Drugs

Question 1

Alteplase

Answer 1

Thrombolysis with alteplase is considered once haemorrhage is excluded (after the CT scan). Alteplase is a tissue plasminogen activator that rapidly breaks down clots. It may be given within 4.5 hours of the symptom onset, based on local protocols and by an appropriately trained team. Patients need close monitoring for complications, particularly intracranial or systemic haemorrhage, with access to immediate imaging if bleeding is suspected.

Question 2

Secondary prevention of a stroke

Answer 2

Secondary Prevention
• Clopidogrel 75mg once daily (alternatively aspirin plus dipyridamole)
• Atorvastatin 20-80mg (not started immediately – usually delayed at least 48 hours)
• Blood pressure and diabetes control
• Addressing modifiable risk factors (e.g., smoking, obesity and exercise)

Question 3

Levodopa

Answer 3

Parkinson’s first line treatment

Levodopa is synthetic dopamine taken orally. It is usually combined with a peripheral decarboxylase inhibitor (e.g., carbidopa and benserazide), which stops it from being metabolised in the body before it reaches the brain. Levodopa is the most effective treatment for symptoms but becomes less effective over time. It is often reserved for when other treatments are not controlling symptoms.

Combination drugs are:
○ Co-beneldopa (levodopa and benserazide), with the trade name Madopa
○ Co-careldopa (levodopa and carbidopa), with the trade name Sinemet

The main side effect of levodopa is dyskinesia. Dyskinesia refers to abnormal movements associated with excessive motor activity. Examples are:
§ Dystonia (where excessive muscle contraction leads to abnormal postures or exaggerated movements)
§ Chorea (abnormal involuntary movements that can be jerking and random)
§ Athetosis (involuntary twisting or writhing movements, usually in the fingers, hands or feet)

		Amantadine is a glutamate antagonist that may be used to manage dyskinesia associated with levodopa.

Question 4

COMT Inhibitors (e.g., entacapone)

Answer 4

COMT Inhibitors (e.g., entacapone) are inhibitors of catechol-o-methyltransferase (COMT). The COMT enzyme metabolises levodopa in both the body and brain. Entacapone is taken with levodopa (and a decarboxylase inhibitor) to slow the breakdown of the levodopa in the brain. It extends the effective duration of the levodopa.

Question 5

Dopamine agonists

Answer 5

Dopamine agonists mimic the action of dopamine in the basal ganglia, stimulating the dopamine receptors. They are less effective than levodopa in reducing symptoms. They are typically used to delay the use of levodopa, then used in combination with levodopa to reduce the required dose. Pulmonary fibrosis is a notable side effect with prolonged use. Examples are:
□ Bromocriptine
□ Pergolide
□ Cabergoline

Question 6

Monoamine oxidase-B inhibitors

Answer 6

Monoamine oxidase-B inhibitors block the action of monoamine oxidase-B enzymes, helping to increase the circulating dopamine. Monoamine oxidase enzymes break down neurotransmitters such as dopamine, serotonin and adrenaline. Monoamine oxidase-B is more specific to dopamine. They are typically used to delay the use of levodopa, then in combination with levodopa to reduce the “end of dose” worsening of symptoms. Examples are:
® Selegiline
® Rasagiline

Question 7

Sodium valproate

Answer 7

Sodium Valproate

This is a first line option for most forms of epilepsy (except focal seizures). It works by increasing the activity of GABA, which has a relaxing effect on the brain. Notable side effects of sodium valproate include:

Teratogenic, so patients need careful advice about contraception
Liver damage and hepatitis
Hair loss
Tremor

There are a lot of warning about the teratogenic effects of sodium valproate and NICE updated their guidelines in 2018 to reflect this. It must be avoided in girls unless there are no suitable alternatives and strict criteria are met to ensure they do not get pregnant.

Question 8

Carbamazepine

Answer 8

Carbamazepine

This is first line for focal seizures. Notable side effects are:

Agranulocytosis
Aplastic anaemia
Induces the P450 system so there are many drug interactions

Question 9

Phenytoin
Use and side effects

Answer 9

Phenytoin
Anti epilepsy medication

Notable side effects:

Folate and vitamin D deficiency
Megaloblastic anaemia (folate deficiency)
Osteomalacia (vitamin D deficiency)

Question 10

Ethosuximide

Use and Notable side effects:

Answer 10

Ethosuximide
Anti epilepsy medication

Notable side effects:

Night terrors
Rashes

Question 11

Lamotrigine

Answer 11

Lamotrigine

Anti epilepsy medications

Notable side effects:
Stevens-Johnson syndrome or DRESS syndrome. These are life threatening skin rashes.
Leukopenia