Nervous System Flashcards
What are some of the different types of dementia?
- Alzheimer’s
- Parkinson’s-associated dementia
- Lewy-body dementia
- Vascular dementia
What symptoms does dementia cause?
Cognitive symptoms:
- Memory loss
- Difficulty thinking
- Language issues
- Loss of orientation
Non-cognitive symptoms:
- Psychiatric and behavioural problems
- Difficulties with daily activities
How is Alzheimer’s disease managed?
For cognitive symptoms
If mild-moderate disease:
Acetycholinesterase inhibitors
If moderate-severe disease:
NMDA glutamate receptor antagonist
What acetylcholinesterase inhibitors are available?
- Donepezil
- Galantamine
- Rivastigmine (used in Parkinson’s associated dementia)
What side-effects are associated with each of the acetylcholinesterase inhibitors?
- Donepezil - neuroleptic malignant syndrome (risk associated with concomitant antipsychotics)
- Galantamine - serious skin reactions, e.g. SJS. Should be stopped at first appearance of skin rash
- Rivastigmine - GI disturbances (withhold until resolved). Transdermal application associated with reduced side-effects.
What side-effects are all of the acetylcholinesterase inhibitors associated with?
Cholinergic side-effects (parasympathomimetics):
DUMB BELS
D = Diarrhoea U = Urination M = Muscle weakness / cramps / miosis B = bronchospasm
B = Bradycardia E = Emesis L = Lacrimation (teary eyes) S = Salivation / sweating
How are non-cognitive symptoms of dementia managed?
1) Antipsychotics - only for severe symptoms causing significant distress or if there’s an immediate risk to self or others.
MHRA states increased risk of stroke and death with antipsychotic use in elderly patents with dementia.
For extreme violence, aggression and extreme agitation, oral benzodiazepines or antipsychotics may be used. If IM needed: haloperidol / olanzapine / lorazepam can be used.
What is epliepsy?
A sudden surge of electrical activity of neurones in the brain. This causes seizures.
What can cause non-epileptic seizures?
- Organic factors, e.g. hypoglycaemia / fever
- Psychogenic, i.e. mental or emotional processes.
True or False - Most AED’s are given BD.
True.
Exceptions: phenobarbital, lamotrigine, perampanel and phenytoin.
What are the common AED’s?
- Phenobarbital
- Carbamazepine
- Gabapentin
- Pregabalin
- Lamotrigine
- Levetiracetam
- Phenytoin
- Sodium valproate
- Topiramate
What are the treatment options for focal seizures?
1st Line:
Lamotrigine / Carbamazepine
Alternatives:
Levetiracetam / Valproate / Oxcarbazepine
What are the treatment options for tonic-clonic seizures?
1st Line:
Valproate / Lamotrigine / Carbamazepine
What are the treatment options for absence seizures?
1st Line:
Ethosuxiumide / Valproate (high risk of tonic-clonic)
Alternative:
Lamotrigine
What are the treatment options for myoclonic seizures?
1st Line:
Valproate
Alternatives:
Topiramate / Levetiracetam
What are the treatment options for atonic / tonic seizures?
Valproate
Which AED’s are advised to be maintained on same brand?
Category 1:
- Carbamazepine
- Phenytoin
- Phenobarbital
- Primidone
Category 2: Based on judgement & patient consultation - Valproate - Lamotrigine - Clonazepam - Topiramate
Why should AED’s be withdrawn gradually?
Abrupt withdrawal can precipitate severe rebound seizures.
How should AED’s be withdrawn?
Gradually under specialist supervision. 1 AED should be withdrawn at a time if the patient is on combination therapy.
True or False - Patients with epilepsy are never allowed to drive? Explain.
False.
Patients will only ever be able to drive a car.
Patients need to be seizure free for at least 1 year.
Patients will be banned from driving when:
- Medication is being changed / withdrawn
- 6 months after last dose
- 6 months after 1st unprovoked seizure
Can AED’s be used in pregnancy?
Ideally no due to risk of teratogenicity.
Valproate - congenital malformations and long-term developmental disorders.
Increased risk of teratogenicity with carbamazepine, phenytoin, phenobarbital, primidone and lamotrigine.
Cleft palate risk with topiramate use in 1st trimester.
True or False - There’s an increased risk of suicidal thoughts and behaviour in patients taking AED’s.
True - symptoms can occur within 1 week of starting. Patients should report any mood changes, distressing thoughts or feelings about suicide or self-harm.
Side-effects of AED’s.
Skin Rashes
- Lamotrigine - SJS, toxic epidermal necrolysis. Higher risk with high initial dose, rapid dose increase and use of valproate.
Blood Dyscrasias
- Report any signs of infection, bruising or bleeding.
Eye Problems
- Vigabatrin - visual field defects.
- Topiramate - acute myopia with secondary ACG.
Encephalopathic Symptoms
- Vagabatrin - marked sedation, stupor and confusion with slow wave EEG.
Which AED’s are CYP450 inhibitors or inducers?
Inhibitors:
-Sodium valproate
Inducers:
- Carbamazepine
- Phenytoin
- Phenobarbital
What is the mechanism of action of phenytoin?
Binds to neuronal sodium channels in their inactive state which prolongs activity.
True or False - Phenytoin can be used in absence and myoclonic seizures.
False - they exacerbate these types of seizures and should be avoided.
What is the therapeutic range for phenytoin?
10-20mg/L
Is phenytoin highly or lowly protein-bound?
Highly protein-bound.
What are the signs of phenytoin toxicity?
SNAtCHeD
S = Slurred speech N = Nystagmus At = Ataxia C = Confusion H = Hyperglycaemia D = Double + blurred vision
True or False = Phenytoin base and sodium are not equivalent.
True:
100mg sodium = 92mg base
What are the side-effects of phenytoin?
- Change in appearance
- Blood dyscrasias
- Hypersensitivity
- Rashes
- Low Vitamin D levels
- Hepatotoxicity
- Suicidal ideation
- Bradycardia & hypotension (IV use)
What are the common phenytoin drug interactions?
Phenytoin Toxicity
- Amiodarone
- Azoles
- Chloramphenicol
- Metronidazole
- Clarithromycin
- SSRI’s
- Valproate
Therapeutic Failure
- St. John’s wort
- Rifampicin
Anticonvulsant effect antagonised
- Quinolones
- Tramadol
- SSRI’s
- Antipsychotics
Increased antifolate effect
- Methotrexate
- Trimethoprim
Reduces concentration of:
- Hormonal contraceptives
- Warfarin
- Corticosteroids
- Thyroid hormones
What is the mechanism of action of carbamazepine?
Inhibits neuronal sodium channels, stabilises membrane potential and reduces neuronal excitability.
What seizures may the use of carbamazepine exacerbate?
- Atonic
- Clonic
- Myoclonic
What is the therapeutic range of carbamazepine? When are levels monitored?
4-12mg/L
Measured after 1-2 weeks.
What are the signs of carbamazepine toxicity?
i HANDBAG
i = In-coordination H = HypOnatraemia A = Ataxia N = Nystagmus D = Drowsiness B = Blurred and double vision A = Arrythmias G = GI disturbance
What are the side-effects of carbamazepine?
- Blood dyscrasias
- Hepatotoxiucity
- Hypersensitivity
- Rashs
- HypOnatraemia
Dose-limiting side-effects include:
Headache, ataxia, drowsiness, N&V, blurred vision, unsteadiness and allergic reactions.
True or False - MR preparations of carbamazepine reduce the risk of side-effects.
True.
What are the main interactions for carbamazepine?
Toxicity:
- Macrolides
- Fluoxetine
- Miconazole
Therapeutic Failure:
- St. John’s wort
- Phenytoin
Anticonvulsant effect antagonised:
- Quinolones
- SSRI’s
- Antipsychotics
- TCA’s
HypOnatraemia:
- Diuretics
- SSRI’s / TCA’s
- NSAIDs
Hepatotoxicity
- Tetracyclines
- Sulfasalazine
- Sodium valproate
- Methotrexate
- Statins
- Fluconazole
- Alcohol
Reduces concentration of:
- Warfarin
- Hormonal contraceptives
What is the mechanism of action of sodium valproate?
Weak inhibitor of neuronal sodium channels, stabilises RMP and reduces neuronal excitability.
What are the side-effects of sodium valproate?
- Hepatotoxicity - discontinue if abnormally prolonged PTT.
- Blood dyscrasias
- Pancreatitis
What are the main interactions of sodium valproate?
Anticonvulsant effect antagonised:
- Quinolones
- SSRI’s/TCA’s
- Antipsychotics
Hepatotoxicity:
- Statins
- Carbamazepine
- Tetracyclines
- Fluconazole
- Methotrexate
- Sulfasalazine
Increases concentration of:
- Other AED’s, e.g. lamotrigine
What is status epilepticus?
Epileptic fits one after the other without regaining consciousness.
What is the management of convulsive status epilepticus?
IV lorazepam
Why should IV diazepam be avoided in convulsive status epilepticus?
Causes thrombophlebitis.
What is the management of non-convulsive status epilepticus?
If incomplete LOC:
Continue / restart usual AED.
Complete LOC / failure to respond to AED:
As convulsive status epilepticus.
What is the management of febrile convulsions?
Paracetamol
If >5 minutes, treat as status epilepticus.
How would status epilepticus be treated in the community?
PR diazepam
Oromucosal midazolam
Repeated once after 10-15 minutes if necessary.
What are the psychological symptoms of anxiety?
- Restlessness
- Worry
- Fear
- Difficulty concentrating
- Irritability
What are the physical symptoms of anxiety?
- Palpitations
- Muscle aches and tension
- Trembling or shaking
- Excessive sweating
- SOB
- Insomnia
What treatment options are available for anxiety treatment?
- Benzodiazepines
- Beta-blockers (for autonomic symptoms)
- Buspirorone
- Antidepressants
- Antipsychotics
What is the mechanism of action of benzodiazepines?
Facilitate and enhance the binding of GABA to GABA receptors to cause widespread depressant effect on synaptic neurotransmission.
What clinical effect do benzodiazepines cause?
- Anxiolysis
- Sedation
- Muscle relaxation
- Anticonvulsant effects
Which benzodiazepines are short-acting and which are long-acting?
Short-acting:
- Lorazepam
- Oxazepam
Long-acting:
- Alprazolam
- Clobazam
- Diazepam
In the elderly, which type of benzodiazepine should be used?
Short-acting
In anxiety, how long should benzodiazepines be used for?
Short-term (2-4 weeks) in severe, disabling anxiety causing patient unacceptable distress.
What are the main side-effects of benzodiazepines?
- Paradoxical increase in hostility aggression
- Overdose (ataxia, drowsiness, dysarthria, nystagmus)
- Sedation
- Dependence - avoid long-term use and avoid abrupt withdrawal.
What are the symptoms of benzodiazepine dependence?
Psychosis, confusion, convulsion and delirium tremens-like symptoms.
What are the symptoms of benzodiazepine withdrawal?
When dose it occur?
How is it managed?
Increased anxiety, insomnia, weight loss, tremors, sweating, loss of appetite, perceptual disorders, tinnitus.
Occurs with 1 day of stopping a short-acting benzo, or 3 weeks of stopping a long-acting benzo.
- Gradually convert (over 1 week) to equivalent diazepam dose ON.
- Reduce diazepam dose by 1-2mg increments every 2-4 weeks.
- Reduce diazepam dose further.
What are the main interactions for benzodiazepines?
Increased sedation and CNS depressant effects:
- Alcohol
- Opioids
- Antihistamines
- Antidepressants
- Barbiturates
Increased plasma concentrations
- Amiodarone
- Diltiazem
- Macrolides
- Fluconazole
What are the main symptoms of ADHD?
Hyperactivity
Impulsivity
Inattention
What is the treatment for ADHD?
Children
1st-Line:
Methylphenidate
2nd-Line:
Lisdexamfetamine
Alternatives:
Atomoxetine / Guanfacine
Adults
1st-Line: Methylphenidate / Lisdexamfetamine
2nd-Line: Atomoxetine
What is the mechanism of action of methylphenidate?
Potent CNS stimulant
Increases dopamine and NA in the brain.
What are the side-effects of methylphenidate?
- Appetite loss
- Insomnia
- Weight loss
- Increased HR and BP
- Tics and Tourette’s syndrome
- Growth restriction in children (allow children catch-up drug-free periods)
Monitor for psychiatric symptoms.
CI for methylphenidate
- CVD
- Hyperthyroidism
- Severe HTN
- Uncontrolled bipolar
- Severe depression
What is the mechanism of action of amfetamines?
Potent CNS stimulant.
Increases dopamine and NA levels in the brain.
What are the side-effects of amfetamines?
- Appetite loss
- Anorexia
- Increased HR and BP
- Tics and Tourette’s syndrome
- Growth restriction in children (allow children catch-up drug-free periods)
What are the symptoms of amfetamine overdose?
- Wakefulness
- Hyperactivity
- Paranoia
- Hallucinations and HTN
Followed by
- Exhaustion
- Convulsions
- Hyperthermia
- Coma
CI of amfetamines
- CVD
- Hyperthyroidism
- Moderate/severe HTN
- Agitated states
What is the mechanism of action of atomoxetine?
NA re-uptake inhibitor - increases levels of NA at synaptic cleft.
What are the side-effects of atomoxetine?
- Suicical ideation
- Hepatotoxicity
- QT prolongation
What monitoring is required for atomoxetine use?
- Pulse & BP
- Psychiatric symptoms
- Appetite, weight and height
At the start of treatment and every 6 months, or following a dose change.
