Two primary hypotheses have been proposed to explain the actions of these drugs. First, the triptans, the ergot alkaloids, and antidepressants may activate 5-HT1D/1B receptors on presynaptic trigeminal nerve endings to inhibit the release of vasodilating peptides, and antiseizure agents may suppress excessive firing of these nerve endings. Second, the vasoconstrictor actions of direct 5-HT agonists (the triptans and ergot) may prevent vasodilation and stretching of the pain endings. It is possible that both mechanisms contribute in the case of some drugs.
Sumatriptan and its congeners are currently first-line therapy for acute severe migraine attacks in most patients (Figure 16–3). However, they should not be used in patients at risk for coronary artery disease. Anti-inflammatory analgesics such as aspirin and ibuprofen are often helpful in controlling the pain of migraine. Rarely, parenteral opioids may be needed in refractory cases. For patients with very severe nausea and vomiting, parenteral metoclopramide may be helpful.
Sumatriptan and the other triptans are selective agonists
Orlistat GI lipase inhibitor Reduces lipid absorption 60–120 mg TID PO Decreased absorption of fat-soluble vitamins, flatulence, fecal incontinence
In population studies, all of the triptan 5-HT1 agonists are as effective or more effective in migraine than other acute drug treatments, eg, parenteral, oral, and rectal ergot alkaloids. However, individual drugs in this class may have different structure to that of the 5-HT nucleus can be seen in the structure below. These receptor types are found in cerebral and meningeal vessels and mediate vasoconstriction. They are also found on neurons and probably function as presynaptic inhibitory receptors.
cent of patients
BID, twice daily; BP, blood pressure; CNS, central nervous system; GI, gastrointestinal; HR, heart rate; PO, by mouth; SC, subcutaneously; TID, three times daily.
Treatment (P = placebo, S = sumatriptan)
FIGURE 16–3 Effects of sumatriptan (734 patients) or placebo (370 patients) on symptoms of acute migraine headache 60 minutes after injection of 6 mg subcutaneously. All differences between placebo and sumatriptan were statistically significant. (Data from Cady RK et al: Treatment of acute migraine with subcutaneous sumatriptan. JAMA for 5-HT1D and 5-HT1B receptors; the similarity of the triptan 1991;265:2831.)
TABLE 16–6 Pharmacokinetics of triptans.