Epilepsy therapetuics by siva

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Pharmacotherapy of Epilepsy:

Pharmacotherapy of Epilepsy Prepared & Presented by Dr. Siva Reddy Challa, Professor & HOD, Dept. of Pharmacology KVSR Siddhartha College of Pharmaceutical Sciences, Siddhartha Nagar, Vijayawada-520010 Andhra Pradesh, INDIA Email: sivareddypharma@gmail.com

GTCS:

GTCS

Pre-ictal or prodrome of epilepsy:

Pre-ictal or prodrome of epilepsy This is the time before the seizure. It can last from minutes to days and make people act and feel differently. Not everyone experiences something at this stage of a seizure. Some people who do experience a preictal stage use it as a warning so they can prepare for the seizure . Many people have an AURA before a seizure. Technically, an aura is a simple partial seizure . Realistically, AN AURA MIGHT MAKE YOU SEE, SMELL, HEAR OR TASTE SOMETHING FOR NO REASON . It can even just make you a bit nauseous, give you a weird feeling in your stomach, cause a ringing in your ears,

Ictal state of epilepsy:

Ictal state of epilepsy This this is the actual seizure . During this time there will be actual physical changes in the person’s body. After all, it’s at this point that the electrical storm in the person’s brain thunders to life. IF THE PERSON WITH EPILEPSY WERE TO BE HOOKED UP TO ANY MEDICAL DEVICES AT THIS POINT, THEY’D SHOW CARDIOVASCULAR, METABOLIC AND EEG CHANGES . A lot of these changes will help a neurologist determine the SEIZURE’S TYPE AND POINT OF ORIGIN , both of which are very important in treating the epilepsy.

Inter-Ictal state of epilepsy:

Inter-Ictal state of epilepsy This is the time between seizures . A lot of people with epilepsy, including more than half of all people with temporal lobe epilepsy, suffer emotional disturbances between seizures. These disturbances range from MILD FEAR TO PATHOLOGICAL LEVELS OF ANXIETY AND DEPRESSION . However, anxiety and depression are by far the most common. these interictal problems are often more incapacitating and difficult to control than the seizures themselves .

Post-Ictal state of epilepsy:

Post-Ictal state of epilepsy This this is the FINAL PHASE , the often slow recovery period after a seizure. It can LAST FROM MINUTES TO HOURS AND VARY QUITE A BIT, PARTLY DEPENDING ON THE TYPE OF SEIZURE EXPERIENCED , the intensity of it, and how long it lasted. It might leave the person FEELING TIRED AND/OR BEWILDERED , among other things, with a change in his or her consciousness or behavior. Sometimes symptoms from this phase can help doctors diagnose the part of the brain involved in the seizure . Many people will not remember anything that happened during the seizure.

Gneralized seizures: GTCS:

Gneralized seizures: GTCS Generalized tonic clonic seizure (formerly known as grand mal seizures) When a person has a tonic clonic seizure, his or her arms and legs will first stiffen. This is the tonic stage. His or her limbs and head will then begin jerking, which is the clonic phase. Like all seizures. During the seizure, the person might bite their tongue or the inside of his or her mouth, experience incontinence, or even decrease or cease his or her breathing (in this case, his or her breathing should return to normal during the tonic (jerking) portion of the seizure). Afterward, the person will likely be confused, not remember what happened, need to sleep for a while and might have a headache. Depending on the person, it can take them from minutes to hours to fully recover.

Gneralized seizures: Absense seizures :

Gneralized seizures: Absense seizures Absence seizures (formerly known as petit mal seizure). These seizures usually last from 2 to15 seconds and may occur just a few times a day, or more than 100 times in a single day. They usually present as blank staring, which one might mistake for daydreaming, physical automatisms, such as lip smacking, fumbling or picking at clothes, or twitching of facial or body muscles. Afterward, the person will likely have no memory of what happened while he or she had the seizure. A lot of people won’t recognize absence seizures as seizures. They occur mostly among children, starting between the age of 4 and 12. They rarely begin after age 20.

Partial seizures :

Partial seizures These are the most common type of seizures. They occur when only a part of one side of the brain is affected. With these seizures, the activity can start in one place in the brain, then move to another, or it could just stay in the one area. If the seizure happens in the brain’s speech area , a person’s ability to talk will be affected . Almost any sort of movement or feeling can be a part of a partial seizure. If the seizure starts off as a partial seizure, then spreads to include the entire brain, it’s referred to as a partial seizure secondarily

Partial Simple seizures :

Partial Simple seizures People RETAIN CONSCIOUSNESS during partial seizures. Sometimes they can even continue conversations through the seizure. They’ll USUALLY REMEMBER WHAT HAPPENED AFTER THE SEIZURE . For instance, they might twitch, roll their eyes, shake their hands or feet or blink rapidly. These movements might start slowly, then increase in rapidity or in the parts of the body involved. IF THEIR SENSES HAVE BEEN AFFECTED, THEY MIGHT HEAR, SMELL, TASTE, FEEL OR SEE SOMETHING THAT IS NOT ACTUALLY THERE.

Simple Partial seizures :

Simple Partial seizures They might feel a breeze when they’re indoors; hear hearing, buzzing or talking that isn’t happening; think something is narrower or wider—or closer or farther—than it is . They could even hallucinate something from their past.

Partial Complex seizures :

Partial Complex seizures People These seizures affect a greater part of the brain than simple partial seizures and they also affect consciousness. Although they can affect any part of the brain, they generally take place in one of the brain’s two temporal lobes. Because of this, people prone to complex partial seizures are often said to have temporal lobe epilepsy (TLE). Usually, when a person has a complex partial seizure, they’ll stop what they’re doing and stare blankly at nothing in particular. They’ll stop interacting with their environment and with other people. (During simple partial seizures they can interact with other people.)

Partial Complex seizures :

Partial Complex seizures They will then often start chewing, picking at their clothes, mumbling nothing in particular, performing repetitive motions, or any combination of these simple, unorganized movements. During complex partial seizures, people might appear conscious and normal because they’ll usually move about and remain standing with their eyes open—but they’ll be Experiencing an altered consciousness. In other words, it’ll be rather like they’re dreaming or in a trance and they won’t be able to respond appropriately to others

Few common causes of epilepsy:

Few common causes of epilepsy

Causes of epilepsy:

Causes of epilepsy

Causes of epilepsy:

Causes of epilepsy

Causes of epilepsy:

Causes of epilepsy

Causes of epilepsy:

Causes of epilepsy

Causes of epilepsy:

Causes of epilepsy

Causes of epilepsy:

Causes of epilepsy

General Approach for epilepsy treatment :

General Approach for epilepsy treatment The treatment of choice depends on the type of epilepsy and on drug-specific adverse effects and patient preferences. Begin with monotherapy ; about 50% to 70% of patients can be maintained on one antiepileptic drug (AED), but all are not seizure free. Up to 60% of patients with epilepsy are noncompliant, and this is the most common reason for treatment failure. Drug therapy may not be indicated in patients who have had only one seizure or those whose seizures have minimal impact on their lives. Patients who have had two or more seizures should generally be started on AEDs.

General Approach for epilepsy treatment :

General Approach for epilepsy treatment The treatment of choice depends on the type of epilepsy and on drug-specific adverse effects and patient preferences. Begin with monotherapy ; about 50% to 70% of patients can be maintained on one antiepileptic drug (AED), but all are not seizure free. Up to 60% of patients with epilepsy are noncompliant, and this is the most common reason for treatment failure. Drug therapy may not be indicated in patients who have had only one seizure or those whose seizures have minimal impact on their lives. Patients who have had two or more seizures should generally be started on AEDs.

General Approach for epilepsy treatment :

General Approach for epilepsy treatment Factors favoring successful withdrawal of AEDs include A SEIZURE-FREE PERIOD OF 2 TO 4 YEARS, COMPLETE SEIZURE CONTROL WITHIN 1 YEAR OF ONSET, AN ONSET OF SEIZURES AFTER AGE 2 YEARS AND BEFORE AGE 35 YEARS, AND A NORMAL EEG.

Withdrawal of AEDs:

Withdrawal of AEDs A 2-year, seizure-free period is suggested for absence and rolandic epilepsy , while a 4-year, seizure-free period is suggested for simple partial, CP, and absence associated with tonic- clonic seizures . According to the American Academy of Neurology guidelines , discontinuation of AEDs may be considered if the patient is seizure free for 2 to 5 years, if there is a single type of partial seizure or primary GTC seizures, if the neurologic examination and IQ are normal, and if the EEG normalized with treatment. AED withdrawal should always be done gradually.

Poor prognostic factors of epilepsy:

Poor prognostic factors of epilepsy A HISTORY OF A HIGH FREQUENCY OF SEIZURES, REPEATED EPISODES OF STATUS EPILEPTICUS, A COMBINATION OF SEIZURE TYPES, AND DEVELOPMENT OF ABNORMAL MENTAL FUNCTIONING.

NICE guidelines for epilepsy treatment :

NICE guidelines for epilepsy treatment The AED treatment strategy should be individualized according to the seizure type, epilepsy syndrome, co-medication and co-morbidity, the child, young person or adult's lifestyle, and the preferences of the person and their family and/or carers as appropriate. (2004) The diagnosis of epilepsy needs to be critically evaluated if events continue despite an optimal dose of a first-line AED. (2004) It is recommended that children, young people and adults should be treated with a single AED (monotherapy) wherever possible. If the initial treatment is unsuccessful, then monotherapy using another drug can be tried. (2004)

NICE guidelines for epilepsy treatment :

NICE guidelines for epilepsy treatment If an AED has failed because of adverse effects or continued seizures, a second drug should be started (which may be an alternative first-line or second-line drug) and built up to an adequate or maximum tolerated dose and then the first drug should be tapered off slowly. [2004] It is recommended that combination therapy (adjunctive or 'add-on' therapy) should only be considered when attempts at monotherapy with AEDs have not resulted in seizure freedom. If using carbamazepine, offer controlled-release carbamazepine preparations. [new 2012]. When prescribing sodium valproate to women and girls of present and future childbearing potential, discuss the possible risk of malformation and neurodevelopmental impairments in an unborn child, particularly with high doses of this AED or when using as part of polytherapy. [new 2012]

NICE guidelines for epilepsy treatment :

NICE guidelines for epilepsy treatment AED therapy should be considered and discussed with children, young people and adults and their family and/or carers as appropriate after a first unprovoked seizure if: the child, young person or adult has a neurological deficit the EEG shows unequivocal epileptic activity the child, young person or adult and/or their family and/or carers consider the risk of having a further seizure unacceptable brain imaging shows a structural abnormality. [2004]

Pharmacological treatment of FOCAL SEIZURES:

Pharmacological treatment of FOCAL SEIZURES Offer carbamazepine or lamotrigine as first-line treatment to children, young people and adults with newly diagnosed focal seizures. [new 2012] Offer levetiracetam, oxcarbazepine or sodium valproate if carbamazepine and lamotrigine are unsuitable or not tolerated carbamazepine and lamotrigine are unsuitable or not tolerated. If the first AED tried is ineffective, offer an alternative from these five AEDs . Be aware of the teratogenic risks of sodium valproate. [new 2012]. Consider adjunctive treatment if a second well-tolerated AED is ineffective

Pharmacological treatment of newly diagnosed GENERALISED TONIC–CLONIC (GTC) SEIZURES:

Pharmacological treatment of newly diagnosed GENERALISED TONIC–CLONIC (GTC) SEIZURES Offer sodium valproate as first-line treatment to children, young people and adults with newly diagnosed GTC seizures. Be aware of teratogenic risks of sodium valproate [new 2012]. Offer lamotrigine if sodium valproate is unsuitable . If the person has myoclonic seizures or is suspected of having juvenile myoclonic epilepsy (JME), be aware that lamotrigine may exacerbate myoclonic seizures. [new 2012]

Pharmacological treatment of ABSENCE SEIZURES:

Pharmacological treatment of ABSENCE SEIZURES Offer ethosuximide or sodium valproate as first-line treatment to children, young people and adults with absence seizures. If there is a high risk of GTC seizures, offer sodium valproate first, unless it is unsuitable. Be aware of teratogenic risks of sodium valproate [new 2012] Offer lamotrigine if ethosuximide and sodium valproate are unsuitable, ineffective or not tolerated. [new 2012] If two first-line AEDs are ineffective in children, young people and adults with absence seizures, consider a combination of two of these three AEDs as adjunctive treatment: ethosuximide, lamotrigine or sodium valproate. Do not offer carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin , tiagabine or vigabatrin . [new 2012]

Pharmacological treatment of MYOCLONIC SEIZURES:

Pharmacological treatment of MYOCLONIC SEIZURES Offer sodium valproate as first-line treatment to children, young people and adults with newly diagnosed myoclonic seizures, unless it is unsuitable. Be aware of teratogenic risks of sodium valproate . [new 2012]. Consider levetiracetam or topiramate if sodium valproate is unsuitable or not tolerated. Be aware that topiramate has a less favourable side-effect profile than levetiracetam and sodium valproate . [new 2012]. Do not offer carbamazepine, gabapentin, oxcarbazepine, phenytoin, pregabalin , tiagabine or vigabatrin . [new 2012]

Pharmacological treatment of TONIC OR ATONIC SEIZURES:

Pharmacological treatment of TONIC OR ATONIC SEIZURES Offer sodium valproate as first-line treatment to children, young people and adults with tonic or atonic seizures. Be aware of teratogenic risks of sodium valproate [new 2012]. Offer lamotrigine as adjunctive treatment to children, young people and adults with tonic or atonic seizures if first-line treatment with sodium valproate is ineffective or not tolerated. [new 2012]. Discuss with a tertiary epilepsy specialist if adjunctive treatment is ineffective or not tolerated. Other AEDs that may be considered by the tertiary epilepsy specialist are rufinamide and topiramate . [new 2012]. Do not offer carbamazepine, gabapentin, oxcarbazepine, pregabalin , tiagabine or vigabatrin . [new 2012]

Pharmacological treatment of INFANTILE SPASMS:

Pharmacological treatment of INFANTILE SPASMS Offer a steroid ( prednisolone or tetracosactide ) or vigabatrin as first-line treatment to infants with infantile spasms that are not due to tuberous sclerosis. Carefully consider the risk–benefit ratio when using vigabatrin or steroids. [new 2012] Offer vigabatrin as first-line treatment to infants with infantile spasms due to tuberous sclerosis . If vigabatrin is ineffective, offer a steroid ( prednisolone or tetracosactide . Carefully consider the risk–benefit ratio when using vigabatrin or steroids. [new 2012]

Indications for monitoring of AED blood levels:

Indications for monitoring of AED blood levels Detection of non-adherence to the prescribed medication Suspected toxicity Adjustment of phenytoin dose Management of pharmacokinetic interactions (for example, changes in Bioavailability, changes in elimination, and co-medication with interacting drugs) Specific clinical conditions, for example, status epilepticus, organ failure and certain situations in pregnancy. [2012]

Withdrawal of pharmacological treatment:

Withdrawal of pharmacological treatment Withdrawal of AEDs must be managed by, or be under the guidance of, the specialist. [2004]. The risks and benefits of continuing or withdrawing AED therapy should be discussed with children, young people and adults, and their families and/or carers as appropriate, who have been seizure free for at least 2 years. [2004] When AED treatment is being discontinued in a child, young person or adult who has been seizure free, it should be carried out slowly (at least 2–3 months) and one drug should be withdrawn at a time. [2004] Particular care should be taken when withdrawing benzodiazepines and barbiturates (may take up to 6 months or longer) because of the possibility of drug-related withdrawal symptoms and/or seizure recurrence . [2004]

Referral for complex or REFRACTORY EPILEPSY:

Referral for complex or REFRACTORY EPILEPSY If seizures are not controlled and/or there is diagnostic uncertainty or treatment failure, children, young people and adults should be referred to tertiary services soon for further assessment. Referral should be considered when one or more of the following criteria are present: The epilepsy is not controlled with medication within 2 years Management is unsuccessful after two drugs The child is aged under 2 years A child, young person or adult experiences, or is at risk of, unacceptable side effects from medication There is a unilateral structural lesion There is psychological and/or psychiatric co-morbidity There is diagnostic doubt as to the nature of the seizures and/or seizure syndrome. [2004]

PSYCHOLOGICAL INTERVENTIONS:

PSYCHOLOGICAL INTERVENTIONS Psychological interventions ( relaxation, cognitive behavior therapy, biofeedback ) may be used in conjunction with AED therapy in adults where either the person or the specialist considers seizure control to be inadequate with optimal AED therapy. This approach may be associated with an improved quality of life in some people. [2004] Psychological interventions (relaxation, cognitive behavior therapy) may be used in children and young people with drug-resistant focal epilepsy . [2004]

KETOGENIC DIET:

KETOGENIC DIET Refer children and young people with epilepsy whose seizures have not responded to appropriate AEDs to a tertiary paediatric epilepsy specialist for consideration of the use of a ketogenic diet. [new 2012].

VAGUS NERVE STIMULATION (VNS):

VAGUS NERVE STIMULATION (VNS) Vagus nerve stimulation is indicated for use as an adjunctive therapy in reducing the frequency of seizures in adults who are refractory to antiepileptic medication but who are not suitable for resective surgery. This includes adults whose epileptic disorder is dominated by focal seizures (with or without secondary generalisation ) or generalised seizures. [2004, amended 2012]

Prolonged or repeated seizures and CONVULSIVE STATUS EPILEPTICUS (treatment in the community):

Prolonged or repeated seizures and CONVULSIVE STATUS EPILEPTICUS (treatment in the community ) Give immediate emergency care and treatment to children, young people and adults who have prolonged (lasting 5 minutes or more) or repeated (three or more in an hour) convulsive seizures in the community . [2012] Only prescribe buccal midazolam or rectal diazepam for use in the community for children, young people and adults who have had a previous episode of prolonged or serial convulsive seizures. [new 2012] Administer buccal midazolam as first-line treatment in children, young people and adults with prolonged or repeated seizures in the community. Administer rectal diazepam if buccal midazolam is not available. If intravenous access is already established and resuscitation facilities are available, administer intravenous lorazepam. [new 2012]

Prolonged or repeated seizures and CONVULSIVE STATUS EPILEPTICUS (treatment in primary and secondary care):

Prolonged or repeated seizures and CONVULSIVE STATUS EPILEPTICUS (treatment in primary and secondary care ) Care must be taken to secure the child, young person or adult's airway and assess his or her respiratory and cardiac function. [2004] Depending on response to treatment, the person's situation and any personalised care plan, call an ambulance, particularly if : the seizure is continuing 5 minutes after the emergency medication has been administered the person has a history of frequent episodes of serial seizures or has convulsive status epilepticus, or this is the first episode requiring emergency treatment or there are concerns or difficulties monitoring the person's airway, breathing, circulation or other vital signs. [new 2012]

Prolonged or repeated seizures and CONVULSIVE STATUS EPILEPTICUS (treatment in the in hospital):

Prolonged or repeated seizures and CONVULSIVE STATUS EPILEPTICUS (treatment in the in hospital ) For children, young people and adults with ongoing generalized tonic– clonic seizures (convulsive status epilepticus) who are in hospital , immediately: SECURE AIRWAY GIVE HIGH-CONCENTRATION OXYGEN ASSESS CARDIAC AND RESPIRATORY FUNCTION CHECK BLOOD GLUCOSE LEVELS AND SECURE INTRAVENOUS ACCESS IN A LARGE VEIN .

Prolonged or repeated seizures and CONVULSIVE STATUS EPILEPTICUS (treatment in the in hospital):

Prolonged or repeated seizures and CONVULSIVE STATUS EPILEPTICUS (treatment in the in hospital ) Administer INTRAVENOUS LORAZEPAM as first-line treatment in hospital in children, young people and adults with ongoing generalized tonic– clonic seizures (convulsive status epilepticus). Administer intravenous diazepam if intravenous lorazepam is unavailable, or buccal midazolam if unable to secure immediate intravenous access . Administer a maximum of two doses of the first-line treatment (including pre-hospital treatment). If seizures continue, administer INTRAVENOUS PHENOBARBITAL or PHENYTOIN as second-line treatment in hospital in children, young people and adults with ongoing generalised tonic– clonic seizures (convulsive status epilepticus).

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