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
