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

of these drugs, causes nausea, vomiting, severe thirst, hypoperfusion, chest pain, blood pressure changes, con- fusion, drug dependency (with prolonged use) and a drug-withdrawal syndrome. Clinically important drug–drug interactions If these drugs are combined with beta-blockers, the risk of peripheral ischaemia and gangrene is increased. Such combinations should be avoided. T riptans The triptans are a relatively new class of drugs that cause cranial vascular constriction and relief of migraine headache pain in many people. These drugs are not associated with the vascular and GI effects of the ergot derivatives. The triptan of choice for a par- ticular individual depends on personal experience and other pre-existing medical conditions. A person may have a poor response to one triptan and respond well to another. Available triptans include eletriptan ( Relpax ) (not available in New Zealand), naratriptan ( Naramig ), riza- triptan ( Maxalt ), sumatriptan ( Imigram , Sumagran , Sumatab ) and zolmitriptan ( Zoltrip, Zomig ). Therapeutic actions and indications The triptans bind to selective serotonin receptor sites to cause vasoconstriction of cranial vessels, reliev- ing the signs and symptoms of migraine headache (see Figure 26.2). They are indicated for the treatment of acute migraine and are not used for prevention of migraines. (See Table 26.2 for usual indications for each of the triptans.) Sumatriptan, the first drug of this class, is used for the treatment of acute migraine attacks and for the treatment of cluster headaches in adults. It can be given orally, subcutaneously or by nasal spray. Naratriptan, rizatriptan and zolmitriptan are used orally only for the treatment of acute migraines. Rizatriptan and zolmitriptan are also available as fast-dissolving tablets. Pharmacokinetics The triptans are rapidly absorbed from many sites; they are metabolised in the liver (sumatriptan by MAO) and are primarily excreted in the urine. They cross the placenta and have been shown to be toxic to the fetus in animal studies. They also enter breast milk. The safety and efficacy of use in children have not been established. Contraindications and cautions Triptans are contraindicated with any of the fol- lowing conditions: allergy to any triptan to avoid

hypersensitivity reactions ; pregnancy because of the possibility of severe adverse effects on the fetus ; and active CAD, which could be exacerbated by the vessel- constricting effects of these drugs. These drugs should be used with caution in elderly people because of the possibility of underlying vascular disease ; in individu- als with risk factors for CAD; in breastfeeding women because of the possibility of adverse effects on the infant ; and in people with renal or hepatic dysfunction, which could alter the metabolism and excretion of the drug. Rizatriptan seems to have more angina-related effects, and it is not recommended for people with a history of CAD, which could be exacerbated by its cardiac effects . Adverse effects The adverse effects associated with the triptans are related to the vasoconstrictive effects of the drugs. CNS effects may include numbness, tingling, burning sen- sation, feelings of coldness or strangeness, dizziness, weakness, myalgia and vertigo. GI effects such as dys- phagia and abdominal discomfort may occur. CV effects can be severe and include blood pressure alterations and tightness or pressure in the chest. Clinically important drug–drug interactions Combining triptans with ergot-containing drugs results in a risk of prolonged vasoactive reactions. There is a risk of severe adverse effects if these drugs are used within 2 weeks after discontinuation of a MAO inhibi- tor because of the increased vasoconstrictive effects that occur. If triptans are to be given, it is imperative that the person has not received an MAO inhibitor in more than 2 weeks. Prototype summary: Sumatriptan Indications: Treatment of acute migraine; treatment of cluster headaches (SC route). Actions: Binds to serotonin receptors to cause vasoconstrictive effects on cranial blood vessels. Pharmacokinetics: Route Onset Peak Duration Nasal spray Varies 5–20 mins Unknown Oral 1–1.5 hours 2–4 hours Up to 24 hours SC Rapid 1–5 hours Up to 24 hours T 1/2 : 115 minutes; metabolised in the liver, excreted in the urine. Adverse effects: Dizziness, vertigo, weakness, myalgia, blood pressure alterations, tightness or pressure in the chest, injection-site discomfort, tingling, burning sensations, numbness.