C H A P T E R 2 6
Opioids, opioid antagonists and antimigraine agents
411
artery bed (see Figure 26.2). These drugs are indicated
for the prevention or abortion of migraine or vascular
headaches. Ergotamine, the prototype drug in this class,
was the mainstay of migraine headache treatment before
the development of triptans. (See Table 26.2 for usual
indications for each drug.)
Pharmacokinetics
The ergot derivatives are rapidly absorbed from many
routes, with an onset of action ranging from 15 to
30 minutes. They are metabolised in the liver and pri-
marily excreted in the bile.
Ergotamine is administered orally or rectally for
rapid absorption.
Contraindications and cautions
Ergot derivatives are contraindicated in the following
circumstances: presence of allergy to ergot preparations
to avoid hypersensitivity reactions
; CAD, hypertension
or peripheral vascular disease,
which could be exacer-
bated by the CV effects of these drugs
; impaired liver
function,
which could alter the metabolism and excre-
tion of these drugs
; and pregnancy or breastfeeding
because of the potential for adverse effects on the fetus
and neonate.
Ergotism (vomiting, diarrhoea, seizures)
has been reported in affected infants.
Caution should be used in two instances: with
pruritus,
which could become worse with drug-
induced vascular constriction,
and with malnutri-
tion
because ergot derivatives stimulate the CTZ and
can cause severe GI reactions, possibly worsening
malnutrition.
Adverse effects
The adverse effects of ergot derivatives can be related
to the drug-induced vascular constriction. CNS effects
include numbness, tingling of extremities and muscle
pain; CV effects such as pulselessness, weakness, chest
pain, arrhythmias, localised oedema and itching and
MI may also occur. In addition, the direct stimulation
of the CTZ can cause GI upset, nausea, vomiting and
diarrhoea. Ergotism, a syndrome associated with the use
TABLE 26.2
DRUGS IN FOCUS Antimigraine agents
Drug name
Dosage/route
Usual indications
Ergot derivatives
ergotamine (Cafergot)
2 tabs PO up to 6 tabs/day, or one supp PR up
to three supps/day
Prevention and abortion of migraine
attacks in adults
Triptans
eletriptan (Relpax)
Initially, 40 mg PO repeat after 2 hours if
needed
Maximum 160 mg/day
Treatment of acute migraines in adults
naratriptan (Naramig)
1–2.5 mg PO with fluid; may repeat in 4 hours
if needed
Treatment of acute migraines in adults
rizatriptan (Maxalt)
5–10 mg PO; may repeat in 2 hours; do not
exceed 30 mg/day
Treatment of acute migraines in adults;
orally disintegrating tablet may be useful
if there is difficulty swallowing
sumatriptan (Imigran,
Sumagran, Sumatab)
50–100 mg PO at first sign of headache, may
repeat in 2 hours; by nasal spray in one
nostril, may repeat in 2 hours; do not exceed
40 mg/day
Treatment of acute migraines, cluster
headaches in adults
zolmitriptan (Zomig)
2.5 mg PO; may repeat in 2 hours; do not
exceed 10 mg/day
Treatment of acute migraines in adults
Prototype summary: Ergotamine
Indications:
Prevention or abortion of vascular
headaches.
Actions:
Constricts cranial blood vessels, decreases
pulsation of cranial arteries and decreases
hyperperfusion of the basilar artery vascular bed;
mechanism of action is not understood.
Pharmacokinetics:
Route
Onset
Peak
Oral
Rapid
0.5–3 hours
PR
Varies
Unknown
T
1/2
:
2.7 hours, then 21 hours; metabolised in the
liver, excreted in the faeces.
Adverse effects:
Numbness, tingling in the
fingers and toes, muscle pain in the extremities,
pulselessness or weakness in the legs, praecordial
distress, tachycardia, bradycardia, ergotism
(nausea, vomiting, diarrhoea, severe thirst,
hypoperfusion, chest pain, confusion).
