CPT S11 - Neurological Disorders Flashcards
What are the two types of seizure?
Partial (AKA focal)
Generalised
Describe a partial seizure
Can be defined as simple or complex, based on the level of consciousness
Can escalate to generalised
What is the pathological process of epilepsy?
Loss of excitatory:inhibitory homeostasis
Increased discharges in focal cortical area
What are the symptoms of partial seizures?
Depends on the area affected Can include; -Involuntary motor disturbance -Behavioural change -"Aura"
Describe generalised seizures
Generated centrally and spread through both hemispheres
Loss of consciousness
Many types
What are the main sub-categories of generalised seizures?
Tonic-clonic (Grand mal)
Absence (Petit mal)
What is status epilepticus?
Prolonged seizure (>5 minutes) or a series of seizures without a recovery interval
Medical emergency
Can lead to death or brain damage
Can occur for any type of epilepsy
What are the dangers of epilepsy?
Physical injury relating to a fall Hypoxia SUDEP Brain damage/dysfunction Cognitive impairment Psychiatric disease ADRs Stigma Loss of livelihood (lorry drivers etc)
What is the cause of epilepsy?
Primary; -No identifiable cause Secondary; -Medical conditions affecting the brain -Vascular disease -Tumours
What can precipitate seizures?
Sensory stimli (strobes)
Brain disease/trauma (stroke, drugs, alcohol)
Metabolic disturbances (hypo/hyperglycaemia)
Infections (infantile febrile convulsions)
Therapeutics
Give some therapeutic targets for epilepsy
Voltage-gated sodium channels
GABA-mediated inhibition
What is the mechanism of action of VGSC blockers in epilepsy?
Can only access binding site during depolarisation
Prolongs inactivation state
So help return rapid discharge rate to normal
Give some examples of VGSC blockers used in epilepsy
Carbamazepine
Phenytoin
Lamotrigine
Give some ADRs for carbamazepine
CNS; -Dizziness -Drowsiness -Ataxia -Motor disturbance -Numbness -Tingling GI; -Upset -Vomiting CV; -BP variation Other; -Rash -Hyponatraemia -Neutropenia (rare)
Give some DDIs for carbamazepine
CYP450 inducer so many many
Basically just check BNF because if they take anything at all it probably interferes
What types of epilepsy may be treated with carbamazepine?
Generalised tonic-clonic
Partial
Give some ADRs for phenytoin
CNS; -Dizziness -Ataxia -Headache -Nystagmus -Nervousness Other; -Gingival hyperplasia -Rash -Stevens Johnson hypersensitivity reaction
Give some DDIs for phenytoin
Another CYP inducer, though not of itself
Therefore many interactions
BNF this because so many
What is the most dangerous thing about phenytoin?
Has zero-order kinetics at therapeutic range
Must monitor free plasma concentration
What types of epilepsy may be treated with phenytoin?
Generalised tonic-clonic
Partial
Give some ADRs for lamotrigine
Less than other VGSC blockers CNS; -Dizziness -Ataxia -Somnolence Other; -Rashes NB - increased ADR profile in children
Give some DDIs for lamotrigine
Not a CYP inducer so fewer than other VGSC blockers
Oral contraceptives reduce LTG plasma concentration
Valproate increases LTG plasma concentration due to competitive binding
Give some examples of GABA enhancing drugs used in epilepsy
Sodium Valproate
Benzodiazepines
What are the ways in which the actions of GABA may be enhanced?
Inhibition of GABA inactivation
Inhibition of GABA re-uptake
Stimulation of GABA synthesis
Give some ADRs for sodium valproate
Generally milder than other AEDs CNS; -Sedation -Ataxia -Tremor Hepatic; -Increased transaminases -Failure
Give some DDIs for valproate
Again, check BNF
Many drugs antagonise its effects esp the psychoactive ones
Crazy shenanigans can occur when combined with other AEDs
What types of epilepsy may be treated with valproate?
Partial
Generalised (both tonic-clonic and absence)
Give some ADRs for benzodiazepines
CNS; -Sedation -Confusion -Impaired coordination -Aggression -Tolerance -Withdrawal seizures Other; -Respiratory depression -CNS depression
Give some DDIs for benzodiazepines in epilepsy
Very few
May even be used as an adjunct
What types of epilepsy may benzodiazepines be used to treat?
Lorazepam and diazepam are used in status epilepticus
Clonazepam may be used for absence seizures in the short term
What are the basic rules of prescribing AEDs?
Aim for monotherapy
ITU sedation is an option in status
Must keep patients under review
Always check the BNF
Are AEDs safe in pregnancy?
No
Must balance risk of teratogenicity and status epilepticus
What needs to be done if a patient is in status epilepticus?
ABC Exclude hypoglycaemia Give lorazepam IV if possible Give PR if not possible Can give phenytoin IV if unsuccessful If still unsuccessful, send to ITU, ventilate, sedate and paralyse
What are the motor features of parkinsons?
Tremor
Rigidity
Bradykinesia
Postural instability
What are some non-motor symptoms of parkinsons?
Mood changes Pain Cognitive change Urinary symptoms Sleep disorder Sweating
What are causes or parkinsonism?
Parkinsons Disease Drug-induced parkinsonism Vascular parkinsonism Progressive supranuclear palsy Multiple systems atrophy Corticobasal degeneration
How is PD differentiated from other causes of parkinsonisms?
Response to treatment
Structural neuroimaging normal
Functional neuroimaging
Describe the pathology of PD
Loss of dopaminergic neurones in the substantia nigra results in reduced inhibition in neostriatum
Reduced inhibition allows increased ACh production
Chain of abnormal signalling leads to impaired mobility
What are the types of treatment in PD?
Symptomatic relief;
- Movement disorders
- Non-motor features
- Neuroprotection
- Surgery
What drug classes are used in PD?
L-DOPA Dopamine receptor antagonisrs MAOI type B inhibitors COMT inhibitors Anticholinergics Amantidine
What are the ADRs of L-DOPA?
Nausea/anorexia (interferes with vomiting centres)
Hypotension (central and peripheral interference)
Psychosis (schizophrenia-like)
Tachycardia
What are the benefits of L-DOPA?
Highly efficacious
Low side-effect profile if taken with a peripheral DOPA-decarboxylase inhibitor eg co-careldopa
What are the disadvantages of L-DOPA?
It's a precursor so requires enzyme conversion Long term loss of efficacy as destruction of dopaminergic neurones continues Causes involuntary movement Motor complications including; -On/off function between doses -Dystonia -Dyskinesia -Freezing
Give some examples of dopamine receptor antagonists
Ergot; -Pergolide -Bromocryptine Non-ergot; -Ropinirole -Pramipexole
Give some dopamine receptor agonist advantages
Direct acting
Fewer dyskinesias and motor complications
Possible neuroprotection
Give some disadvantages of dopamine receptor agonists
Less efficacious than L-DOPA
Impulse control disorders
More psychiatric ADRs (these are dose-limiting)
Expensive
What are impulse control disorders?
Also called dopamine dysregulation syndrome Pathological gambling Hypersexuality Compulsive shopping Desire to increase dosage
Give some dopamine receptor agonist ADRs
Sedation Hallucinations Confusion Nausea Hypotension
What is the action and mechanism of Catechol-O-methyl Transferase (COMT) Inhibitors in PD treatment?
Reduces the peripheral breakdown of L-DOPA to 3-O-methyldopa and so enhances the actions of L-DOPA within the CNS
What is the action of MAO B Inhibitors in PD?
MAO B metabolises dopamine
Inhibition potentiates it
What is the role of anticholinergics in the treatment of PD?
Minor
Treats tremor
No effect on bradykinesia
Significant side effects
What is the role of Amantidine in the treatment of PD?
Poorly effective
Uncertain mechanism
Few side effects
What are the main symptoms of myasthenia gravis?
Fluctuation Fatiguable Weakness Commonly; -Extraoccular muscles -Bulbar involvement -Limb weakness -Respiratory muscle involvement
Give examples of drugs which can exacerbate myasthenia gravis
Aminoglycosides
Beta blockers
ACEi
Basically anything affecting neuromuscular transmission
What are the complications of myasthenia gravis?
Acute exacerbation (myasthenic crisis) Overtreatment (cholinergic crisis)
