Anticonvulsants, Anti-seizure, Antiepileptic

the individual episode; caused by excessive and/or synchronous electrical activity of neurons in the brain

Seizure

the brain disease causing a persistent tendency to have recurrent, unprovoked seizures

Epilepsy

Epilepsy is the underlying chronic brain disorder, not the?

individual seizure episode

Focal seizure also known as?

Partial or localized seizure

Begins in a localized area of one cerebral hemisphere.

Focal seizure

Initially localized or asymmetrical motor, autonomic, or behavioral signs.

Focal seizure

Simple focal also known as?

Simple partial; cortical focal

Focal seizure without apparent impairment of consciousness.

Simple focal

Animal remains responsive; localized facial, eyelid, ear, or limb twitching may occur.

Simple focal

Complex focal also known as?

Complex partial; psychomotor

Focal seizure with altered awareness or responsiveness.

Complex focal

Staring, confusion, fly-biting, repetitive chewing, sudden fear, aggression, or abnormal behavior.

Complex focal

Involves both cerebral hemispheres from the beginning.

Generalized seizure

Bilateral, usually symmetrical signs; loss of consciousness is common in convulsive forms.

Generalized seizure

Tonic-clonic also known as?

Grand mal

Generalized seizure with tonic and clonic phases.

Tonic-clonic

Initial whole-body rigidity followed by rhythmic paddling or jerking.

Tonic-clonic

Generalized seizure with sustained ↑ muscle tone

Tonic

Body and limbs become stiff or rigid without prominent rhythmic jerking

Tonic

Generalized seizure with repetitive muscle contraction and relaxation.

Clonic

Bilateral rhythmic jerking or paddling without a prolonged rigid phase

Clonic

Generalized seizure with brief, shock-like muscle contractions.

Myoclonic

Sudden, very brief muscle jerks; consciousness may be retained.

Myoclonic

Atonic also known as?

Drop attack

Generalized seizure with sudden loss of muscle tone

Atonic

Animal suddenly becomes limp, buckles, or collapses.

Atonic

Absence also known as?

Petit mal; absence-like seizure

Brief generalized nonconvulsive seizure with impaired awareness.

Absence

Sudden staring or pause in activity without prominent collapse or paddling.

Absence

Idiopathic epilepsy also known as?

Primary epilepsy

Recurrent unprovoked seizures without an identified structural or reactive cause

Idiopathic epilepsy

Idiopathic epilepsy may be ________ or ___________

genetic or presumed genetic

Animal is generally neurologically normal between seizures.

Idiopathic epilepsy

Symptomatic epilepsy also known as?

Secondary or structural epilepsy

Epilepsy caused by an identifiable brain lesion or disease.

Symptomatic epilepsy

Symptomatic epilepsy may have persistent?

neurological abnormalities

Symptomatic epilepsy possible causes

• brain tumors,

• inflammation,

• trauma,

• congenital disease.

Cluster seizures also known as?

Serial seizures

More than two self-limiting seizures within 24 hours.

Cluster seizures

Recovery or partial recovery occurs between individual seizures.

Cluster seizures

Continuous seizure activity lasting more than 5 minutes

Status epilepticus

Status epilepticus are repeated seizures without?

without recovery between episodes

Persistent seizure activity; life-threatening emergency requiring immediate treatment.

Status epilepticus

Causes of seizure

• ↑ Excitation (Glutamate/ACh) → Seizure

• ↓ Inhibition (GABA) → Seizure

• Channel/Pump dysfunction → Seizure

• ↑ K⁺ or ↓ Ca²⁺ → Seizure

What happens in increased excitatory neurotransmission?

↑ Glutamate and/or acetylcholine release.

What happens in decreased inhibitory neurotransmission?

↓ GABA release.

What happens when GABA-mediated Cl⁻ influx is impaired?

↓ Hyperpolarization

Barbiturates

• Phenobarbital

• Mephobarbital

• Pentobarbital

Broad-spectrum, first-line maintenance anticonvulsant in dogs and cats.

Phenobarbital

Phenobarbital is a first line maintenance of?

anticonvulsant in dogs and cats.

Phenobarbital serious effects

• hepatotoxicity

• rarely, bone marrow dyscrasia.

Disruption/discontinue of phenobarbital will cause?

rebound seizures/status epilepticus

Metabolized in the liver to phenobarbital

Mephobarbital

Pentobarbital is effective against?

Refractory status epilepticus

Deoxybarbiturates example

Primidone

Metabolized in the liver → Phenobarbital + PEMA → Phenobarbital enhances GABA-A receptor activity

Primidone

PEMA

phenylethylmalonamide

Phenobarbital is responsible for most of the?

Anticonvulsant effect

Also inhibit repetitive firing through voltage-gated Na⁺ channels.

Primidone

Primidone is not recommended to which animal?

Cats

Primidone is no longer recommended for?

routine veterinary seizure management (phenobarbital yes)

Hydantoins

• Phenytoin

• Mephenytoin

• Fosphenytoin

blockade of voltage-gated sodium channels

Phenytoin

Phenytoin is not effective for?

absence seizures

Adverse effect of phenytoin

gingival hyperplasia and hepatotoxicity

Metabolized to the active metabolite nirvanol.

Mephenytoin

A water-soluble prodrug of phenytoin

Fosphenytoin

Fosphenytoin route of admin

IV administration and causes less local irritation than injectable phenytoin

Fosphenytoin is effective against?

Status epilepticus in dogs

Effective for persistent generalized seizure activity after inadequate response to initial treatment

Fosphenytoin

Benzodiazepines’ broad spectrum

Diazepam

Benzodiazepines

• Diazepam

• Clonazepam

• Clorazepate

Prodrug → converted to nordiazepam

Clorazepate

Aliphatic Carboxylic Acids

Valproic Acid and Sodium Valproate

Blocking voltage-gated Na⁺ channel → ↓ repetitive firing

Valproic Acid and Sodium Valproate

↑ GABA synthesis and ↓ GABA degradation → ↑ CNS GABA concentration

Valproic Acid and Sodium Valproate

Valproic Acid and Sodium Valproate blocks which channel?

Blocking T-type Ca²⁺ channels

Valproic Acid and Sodium Valproate is effective in which seizures

• Focal seizures

• Generalized tonic–clonic seizures

• Myoclonic seizures

• ABSENCE SEIZURES

Valproic Acid and Sodium Valproate’s adverse effect

hepatotoxicity

Bromides

• Potassium Bromide

• Sodium Bromide

Bromide ions compete with chloride ions and pass through GABA-A chloride channels, causing neuronal hyperpolarization.

Potassium Bromide

Succinimides

Ethosuximide

T-Type Calcium Channel Blockade

Ethosuximide

Ethosuximide specific seizure type

Absence seizures

May help control distemper-associated myoclonus or reflex spasms in dogs

Ethosuximide

Ethosuximide is not effective for?

generalized tonic-clonic convulsions

GABA Analogues

• Gabapentin

• Pregabalin

• Vigabatrin

Gabapentin binds to?

alpha-2-delta-1 subunit of voltagegated calcium channels

Binds to the alpha-2-delta-1 subunit of voltagegated calcium channels → ↓ Ca²⁺ entry → ↓ release of glutamate and other excitatory neurotransmitters.

Gabapentin

Gabapentin is more commonly used for?

neuropathic pain than for epilepsy

Similar to gabapentin

Pregabalin

Irreversibly inhibits GABA transaminase → ↓ GABA breakdown → ↑ synaptic GABA → ↑ neuronal inhibition.

Vigabatrin

Vigabatrin irreversibly inhibits ____________

inhibits GABA transaminase

Dicarbamates

Felbamate

3 MOA of Felbamate

• Blocks NMDA receptors,

• inhibits voltage-gated Na⁺ channels,

• enhances GABA-A receptors.

Felbamate is mainly an adjunct for?

drug-resistant epilepsy

Sulfonamides

Zonisamide

Sodium channel blockade & Calcium channel blockade

Zonisamide

Pyrrolidines

Levetiracetam

Levetiracetam binds to?

SV2A vesicle proteins