Neuropharmacology Flashcards
What is epilepsy characterised by?
Recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge.
How can we classify epilesp?
- Idiopathic
- Structural
What are the 3 possible causes of idiopathic epilepsy?
- Proven genetic background
- Suspected genetic background
- Unknown cause and no indication of structural epilepsy
What are the 2 causes of structural epilepsy?
- Epilepsy caused by identified cerebral pathology
- Unknown cause
Name the 3 types of epileptic seizures
- Focal epileptic seizure (partial)
- Generalized epileptic seizures (primary generalized seizure)
- Focal epileptic seizure evolving to become generalized (focal seizure with secondary generalization)
What is causing the seizures in idiopathic seizures?
There is no disease in the brain but the epileptic seizures are caused by a functional problem (chemical unbalance between excitatory and inhibitory messengers of the brain).
What causes the seizures with structural epilepsy?
The epileptic seizures are a sign of a disease in the brain. This disease might be a brain tumour, an inflammation or infection of the brain (encephalitis), a brain malformation, a recent or previous stroke or head trauma. Diagnosis of secondary epilepsy is based on looking for brain disease using MRI or CT-scan of the brain and CSF analysis.
How will a focal epileptic seizure present?
Will present with focal motor, autonomic or behavioural signs alone or in combination.
Fly catching
How were focal seizures once divided?
Simple: partial seizures the dog is usually alert and aware of its surroundings.
Complex: consciousness is altered, fly catching, aggression, running, resonant vocal sounds, crouching or hiding.
What is a Generalized epileptic seizure?
How do they present?
An epileptic seizure with clinical signs indicating activity involving both cerebral hemispheres from the start.
In dogs and cats the seizure presents predominantly as immediate ‘convulsions’ and loss of consciousness. Salivation, urination and/or defecation often also occur during convulsions.
What are the stages of clonic tonic convulsions?
What happens in each stage?
–Prodome : subtle changes in behaviour (often overseen; hours – days)
–(aura) or preictus: anxiety, excitability, barking; seconds - minutes
–ictus or seizure stage : convulsions (clonic – tonic), loss of consciousness, urination, defecation, salivation; seconds – minutes; > 30 minutes = status
–postictus: exhaustion, also aggression or increasing appetite: minutes - days
How many of seizures in dogs are of the generalized tonic clonic type?
80%
Name a breed prediposed to generalized tonic seizures (2)
- Poodle
- Dachsund
What happens when seizures begin in a dog?
The dog stiffens and falls; they then begin jerking movements
They are not in pain during the seizure and cannot control their bladder or bowels.
What is status epilepticus?
Continuous seizure activity lasting >5 minutes
Or
Two or more discrete seizures with incomplete recovery of consciousness between them for 30 minutes
What is a cluster seizure?
Two or more seizures occur in 24 hours, separated by normal interictal periods
Anticonvulsant Therapy:
A) What is the goal?
B) What normally happens?
A) Eradication of all seizure activity
B) Reduction of severity, frequency and duration of seizures
When would we do acute Anticonvulsant Therapy?
- Status epilepticus
- Cluster seizures
- Seziures resulting from toxins
When would we use chronic Anticonvulsant Therapy?
- Epilepsy
- Adjunctive in animal with brain disease
What is selection of Antiepileptic drugs (AED) based on?
- Efficacy
- Pharmacokinetic properties
Adverse effects
Name 3 occasions we start anti-convulsant therapy (4)
- Identifiable structural lesion present or prior history of brain disease or injury;
- Acute repetitive seizures or, status epilepticus (ictal event ≥5 minutes or ≥3 or more;
- Generalized seizures within a 24‐hour period); ≥2 or more seizure events within a 6‐month period;
- Prolonged, severe, or unusual postictal periods
How do drugs of NMDA and GABA A receptors work?
Both receptors are multimeric ligand-gated ion channels. Drugs can act as agonists or antagonists at the neurotransmitter receptor site or at modulatory sites associated with the receptor. They can also act to block the ion channel at one or more distinct sites. In the case of the GABA-A receptor, the mechanism by which ‘channel modulators’ (e.g. ethanol, anesthetic agents) facilitate channel opening is uncertain; they may affect both ligand binding and channel sites. The location of the different binding sites shown in the figure is largely imaginary, although study of mutated receptors is beginning to reveal where they actually reside.
What are the clinical applications of phenobarbital?
Broad-spectrum anticonvulsant in dogs and cats,
effective at subhypnotic doses
What is the mechanism of action of Phenobarbital (Phenobarbitone)?
- increasing the activity of the inhibitory neurotransmitter GABA
- interaction with glutamate receptors to reduce neuronal excitotoxicity?
• inhibition of voltage-gated calcium channels
(= reduced excitation)
