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71 terms

Anticonvulsants

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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