BASIC - NEUROLOGY Flashcards
Indications of carbamazepines?
- 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
Mechanism of carbamazepines?
- Inhibit neuronal sodium channels, stabilising resting membranes potentials and reducing neuronal excitability
- Inhibit spread of seizure activity in epilepsy
Side effects of carbamazepines?
- 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%
Contraindications of carbamazepines?
- AV conduction abnormalities (unless paced)
- History of bone marrow depression
- Prior antiepileptic hypersensitivity syndrome
Cautions of carbamazepines?
- Pregnancy – need high dose folic acid
- Cardiac, hepatic and renal disease
Interactions of carbamazepines?
- Induces CYP450 enzymes
- Metabolised by CYP450 enzymes
- Efficacy reduced by drugs that lower seizure threshold
o SSRIs, TCAs, antipsychotics and tramadol
Dosing of carbamazepines?
- 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- Treatment must be withdrawn gradually over at least 4 weeks – seizure recurrence risk
Communication to patient of carbamazepines?
- Must not drive until seizure free for 12 months
- Cannot drive 6 months after changing or stopping treatment
Monitoring of carbamazepines?
- Report any unusual symptoms
- Plasma concentration for response (4-12mg/litre) measured after 2 weeks
- FBC, U&Es, LFTS may be beneficial
Indications of phenytoin?
- Control seizures in status epilepticus when benzodiazepines are ineffective
- Reduce frequency of focal or generalised seizures in epilepsy (if other drugs not suitable)
Mechanism of phenytoin?
- 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
Side effects of phenytoin?
- 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%
Contraindications of phenytoin?
- 2nd and 3rd degree heart block
- Sinus bradycardia
Cautions of phenytoin?
- Dose reduction in hepatic impairment
- Pregnancy – need high dose folic acid (foetal hydantoin syndrome – craniofacial abnormalities and reduced IQ)
Interactions of phenytoin?
- Induces CYP450 enzymes
- Metabolised by CYP450 enzymes
- Efficacy reduced by drugs that lower seizure threshold
o SSRIs, TCAs, antipsychotics and tramadol
Dosing of phenytoin?
- 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
Communication to patient of phenytoin?
- Must not drive until seizure free for 12 months
- Cannot drive 6 months after changing or stopping treatment
Monitoring of phenytoin?
- 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
Indications of sodium valproate?
- 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
MEchanism of sodium valproate?
- Weak inhibitor of neuronal Na channels, stabilising resting membrane potentials and reducing neuronal excitability
- Increases content of GABA, principal inhibitory neurotransmitter
Side effects of sodium valproate?
- 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
Contraindications of sodium valproate?
o Suspected mitochondrial disorder
o Personal or family history of hepatic dysfunction
Cautions of sodium valproate?
- 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
Interactions of sodium valproate?
- Inhibits CYP450 enzymes
- Metabolised by CYP450
- Efficacy reduced by drugs that lower seizure threshold
o SSRIs, TCAs, antipsychotics and tramadol
Dosing of sodium valproate?
- Sodium valproate – prescribed for epilepsy – 600mg
- Valproic acid – used in bipolar disorders – 750mg
- Withdraw over 4 weeks gradually
Communication to patient of sodium valproate?
- 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
Monitoring of sodium valproate?
- LFT before and during 6 months of treatment
Names of dopaminergic Parkinsons’ drugs?
Levodopa (co-careldopa, co-beneldopa), ropinirole, pramipexol
Co-careldopa = Levodopa + benserazide
Co-beneldopa = Levodopa + carbidopa
Indications of Levodopa?
- 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
Mechanism of Levodopa?
- 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
Side effects of Levodopa?
- 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
Interactions of Levodopa?
- 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
Prescription of Levodopa?
- Take at times that produce best symptom control
- Never stop abruptly – risk of neuroleptic malignant syndrome
Monitoring of Levodopa?
- Blood pressure
Names of anticholinergics used in neurology?
Procyclidine, trihexyphenidyl
Indications of procyclidine?
- Parkinsonism, extrapyramidal symptoms (not tardive dyskinesia)
- Acute dystonia
Mechanism of procyclidine?
- Reducing effects of relative central cholinergic excess that occurs due to dopamine deficiency
Side effects of procyclidine?
- Constipation
- Dry mouth
- Urinary retention
- Blurred vision
Contraindications of procyclidine?
- GI obstruction
- Myasthenia gravis
Cautions of procyclidine?
- CV disease
- Hypertension
- Prostatic hypertrophy
- Renal and Hepatic impairment
Interactions of procyclidine?
- Additive effects to antimuscarinics
Prescription of procyclidine?
- 2.5mg TDS oral initially – Parkinsonism/Extrapyramidal symptoms
- 5-10mg IM/IV – acute dystonia
- Lower end of range of medication for elderly
Names of triptans?
Sumatriptan, almotriptan, eletriptan, rizatriptan, zolmitriptan
Indications of triptans?
- Acute migraine
- Acute Cluster headache
Mechanism of triptans?
- Agonist of serotonin receptors (5-HT 1B&1D) in blood vessels (causing constriction) and never endings in brain
- Inhibition of pro-inflammatory neuropeptides
Side effects of triptans?
- Recurrence of migraine
- Dizziness, dyspnoea, flushing
- Nausea, vomiting
- Coronary artery spasm
Contraindications of triptans?
- Coronary vasospasm
- Ischaemic heart disease
- Moderate and severe hypertension
- Previous CVA/MI/TIA
- Prinzmetal angina
Cautions of triptans?
- Conditions predisposing to CAD
- History of seizures
Interactions of triptans?
- Risk of serotonin syndrome increased with SSRIs, lithium, NaSSA, methadone, tramadol
Prescription of triptans?
- 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
Communication to patient in triptans?
- Take as soon as migraine starts
