Drugs Acting on Smooth Muscle

Drugs Used to Influence Smooth MuscleOrgans

Bronchodilators. Narrowing of bronchioles
raises airway resistance, e.g., in
bronchial or bronchitic asthma. Several
substances that are employed as bronchodilators
are described elsewhere in
more detail: 2-sympathomimetics
( given by pulmonary, parenteral, or
oral route), the methylxanthine theophylline
( given parenterally ororally),
as well as the parasympatholytic
ipratropium ( given by inhalation).
Spasmolytics. N-Butylscopolamine
is used for the relief of painful
spasms of the biliary or ureteral ducts.
Its poor absorption (N.B. quaternary N;
absorption rate <10%) necessitates parenteral
administration. Because the
therapeutic effect is usually weak, a potent
analgesic is given concurrently, e.g.,
the opioid meperidine. Note that some
spasms of intestinal musculature can be
effectively relieved by organic nitrates
(in biliary colic) or by nifedipine (esophageal
hypertension and achalasia).
Myometrial relaxants (Tocolytics).
2-Sympathomimetics such as fenoterol
or ritodrine, given orally or parenterally,
can prevent premature labor
or interrupt labor in progress when dangerous
complications necessitate cesarean
section. Tachycardia is a side effect
produced reflexly because of !2-mediated
vasodilation or direct stimulation of
cardiac !1-receptors. Magnesium sulfate,
given i.v., is a useful alternative
when -mimetics are contraindicated,
but must be carefully titrated because
its nonspecific calcium antagonism
leads to blockade of cardiac impulse
conduction and of neuromuscular
transmission.
Myometrial stimulants. The neurohypophyseal
hormone oxytocin is given parenterally
(or by the nasal or buccal route) before, during, or after
labor in order to prompt uterine contractions
or to enhance them. Certain
prostaglandins or analogues of them
(F2": dinoprost; E2: dinoprostone,
misoprostol, sulprostone) are capable of
inducing rhythmic uterine contractions
and cervical relaxation at any time. They
are mostly employed as abortifacients
(oral or vaginal application of misoprostol
in combination with mifepristone.
Ergot alkaloids are obtained from
Secale cornutum (ergot), the sclerotium
of a fungus (Claviceps purpurea) parasitizing
rye. Consumption of flour from
contaminated grain was once the cause
of epidemic poisonings (ergotism) characterized
by gangrene of the extremities
(St. Anthony’s fire) and CNS disturbances
(hallucinations).
Ergot alkaloids contain lysergic acid
(formula in A shows an amide). They act
on uterine and vascular muscle. Ergometrine
particularly stimulates the uterus.
It readily induces a tonic contraction
of the myometrium (tetanus uteri). This
jeopardizes placental blood flow and fetal
O2 supply. The semisynthetic derivative
methylergometrine is therefore
used only after delivery for uterine contractions
that are too weak.
Ergotamine, as well as the ergotoxine
alkaloids (ergocristine, ergocryptine,
ergocornine), have a predominantly
vascular action. Depending on the initial
caliber, constriction or dilation may
be elicited. The mechanism of action is
unclear; a mixed antagonism at "-
adrenoceptors and agonism at 5-HT-receptors
may be important. Ergotamine
is used in the treatment of migraine.
Its congener, dihydroergotamine,
is furthermore employed in orthostatic
complaints .
Other lysergic acid derivatives are
the 5-HT antagonist methysergide, the
dopamine agonists bromocriptine, pergolide,
and cabergolide ,
and the hallucinogen lysergic acid diethylamide
(LSD).