McKenna's Pharmacology for Nursing, 2e

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P A R T 4  Drugs acting on the central and peripheral nervous systems

TABLE 24.3

DRUGS IN FOCUS Adjunctive antiparkinsonism drugs

Drug name

Dosage/route

Usual indications

entacapone (Comtan)

200 mg PO taken with levodopa–carbidopa, maximum of eight doses per day

Adjunctive treatment of idiopathic Parkin­ son’s disease with levodopa–carbidopa for people who are experiencing “wearing off” of drug effects Adjunctive treatment or treatment of idiopathic Parkinson’s disease Adjunctive treatment of idiopathic Parkin­ son’s disease with levodopa–carbidopa in people whose response to that therapy has decreased

rasagiline (Azilect)

1 mg PO once daily with or without levodopa

selegiline (Selgene, Eldepryl)

5 mg PO b.d. (at breakfast and lunch); attempt to decrease levodopa–carbidopa dose after 2–3 days

tolcapone (Tasmar)

100 mg PO t.d.s.; maximum daily dose 600 mg Adjunctive treatment of idiopathic Parkin­ son’s disease with levodopa–carbidopa

ADJUNCTIVE AGENTS Adjunctive agents used to improve response to tradi- tional therapy include entacapone ( Comtan ), rasagiline ( Azilect ) (not available in New Zealand), tolcapone ( Tasmar ) (not available in Australia) and selegiline ( Eldepryl, Selgene ). See Table 24.3 for additional information. Entacapone is used with carbidopa–levodopa to increase the plasma concentration and duration of action of levodopa. It does this by inhibiting catecholamine- O -methyl transferase (COMT), a natur­ ally occurring enzyme that eliminates catecholamines, including dopamine. It is given with the carbidopa– levodopa at a dose of 200 mg PO, with a maximum of eight doses a day. It is readily absorbed from the GI tract, metabolised in the liver and excreted in urine and faeces. Women of childbearing age should be encour- aged to use barrier contraceptives while taking this drug, which crosses the placenta and could have adverse effects on the fetus. Rasagiline is an irreversible MAO type B selective inhibitor and its mechanism of action in Parkinson’s disease is not understood. It is believed that MAO inhib­ ition leads to elevated dopamine levels and promotes increased extracellular dopamine levels in the striatum. It is rapidly absorbed with peak levels achieved in approximately half an hour. It undergoes hepatic metab- olism after GI absorption and is excreted in the urine and faeces. Being a MAO inhibitor, there is a risk of development of hypertensive crisis. When combined with antidepressant treatment, there is an increased risk of serotonin syndrome. As prolactin secretion is blocked, rasagiline may inhibit breastfeeding. Tolcapone works in a similar way with carbidopa– levodopa to further increase plasma levels of levodopa. Tolcapone also blocks the enzyme COMT, which is responsible for the breakdown of dopamine. Because this drug has been associated with fulminant and potentially

fatal liver damage, it is contraindicated in the presence of liver disease. Tolcapone is reserved for use in later stages of Parkinson’s disease, when carbidopa–levodopa is losing its effectiveness. It undergoes hepatic metabo- lism after GI absorption and is excreted in the urine and faeces. It is given in doses of 100 or 200 mg PO three times a day, up to a maximum of 600 mg/day. Women of childbearing age should be encouraged to use barrier contraceptives while taking this drug, which crosses the placenta and could have adverse effects on the fetus. Selegiline is used with carbidopa–levodopa after people have shown signs of deteriorating response to this treatment. Its mechanism of action is not under- stood. It does irreversibly inhibit MAO, which has an important role in the breakdown of catecholamines, including dopamine. The maximum daily dose of the drug is 10 mg, and the dose of levodopa needs to be reduced when this drug is started. It is well absorbed from the GI tract, extensively metabolised in the liver and excreted in urine. It is not known whether this drug crosses the placenta, but it should be used in pregnancy only if the benefits to the mother clearly outweigh any potential risks to the fetus. Because of the risk of MAO inhibitor–induced hypertensive effects, people should be urged to immediately report severe headache and any other unusual symptoms which they have not experi- enced before.

Care considerations for people receiving adjunctive agents

Care considerations for people receiving the drugs listed in this section are similar to those for people receiving the dopaminergic drugs. Details related to each individual drug can be found in the specific drug monograph in your drug guide.