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However, these mechanisms have not been confirmed. Faculty may discuss investigational products
or off-label uses of products regulated by the US Food and Drug Administration. Because of these
adverse effects, phenytoin use in children should generally be avoided. Sodium thiopental is mainly
metabolized to pentobarbital. This lack of selectivity allows the benzodiazepines to be used as
anticonvulsants, sedatives, hypnotics, anxiolytics muscle relaxants and general anesthetics, the
activity is determined by the dose and the desires of the company. Besides, knowledge of principle
pharmacological propert. Backward logistic regression analysis was done to identify predictors of
poor seizure control. By using our site, you agree to our collection of information through the use of
cookies. To browse Academia.edu and the wider internet faster and more securely, please take a few
seconds to upgrade your browser. To receive credit and a certificate, you must pass the test questions
with a minimum score of 100%. Maintaining AEDs within laboratory-defined therapeutic ranges is a
myth, with professionals overestimating values in most clinical settings. To stimulate the
development of even better compounds, the demonstrated benefits and risks of current new AEDs
are reviewed. LVT has no interactions with other AEDs, warfarin, or oral contraceptives making it an
ideal drug for use when a physician is unsure of the seizure type or epilepsy syndrome. Compare and
contrast the terms seizure, convulsion and epilepsy. Sodium channels are primary targets of many
AEDs such as phenytoin, carbamazepine, and lacosamide. 5 Examples of drugs that act on calcium
channels are lamotrigine and ethosuximide. IV fosphenytoin does not carry these risks, and is the
preferred formulation when parenteral phenytoin use is indicated. Both trimethadione and
dimethadione are excreted in the urine and are very toxic Paramethadione is also N dealkylated, half
life is 12-24 hours. MECHANISMS AND EFFECTS Carbamazepine blocks voltage-sensitive
sodium channels in neuronal cell membranes. The characteristic event is the seizure, which is often
associated with convulsion, but may occur in many other forms. Groups at other positions have the
same electronic effects. When compared to phenytoin, no difference was found in primary outcomes
but PB was more likely to be discontinued due to side effects of irritability and hyperactivity.
Compare and contrast the first line drugs of choice for AED. These actions further increase NMDA
receptor activation and calcium influx, which are believed to contribute to the depolarization shift
that is observed in seizure foci. The BDZ—3 receptors are located in peripheral tissues and not
involved in hypnotic efficacy. Compare and contrast the first line drugs of choice for AED. There are
no systematic studies available regarding these high-risk groups, and there is little or no availability
of any documented evidence that allow the quantification of the actual effect of these problems.
However, physicians and pharmacists should remain alert to the problems and risks while
substituting the generics. It is a Chronic medical condition characterized by 2 or more unprovoked
seizures. You will be able to get a quick price and instant permission to reuse the content in many
different ways. This allows dosing up to four hours before a patient needs to be awake. Felbamate
and topiramate exert their antiepileptic action through multiple mechanisms—attenuation of
excitatory neurotransmission is one of them.
Download Free PDF View PDF Saudi medical journal Short-term efficacy and safety of valproate
sustained-release formulation in newly diagnosed partial epilepsy VIPe-study. Gabapentin increases
GABA release, whereas valproate inhibits GABA degradation. So most activity are due to
metabolite, followed by p-hydroxylation and conjugation Phensuximide possesses the bulky group at
C3 which is good for absence but also picks up some generalized tonic-clonic activity. However, the
available literature on epilepsy indicate that substitution of AEDs is problematic, especially in certain
patient groups. These newer agents are particularly useful because complex partial seizures are more
resistant to treatment than are other types of seizures. Recruited 98 patients with epilepsy who
fulfilled the eligibility criteria from April 2016 to August 2016 from the outpatient department of
Neurology,King George hospital. In this example, they are seen in the left frontal and left temporal
lobes, but they are not seen in other lobes. (C) During a generalized tonic-clonic seizure, the tonic
phase is characterized by low-frequency and high-amplitude waves, whereas the clonic phase shows
synchronous oscillations. (D) During a generalized absence seizure, a synchronous 3-Hz spike-and-
wave pattern is seen throughout the cortex. Carbamates are salts or esters of the hypothetical
carbamic acid (H2NCOOH), similar to meprobamate. Seizures have been described as far back as in
the Babylonian tablets dating to 1067 BC. Drug use patterns and sociodemographic data of the study
participants were accustomed to descriptive statistics. Major metabolite is from oxidation of the
ethyl group, hydroxyethyl and conjugated hydroxyethyl, both are inactive Methsuximide has a bulky
group at C3 which is good for absence but also picks up some partial seizures activity.
Pharmacokinetics characteristics of AEDs The AEDs have numerous pharmacokinetics factors that
may upsurge the probability of problems associated with generic substitution (Table 2 ) (Crawford et
al. 2006; Walker and Patsalos 1995; Perucca 1999; Morselli and Franco-Morselli 1980; Bauer et al.
1982 ). Table 2 Pharmacokinetics characteristics of AEDs which may increase the probability of
problems associated with their generic substitution Full size table. Fortunately at blood pH of 7.4
benzodiazepines exists in the closed ring B form. The depolarization shift can cause adjacent
neurons to discharge synchronously and thereby precipitate a seizure. It is a Chronic medical
condition characterized by 2 or more unprovoked seizures. For instance, compromising potential
breakthrough seizures and toxicity associated with the generic substitutions of branded
carbamazepine and phenytoin respectively (Gidal and Tomson 2008 ). Effects on GABAergic
Systems Antiepileptic drugs facilitate GABA neurotransmission by various means. The type of
seizure determines the choice of drug. Conclusion: Most of the patients were maintained by
monotherapy, and largely this was by the older antiepileptic drug, phenobarbitone. Nevertheless, the
major factor attributed to the extensive use of generic substituents is the reduced cost, yet low cost
based generic substitution in epilepsy patients without taking into considerations the unique behavior
of the disease is questionable (Jobst and Holmes 2004 ). Risk of recurrent seizures after two
unprovoked seizures. Recent discoveries in molecular biology and genetics have elucidated a genetic
basis for some epilepsy syndromes, which will lead to new treatments. Careful consideration of
maternal and fetal health is warranted when using AEDs. To receive credit and a certificate, you
must pass the test questions with a minimum score of 100%. Seizures are symptoms that occur in
acute illness, i.e., provoked seizures, or in epilepsy, ie, unprovoked seizures. Although OXC and CBZ
share a common mechanism of action, some patients who are inadequately treated with CBZ improve
after switching to OXC. For example, a seizure may first involve the fingers, then the hand, and
finally the entire arm. Calcium contributes to the long-term potentiation of excitatory glutamate
neurotransmission by activating the synthesis of nitric oxide. Consequently, the generic substitution
of AEDs affects the successful treatment and quality of life of the patients. Besides, knowledge of
principle pharmacological propert.
As far as two different generics of the same brand are concerned, there could be differences in their
C max and AUC values. Patient-related information on their previous experiences of the generic
substitution could also be beneficial to identify the risk-to-benefit ratio of generic substitution. This
causes disproportional increase in PHT serum level with small increments to the dose at higher levels.
Two other drugs that are effective against partial seizures as well as generalized tonic-clonic seizures
are phenobarbital and primidone. Electroencephalographic abnormalities are seen in one or more
lobes of a cerebral hemisphere, and the patient may exhibit motor, sensory, and autonomic
symptoms. In simple partial seizures, consciousness is not altered. IV fosphenytoin does not carry
these risks, and is the preferred formulation when parenteral phenytoin use is indicated. Table 3
Special categories of patients recommended for exclusion from the compulsory generic substitution
(Lamy 1986; Kramer et al. 2007; Crawford et al. 2006 ) Full size table. With this approach, about
14% of patients who are resistant to the initial therapy achieve seizure freedom with alternative
monotherapy. 8. When used with LTG, it can raise LTG levels and precipitate fatal skin reactions
such as Stevens-Johnson syndrome. The present study has attempted to reveal the practical use of
AEDs in epilepsy Outpatient Clinic of Bishoftu General Hospital (BGH), East Shewa, Ethiopia.
Rarely, its use has been associated with aplastic anemia. Sodium channels are primary targets of
many AEDs such as phenytoin, carbamazepine, and lacosamide. 5 Examples of drugs that act on
calcium channels are lamotrigine and ethosuximide. Trials have shown that 47% of patients became
seizure free on the first appropriately selected and dosed AED. Complex partial seizures often
originate in the temporal lobe, in which case the disorder is called either temporal lobe epilepsy or
psychomotor epilepsy. It is poorly soluble in water, and different pharmaceutical formulations of it
may have different bioavailability. Hypnotic efficacy may not differ between benzodiazepine and
the newer selective agents. Guideline No. 70. Edinburgh. SIGN Neuvonen PJ (1985) Bioavailability
and central side effects of different carbamazepine tablets. According to the FDA, when two drugs
are bioequivalent, it means that both of them will provide similar and desired clinical effects. The
reasons could be the pharmacokinetics properties of AEDs and unique characteristics of some
epilepsy patients. It is a benzodiazepine and acts by potentiation of GABAergic neurotransmission
by binding to the GABA-A receptor. Followed by p-hydroxylation and conjugation Miscellaneous
Dibenzazepines structurally related to the TCAs. In these online self-assessment activities, read our
reference articles and test your knowledge with more than 7946 hours of CE. Laureen Trail Spring
2003. History. Humans have always sought ways to induce sleep, relieve stress and anxiety Natural
CNS depressants Alcohol Morphine (opium alkaloid) Manufactured CNS depressants. AEDs such as
carbamazepine when given in patients with absence epilepsy or in patients with generalized epilepsy
can exacerbate seizures. Recommendations from the international societies We have summarized the
recommendations of various neurological societies in Table 4. Epilepsy: Sudden and excessive
electrical activity in brain (excessive firing of neurons). Seizures are symptoms that occur in acute
illness, i.e., provoked seizures, or in epilepsy, ie, unprovoked seizures. Nevertheless, the risks of
significant adverse effects and drug interaction increase when more than one drug is used. Recent
discoveries in molecular biology and genetics have elucidated a genetic basis for some epilepsy
syndromes, which will lead to new treatments. Due to the potential risk of losing the control over
seizures, various guidelines recommend that the well-controlled epileptic patients should avoid
switching from brand-to-generic products, generic-to-brand products and generic-to-generic
products.
INDICATIONS In addition to its use in treating partial seizures and generalized tonic-clonic
seizures, carbamazepine is the drug of choice for trigeminal neuralgia ( tic douloureux ), a condition
that can cause chronic and intense pain on one or both sides of the face. High serum levels cause
nystagmus, ataxia, drowsiness, and incoordination. PHT also has interactions with other tightly
protein bound drugs like VPA and can increase their active drug levels. Consequently, the
classification of seizure as well as the use of drugs with potential drug interaction, dose and duration
problem needs urgent interventions. If a switch must be made, serum drug levels should be
monitored. Effects on GABAergic Systems Antiepileptic drugs facilitate GABA neurotransmission
by various means. Gabapentin increases GABA release, whereas valproate inhibits GABA
degradation. The depolarization shift consists of abnormally prolonged action potentials
(depolarizations) that have spikelets. It can also reduce levels of digoxin, steroids, vitamin K, and
other drugs. Carbamazepine and phenytoin have a similar mechanism of action and clinical
effectiveness, and both drugs induce cytochrome P450 enzymes and increase drug metabolism.
Statistical significance was considered at p value Download Free PDF View PDF See Full PDF
Download PDF Loading Preview Sorry, preview is currently unavailable. Patients demographic
details, clinical diagnosis, type of epilepsy, type of AED used, drug dose and frequency of 100
outpatients who attended the psychiatry OPD was recorded. Drugs such as bupropion, tramadol,
clozapine, and olanzapine can lower the seizure threshold in patients with epilepsy. Compare and
contrast the first line drugs of choice for AED. Table 1 Potential problems reported with generic
substitution of AEDs Full size table. ANTIEPILEPTIC DRUG DEVELOPMENT. Retigabine.
Rufinamide Lacosamide Brivaracetam. ?. 20. Pregabalin. Zonisamide. Levetiracetam.
Oxcarbazepine. Tiagabine. 15. Fosphenytoin. Topiramate. In addition, there is currently no drug
available which prevents the development of epilepsy, e.g. after head trauma. Thus, there is an unmet
need for safer and more effective drugs, especially for chronic, drug-resistant epilepsy. Some of
these drugs have the potential to become drugs of first choice in newly diagnosed epilepsy. Along
with pancuronium bromide and potassium chloride, thiopental is used in 34 states of the U.S. to
execute prisoners by lethal injection. Ineligible companies are organizations whose primary business
is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.
Many antiepileptic drugs, including carbamazepine, lamotrigine, phenytoin, and topiramate, prolong
the time that the sodium channel’s inactivation gate remains closed, and this delays the formation of
the next action potential. Other situations when drugs can worsen seizures are when AEDs are
rapidly withdrawn—especially benzodiazepines and phenobarbital. 22 This observation is based on
retrospective data and needs more evaluation. It is not a disease, it is a syndrome ( what is the
difference ). Seizure. Etiology. Idiopathic. Symptomatic. Inherited abnormality in the C.N.S. Novel
antiepileptic drugs, mainly associated with an inhibition of voltage-dependent sodium channels are
lamotrigine and oxcarbazepine. INTERACTIONS Carbamazepine is a potent inducer of cytochrome
P450 enzymes that metabolize a wide range of drugs. The type of seizure determines the choice of
drug. It is however a schedule II drug due to dependency. But, due to the limited data available on
the generic substitution of AEDs in migraine patients, and no such recommendations from the
headache organizations (American Academy of Neurology and American Headache Society), we
mainly focused on the potential problems and recommendations regarding generic substitution of
AEDs in epilepsy patients. Generalized absence seizures, or petit mal seizures, are characterized by
abrupt loss of consciousness and decreased muscle tone, and they can include a mild clonic
component, automatisms, and autonomic effects. The newer agents, such as lamotrigine, topiramate,
tiagabine, levetiracetam, zonisamide, and pregabalin, are considered adjunct agents and primarily
used in combination with older drugs for the treatment of partial seizures.