NEU 6 Flashcards
What are the different types of epileptic seizures?
- Focal (partial) epileptic seizure
- Generalised epileptic seizures (previously called primary generalised seizure)
- Focal seizure with secondary generalisation
Describe the sibdivisions of focal seizures
- Simple: animal usually alert and aware of its surroundings
- Complex: consciousness is altered, fly catching, aggression, running, resonant vocal sounds, crouching or hiding
What is meant by a focal seizure?
A seizure that presents with focal motor, autonomic or behavioural signs alone or in combination
Describe the stages of epileptic seizures in the dog.
- Prodome: subtle changes in behaviour (often overlooked, hours or days)
- Aura or preictus: anxiety, excitability, barking (seconds to minutes)
- Icuts or seizure stage: convulsions (clonic/tonic), loss of consciousness, urination, defecation, salivation (seconds to minutes)
- Postictus: exhaustion, also aggression or increasing appetite (minutes - days)
Describe the mechanisms by which anticonvulsants work
- Decrease excitation or increase inhibition
- Alter intinsic membrane properties (mostly Na+ channels)
- Increase inhibitory transmitter function (mostly GABA system)
- Decrease excitatoy transmitter function (glutamate system)
What drugs are primarily used in veterinary medicine to treat seizures?
- Benzodiazepines
- Barbiturates
- Imepitoin (pexion)
- Bromide
Describe how inhibitory function can be increased to treat seizures
- GABA receptor-Cl- channel complex binding sites, potentiates endogenous GABA (benzodiazepines, barbiturates)
- GABA transaminase inhibition, GABA build up
- Triggered GABA release from presynaptic terminal
- Ion competition with chloride for passage through Cl- channel, increased hyperpolarisation
- Partial agonists at GABA-A receptors (imepitoin)
Describe the mechanism of action of barbiturates
- Bind to GABA receptor Cl- channel complex
- Potentiate GABA
- Metabolised by liver, enzyme induction
- Long half life
- Phenobarbital is drug of choice in cats and dogs, less toxic than benzodiazepine
- Bind to sam receptor but different site as BZD do not need GABA, open channel, influx of Cl-
Describe the mechanism of action of benzodiazepines
- Bind to GABA-A receptors, facilitate endogenous GABA effects
- Also used for sedative-hypnotic, anxiolytic, muscle relaxant and appetite stimulant effects
- Metabolised by liver
- Can be quitte toxic in cats
- Diazepam
- Bind to binding site, agonist effect, facilitate effect and increase frequency of Cl- travel through channel = hyperpolarisation and inhibitory postsynaptic potential
Describe the mechanism of action of bromide as an anticonvulsant
- Competes with Cl- in Cl- channel
- Has more of a hyperpolarising effect than Cl-
- Distributed through body like Cl-
- Very long half life (2-3 months to steady state)
Describe the mechanism of action of imepitoin (pexion)
- Partial agonist
- Potentiates amplitude of GABA - evoked currents by acting at the benzodiazepines recognition site of the GABA-A receptor
- Low affinity partial agonist with low intrinsic activity
- Binds to same site and receptor as a BZD but is not one
List the drugs that can be used to treat anxiety behaviours
- Benzodiazepines
- Tricyclic antidepressants
- Selective Serotonin Uptake Inhibitors (SSRIs)
- Monoamine oxidase inhibitors (MAOIs, not first choice as anxiolytic drug)
- Azapirones
Describe the mechanism of action of benzodiazepines as an anxiolytic drug
- Activate specific benzodiazepine receptor that facilitates inhibitory GABAergic
transmission - Amygdala has BZD receptors
- Reduce anxiety and agression
- Some memory impairment
- Dependence is a problem (need to reduce dose slowly)
Describe the mechanism of tricyclic antidepressants as anxiolytic drugs
- Enhance functioanl acitivity of norepinephrine and serotonin
- Block reuptake of both NTs
- Treat separation anxiety
- Increase availability of serotonin and NE
- Serotonin associated with mood, NE associated with activity
Describe the mechanism of action of selective serotonin reuptake inhibitors (SSRIs) as anxiolytic drugs
- Block reuptake of serotonin
- So increases its functional activity
- Adaptive changes in pre- and postsynaptic receptors (1-4 weeks for benefit), postsynaptic side more receptors and higher affinity for serotonin
Describe the mechanism of action of monoamine oxidase inhibitors as anxiolytic drugs
- Not first choice as anxiolytic drugs
- Enhance functional activity of norepinephrine, serotonin, dopamine
- Inhibit degredation of NTs by monoamine oxidase
Describe the mechanism of action of azapirones as anxiolytic drugs
- Activate a specific serotonin receptor
What is canine cognitive disorder?
- Similar to Alzheimer’s
- Can be summarised by DISH: disorientation, interaction changes, sleep changes, house soiling
Which drug can be used to treat canine cognitive disorder and give its mechanism of action?
- Segeline
- MAOI
- Irreversibe
- Greater affinity for MAO-B (dopamine is the substrate) than MAO-A
- Selectivity not absolute
- Species variations in dopamine metabolism
- Allows more dopamine to be available for release
List some common side effects of anxiolytic drugs
- Sedation
- Appetite changes
- Diarrhoea
- Vomiting
- Anorexia
List the common side effects of selegiline
- Restlessness
- Agitation
- Vomiting
- Disorientation
- Diarrhoea
- Nausea
- Diminished hearing
List the common side effects of anticonvulsants
- Sedation
- Nystagmus
- Ataxia
- Polydipsia
- Polyphagia
- CV and respiratory depression
- Gastric irritation
What does ARAS stand for?
Ascending activating reticular system
Describe the reticular formation
- Consists of network of grey and white matter
- Deep thoruhgout brainstem thoruhg pons, midbrain and diencephalon
- Continuous with similar system in spinal cord located deeply around grey matter
- Phylogenetically older region of the brain
- Can be divided into 2 functional divisions: ascending and descending