Drugs - Neurology Flashcards
Give 4 types of antiepileptic drugs
- Sodium valproate
- Phenytoin
- Carbamazepine
- Lamotrigine
What is the 1st line antiepileptic indicated in generalised tonic clonic seizures
Sodium valproate
Give the 1st line antiepileptic indicated in women of childbearing age/pregnancy
Lamotrigine
What is the 1st line antiepileptic indicated in absence seizures
Sodium valproate
What is the 1st line antiepileptic indicated in focal seizures?
Carbamazepine
What is the 1st line antiepileptic indicated in myoclonic seizures?
Sodium valproate
Mechanism of sodium valproate?
Increases activity of GABA (principal inhibitory neurotransmitter) which has a relaxing effect on brain.
Which antiepileptic drug is associated with the greatest risk of foetal abnormalities?
Sodium valproate
Contraindications of sodium valproate?
- Avoid where possible in women of child-bearing age, particularly around the time of contraception and first trimester of pregnancy
- Hepatic & renal impairment
How does sodium valproate interact with the P450 system?
- Sodium valproate is a P450 enzyme inhibitor
- Sodium valproate itself is metabolised by P450 enzymes so is affected by enzyme inducers & inhibitors
How long must patients be seizure free for before they can drive?
12 months
1st line pharmacological management of trigeminal neuralgia?
Carbamazepine
Side effects of carbamazepine?
- GI upset
- Neurological effects e.g. ataxia, dizziness
- Hypersensitivity (10%)
- Oedema
- Hyponatraemia due to ADH-like effect
- Agranulocytosis (a life-threatening blood disorder where the body doesn’t make enough neutrophils)
- Aplastic anaemia
Contraindications of carbamazepine?
- Pregnancy → teratogenic
- Hypersensitivity
- Hepatic, renal or cardiac disease – increased risk of toxicity
How does carbamazepine interact with the P450 system?
- Carbamazepine is a P450 enzyme inducer
- Carbamazepine itself is metabolised by P450 enzymes so it affected by enzyme inducers & inhibitors
Side effects of phenytoin?
- Folate and vitamin D deficiency:
- Megaloblastic anaemia (folate deficiency)
- Osteomalacia (vitamin D deficiency)
Give some symptoms of phenytoin toxicity
Nystagmus, diplopia, slurred speech, ataxia, confusion, and hyperglycaemia.
How does phenytoin interact with the P450 system?
- P450 enzyme inducer
- Is also metabolised by the P450 system so is affected by enzyme inducers & inhibitors
What severe hypersensitivity reactions can antiepileptics be associated with?
Increased risk for Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN)
How is lamotrigine metabolised?
By glucuronidation
The interactions of lamotrigine arise from its metabolism by glucuronidation. Which drugs:
a) induce glucuronidation?
b) inhibit glucuronidation?
Drugs that induce glucuronidation → carbamazepine, phenytoin, oestrogens, rifampicin and protease inhibitors (these can cause lamotrigine levels to fall)
Drugs that inhibit glucuronidation → sodium valproate (can cause levels to rise and potential toxicity)
In Parkinson’s disease, there is a deficiency of dopamine in which pathway?
In the nigrostriatal pathway that links the substantia nigra in the midbrain to the corpus striatum in the basal ganglia.
How does a lack of dopamine generate features of Parkinson’s e.g. bradycardia, rigidity?
Via direct and indirect circuits, this causes the basal ganglia to exert greater inhibitory effects on the thalamus which, in turn, reduces excitatory input to the motor cortex
In the treatment of Parkinson’s, why is it not possible to give dopamine itself? Why is levodopa given instead?
As is does not cross the BBB
By contrast, levodopa is a precursor of dopamine that can enter the brain via a membrane transporter
What is levodopa always given alongside?
Peripheral decarboxylase inhibitors (e.g. carbidopa, benserazide)
Why is levodopa always given alongside peripheral decarboxylase inhibitors?
These drugs stop levodopa being broken down in the body before it gets the chance to enter the brain.
Give 2 peripheral decarboxylase inhibitors given alongside levodopa
- Carbidopa (co-careldopa = levodopa + carbidopa)
- Benserazide (co-benyldopa = levodopa + benserazide)
Indications for levodopa?
Parkinson’s disease
- Levodopa is the most effective treatment for symptoms but becomes less effective over time
- It is often reserved for when other treatments are not managing to control symptoms (e.g. ropinirole, pramipexol)
Pharmacological management of status epilepticus?
1st line → benzodiazepines e.g. IV lorazepam (repeated once after 10−20 minutes if the seizure continues)
2nd line → phenytoin infusion
Side effects of levodopa?
- Dyskinesias (often occurs when dose is too high)
- Postural hypotension
- Wearing off effect – symptoms worsen towards end of the dosage interval (seems to get worse as duration of therapy increases)
- GI upset
What is dyskinesia?
Dyskinesia is uncontrolled, involuntary movement that may occur with long-term levodopa use
How can peripheral side effects of levodopa be reduced?
Peripheral side effects can be reduced by the co-administration of a peripheral dopa decarboxylase inhibitor e.g. carbidopa.
What can be given to manage postural hypotension?
Fludrocortisone
Why is levodopa is always given with a peripheral doxa-decarboxylase inhibitor?
To reduce its conversion to dopamine outside the brain → this desirable interaction reduces nausea and lowers the dose needed for therapeutic effect
Why should dopaminergic agents should not usually be combined with antipsychotics or metoclopramide?
due to opposing effects on dopamine receptors
What agents are preferred in early, non-severe Parkinson’s?
Dopamine agonists e.g. Ropinirole, Pramipexol
When is levodopa indicated in Parkinson’s?
Levodopa is the more effective option when symptoms are disabling
What unique side effect can dopamine agonists E.g. Ropinirole, Pramipexol lead to?
Can lead to impulsivity e.g. pathological gambling, hypersexuality
What does the nigrostriatal pathway connect?
The substantia nigra with the corpus striatum of the basal ganglia
Give 2 other classes of drugs indicated in Parkinson’s disease
COMT Inhibitors
Monoamine Oxidase-B Inhibitors
What is the 1st line pharmacological agent used to ease the symptoms of a migraine attack or cluster headache?
Triptans (e.g. Sumatriptan, Almotriptan)
What class of drug are triptans?
5HT receptor agonist (serotonin receptor agonist)
2 main indications for triptans?
- Migraine attack
- Cluster headache
Which 2 anticholinergics may be indicated in Parkinso’s?
Procyclidine,
Purpose of anticholinergics in Parkinson’s?
Antispasmodic drugs used to treat stiffness, tremors, spasms and poor muscle control.
