Neurological drugs Flashcards
Name two L-DOPA’s/peripheral decarboxylases
Simemet Madopar
What are the mechanisms for how madopar/simemet work?
Aim to increase dopaminergic stimulation of the striatum.
Dopamine cannot be given as it cannot cross BBB -
Simemet/madopar = L-DOPA which is precursor for dopamine and can cross BBB via membrane transporter
- L-DOPA – dopa -decarboxylase –> dopamine –> dopaminergic receptors
What are the indications for simemet/madopar?
- Parkinson’s/secondary Parkinson’s (but deal with underlying cause first! e.g. causative drug)
What are the contraindications for simemet/madopar?
Caution in:
- Elderly
- Existing psychiatric/cognitive disease (can cause confusion/hallucinations)
- CV disease (can cause hypotension)
What are the SEs of simemet/madopar?
- Nausea
- Drowsiness
- Confusion
- Compulsive behaviours - gambling, sexual, money
- Hallucinations
- Hypotension
- Off effects - at end of dosage interval, Sx get worse. (Sx worsen with Tx duration)
On effects - dyskinesia/involuntary movements - start of dosage interval/increased dose/increased frequency
What are the potential interactions of simemet/madopar?
Should be given in combo with dopa-decarboxylase inhibitors (e.g. carbidopa) - prevents L-DOPA decarboxylation OUTSIDE brain
- Should not be given in combo with metoclopramide or anti-psychotics (contradictory effects on dopamine receptors)
What is phenytoin?
Anti-convulsive
What is the mechanism for how phenytoin exerts its action?
Reduces neuronal excitability and electrical conduction. Therefore, reduces seizure activity - Blocks inactive Na+ channels in neurons
- remain in inactive state so prevents the influx of Na into neurone
- Prevents the drift of membrane potential from resting to threshold to trigger AP
What are the indications for phenytoin?
- Control seizures in status epilepticus where benzos have been ineffective 2. Reduce frequencies of generalised/focal seizures (but other drugs with fewer SEs preferred)
What are the CIs for the use of phenytoin?
- Zero order kinetics - phenytoin metabolism by liver is constant irrespective of plasma concentration. Reduced with hepatic impairment (increased risk of toxicity)
- Low therapeutic index
- Neonatal phenytoin exposure - foetal hydantoin syndrome - craniofacial abnormalities and reduced IQ (due to increased folic acid metabolism)
- Pregnant women should increase folic acid intake if taking drug
What are the SEs of phenytoin?
Change in appearance - hirtuism, gum hypertrophy, skin coarsening, acne
- Dose dependent neurological defecits - diplopia, nystagmus, ataxia, reduced consciousness/sedation
- haematological/osteomalacia - increased Vit D/folate metabolism Hypersensitivity syndrome
- mild to severe antiepileptic hypersensitivity syndrome
Phenytoin overdose - death due to CV and respiratory depression (can cause severe cardiac arrythmia)
What type of drug is carbamazepine?
Anticonvulsant
What is the mechanism by which carbamazepine works?
- Blocks Na channels - stabilises neuronal resting potential and reduces neuronal excitability
- Reduces seizure activity in epilepsy
- Blocks synaptic transmission from trigeminal nuclei - reduces neuralgic pain -
Stabilises mood in bipolar disorder by reducing electrical kindling of limbic system and temporal lobe
What are the indications for carbamazepine?
- 1st line for partial seizures. 2nd line for generalised seizures. Do not use for atonic/tonic/myoclonic as can make worse
- First line for trigeminal neuralgia - control pain and reduce frequency/severity of attacks
- Bipolar disorder - prophylaxis where other treatments = ineffective/resisted
What are the CIs for carbamazepine?
Pregnancy - In utero exposure -> neural tube defects, cardiac and urinary tract defects, cleft palate. (take high dose folic acid)
Hypersensitivity/anti epileptic hypersensitivity syndrome
Cardiac/renal/hepatic disease - increases toxicity
What are the SEs of carbamazepines?
- GI disturbance - N/V
- Rash/hypersensitivity (10%)
- Anti epileptic hypersensitivity syndrome
- Hyponatraemia/oedema - anti diuretic hormone like effect
What are the potential drug interactions of carbamazepine?
- CYP450 inducer - reduces concentration and efficacy of drugs metabolised by CYP450 e.g. warfarin, oestrogen, progesterone
- Carbamazepine metabolised by CYP450 - inhibitors increase risk of toxicity e.g. macrolides
- Complex interaction with other anti-epileptic drugs
- Drugs that reduce seizure threshold reduce efficacy of anti-epileptic drugs e.g. SSRIs, antipsychotics, tramadol, antipsychotics
What is sodium valproate?
Anticonvulsant
What is the mechanism for sodium valproate?
- Weak inhibitor of Na channels - stabilises resting potential and reduces neuronal excitability
Also increases levels of GABA - inhibitory neurotransmitter - regulates neuronal activity (by reducing)
What are the indications for sodium valproate?
- 1st line for generalised and absence seizures. Second line for focal seizures
- Bipolar disorder - Tx of acute mania and prophylaxis for recurrent episodes
What are the CIs of sodium valproate?
Pregnancy - esp at time of conception/1st trimester - neural tube defects, craniofacial, cardiac and limb abnormalities.
Devleopmental delay Renal and hepatic impairment
What are the SEs of sodium valproate?
V Appetite/weight increase
Liver failure (increased LFTs)
Pancreatitis
Reversible hair loss (grows back curly!)
Oedema
Ataxia (neurological symtpoms)
Tetragonecity, thrombocytopenia, tremor
Encephalopathy
What are the potential drug interactions of sodium valproate?
- CYP450 INHIBITOR - increases concentration/risk of toxicity of drugs metabolised by CYP450 e.g. warfarin - sodium valproate metabolised by CYP450
- drugs that induce CYP450 reduces sodium valproate concentration and increases risk of seizures (e.g. carbamezapine, phenytoin)
- Drugs that lower seizure threshold e.g. SSRIs, anti-psychotics, tricyclic antidepressants, tramadol
What type of drug is lamotrigine?
Anticonvulsant
What is the mechanism by which lamotrigine works?
Blocks Na channels - stabilising neurons and reducing neuronal excitability
What are the indications for lamotrigine?
- 2nd line for generalised seizures (inc Lennox-Gestault and tonic-clonic seizures)
- Bipolar disorders - stabilises mood and reduces depression
What are the CI for lamotrigine?
- Can be SAFELY used in pregnancy!!
- Hypersensitivity reactions - rash
- Steven Johnsons syndrome (serious reaction)
- Renal and hepatic impairment (increased risk of toxicity)
What are the SEs of lamotrigine?
- GI - n/v/d
- Neuro - confusion, agitation, drowsiness, ataxia, diplopia, nystagmus
What are the potential drug interactions of lamotrigine?
- Efficacy reduced by drugs that lower seizure threshold - e.g. SSRIs, tricyclics, anti-psychotics, tramadol
- Metabolised by CYP450 - concentration increased by sodium valproate (inhibits CYP450) and reduced by phenytoin and carbamazepine (inhibit CYP450)
