Neurology Drugs

Question 1

Phenytoin class

Answer 1

Anti-convulsants

Question 2

Phenytoin indication

Answer 2

1. To control seizures in status epilepticus where benzodiazepines are ineffective
2. To reduce frequency of generalised or focal seizures in epilepsy, although drugs with fewer adverse effects and interaction are preferred.

Question 3

Phenytoin MOA

Answer 3

• 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

Question 4

Phenytoin administration

Answer 4

IV: for status epilepticus, loading dose 20mg/kg then 100mg 6-8 hourly

Oral: long-term for chronic epilepsy, 150-300mg daily

Question 5

Phenytoin contraindications

Answer 5

• 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

Question 6

Phenytoin side effetcts

Answer 6

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

Question 7

Phenytoin interactions

Answer 7

• Metabolised by P450 enzymes
• Also a P450 enzyme inducer
• Efficacy reduced by drugs that lower the seizure threshold: SSRIs, tricyclics, antipsychotics, tramadol

Question 8

Carbamazepine class

Answer 8

Anti-convulsant

Question 9

Carbamazepine indications

Answer 9

1. Epilepsy: 1st line for focal seizures ± secondary generalisation, and primary general seizures
2. Trigeminal neuralgia: 1st line to control pain and reduce attack frequency and severity
3. Bipolar disorder: prophylactic approach in patients resistant / intolerant to other medication

Question 10

Carbamazepine MOA

Answer 10

• 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

Question 11

Carbamazepine administration

Answer 11

Oral
Rectal 2nd line
Start low dose then increase gradually

Question 12

Carbamazepine contraidications

Answer 12

• Associated with neural tube defects, discuss with specialist
• Antiepileptic hypersensitivity - cross-sensitivity with phenytoin
• Caution in hepatic / renal / cardiac disease

Question 13

Carbamazepine side effects

Answer 13

• 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

Question 14

Carbamazepine interactions

Answer 14

• P450 inducer
• Metabolised by P450
• Complex interactions with other antiepileptic drugs
• Efficacy reduced by drugs that lower seizure threshold: tricyclics, SSRIs, tramadol, antipsychotics

Question 15

Sodium valproate class

Answer 15

Anti-convulsant

Question 16

Sodium valproate indications

Answer 16

1. Epilepsy: first line treatment for focal seizures ± secondary generalisation, and primary general seizures
2. Bipolar disorder: acute management of manic episodes, prophylactic to prevent recurrence

Question 17

Sodium valproate MOA

Answer 17

• Weakly inhibits Na+ channels, stabilising membrane potential and reducing excitability
• Increases brain content of GABA (primary inhibitory neurotransmitter)

Question 18

Sodium valproate administration

Answer 18

Oral

Sodium valproate 600mg for epilepsy

Question 19

Sodium valproate contraindications

Answer 19

• 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

Question 20

Sodium valproate side effects

Answer 20

• 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

Question 21

Sodium valproate interactions

Answer 21

• P450 inhibitor
• Aspirin: displaces from binding site = increased adverse effects
• Efficacy reduced by drugs that lower the seizure threshold: antipsychotics, tricyclics, SSRIs, tramadol

Question 22

Lamotrigine class

Answer 22

Anti-convulsants

Question 23

Lamotrigine indications

Answer 23

1. Monotherapy of focal seizures, primary and secondary generalised tonic-clonic seizures
2. Maintenance treatment of bipolar I disorder and depression

Question 24

Lamotrigine MOA

Answer 24

Inhibition of neuronal Na+ channels which prevents influx of Na+ therefore reducing neuronal excitability

Question 25

Lamotrigine contraindications

Answer 25

1. Myoclonic seizures: may exacerbate these 2. Parkinson's disease: may exacerbate 3. Hepatic and renal impairment: have caution

Question 26

Lamotrigine side effects

Answer 26

Commonly has GI and neurological disturbance Can cause antiepileptic hypersensitivity syndrome

Question 27

Levetiracetam class

Answer 27

Anti-convulsants

Question 28

Levetiracetam indications

Answer 28

1. Monotherapy or adjunct of focal seizures ± secondary generalisation 2. Adjunctive therapy of myoclonic seizures and tonic-clonic seizures

Question 29

Levetiracetam MOA

Answer 29

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.

Question 30

Levetiracetam contraindications

Answer 30

- Pancytopenia - Depressive thoughts - Ataxic gait - Hallucinations - CKD

Question 31

Levetiracetam side effects

Answer 31

``` GI upset Neurological disturbance Nasal irritation General malaise Convulsions Rash ```

Question 32

Levetiracetam interactions

Answer 32

- Sedatives - Anxiety drugs - Concurrent use can increase risk of CNS depression which may affect ability to perform skilled tasks

Question 33

Levetiracetam patient info

Answer 33

Avoid alcohol

Question 34

L-Dopa class

Answer 34

CNS agent

Question 35

L-dopa indication

Answer 35

1. Parkinson's disease: used to increase dopamine

Question 36

L-Dopa MOA

Answer 36

- 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

Question 37

L-Dopa administration

Answer 37

Oral | Peripheral DOPA decarboxylase prescribed alongside to prevent peripheral dopamine synthesis. E.g. modapar

Question 38

L-Dopa contraindications

Answer 38

``` Caution in: Cushings / other endocrine disorders DM Convulsions CVD Psychiatric illness Pulmonary disease Susceptibility to angle-closure glaucoma ```

Question 39

L-Dopa side effects

Answer 39

Associated with impulse control disorders e.g. gambling, binge eating and hypersexuality Psychiatric disturbance Neurological disturbance Vomiting

Question 40

L-Dopa interactions

Answer 40

Beta-blockers: hypotension