DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Table 13–6
Natural and Semisynthetic Ergot Alkaloids
A. AMINE ALKALOIDS AND CONGENERS B. AMINO ACID ALKALOIDS
ALKALOID X Y ALKALOID d R(2') R'(5')
d-Lysergic acid
Ergotamine
d-Isolysergic acid
Ergosine
d-Lysergic acid
Ergostine
diethylamide (LSD)
Ergotoxine group:
Ergonovine
Ergocornine
(ergometrine)
Ergocristine
α-Ergocryptine
Methylergonovine
β-Ergocryptine
Methysergide a
Bromocriptine e
Lisuride b
Lysergol
Lergotrile c
Metergoline a,b
a
Contains methyl substitution at N1. b Contains hydrogen atoms at C9 and C10. c Contains chlorine atom at C2. d Dihydro derivatives contain hydrogen
atoms at C9 and C10. e Contains bromine atom at C2.
about twice that number after parenteral administration. This side
effect is problematic, since nausea and sometimes vomiting are part
of the symptomatology of a migraine headache. Leg weakness is
common, and muscle pains that occasionally are severe may occur
in the extremities. Numbness and tingling of fingers and toes are
other reminders of the ergotism that this alkaloid may cause.
Precordial distress and pain suggestive of angina pectoris, as well as
transient tachycardia or bradycardia, also have been noted, presumably
as a result of coronary vasospasm induced by ergotamine.
Localized edema and itching may occur in an occasional hypersensitive
patient, but usually do not necessitate interruption of ergotamine
therapy. In the event of acute or chronic poisoning (ergotism),
treatment consists of complete withdrawal of the offending drug and
symptomatic measures to maintain adequate circulation by agents
such as anticoagulants, low-molecular-weight dextran, and potent
vasodilator drugs such as intravenous sodium nitroprusside.
Dihydroergotamine has lower potency than does ergotamine as an
emetic, vasoconstrictor, and oxytocic.
Ergot alkaloids are contraindicated in women who are, or
may become, pregnant because the drugs may cause fetal distress
and miscarriage. Ergot alkaloids also are contraindicated in patients
with peripheral vascular disease, coronary artery disease, hypertension,
impaired hepatic or renal function, and sepsis. Ergot alkaloids
should not be taken within 24 hours of the use of the triptans, and
should not be used concurrently with other drugs that can cause
vasoconstriction.
Use of Ergot Alkaloids in Postpartum Hemorrhage. All of the
natural ergot alkaloids markedly increase the motor activity of the
uterus. After small doses, uterine contractions are increased in
force or frequency, or both, but are followed by a normal degree of
relaxation. As the dose is increased, contractions become more
forceful and prolonged, resting tone is dramatically increased, and
sustained contracture can result. Although this characteristic
precludes their use for induction or facilitation of labor, it is quite
compatible with their use postpartum or after abortion to control
bleeding and maintain uterine contraction. The gravid uterus is
very sensitive, and small doses of ergot alkaloids can be given
immediately postpartum to obtain a marked uterine response, usually
without significant side effects. In current obstetric practice,