BASIC - NEUROLOGY

Question 1

Indications of carbamazepines?

Answer 1

• Epilepsy – 1st line for focal seizures and primary generalised tonic-clonic seizures
• Trigeminal neuralgia - 1st line to control pain and reduce frequency/severity
• Bipolar disorder - option

Question 2

Mechanism of carbamazepines?

Answer 2

• Inhibit neuronal sodium channels, stabilising resting membranes potentials and reducing neuronal excitability
• Inhibit spread of seizure activity in epilepsy

Question 3

Side effects of carbamazepines?

Answer 3

• N&V
• Dizziness and ataxia
• Oedema & hyponatraemia
• Bone marrow suppression (agranulocytosis)
• Hypersensitivity – 10% (Mild maculopapular skin rash)
• Antiepileptic hypersensitivity syndrome – 1 in 5000, mortality 10%

Question 4

Contraindications of carbamazepines?

Answer 4

• AV conduction abnormalities (unless paced)
• History of bone marrow depression
• Prior antiepileptic hypersensitivity syndrome

Question 5

Cautions of carbamazepines?

Answer 5

• Pregnancy – need high dose folic acid

- Cardiac, hepatic and renal disease

Question 6

Interactions of carbamazepines?

Answer 6

• Induces CYP450 enzymes
• Metabolised by CYP450 enzymes
• Efficacy reduced by drugs that lower seizure threshold
  o SSRIs, TCAs, antipsychotics and tramadol

Question 7

Dosing of carbamazepines?

Answer 7

• Oral or rectal only
• Started at low dose (100-200mg OD/BD) and increased gradually to maximum of 1.6g/day
• Treatment must be withdrawn gradually over at least 4 weeks – seizure recurrence risk

Question 8

Communication to patient of carbamazepines?

Answer 8

• Must not drive until seizure free for 12 months

- Cannot drive 6 months after changing or stopping treatment

Question 9

Monitoring of carbamazepines?

Answer 9

• Report any unusual symptoms
• Plasma concentration for response (4-12mg/litre) measured after 2 weeks
• FBC, U&Es, LFTS may be beneficial

Question 10

Indications of phenytoin?

Answer 10

• Control seizures in status epilepticus when benzodiazepines are ineffective
• Reduce frequency of focal or generalised seizures in epilepsy (if other drugs not suitable)

Question 11

Mechanism of phenytoin?

Answer 11

• Bind to neuronal sodium channels in inactive state, prolonging inactivity and preventing Na influx
• Prevents drift of membrane potential from resting to threshold value
• Reducing neuronal excitability
• Inhibit spread of seizure activity in epilepsy
• Similar effect seen in Purkinje fibres – account for antiarrhythmic and cardiotoxic effects
• Low therapeutic index

Question 12

Side effects of phenytoin?

Answer 12

• Long-term – skin coarsening, acne, hirsutism and gum hypertrophy
• Cerebellar toxcitiy (ataxia, nystagmus, discoordination), impaired cognition
• Haematological disorders (folic acid metabolism)
• Osteomalacia (vitamin D metabolism)
• Hypersensitivity and Antiepileptic hypersensitivity syndrome – 1 in 5000, mortality 10%

Question 13

Contraindications of phenytoin?

Answer 13

• 2nd and 3rd degree heart block

- Sinus bradycardia

Question 14

Cautions of phenytoin?

Answer 14

• Dose reduction in hepatic impairment

- Pregnancy – need high dose folic acid (foetal hydantoin syndrome – craniofacial abnormalities and reduced IQ)

Question 15

Interactions of phenytoin?

Answer 15

• Induces CYP450 enzymes
• Metabolised by CYP450 enzymes
• Efficacy reduced by drugs that lower seizure threshold
  o SSRIs, TCAs, antipsychotics and tramadol

Question 16

Dosing of phenytoin?

Answer 16

• Status epilepticus – IV loading dose 20mg/kg (max 2g), followed by maintenance dose 100mg 6-8 hourly
• Chronic epilepsy – 150-300mg daily
• Treatment must be withdrawn gradually

Question 17

Communication to patient of phenytoin?

Answer 17

• Must not drive until seizure free for 12 months

- Cannot drive 6 months after changing or stopping treatment

Question 18

Monitoring of phenytoin?

Answer 18

• Recommends FBC before treatment
• Plasma phenytoin concentrations measured immediately before next dose (10-20mg/L) – if needed, make small change to dose
• After dose change, wait 7 days before repeating blood tests
• Monitor BP, ECG during IV treatment

Question 19

Indications of sodium valproate?

Answer 19

• Epilepsy – 1st choice in generalised or absence seizures and option in focal
• Bipolar disorder – Option for acute treatment of manic episodes and prophylaxis against recurrence

Question 20

MEchanism of sodium valproate?

Answer 20

• Weak inhibitor of neuronal Na channels, stabilising resting membrane potentials and reducing neuronal excitability
• Increases content of GABA, principal inhibitory neurotransmitter

Question 21

Side effects of sodium valproate?

Answer 21

• Nausea, gastric irritation and diarrhoea
• Tremor, ataxia
• Behavioural disturbances
• Thrombocytopenia
• Transient rise in liver enzymes
• Hypersensitivity reactions
  o Hair loss – regrowth curlier than original hair
• Rare – pancreatitis, hepatic dysfnction, bone marrow failure, antiepileptic hypersensitivity syndrome

Question 22

Contraindications of sodium valproate?

Answer 22

o Suspected mitochondrial disorder

o Personal or family history of hepatic dysfunction

Question 23

Cautions of sodium valproate?

Answer 23

• Avoid in women of child-bearing age (particularly first trimester and conception)
  o Teratogenic - risk of foetal abnormalities
  o Only used if on contraception and other treatment not suitable
• Avoid in hepatic impairment
• Dose reduction in severe renal impairment

Question 24

Interactions of sodium valproate?

Answer 24

• Inhibits CYP450 enzymes
• Metabolised by CYP450
• Efficacy reduced by drugs that lower seizure threshold
  o SSRIs, TCAs, antipsychotics and tramadol

Question 25

Dosing of sodium valproate?

Answer 25

- Sodium valproate – prescribed for epilepsy – 600mg - Valproic acid – used in bipolar disorders – 750mg - Withdraw over 4 weeks gradually

Question 26

Communication to patient of sodium valproate?

Answer 26

- Must not drive until seizure free for 12 months - Cannot drive 6 months after changing or stopping treatment - Recognised symptoms of liver dysfunction and blood abnormalities and seek advice immediately - Contraception o Pregnancy excluded before starting treatment o Need effective contraception before use and during treatment

Question 27

Monitoring of sodium valproate?

Answer 27

- LFT before and during 6 months of treatment

Question 28

Names of dopaminergic Parkinsons' drugs?

Answer 28

Levodopa (co-careldopa, co-beneldopa), ropinirole, pramipexol Co-careldopa = Levodopa + benserazide Co-beneldopa = Levodopa + carbidopa

Question 29

Indications of Levodopa?

Answer 29

- Early Parkinson’s disease when dopamine agonoists (ropinirole, pramipexol) preferred over levodopa - Later Parkinson’s disease – levodopa and add on option of dopamine agonists - Secondary Parkinsonism

Question 30

Mechanism of Levodopa?

Answer 30

- In Parkinson’s disease, deficiency of dopamine in nigrostriatal pathway o Causes basal ganglia to exert greater inhibitory effects on thalamus which reduces excitatory input to motor cortex o Generates bradykinesia, rigidity - Treatment increases dopaminergic stimulation to striatum o Dopamine does not cross BBB so Levodopa is a precursor that enters brain o Ropinirole and pramipexol are selective agonists for D2 receptor in striatum

Question 31

Side effects of Levodopa?

Answer 31

- Nausea, drowsiness, confusion, hallucinations and hypotension - Levodopa o Weaning off effect – patient’s symptoms worsen towards end of dose  Gets worse over time – need to increase dose/frequency but may lead to dyskinesias at beginning – on-off effect

Question 32

Interactions of Levodopa?

Answer 32

- Levodopa given with peripheral dopa-decarboxylase inhibitor to reduce conversion to dopamine outside brain - Do not combine with antipsychotics or metoclopramide – contradictory effects on dopamine receptors

Question 33

Prescription of Levodopa?

Answer 33

- Take at times that produce best symptom control | - Never stop abruptly – risk of neuroleptic malignant syndrome

Question 34

Monitoring of Levodopa?

Answer 34

- Blood pressure

Question 35

Names of anticholinergics used in neurology?

Answer 35

Procyclidine, trihexyphenidyl

Question 36

Indications of procyclidine?

Answer 36

- Parkinsonism, extrapyramidal symptoms (not tardive dyskinesia) - Acute dystonia

Question 37

Mechanism of procyclidine?

Answer 37

- Reducing effects of relative central cholinergic excess that occurs due to dopamine deficiency

Question 38

Side effects of procyclidine?

Answer 38

- Constipation - Dry mouth - Urinary retention - Blurred vision

Question 39

Contraindications of procyclidine?

Answer 39

- GI obstruction | - Myasthenia gravis

Question 40

Cautions of procyclidine?

Answer 40

- CV disease - Hypertension - Prostatic hypertrophy - Renal and Hepatic impairment

Question 41

Interactions of procyclidine?

Answer 41

- Additive effects to antimuscarinics

Question 42

Prescription of procyclidine?

Answer 42

- 2.5mg TDS oral initially – Parkinsonism/Extrapyramidal symptoms - 5-10mg IM/IV – acute dystonia - Lower end of range of medication for elderly

Question 43

Names of triptans?

Answer 43

Sumatriptan, almotriptan, eletriptan, rizatriptan, zolmitriptan

Question 44

Indications of triptans?

Answer 44

- Acute migraine | - Acute Cluster headache

Question 45

Mechanism of triptans?

Answer 45

- Agonist of serotonin receptors (5-HT 1B&1D) in blood vessels (causing constriction) and never endings in brain - Inhibition of pro-inflammatory neuropeptides

Question 46

Side effects of triptans?

Answer 46

- Recurrence of migraine - Dizziness, dyspnoea, flushing - Nausea, vomiting - Coronary artery spasm

Question 47

Contraindications of triptans?

Answer 47

- Coronary vasospasm - Ischaemic heart disease - Moderate and severe hypertension - Previous CVA/MI/TIA - Prinzmetal angina

Question 48

Cautions of triptans?

Answer 48

- Conditions predisposing to CAD | - History of seizures

Question 49

Interactions of triptans?

Answer 49

- Risk of serotonin syndrome increased with SSRIs, lithium, NaSSA, methadone, tramadol

Question 50

Prescription of triptans?

Answer 50

- Sumatriptan can be given OTC if evidence of prescribed before - Initially oral 50-100mg for 1 dose, followed by 50-100mg after at least 2 hours (if migraine recurs, not for same attack) - Either oral, intranasal

Question 51

Communication to patient in triptans?

Answer 51

- Take as soon as migraine starts