L dopa/peripheral decarboxylase inhibitors

Question 1

Indications

Answer 1

1. Dopaminergic drugs are used in early Parkinson’s disease, when dopamine agonists (e.g. ropinirole, pramipexol) may be preferred over levodopa.
2. In later Parkinson’s disease, levodopa is an integral part of management, while dopamine agonists are an option for add-on therapy.
3. Levodopa and dopamine agonists may be options for secondary parkinsonism (parkinsonian symptoms due to a cause other than idiopathic Parkinson’s disease), but addressing the underlying cause (e.g. discontinuation of an offending drug) generally takes precedence.

Question 2

Mechanisms of action

Answer 2

In Parkinson’s disease, there is a deficiency of dopamine in the nigrostriatal pathway that links the substantia nigra in the midbrain to the corpus striatum in the basal ganglia. 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. This generates the features of Parkinson’s disease, such as bradykinesia and rigidity. Treatment seeks to increase dopaminergic stimulation to the striatum. It is not possible to give dopamine itself because it does not cross the blood–brain barrier. By contrast, levodopa (L-dopa) is a precursor of dopamine that can enter the brain via a membrane transporter

Question 3

Adverse effects

Answer 3

Nausea
Drowsiness
Confusion
Hallucinations

Question 4

Warnings

Answer 4

Dopaminergic drugs should be used cautiously in the elderly and those with existing cognitive or psychiatric disease, due to the risk of causing confusion and hallucinations. They should also be used cautiously in those with cardiovascular disease, because of the risk of hypotension.

Question 5

Interactions?

Answer 5

Levodopa is always given with a peripheral dopa-decarboxylase inhibitor (e.g. carbidopa) to reduce its conversion to dopamine outside the brain. This desirable interaction reduces nausea and lowers the dose needed for therapeutic effect. Dopaminergic agents should not usually be combined with antipsychotics (particularly first-generation) or metoclopramide because their effects on dopamine receptors are contradictory.

Question 6

Prescribing

Answer 6

Starting or altering pharmacological therapy in Parkinson’s disease should be done only under specialist advice. Many specialists prefer dopamine agonists in early disease then add levodopa when symptoms become disabling. The aim of this is to defer development of on–off effects until as late as possible. Levodopa is only available in combined preparations with peripheral dopa-decarboxylase inhibitors: with benserazide (co-beneldopa) or carbidopa (co-careldopa).

Question 7

Administration

Answer 7

It is very important with levodopa that doses are taken at times that produce the best symptom control for the patient. This is especially important if the patient is admitted to hospital (see Clinical tip).

Question 8

Communication

Answer 8

Close communication is essential between the patient and specialists in Parkinson’s disease. Often a clinical nurse specialist will form the vital link in this partnership. You should engage with the specialist team to support this.

Question 9

Monitoring

Answer 9

The best form of monitoring for clinical efficacy and side effects is an assessment by a Parkinson’s disease specialist. Blood pressure should be monitored in all patients receiving dopaminergic therapy, particularly those with existing cardiovascular disease.