Flashcards in Session 11 Deck (40):
What is epilepsy?
Episodic discharge of abnormal high frequency electrical activity in brain leading to seizure.
Describe the symptoms of partial seizures.
Involuntary motor disturbances, behavioural changes or an aura.
What are tonic-clonic seizures?
Body becomes rigid and patient commonly falls to the floor, tongue is bitten and incontinence of both urine and faeces. Clonic phase begins with generalised convulsions, frothing at the mouth and rhythmic jerking of muscles.
What are absence seizures?
Patient will stare, eyelids may twitch, and a few muscle jerks occur. Normal activity is resumed after an attack.
What are the differences between primary and secondary causes of epilepsy?
Primary: inherent tendency of an individual towards seizures, where there is no identifiable cause.
Secondary: consequence of a medical condition affecting the brain, e.g. vascular disease or tumours.
Give three other causes of seizures apart from epilepsy.
Brain disease, drugs, pyrexia, hypoglycaemia, infections, cerebrovascular accident, metabolic disturbances, provoked seizures.
What are the four causes of epilepsy?
1) increased excitatory activity
2) decreased inhibitory activity
3) loss of homeostatic control
4) spread of neuronal hyperactivity.
What are the epileptic targets for the treatment of epilepsy?
-Enhancement of GABA action
-Inhibition of sodium channel function
-Inhibition of calcium channel function
-Inhibition of glutamate release or function
How do benzodiazepines and valproate sodium work?
Act on GABA-agonists, hence opening chloride ion channels, increasing the threshold for an AP. Causing an inhibitory effect on neurones, reducing the likelihood of epileptic neuronal hyperactivity.
How do phenytoin, carbamezepine and lamotrigene work?
Bind to inactivated sodium channels, acting on the neurones causing the high-frequency discharge that occurs in an epileptic fit. Hence reduce the number of functional channels available to generate action potentials.
Used to treat generalised tonic-clonic and partial seizures. Can cause dizziness, drowsy, vomiting, bone marrow depression. Strong CYP450 inducer.
CYP450 inducer. Not used to treat absence seizures. Can cause dizziness, ataxia, nystagmus and nervousness.
Prolongs inactivation state of VGSCs. Used to treat partial and generalised seizures.
Enhances GABA-mediated inhibition. Used to treat partial, tonic-clonic and absence seizures. Can cause sedation, ataxia, tremor and weight gain.
Enhances the binding of GABA to chloride channels, increasing chloride current into the neurone, increasing threshold for an AP.
Give two ADRs of benzodiazepines.
Sedation, confusion, aggression, dependence, respiratory and CNS depression.
What must be considered when managing epilepsy in a pregnant women?
Increased risk of seizures if treatment is stopped.
Certain AEDs are associated with congenital malformations, especially valproate.
Lamotrigene is the safest.
Give folate supplements to reduce risk of neural tube defects.
What is the link between AEDs and contraception?
Failure rate times 4 with carbamezepine and phenytoin.
What is status epilepticus?
A single convulsion lasting more than 30 minutes, or convulsions occurring back to back with no recovery time between them.
What can uncontrolled convulsions lead to?
Hypoxia, physical injury, sudden death.
What is the treatment for status epilepticus?
Protect the airways, deliver oxygen, identify the cause and terminate the seizure. First line treatment is benzodiazepines, e.g. lorazepam IV. Then IV phenytoin. If still failing, ITU referral and paralysis and intubation required.
Give three causes of Parkinsonism
Drug induced, vascular, multiple systems atrophy, corticobasal degeneration, progressive supranuclear palsy.
What is idiopathic parkinson's disease?
Neurodegenerative disorder that has a progressive loss of dopaminergic neurones in the substantia nigra.
What is the classic triad of parkinsonism?
Tremor, rigidity and bradykinesia.
How does loss of dopaminergic neurones result in parkinsonism?
Causes reduced inhibition in the neostriatum, allowing increased production of ACh. Chain of abnormal signalling leads to impaired mobility.
What is multiple system atrophy?
Associated with degeneration of nerve cells in specific areas of the brain. Causes problems with movement, balance and autonomic functions.
What is Wilson's disease?
Accumulation of copper in the tissues, resulting in neurological and hepatic disease. Copper-dopamine complexes form, resulting in parkinsonism.
What is corticobasal degeneration?
Neurodegenerative disease involving the cerebral cortex and basal ganglia. Marked disorders in movement and cognitive dysfunction.
Describe dopamine synthesis.
L-tyrosine > L-DOPA > Dopamine.
How is dopamine degraded?
Via monoamine oxidase or catechol-O-methyl transferase enzyme.
Describe the function of L-DOPA.
L-dopa crosses the blood brain barrier, taken up by dopaminergic cells in the substantia nigra and converted to dopamine.
What is given alongside L-DOPA?
A peripheral DOPA decarboxylase inhibitor, to prevent peripheral breakdown. E.g. carbidopa.
Describe the role of dopamine receptor agonists?
Bind to dopamine receptor agonists directly to produce the required response. E.g. Apomorphine.
What are impulse control disorders?
Dopamine dysregulation syndrome, including:
-desire to increase dosage
-punding (collecting and organising things)
Describe the role of monoamine oxidase B inhibitors.
Enhances dopamine levels in the brain by preventing degredation. E.g. Rasagaline.
Describe the role of COMT inhibitors.
E.g. Entacapine. Reduces peripheral breakdown of L-DOPA.
Describe the role of anticholinergics in the management of parkinson's disease.
Antagonistic effect to dopamine. Able to treat tremors. Have no effect on bradykinesia.
What is myasthenia gravis?
Autoimmune condition, causing blockage/degredation of the nAChR at the NMJ by antibodies. Causes a fluctuating fatiguability in skeletal muscles, especially extraocular muscles.
How is myasthenia gravis treated?
Acetylcholinesterase inhibitors. However, an excess dose can cause a cholinergic crisis.