McKenna's Pharmacology for Nursing, 2e

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

(see Table 24.1 for usual indications for each of these agents). Levodopa is the mainstay of treatment for Parkinson’s disease. This precursor of dopamine crosses the blood–brain barrier and is converted into dopamine. In this way, it acts like a replacement therapy. Although levodopa is almost always given in combination form with carbidopa as a fixed-combination drug ( Sinemet ), other drugs besides carbidopa may be used (see Adjunct­ ive agents). When used with carbidopa, the enzyme dopa decarboxylase is inhibited in the periphery, diminish­ ing the metabolism of levodopa in the gastrointestinal (GI) tract and in peripheral tissues, thereby leading to higher levels crossing the blood–brain barrier. Because the carbidopa decreases the amount of levodopa needed to reach a therapeutic level in the brain, the dose of levodopa can be decreased, which reduces the incidence of adverse side effects. Amantadine is an antiviral drug that also seems to increase the release of dopamine, being effective as long as there is a possibility of more dopamine release. Apomorphine is a newer adjunctive therapy for Parkinson’s disease that directly binds with postsyn- aptic dopamine receptors. Similar to apomorphine, bromocriptine, pergolide and pramipexol act as direct dopamine agonists on dopamine-receptor sites in the substantia nigra. Because bromocriptine does not depend on cells in the area to biotransform it or to increase the release of already produced dopamine, it may be effect­ ive longer than levodopa or amantadine. Ropinirole and rotigotine are newer drugs that directly stimulate dopamine receptors. They are also used to treat restless leg syndrome. Pharmacokinetics The dopaminergics are usually given orally and are generally well absorbed from the GI tract and widely distributed in the body. Apomorphine, however, must be given subcutaneously. The dopaminergics are metabo- lised in the liver and peripheral cells and excreted in the urine. They cross the placenta and enter breast milk. Contraindications and cautions The dopaminergics are contraindicated in the presence of any known allergy to the drug or drug components to prevent hypersensitivity reactions , and in angle- closure glaucoma, which could be exacerbated by these drugs. Dopaminergics enter breast milk and should not be used during breastfeeding because of the potential for adverse effects in the baby. In addition, levodopa is contraindicated in people with history or presence of suspicious skin lesions because this drug has been asso- ciated with the development of melanoma. Administer dopaminergic agents cautiously with people who have any condition that could be exacerbated by dopamine receptor stimulation , such as cardiovascular

disease, including myocardial infarction, arrhythmias and hypertension; bronchial asthma; history of peptic ulcers; urinary tract obstruction; and psychiatric disorders. Care is also necessary during pregnancy because these drugs cross the placenta and could adversely affect the fetus , and in people with renal and hepatic disease, which could interfere with the metabolism and excretion of the drug. Closely monitor cardiac status in people receiving apo- morphine because of the associated risk for hypotension and prolonged QT interval. Adverse effects The adverse effects associated with the dopaminergics usually result from stimulation of dopamine receptors. CNS effects may include anxiety, nervousness, headache, malaise, fatigue, confusion, mental changes, blurred vision, muscle twitching and ataxia. Peripheral effects may include anorexia, nausea, vomiting, dysphagia, and constipation or diarrhoea; cardiac arrhythmias, hypo- tension and palpitations; bizarre breathing patterns; urinary retention; and flushing, increased sweating and hot flushes. Bone marrow depression and hepatic dys- function have also been reported. Clinically important drug–drug interactions If dopaminergics are combined with monoamine oxidase (MAO) inhibitors, therapeutic effects increase and a risk of hypertensive crisis exists. The MAO inhib­ itor should be stopped 14 days before beginning therapy with a dopaminergic. Prototype summary: Levodopa Indications: Treatment of parkinsonism and Parkinson’s disease. Actions: Precursor of dopamine, which is deficient in parkinsonism; crosses the blood–brain barrier, where it is converted to dopamine and acts as a replacement neurotransmitter; effective for 2 to 5 years in relieving the symptoms of Parkinson’s disease. Pharmacokinetics: Route Onset Peak Duration Oral Varies 0.5–2 hours 5 hours T 1/2 : 1 to 3 hours; metabolised in the liver, excreted in the urine. Adverse effects: Adventitious movements, ataxia, increased hand tremor, dizziness, numbness, weakness, agitation, anxiety, anorexia, nausea, dry mouth, dysphagia, urinary retention, flushing, cardiac irregularities.