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Species

Dogs, cats and horses
Not limited

Seizures

Clinical manifestation of abnormal electrical activity in the brain

Epilepsy

Multiple seizures occurring over a prolonged period of time (two or more over a month or more)
Unpredictable and often violent seizures

Not all seizures involve

Convulsions

Convulsion

Abnormal violent and involuntary contraction or series of contractions of the muscles

Seizures associated with

Episodic high frequency discharge of impulses by a group of neurons
May spread to other parts of brain

Seizure clinical signs determined by

Brain location

EEG

Electroencephalography

Provoked or reactive seizures

Reaction of normal brain to intoxication, metabolic insult or short term illness

Cluster seizures

Two or more discrete seizures within 24 hours

Epilepsy types

Idiopathic or primary
Symptomatic

Epilepsy types characterized on

The basis of the seizure
Partial vs. generalized
simple vs. complex

Simple seizure

No loss of consciousness

Complex seizure

Loss on consciousness

Partial seizures

Localized

Generalized seizures

Involve the whole brain

Status epilepticus

Continuous seizure activity lasting more than 5 minutes or when the animal does not recovery fully between recurrent seizures

Common causes of epilepsy

Manifestation of underlying brain disorder
Idiopathic or secondary

Secondary epilepsy

Structural
Metabolic

Structural secondary epilepsy

Brain tumor
Encephalitis

Metabolic secondary epilepsy

Hepatic encephalopathy

Epileptogenesis

Facilitation of excitatory neurotransmission: Glutamate and aspartate
Reduction of inhibitory neurotransmission: GABA

Repeated seizure activity can lead to

Neuronal degeneration
Excitotoxicity

Treatment for cluster seizures and status epilepticus

Stop seizures, treat seizure associated problems
Attentive monitoring and nursing care

Seizure associated problems

Brain edema
Hyperthermia
Aspiration pneumonia
Disseminated intravascular coagulation
Permanent brain injury

Emergency treatment of seizures and epilepsy

Stimulation of GABA
GABA agonists
Inhibition of Na channels

Stimulation of GABA

Barbiturates
Benzodiazepines
Valproate

GABA agonists

Propofol
Etomidate

Inhibition of Na channels

(fos-)phenytoin (emergency and maintenance)
Carbamazepine
Valproate
Iamotrigine
Zonisamide

Inhibition of Ca channels

Gabapentin
Pregabalin
Valproate
Ethosuximide
Zonisamide

Other maintenance drugs

Potassium bromide
Vigabatrin
Valproate

Maintenance therapy for epilepsy

Stimulation of GABA
Inhibition of Na channels
Inhibition of Ca channels
Others

Drug of choice for seizures

Benzodiazepines

Benzodiazepines

Emergency treatment and maintenance
Diazepam, midazolam, clonazepam, lorazepam
Tolerance and cros tolerance

Benzodiazepines enhancement of GABAa activation

Increase in frequency of opening

Midazolam

More potent
Shorter half life

Clonazepam

Inhibition of T type calcium channels

Lorazepam

More potent
Longer half life
Short duration of action

Benzodiazepines side effects

Sedation
Withdrawal syndrome, exacerbation of seizures

Barbiturates

Treatment of acute seizures and maintenance therapy
Phenobarbital

Barbiturate of GABAa activation

Prolongs opening of chloride channel

Phenobarbital effective in

60-80% dogs

Barbiturate side effects

Autoinduction, CYP450 enzyme in liver
Sedation, polyphagia, PU/PD
Hepatotoxicity, minimal in cats

Potassium bromide

Initial seizure therapy and add on therapy
Glomerular filtration competes with chloride, tubular reabsorption: Long half life, needs loading dose

Potassium bromide mode of action

Competition with chloride
Hyperpolarization of neuronal membranes

Potassium bromide side effects

Bromism
Sedation
Ataxia
Pancreatitis
Pneumonitis in cats

Felbamate

Demonstrated efficacy for both local and generalized seizures

Felbamate mode of action

Blocking NMDA mediated neuronal excitation
Potentiation of GABA mediated neuronal inhibition
Inhibition of voltage sensitive neuronal sodium and calcium channel
Protects neurons from hypoxic or ischemic damage

Felbamate pharmacokinetics

Well absorbed after oral administration
Adults vs. puppies
Wide safety margin, infrequent toxicity, bone marrow suppression rare

Gabapentin and pregabalin

Structural analogue of GABA

Gabapentin and pregabalin mode of action

May enhance release of GABA
Binds to P/Q calcium channel

Binding to P/Q calcium channel

Reduced trafficking to plasma membrane of these channels
Reduces calcium entry into nerve terminals and release of neurotransmitters and modulators

Gabapentin and pregabalin absorption depends on

L amino acid carrier
Saturable process

Gabapentin and pregabalin pharmacokinetics

Relatively safe and free of side effects
Excreted unchanged in urine and 30-40% metabolized
Short half life

Pregabalin

More potent

Gabapentin and pregabalin administered

3-4 times daily
Not practical

Levetiracetam

Analogue of piracetam
Similar to brivaracetam but more potent

Levetiracetam mode of action

Binds to synaptic vesicle protein 2A
SV2A vesicle docking and fusion

Levetiracetam pharmacokinetics

Renal excretion

Zonisamide

Sulfonamide compound

Zonisamide mode of action

Inhibition of sodium and T type calcium channels
Free of major unwanted effects

Zonisamide pharmacokinetics

Long plasma half life
Partly excreted unchanged, partly glucuronidated

Valproate

Not related to any other anticonvulsant drug

Valproate mode of action

Multiple possible mechanisms
Weak inhibition of GABA transaminase
Some effect on sodium and T type calcium channels

Valproate limited use in vet med

Short half life
Used as multi-therapy
Vomiting reduced by concurrent food intake

(fos-) phenytoin mode of action

Use dependent block of sodium channels

(fos-) phenytoin pharmacokinetics

Well absorbed orally, highly plasma protein bound
Metabolized by mixed function oxidases, shows characteristics of saturation
Excreted as glucuronide
Causes enzyme induction

(fos-) phenytoin converted to

Pheytoin by phosphatases

Vigabatrin mode of action

Inhibition of GABA metabolizing enzyme GABA transaminase
Forms irreversible covalent bond, increases GABA content and release

Vigabatrin side effects

Peripheral visual field defect
Depression

Carbamazepine

Tricyclic antidepressant
Pharmacologically and clinically resembles phenytoin
Also used to treat neuropathic pain and manic depressive illness
Slow absorption, long half life
Hepatic metabolism, active metabolites
Strong inducer of hepatic enzymes

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