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EpilepsyPharmacotherape

utics III

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Definition0 Epilepsy is a brain disorder in which clusters of nerve cells, or

neurons, in the brain sometimes signal abnormally.

0 Neurons normally generate electrochemical impulses that act on other neurons, glands, and muscles to produce human thoughts, feelings, and actions.

0 In epilepsy, the normal pattern of neuronal activity becomes disturbed, causing strange sensations, emotions, and behavior, or sometimes convulsions, muscle spasms, and loss of consciousness.

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Epidemiology0 More than 2 million people in the United States -- about 1 in 100 --

have experienced an unprovoked seizure or been diagnosed with epilepsy.

0 For about 80 percent of those diagnosed with epilepsy, seizures can be controlled with modern medicines and surgical techniques.

0 However, about 25 to 30 percent of people with epilepsy will continue to experience seizures even with the best available treatment.

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Aetiology0 Epilepsy is a disorder with many possible causes. Anything that

disturbs the normal pattern of neuron activity -- from illness to brain damage to abnormal brain development -- can lead to seizures.

0 Epilepsy may develop because of an abnormality in brain wiring, an imbalance of nerve signaling chemicals called neurotransmitters, or some combination of these factors.

0 Researchers believe that some people with epilepsy have an abnormally high level of excitatory neurotransmitters that increase neuronal activity, while others have an abnormally low level of inhibitory neurotransmitters that decrease neuronal activity in the brain. Either situation can result in too much neuronal activity and cause epilepsy.

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Continuation………….0 Neurotransmitters that plays a role in epilepsy is GABA, or gamma-

aminobutyric acid, which is an inhibitory neurotransmitter.

0 In some cases, the brain's attempts to repair itself after a head injury, stroke, or other problem may inadvertently generate abnormal nerve connections that lead to epilepsy.

0 Abnormalities in brain wiring that occur during brain development also may disturb neuronal activity and lead to epilepsy.

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Continuation…………….0 The cause is unknown in 70% of cases0 Brain Trauma (ex. injury, stroke)0 Brain Lesions (ex. tumors)0 Poisoning (ex. lead)0 Infections of the brain (ex. meningitis, encephalitis, measles)0 Brain injury at birth0 Genetic causes0 Abnormal brain development0 Chronic alcohol/ drug abuse

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Classification0 There are many different types of seizures, some that affect the whole

brain (generalised) and some that affect part of the brain (partial).0 Common generalised seizures Tonic-clonic seizures (sometimes called grand mal) Absence seizures (sometimes called petit mal) Myoclonic seizures Atonic seziure Intractable seziure0 Common partial seizures Simple partial seizures Complex partial Secondary generalisation. Status epilepticus.

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Tonic-clonic seizures (sometimes called grand mal)

0 The person loses consciousness, goes stiff and falls to the ground. Sometimes they appear to cry out.

0 The skin (particularly around the mouth and under the finger nails) may appear blue in colour.

0 There can be loss of bladder or bowel control. The limbs jerk as the muscles contract and relax in quick succession.

0 The person may bite their tongue and the inside of their cheeks. Slowly they will regain consciousness, but may well be groggy or confused.

0 Very often, the person remains sleepy and may have a headache and aching limbs.

Tonic-clonic seziure

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Absence seizures (sometimes called petit mal)

0 During an absence seizure the person is momentarily unconscious.

0 It may appear that they are daydreaming or switching off. However, they are totally unaware of what is happening around them and they cannot be woken up.

0 Absence seizures are most common in childhood. Absence seizures usually begin between ages 4 and 14. The children who get them usually have normal development and intelligence.

0 And nearly 70% of cases, absence seizures stop by age 18. 

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Myoclonic seizures

0 These are sudden jerks.

0 They can affect the whole body, but are usually restricted to one or both arms and sometimes the head.

0 The person is not conscious, but the seizure is so brief that the person appears to remain fully conscious.

0  "Myo" means muscle and "clonus" (KLOH-nus) means rapidly alternating contraction and relaxation—jerking or twitching—of a muscle.

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Atonic seizures

0 Atonic seizures cause a sudden loss of muscle tone.0 Motor symptoms include head drops, loss of posture, or sudden

collapse.0 Because they occur without warning, atonic seizures can result in

injuries to the head and face. Protective headgear is sometimes used by children and adults.

0 Other names include drop attacks, astatic or akinetic seizures.

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Intractable Seizures

0 Seizures of any kind that do not respond to medications.

0 Twenty percent of people with epilepsy have seizures that are resistant to medication, otherwise known as refractory epilepsy.

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Simple partial seizures

0 The person remains fully conscious, but they are unable to stop or control the seizure.

0 Examples of symptoms are the movement of a limb; tingling; experiencing a non-existent smell or taste; going pale; sweating; or experiencing a churning feeling in the stomach.

0 Other symptoms can be feelings of fear, panic, sadness or happiness.

0 When seizures occur in the part of the brain responsible for vision, people can see flashing or balls of light, or experience temporary absence of vision.

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Complex partial

0 The person is only partly conscious and although it may appear that they are fully aware of what they are doing, this isn’t the case.

0 Examples of symptoms are chewing and swallowing, fumbling with buttons, repeatedly scratching the head or searching for an object. Some people may remove items of clothing.

0 Sometimes the seizures can involve complex body movements, apparently strange behaviour or actions of a sexual nature.

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Secondarily generalized

0 The generalized, convulsive phase of these seizures usually lasts no more than a few minutes, the same as primary generalized seizures.

0 The preceding partial seizure is usually not very long. Sometimes this part is so brief that it is hard to detect.

0 These seizures are called "secondarily generalized" because they only become generalized (spread to both sides of the brain) after the initial or "primary" event, a partial seizure, has already begun.

0 They happen when a burst of electrical activity in a limited area (the partial seizure)

spreads throughout the brain. Sometimes the person does not recall the first part of the seizure. These seizures occur in more than 30% of people with partial epilepsy.

They can affect people of all ages who have partial seizures.

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Status Epilepticus0 Most seizures end after a few minutes. If seizures are prolonged, or

occur in a series,there is an increased risk of status epilepticus, a true life threatening emergency.

0 Status epilepticus is usually defined as 30 minutes of uninterrupted seizure activity or repeat seizures without a return to consciousness.

0 The Epilepsy Foundation advises parents and the public to call for emergency assistance

0 when a convulsive seizure lasts for more than five minutes without signs of stopping,

or0 when successive seizures last more than five minutes without a

return to consciousness.

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Pathophysiology0 Nerve impulse propagates in the brain in a synchronous manner and for

that the electrical potential reaches to zero. Any type of process which damages or cause irritation to the grey matter of the brain may cause activation or inactivation of neurons causes by unknown mechanism.

0 This leads to sudden, excessive, synchronous discharge which results in an electrical potential. If the discharge remains localized it results in partial seizures or it may spread and involve the entire cerebrum causing generalized seizures.

0 Imbalance of excitatory transmitters such as G-amino butyric acid and selective central nervous system, calcium channel blockers may be involved in the seizure disorders.

 

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Continued…..0 The excessive neuronal disorderly discharge involving in the

entire brain results in loss of consciousness, disturbances in sensation and conclusive movements. After peak of seizures there is decrease in frequency of neuronal discharge. It leads to the end of seizures .

0 The seizure may be ending due to loss of cerebral energy reserves, local tissue anoxia, accumulation of toxic metabolites of neuronal metabolism and inhibitory neuronal feed back mechanisms.

 

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Signs and symptoms0 "Blackouts" or periods of confused memory0 Episodes of staring or unexplained periods of unresponsiveness0 Involuntary movement of arms and legs0 "Fainting spells" with incontinence or followed by excessive fatigue0 Odd sounds, distorted perceptions, or episodic feelings of fear that

cannot be explained. 0 Strange sensations0 Visual hallucinations0 Emotional changes0 Muscle spasms0 Convulsions0 Other symptoms, depending on where in the brain the seizures begin. 

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Diagnosis0 EEG0 MRI0 BLOOD TESTS

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Diagnosis0 An EEG, or electroencephalogram, is a test that can help diagnose 

epilepsy

0 During an EEG, the electrical signals of the brain are recorded. This electrical activity is detected by electrodes, or sensors, placed on the patient's scalp and transmitted to a machine that records the activity.

0 Electrical signals produced by the brain neurons are picked up by the electrodes and transmitted to a machine, where they produce separate graphs on moving paper recorded in ink or on a computer screen.

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Continued……0 CT and MRI scans reveal the structure of the brain, which can be useful for

identifying brain tumors, cysts, and other structural abnormalities. An adapted kind of MRI called functional MRI (fMRI) can be used to monitor the brain's activity and detect abnormalities .

0  SPECT (single photon emission computed tomography) is a relatively new kind of brain scan that is sometimes used to locate seizure foci in the brain.

0 Doctors may use an experimental type of brain scan called a magnetoencephalogram, or MEG.

0 MEG detects the magnetic signals generated by neurons to allow doctors to monitor brain activity at different points in the brain over time, revealing different brain functions.

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0 Doctors also are experimenting with brain scans called magnetic resonance spectroscopy (MRS) that can detect abnormalities in the brain's biochemical processes, and with near-infrared spectroscopy, a technique that can detect oxygen levels in brain tissue.

0 These blood samples are often screened for metabolic or genetic disorders that may be associated with the seizures. They also may be used to check for underlying problems such as infections, lead poisoning, anemia, and diabetes that may be causing or triggering the seizures.

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Non-pharmacological treatment

0 First Aid for Generalized Tonic-Clonic Seizures:0 Stay calm, note time seizure began and duration of event0 Lay person down and turn on left side0 Place something soft under head0 Clear objects away from jerking extremities0 Loosen tight clothing around the neck0 Protect head and remove glasses0 Do not restrain0 Provide privacy if possible0 Stay with the person until the seizure ends and a full return to

consciousness is observed

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Tonic-Clonic Seizure in a Wheelchair:

0 Do not remove from wheelchair unless absolutely necessary0 Secure wheelchair to prevent movement0 Fasten seatbelt (loosely) to prevent person from falling out of

wheelchair0 Protect and support head0 Ensure breathing is unobstructed and allow secretions to flow

from mouth0 Pad wheelchair to prevent injuries to limbs0 Follow relevant seizure first aid protocol

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Treatment (pharmacologically)0 Classification:

0 hydantoins : phenytoin

0 Barbiturates: phenobarbitone

0 Iminostilbene: carbamazepine

0 Succinimide: ethosuximide

0 GABA transaminase inhibitiors: valproic acid

0 Benzodiazepines: diazepam

0 GABA analouges: vigabatrin.

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Phenytion0 Mechanism of action blocks sodium channels in activated state blocks high frequency firing delays recovery of sodium channels from inactivation stabilizes the neuronal membrane inhibits generation of action potentials inhibits spread of seziures0 Adverse effects epigastric pain ataxia anorexia0 Drug interactions cimetidine and chlormphenicol inhibit metabolism of phenytoin.0 Dose 20mg/kg

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Carbamazepine0 It’s a tricyclic compound0 Commonly used as antiepileptic drugs0 Mechanism of action: similar to phenytion0 Useful in treating trigeminal neuralgia and glosso-pharyngeal

neuralgia0 Found to be beneficial in mood disorders and has mild anti diuretic

effects0 Adverse effects : vertigo ,blurring of vision ,dizziness.0 Dose : 200-400mg TDS0 Drug interaction : its an enzyme inducer enhance its own

metabolism and of other drugs like phenytoin , valproic acid.

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Ethosuximide 0 Its an succinimde

0 It raises the seizure threshold

0 Mechanism of action : it reduces the low threshold calcium currents (T-currents) in the thalamic neurons which are responsible for absence seziures.

0 Advrse effects: lethargy ,euphoria ,leukopenia , urticaria .

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Valproic acid0 It ‘s an salt of sodium valproate 0 Effective in antiepileptic drugs for absence , partial and generalised

seziures.0 Mechanism of action : increased synthesis of GABA by increased activity of GABA

synthesase enzyme decreasing the metabolism of GABA by inhibiting GABA

transaminase enzyme . blocks sodium channels decreases the low threshold calcium( t-currents in the

thalamus)0 Adverse effects: tremors ,rashes, alopecia.0 Drug interactions : it inhibits the clearance of lamotrigine

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0 Diazepam is a drug of choice in status epilepticus and febrile convulsions

0 Lorazepam may be used in place of diazepam dose : 0.1mg/kg IV

0 Clonazepam is a potent antiepileptic useful in absence and myoclonic seizures

0 Vigabatrine is an GABA analouge which acts by irreversibily inhibiting the enzyme GABA transminase thereby raising brain GABA levels

0 0 Lamotrigine is abroad spectrum antiepileptic activity . Prolongs

the activation of sodium channels and also inhibits the release of excitatory amino acids like glutamate dose:50-300mg/day

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