(LAB) Anti-Convulsant

Anti-Convulsant

• Also known as ANTIEPILEPTIC DRUGS, ANTISEIZURE DRUGS

• used in the treatment of seizure disorders, in particular grand mal, petit mal, and psychomotor seizures and other specialized seizure disorders such as tic douloureux (trigeminal neuralgia)

Anti-Convulsant

• Also used for treatment of bipolar disorder; act as mood stabilizers

• Used for treatment of neuropathic pain.

Anti-Convulsant

Goal: to suppress the rapid and excessive firing of neurons that start a seizure

Epilepsy

A chronic medical condition produced by sudden changes in the electrical function of the brain.

• Is defined as two or more than two unprovoked seizures occurring in an individual.

Epilepsy

Characterized by recurrent paroxysmal episodes of uncontrolled excitation of brain neurons.

Epilepsy

Causes:

head trauma,

meningitis,

childhood fevers,

brain tumor,

degenerative diseases of the cerebral circulation

Convulsion

A medical condition where **body muscles contract and relax rapidly and repeatedly**, resulting in an uncontrolled shaking of the body.

Seizure

Defined by a release of excessive and uncontrolled electrical activity in the brain.

Seizure

Can range from **tingling in a finger to grand mal** (generalized) seizures, during which people lose consciousness, become stiff, and jerk.

Seizure

NOT A DISEASE; THIS IS AN EVENT!!

Types of Seizures

Partial (focal/local) seizure

Generalized Seizure

Partial (focal/local) seizure

Simple partial (Jacksonian)

Complex partial (psychomotor)

With secondary generalization

Generalized Seizure

Clonic seizure

Atonic seizures

Myoclonic seizure

Photosensitive seizures

Tonic seizure

Absence seizure (Petit mal epilepsy)

Tonic-clonic seizures (Grand mal epilepsy)

Simple Partial Seizure

• Affects a small part of the brain.

• These seizures can cause twitching or a change in sensation, such as a strange taste or smell.

Simple Partial Seizure

• Seizures may be limited to a single limb or muscle group may show sequential involvement of body parts (epileptic march).

Simple Partial Seizure

• May have autonomic symptoms or signs such as epigastric sensations, sweating, papillary dilation.

• **Consciousness is not impaired**

Complex Partial Seizure

•The electrical discharge is **confined in certain parts of the temporal lobe** concerned with mood as well as muscle

Complex Partial Seizure

• May have autonomic activity such as pupil dilation and flushing

•**Consciousness is impaired** (lasting 30 seconds to 2 minutes).

Absence Seizures/Petit Mal Seizures

• Loss of consciousness without involving motor area

• MOST COMMON IN CHILDREN (4-12 yrs).

Typical absence seizures

nonconvulsive with muscle tone preserved; seizure usually lasts less than 10 seconds.

Atypical absence seizures

convulsive, longer in duration (up to 20 seconds), a change in muscle tone and movement is usually observed (smacking the lips or chewing movements, rubbing fingers together or making other hand motions, etc).

Myoclonic Seizures

Sudden and brief shock-like contraction which may involve the entire body or be confined to the face, trunk or extremities

Clonic Seizure

Repetitive jerking and twitching of the body extremities

Tonic Seizure

Muscles stiffen up, person loses consciousness, body grows rigid

Tonic-Clonic Seizures (Grand Mal Epilepsy)

• Generalized convulsion occurring in the tonic phase and the clonic phase.

Tonic-Clonic Seizures (Grand Mal Epilepsy)

• Loss of consciousness; sudden sharp tonic contractions of muscles, falling to ground, followed by clonic convulsive movements.

• Patient may bite his tongue & may lose control of his bladder or bowel.

Atonic Seizures/ Akinetic Seizures

Sudden lack of muscle tone (muscle is relax), causing the inability to sit and stand

Photosensitive Seizures

• These are very rare, even for people with epilepsy (

Mechanisms of Action

An effect mediated by promoting the inactivated state of voltage-activated Na+ channels by blocking those channels.

Mechanisms of Action

A second mechanism appears to involve enhanced gaminobutyric acid (GABA)- mediated synaptic inhibition

Mechanisms of Action

Limit activation of a particular voltage-activated Ca2+ channel known as the T current channels by blocking the channels.

Phenytoin

Brand name: Dilantin

Phenytoin

 Used for partial seizures & generalized tonic-clonic seizures

 NOT effective for absence seizures.

Phenytoin

 Also can be used for treatment of ventricular fibrillation

 Used as short-term prophylactic agent in brain injury to prevent loss of functional tissue.

Fosphenytoin

Injectable proform of Phenytoin

Phenytoin

 Well absorbed when given orally, however, it is also available as intravascularly. (For emergency)

 Approx. 90-95% protein bound

20 hours

Phenytoin Half-life

10-20 µg/ml

Therapeutic range Phenytoin

>20 µg/ml

Toxic level Phenytoin

Side effects Phenytoin Dose Related

GI upset, neurological (headache, vertigo, ataxia, diplopia, nystagmus), sedation

Side effects Phenytoin Non-Dose Related

gingival hyperplasia, hirsutism, megaloblastic anemia (folate deficiency), hypersensitivity reactions (mainly skin rashes and lesions, mouth ulcer), hepatitis, fetal malformations (cleft palate), bleeding disorders (in infants), impaired vitamin D metabolism leading to osteomalacia

Carbamazepine

 Brand name: Tegretol

Carbamazepine

 A Tricyclic compound that is commonly used for treatment of mania and trigeminal neuralgia.

Carbamazepine

 Less frequently used

 Available as an ORAL FORM ONLY

epioxide

Active form of CBZ

dihydroxide

Inactive form of CBZ

Carbamazepine

Excreted in urine as glucuronide conjugate

30 hours

Half-life Carbamazepine

4-12ug/ml

Therapeutic range Carbamazepine

Ethosuximide (Zarontin)

 Used for control of petit mal seizure and it is administered as an ORAL preparation.

Ethosuximide (Zarontin)

Drug of choice for petit mal seizures.

Valproic Acid

 Brand name: Sodium Valproate, Depakene, Depakote

Valproic Acid

 Very effective against absence seizure, myoclonic seizure, tonic-clonic seizure

Valproic Acid

 LESS EFFECTIVE as compared to carbamazepine for partial seizures.

 Like carbamazepine, it can also be used for treatment of mania.

Valproic Acid

 Available as CAPSULE, SYRUP, IV

 93% protein bound with HIGH ORAL BIOAVAILABILITY

Valproic Acid

 Inhibits metabolism of several drugs such as phenytoin, carbamazepine, topiramate and phenobarbital

 Excreted in urine (glucuronide)

15 hours

Half-life Valproic Acid

50-120ug/ml

Therapeutic range Valproic Acid

Side effects Valproic Acid

nausea, vomiting and GIT disturbances (start with low doses), increased appetite & weight gain, transient hair loss, hepatotoxicity, thrombocytopenia, neural tube defect (e.g. spina bifida) in the offspring of women, pancreatitis, hyperammonemia, hallucination

Phenobarbital

 Long-acting barbiturate that controls grand-mal tonicclonic seizure and focal epileptic

 NOT USED for Petit mal seizure

Primidone (Mysoline)

Inactive proform of Phenobarbital

Phenobarbital and Primidone

Both need to be measured to assess the total potential amount of phenobarbital in circulation.

Phenobarbital

 Oral absorption is SLOW BUT COMPLETE

 50% protein bound

 Eliminate primarily by hepatic metabolism

10 hours after an oral dose

Peak serum concentration Phenobarbital

70-100 hours

Serum half-life Phenobarbital

15- 30 ug/mL

Therapeutic range Phenobarbital

>40 ug/mL

Toxic level Phenobarbital

Oxcarbazepine

o safety profile similar to CBZ

o hyponatremia is also problem, however it is less likely to cause rash than CBZ.

Felbamate

 Orally administered drug

 Indicated in severe epilepsies such as children with the mixed seizure disorder Lennox-Gastaut syndrome and in adults with refractory epilepsy

1-4 hours

Peak serum concentrations Felbamate

14-22 hours in adults

Half-life Felbamate

30-60 ug/ml

Therapeutic range Felbamate

Side effects Felbamate

fatal aplastic anemia and hepatic failure

Gabapentin

 Chemically similar to neurotransmitter gamma aminobutyric acid (GABA)

Gabapentin

 Administered ORALLY in which it is reduced when antacids are administered concurrently.

5-9 hours

(patient with normal renal function) Half-life Gabapentin

12-20 ug/ml

Therapeutic range Gabapentin

Gabapentin

 May be the most likely treatment consideration in patients with liver disease and in treating partial-onset seizures in patient with acute intermittent porphyria.

Toxic effects Gabapentin

ataxia, somnolence (drowsiness)

Lamotrigine

 Orally administered

 Indicated in patients with partial and generalized seizures

 HEPATIC metabolism accounts for the majority of elimination

15-30 hours

Half-life Lamotrigine

2\.5-15 ug/ml

Therapeutic range Lamotrigine

Topiramate

 Nearly completely available after oral administration

 Majority is eliminated by RENAL filtration; the remainder is eliminated by hepatic metabolism

 Indicated in partial and generalized seizures.

1-4 hours

Peak concentration Topiramate

Tiagabine

 Approximately 96% protein bound

 Highly metabolized by the HEPATIC MIXED-FUNCTION OXIDASE PATHWAY

 Indicated in treating partial seizures

0\.5 - 2 hours

Peak Tiagabine

4 - 13 hours

Half-life Tiagabine

Side effects Tiagabine

symptoms of confusion, difficulty speaking clearly(stuttering), mild sedation, and a tingling sensation in the body’s extremities (paresthenia), especially in the hands and fingers.

Levetiracetam

 Orally administered

 Indicated in partial and generalized seizures

 Does not bind to serum proteins.

6 - 8 hours

Half-life Levetiracetam

8-26 ug/ml

Therapeutic range Levetiracetam

Oxcarbazepine

 Prodrug, almost immediately metabolized to licarbazepine

 Indicated for the monotherapy of partial seizures and in secondarily generalized tonic-clonic seizures.

 40% protein bound

 Metabolized in the LIVER

8 hours

Peak concentration Oxcarbazepine

8 - 10 hours

Half-life Oxcarbazepine

Zonisamide

 ORALLY administered

 Absorbed from the gastrointestinal tract on the order of 65% or higher

4 - 7 hours

Peak serum concentration Zonisamide

Zonisamide

 Accumulates extensive in erythrocytes

50 - 70 hours

Half-life Zonisamide

o May reduce to 23-35 hours when other enzymeinducing AEDs are being administered concurrently.

10-38 ug/ml.

Therapeutic range Zonisamide

Diagnostic and Treatment

• Electroencephalogram (EEG)

• Brain Scan

• Ketogenic Diet

• Vagus Nerve Stimulation

• Surgery