Antiepileptic drugs

Types of epilepsy (reading only)

1- Partial Seizures ( Focal Seizures ) 2- Generalized Seizures
- NO loss of conscious Tonic clonic - loss of consciousness - tonic spasm (1 min) clonic jerking
Simple - Clonic jerking of single limb or a muscle group lasting for about 2 min. seizures - Flaccid relaxation - confusion & fatigue - sleep
partial - there maybe some sensory disturbances. Absence - there is brief loss of consciousness lasting only for 10 to 15 sec. with mild or no motor
seizures disturbances.
Complex - there is brief loss of consciousness followed by amnesia.
partial - Purposeless movements & sensory hallucinations. Myoclonic - NO loss of conscious
seizures - Short jerking of the whole body or one of the extremities.
Partial with Partial seizures that is followed immediately by generalized attack due to spread of discharge.
secondarily Atonic
- Sudden loss of posture tone Fall.
seizures seizures

3- Status Epilepticus
Epilepticus - Severe sustained seizures without period or recovery. - It occurs in all types of epilepsy especially if treatment is irregular or suddenly stopped.

Mechanism of action of antiepileptic drugs Drug Choice

- First choice: Carbamazapine & Phenytoin
Tonic clonic
- Alternative : Valproate.
seizures
Drugs that are effective in seizure reduction accomplish this by - Phenobarbital & primidone (Barbiturates)
variety of mechanisms: - First choice: Carbamazapine & Phenytoin
Simple partial - Alternative : Valproate - Lamotrigine , Vigabatrin , Gabapentin ( mono or add on )
1- blockade of voltage-gated channels (Na+ or Ca2+), - Phenobarbital & primidone
2- enhancement of inhibitory GABAergic impulses, - First choice: Ethosuximide
3- interference with excitatory glutamate transmission. Absence seizures - Alternative : Valproat - Lamotrigine - clonazepam
- Acetazolamide.
The antiepilepsy drugs suppress seizures but do not recur or prevent - Mixed :
Absence seizures + Tonic clonic - First choice: Valproate
epilepsy. - Alternative : clonazepam
- Myoclonic seizures

Status Epilepticus Diazepam – clonazepam – Phenytoin – Phenobarbiton - Paraldehyde

Antiepileptic Drugs
Phenytoin Carbamazepine Barbiturates & Benzodiazepines
- Normal concentration of drug : (check Ahmados sedatives & hypnotics papers)
It blocks voltage-gated sodium channels by selectively binding
to the channel in the inactive state thereby inhibiting the
generation of repetitive action potentials in the epileptic focus The primary mechanism of action is the enhancement of
and preventing their spread. Mechanism like phenytoin inhibitory effects of GABA-mediated neurons, via
increase the frequency of chloride channel opening by
- At very high concentrations, binding to the GABAA receptor.
phenytoin can block voltage-dependent calcium channels and
interfere with the release of monoaminergic neurotransmitters. Diazepam, and lorazepam are most often used as an therapy for :
1- myoclonic 2- partial 3- generalized tonic-clonic seizures.

Side effects Side effects Side effects

- Depression of the CNS occurs particularly in the cerebellum
and vestibular system, causing : - nystagmus , ataxia - Rash - Anorexia
- peripheral neuropathies - osteoporosis. - Nystagmus - anti-diuretic
- confusion & Hallucinations. - Hepatotoxicity. - Ataxia - Hepatitis
- Teratogenic - Bone marrow inhibition (check Ahmados sedatives & hypnotics papers)
- Hormones: release of A.D.H & insulin (hyperglycemia)
- Hirsutism. - Teratogenic.
Fosphenytoin Oxcarbazepine
It is a prodrug and is rapidly converted to phenytoin in It is a prodrug that is rapidly reduced to the 10-monohydroxy
the blood, providing high levels of phenytoin within min. (MHD) MHD blocks sodium channels preventing the spread of
the abnormal discharge producing anticonvulsant activity.

Phernytoin , Carbamazepine & Barbiturates 1-Hepatic microsomal enzyme inducer (drug interactions) 2-Treat Tonic clonic & partial seizures 3-wosens Absence

Ethosuximide Divalproex Acetazolamide

It blocks T-type calcium channels so, reduces Divalproex sodium is a combination of: It's carbonic anhydrase inhibitor Increase CO2
propagation of abnormal electrical activity in the brain sodium valproate + valproic acid & Acidosis decrease CNS excitability
and is reduced to valproate when it reaches the gastrointestinal tract.
It is effective in treating only primary generalized
absence seizures. Usefula in Absence seizures
- Proposed mechanisms of action include:
1-sodium channel blockade,
Side effects 2- blockade of GABA transaminase, Side effects
- CNS Drowsiness , Lethargy , behavioral changes 3- action at the T-type calcium channels. - Hypokalemia - alkaline urine
- GIT upset - Sedation - acidosis
These many mechanisms provide a broad spectrum of activity
- Allergy against seizures.

Trimethadione Side effects

- GI distress,
- hepatotoxicity due to formation of toxic metabolite,
Mechanism like Ethosuximide - pancreatitis
Side effects - alopecia,
- tremor,
- CNS Drowsiness , Lethargy , behavioral changes - Photosensitivity
- GIT upset - Hepatic microsomal enzyme inhibitor.
- Allergy
- Hepatotoxicity – Nephrotoxicity – Bone marrow depression

New Anti-Epileptic Drugs

Lamotrigine
The drug blocks :
1- sodium channels
2- voltage dependent
calcium channels.
Topiramate
1- It blocks sodium channels;
2- The primary mechanism of
action is the enhancement of
inhibitory effects of GABA-
mediated neurons
3- antagonize the excitatory
transmitters e.g: glutamate .
Felbamate
1- It blocks sodium channels;
2- The primary mechanism of
action is the enhancement of
inhibitory effects of GABA-
mediated neurons
3- antagonize the excitatory
transmitters e.g: glutamate
Gabapentin Tiagabin Vigabatrin
Tiagabine blocks GABA uptake
Gabapentin is an analog of GABA. It's irreversible inhibitor of
into presynaptic neurons,
GABA transaminase
permitting more GABA to be
It increases the release of resulting in increase the GABA
available for receptor binding
GABA
thus, enhanced inhibitory
activity.

Side effect : Side effect : Side effect : Side effect : Side effect : Side effect :
Rash - Dermatits Sedation - confusion Fatal aplastic anemia Sedation - ataxia tiredness, dizziness, GIT upset. Depression - Psychosis