tags
Related Search
We Need Your Support
Thank you for visiting our website and your interest in our free products and services. We are nonprofit website to share and download documents. To the running of this website, we need your help to support us.

Thanks to everyone for your continued support.

No, Thanks