Anti Epileptic Drugs AEDs Flashcards
- Define an epileptic seizure (vet)
epileptic seizure is defined “a transient occurrence of signs due to abnormal excessive or synchronous simultaneous neuronal activity in the brain. It consists of 4 clinical phases
What are the epileptic phases/ components?
- Prodromal phase
- Aura
- Ictus
- Post ictal phase
Describe the epileptic clinical components/ phases
- Prodromal phase – before the seizure begins, the animal will exhibit behavioural changes such as whining and hiding. This phase may be hours to days before the seizure event itself.
- Aura – this phase is the first part of the seizure itself, and occurs hours to minutes before the seizure event. Odd behaviour such as pacing and barking, and autonomic signs such as salivating, may occur during this phase.
- Ictus – this is the seizure proper, consisting of involuntary muscle movements, twitches and changes in tone.
- Post-ictal phase – this phase follows the ictal phase, and consists of a period of time in which the animal may be disorientated, show changes in appetite, thirst and toileting behaviour and even experience neurological deficits.
What to remember when an owner comes in with dog that has had an epileptic fit?
- establish that the animal has indeed had an epileptic seizure, and not another non-epileptic episode such as vasovagal syncope.
- to be seizure must have the 4 phases
- often seizures are idopathic - we don’t know what caused them but there is an underlying disease often
Different types of seizure
- Isolated seizure = 1 seizure in 24 hours
- Cluster = 2 or more seizures within 24 hours
- Status epilepticus = seizures lasting over 5 minutes, or repeated seizures without returning to normal between them ☹ Either really long ictus that lasts more than 5 mins or lots of ictal episodes.
Localisation of seizures
• Epileptic seizures are by their very nature are always localised to the forebrain (the telencephalon and/or the diencephalon) – there can be no other source.
o Can be due to extracranial disease too! E.g. disease of liver toxins cross blood brain barrier
• They may be focal, localised, involving a specific site in the cerebrum, or
o If focal seizure depends on site e.g. motor cortex
• Generalised, involving the whole of both hemispheres.
o Frequently, generalised seizures result from the progression of a focal seizure
Aetiology of seizure
Many different aetiologies possible:
• Tumours
• Toxins
• Ion channel abnormalities (common genetic issue)
o Much more prevalent in pure breed
o Abnormal firing due to abnormal ion channels
MRI everything can look normal
SOO in essence they occur due to an imbalance of (EX) excitation and (insufficient) inhibition in the neurotransmission in the brain leading to excessive and, crucially, synchronous (simultaneous) depolarisation of enough neurones in the brain will lead to a seizure
What is the main excitatory NT in brain?
Main inhibitory NT in brain?
Therefore What is targeted in AEDS MOAs
3
- Glutamate is the main excitatory neurotransmitter and the brain
- GABA is the main inhibitory neurotransmitter.
- Transmission/ inhibition of the action potential depends on the correct functioning of ion channels, so it is logical that these three factors provide pharmacological targets for AEDs.
- Drugs which enhance the action of GABA
- Drugs which suppress the action of glutamate
- Drugs which modulate the movement of cations (Na+ and Ca2+)
Why treat seizure if won’t cure disease
- Well, damage to neural tissue can lead to epilepsy, but equally epileptic activity in the brain causes damage and leads to increased numbers of pacemaker cells (a process called kindling) and, hence, increased seizure activity.
- The more epileptic foci develop, the less successful drug treatment with AEDs is likely to be. It is clear, therefore, that if we can reduce or suppress seizure activity with AEDs we can reduce the progression of the clinical signs.
- Epileptic activity increased number of pacemaker cells recruited = kindling (damaged cells become foci of pace maker cells, increasing focus) SEIZURES BEGET SEIZURES
- More epileptic foci – less likely for treatment to work
- Become life threatening, cluster seizures and status epilepticus
Life threatening seizures and why LT
cluster seizures or status epilepticus (SE).
In SE:
• blood pressure and body temperature rise to dangerous levels, acidosis develops,
• prolonged seizure activity can lead to irreversible changes in the brain and eventually severe hypoglycaemia, organ failure and death.
Treatment AIM:
- reduce the frequency and severity of seizures
- minimise the side effects of drugs
- maximise the quality of life.
- An animal with 50% reduction or more in seizure activity is considered to have responded to treatment
- Only about two-thirds of treated animals respond, so good counselling and management of owner expectation is very important.
- Many animals will continue to have seizures on medication
Anti epileptic drugs MOA
The AEDS available at the mo have 3 main MOA
- Drugs which enhance the action of GABA
- Drugs which suppress the action of glutamate
- Drugs which modulate the movement of cations
Most of the drugs have more than 1 MOA
What to remember about AEDs and how to minimise side effects?
- drugs in use often have problematic pharmacokinetics
- Ideally, to minimise side effects, these would be used as single agents but many animals more than 1 AED therefore require carefully balanced combination therapy to manage their seizures adequately.
Why not use many of the human anti epileptic drugs?
Many drugs which are used for management of epilepsy in humans are not appropriate for use in veterinary species, because their pharmacokinetic properties and animal physiology render them either ineffective or unsafe in these species
List first line AEDs we use
- Phenobarbital (Epiphen ®)
- Potassium bromide (Libromide ®)
- Imepitoin (Pexion ®)
