Neurology Drugs Flashcards
Phenytoin class
Anti-convulsants
Phenytoin indication
- To control seizures in status epilepticus where benzodiazepines are ineffective
- To reduce frequency of generalised or focal seizures in epilepsy, although drugs with fewer adverse effects and interaction are preferred.
Phenytoin MOA
- Reduces neuronal excitability which inhibits spread of seizure activity
- Binds to neuronal Na+ channels in their inactive state and prevents Na+ influx, therefore preventing an action potential
- Also does this in cardiac Purkinje fibres which accounts for antiarrhythmic and cardiotoxic effects
Phenytoin administration
IV: for status epilepticus, loading dose 20mg/kg then 100mg 6-8 hourly
Oral: long-term for chronic epilepsy, 150-300mg daily
Phenytoin contraindications
- Reduce in hepatic impairment as metabolised by liver with zero order kinetics and has a low therapeutic index
- Associated with foetal hydantoin syndrome in pregnancy
Phenytoin side effetcts
Long-term:
Causes change in appearance: skin coarsening, acne, hirsutism, gum hypertrophy
Neurological effects: cerebellar toxicity (=nystagmus, ataxia, discoordination) , impaired cognition / cosciouness
Haematological disorders and osteomalacia due to induction of folic acid and vitamin D metabolism
Hypersensitivity: mild skin rash to life-threatening anti-epileptic hypersensitivity reaction
Phenytoin toxicity: death through cardiovascular collapse and respiratory depression
Antiepileptic hypersensitivity: 1 in 5000 patients, within 2 months treatment commencing. Features include:
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis
- Fever
- Lymphadenopathy
- Systemic involvement
- 10% mortality
Phenytoin interactions
- Metabolised by P450 enzymes
- Also a P450 enzyme inducer
- Efficacy reduced by drugs that lower the seizure threshold: SSRIs, tricyclics, antipsychotics, tramadol
Carbamazepine class
Anti-convulsant
Carbamazepine indications
- Epilepsy: 1st line for focal seizures ± secondary generalisation, and primary general seizures
- Trigeminal neuralgia: 1st line to control pain and reduce attack frequency and severity
- Bipolar disorder: prophylactic approach in patients resistant / intolerant to other medication
Carbamazepine MOA
- Inhibits neuronal sodium channels and reducing excitability, similar to phenytoin.
- Inhibits speed of transmission in epilepsy
- Blocks synaptic transmission in trigeminal nucleus for TGN
- Stabilises mood in BP by reducing electrical kindling in temporal lobe and limbic system
Carbamazepine administration
Oral
Rectal 2nd line
Start low dose then increase gradually
Carbamazepine contraidications
- Associated with neural tube defects, discuss with specialist
- Antiepileptic hypersensitivity - cross-sensitivity with phenytoin
- Caution in hepatic / renal / cardiac disease
Carbamazepine side effects
- GI upset: nausea and vomiting
- Neurological: dizziness and ataxia
- Hypersensitivity: affects 10% - maculopapular skin rash
- Antiepileptic hypersensitivity reaction
- Oedema and hyponatraemia due to ADH-like effect
Carbamazepine interactions
- P450 inducer
- Metabolised by P450
- Complex interactions with other antiepileptic drugs
- Efficacy reduced by drugs that lower seizure threshold: tricyclics, SSRIs, tramadol, antipsychotics
Sodium valproate class
Anti-convulsant
Sodium valproate indications
- Epilepsy: first line treatment for focal seizures ± secondary generalisation, and primary general seizures
- Bipolar disorder: acute management of manic episodes, prophylactic to prevent recurrence
Sodium valproate MOA
- Weakly inhibits Na+ channels, stabilising membrane potential and reducing excitability
- Increases brain content of GABA (primary inhibitory neurotransmitter)
Sodium valproate administration
Oral
Sodium valproate 600mg for epilepsy
Sodium valproate contraindications
- Women of childbearing age: greatest risk of neural tube defects, foetal abnormalities (cardiac / craniofacial / limb), developmental delay
- Avoid in hepatic impairment
- Dose reduction in renal impairment
Sodium valproate side effects
- GI upset: nausea, gastric irritation, diarrhoea
- Neurological / psychiatric: tremor, ataxia, behavioural disturbance
- thrombocytopenia,
- transient increase in liver enzymes
- Hypersensitivity: hair loss, with subsequent air regrowth being curlier
- Idiosyncratic: severe liver injury, pancreatitis, bone marrow failure, antiepileptic hypersensitivity syndrome
Sodium valproate interactions
- P450 inhibitor
- Aspirin: displaces from binding site = increased adverse effects
- Efficacy reduced by drugs that lower the seizure threshold: antipsychotics, tricyclics, SSRIs, tramadol
Lamotrigine class
Anti-convulsants
Lamotrigine indications
- Monotherapy of focal seizures, primary and secondary generalised tonic-clonic seizures
- Maintenance treatment of bipolar I disorder and depression
Lamotrigine MOA
Inhibition of neuronal Na+ channels which prevents influx of Na+ therefore reducing neuronal excitability
Lamotrigine contraindications
- Myoclonic seizures: may exacerbate these
- Parkinson’s disease: may exacerbate
- Hepatic and renal impairment: have caution
Lamotrigine side effects
Commonly has GI and neurological disturbance
Can cause antiepileptic hypersensitivity syndrome
Levetiracetam class
Anti-convulsants
Levetiracetam indications
- Monotherapy or adjunct of focal seizures ± secondary generalisation
- Adjunctive therapy of myoclonic seizures and tonic-clonic seizures
Levetiracetam MOA
Not understood.
May selectively prevent hyper synchronisation of epileptiform burst firing and propagation of seizure activity.
Binds to synaptic vesicle protein involved in vesicle exocytosis.
Levetiracetam contraindications
- Pancytopenia
- Depressive thoughts
- Ataxic gait
- Hallucinations
- CKD
Levetiracetam side effects
GI upset Neurological disturbance Nasal irritation General malaise Convulsions Rash
Levetiracetam interactions
- Sedatives
- Anxiety drugs
- Concurrent use can increase risk of CNS depression which may affect ability to perform skilled tasks
Levetiracetam patient info
Avoid alcohol
L-Dopa class
CNS agent
L-dopa indication
- Parkinson’s disease: used to increase dopamine
L-Dopa MOA
- 60-80% decrease in dopamine in substantia nigra in symptomatic parkinson’s
- Levodopa is precursor of dopamine, dopaminergic transmission enhanced by exogenous supply
- Levodopa crosses blood-brain barrier and decarboxylated to dopamine
- Newly formed dopamine stimulates dopaminergic receptors
L-Dopa administration
Oral
Peripheral DOPA decarboxylase prescribed alongside to prevent peripheral dopamine synthesis. E.g. modapar
L-Dopa contraindications
Caution in: Cushings / other endocrine disorders DM Convulsions CVD Psychiatric illness Pulmonary disease Susceptibility to angle-closure glaucoma
L-Dopa side effects
Associated with impulse control disorders e.g. gambling, binge eating and hypersexuality
Psychiatric disturbance
Neurological disturbance
Vomiting
L-Dopa interactions
Beta-blockers: hypotension
