412
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.
