NE5 Anti-epileptic drugs

Lamotrigine and zonisamide affect both Na+ and Ca++ channels.

Ethosuximide and pregabalin affect calcium channels.

Vigabatrin is used as an adjuct therapy for infantile seizures.

Sodium valproate increases GABA levels by decreasing breakdown.

GABA receptor upregulators: [blank_start]Barbiturates[blank_end]. - Examples: [blank_start]Phenobarbital, Primidone[blank_end] - Action: Enhances GABA neurotransmission, [blank_start]mimics[blank_end] GABA neurotransmission, suppresses [blank_start]motor and polysynaptic[blank_end] transmission throughout the CNS - Use: all forms of epilepsy EXCEPT [blank_start]absence[blank_end] epilepsy; status epilepticus, phenobarbitol 1st -line therapy for [blank_start]infantile seizures[blank_end] - Pros: Oldest prescribed AED; WHO list; CHEAP; long [blank_start]half-life[blank_end] - Cons: CNS [blank_start]sedation[blank_end]; phenobarbitol - relatively-[blank_start]narrow[blank_end] therapeutic window; substance [blank_start]abuse[blank_end] issues; CYP inducer

Zonisamide: Action: Blocks [blank_start]Na+ VG and T-type Ca++[blank_end] ion channels; binds and activates GABA receptor Use: mono- and adjunctive therapy for focal epilepsy; Lennox-Gastaut syndrome; Parkinson disease Powerful antiepileptic, costly, [blank_start]not[blank_end] available in NZ.

Topiramate - Action: Blocks [blank_start]Na+ VG[blank_end] channels; potentiates GABA [blank_start]receptors[blank_end] and effect; inhibits carbonic anhydrase - Use: mono- and adjunctive therapy for multiple forms of epilepsy; migraine prophylaxis, idiopathic intracranial hypertension - Pros: No serum monitoring; relatively [blank_start]cheap[blank_end] - Cons: 20+yrs of use; CNS [blank_start]sedation[blank_end]; renal and ophthalmologic complications; side effects; unclear regarding pregnancy/lactation risk

Retigabine (Onelink) Action: Activates [blank_start]K+[blank_end] ion channel to return depolarised neurons to [blank_start]resting[blank_end] state and reducing neuronal excitability Use: [blank_start]adjunctive[blank_end] management of focal epilepsy Pros: Quick [blank_start]absorption[blank_end]; unique [blank_start]mechanism[blank_end] of activity Cons: cardiac and ophthalmologic complications; side effects; costly

Racetams - Examples: Levetiracetam (Keppra), Piracetam (Nootropil) - Action: Block [blank_start]N-type Ca++[blank_end] ion channels; modulate AMPA receptors - Use: focal epilepsy (mono- and adjunctive therapeutic uses); generalised GTC and myoclonic epilepsy - Pros: Wide therapeutic use in epilepsy (L); limited [blank_start]side[blank_end] effects

DA agonists - [blank_start]Non[blank_end]-ergot derivatives: e.g. Pramipexole, Ropinirole • [blank_start]Better[blank_end] tolerated (but still nausea, hypotension, constipation) • Dyskinesias • Sudden onset of [blank_start]sleep[blank_end] - caution re: driving • Adjunct: [blank_start]confusion, hallucinations[blank_end] [blank_start]Apomorphine[blank_end] (specialist supervision) • Good for unpredictable ‘off’ periods, [blank_start]s.c.[blank_end] administration • 2 days pre-treatment with [blank_start]domperidone[blank_end]

Amantadine: • [blank_start]Weak[blank_end] DA agonist • Modest anti-PD effect • Tolerance • Confusion/[blank_start]hallucinations[blank_end] • Useful for [blank_start]L-DOPA induced dyskinesia[blank_end] in late disease Unwanted Effects: [blank_start]insomnia, peripheral oedema[blank_end] (decrease dose in renal impairment)

Selective MAO-[blank_start]B[blank_end] inhibitors: E.g. [blank_start]Selegiline[blank_end] and rasagiline • Decrease [blank_start]breakdown[blank_end] of DA in [blank_start]striatum[blank_end] • Prolong [blank_start]duration[blank_end] of action • First used as adjunct to L-DOPA, to decrease dose requirement (1/3) • ‘L-DOPA sparing’ • Mow also used with DA agonists • Decreases end-of-dose [blank_start]deterioration[blank_end] • UEs: Nausea, [blank_start]dry[blank_end] mouth, dyspepsia, constipation, [blank_start]transient dizziness[blank_end] (common)

Inhibition of cholinergic activity - Anti[blank_start]muscarinic[blank_end] drugs e.g. Benztropine (benatropine), [blank_start]procyclidine[blank_end] • Decrease relative [blank_start]central cholinergic excess[blank_end] • Little effect on [blank_start]bradykinesia[blank_end] • Modest effect - [blank_start]tremor and rigidity, sialorrhea[blank_end] (excessive salivation) Unwanted effects: - (peripheral) worsen PD-related [blank_start]constipation, dry[blank_end] mouth. Also [blank_start]blurred[blank_end] vision, urinary [blank_start]retention[blank_end]. - (Central) [blank_start]confusion, memory impairment,[blank_end] restlessness (elderly)

Drug-induced Parkinsonism - [blank_start]7[blank_end]% of PD. [blank_start]Women[blank_end]>men. HIGH RISK 1. Dopamine [blank_start]D2 receptor blockers[blank_end]: Antipsychotics - Typicals e.g. [blank_start]haloperidol[blank_end] Atypicals ((lower incidence): e.g. [blank_start]risperidone, olanzapine[blank_end] [blank_start]Antiemetics[blank_end] - e.g. metoclopromide

Methyldopa (centrally acting antihypertensive) is a dopamine depleter.

Which of these drug classes is not an intermediate risk for drug induced PD?