Drugs acting on the myometrium Flashcards
Classify drugs acting on myometrium?
●drugs that stimulate contractions of myometrium (tocomimetics):
– drugs that cause rhythmic contractions:
oxytocin,
dinoprostone,
dinoprost,
misoprostol;
– drugs that cause tonic contractions:
ergometrine – INN (ergonovine – USAN),
ergotamine;
●drugs that inhibit contractions of myometrium
(tocolytics):
– selective beta-2 adrenergic agonists: ritodrine,
hexoprenaline,
terbutaline,
fenoterol;
Ritodrine
– antagonist of oxytocin receptors: atosiban;
– Ca++ channel blocker:
nifedipine
About Oxytocin & MOA?
> > Oxytocin is a hormone of the posterior
lobe of the pituitary gland.
It stimulates the contractility of the myometrium through the activation of the oxytocin receptors.
In the early period of pregnancy,
the number of the oxytocin receptors in the uterus is small,
but in the second half of pregnancy,
the expression of the oxytocin receptors increases leading to the increased sensitivity of the uterus to oxytocin.
> Oxytocin also contributes to lactation.
Oxytocin is used as intravenous infusion not only for the stimulation of labor,
but also in postpartum bleeding because in higher doses it induces tonic (sustained) contraction of the myometrium,
Adverse effects of oxytocin?
●Oxytocin, as well as other drugs stimulating contractions of the myometrium,
can cause excessive stimulation of the myometrium leading to the impairment of the blood supply to the fetus
●Uterine rupture is also possible.
Preparations of prostaglandins & Their Characteristics?
●dinoprostone (prostaglandin E2)
●dinoprost (prostaglandin F2)
●misoprostol (a synthetic analog of
prostaglandin E2).
The effects of prostaglandins on the uterus are the same in all periods of the pregnancy, so they can be used for both labor stimulation
(in late pregnancy)
and
induction of abortion
(in early pregnancy).
Application & Adverse effects of the preparation of prostaglandins?
Application:
for labor stimulation –
dinoprostone into vagina (as vaginal suppositories or vaginal slabs),
dinoprost as intravenous injection,
or
misoprostol as tablets orally can be administered; for induction of abortions’
– dinoprostone intravaginal, dinoprost as intraamniotic injection,
or
misoprostol orally
(usually together with antagonist of progesterone receptors mifepristone) can be used.
Adverse effects.
Systemic administration of dinoprostone can lead
to the vasodilation and hypotension
(but in intravaginal administration
possibility of this effect is low).
Dinoprost, on the contrary,
causes vasoconstriction.
Misoprostol administered orally can cause diarrhea
Drugs that cause tonic (prolonged, sustained) contractions?
●ergometrine,
●ergotamine
are used in postpartum bleeding
(bleeding after delivery) orally or by intravenous or
intramuscular injections.
These drugs are alkaloids derived from fungus Ergot (Claviceps purpurea),
that grows on rye and some other related cereal plants.
Ergot alkaloids?(MOA & Adverse effects)
●The mechanism of the action of the Ergot alkaloids,
is complicated,
they interact with
adrenergic receptors,
dopamine receptors and
serotonin receptors.
For example,
ergometrine is an agonist of
alpha adrenoceptors and serotonin 5-HT2 receptors, but the role of these receptors
in the mechanism of the effect on the uterus has not been proven.
Adverse effects,,
Include nausea and vomiting
(due to the activation of the vomiting center).
The overdose can cause prolonged
vasoconstriction leading to gangrenes.
Higher doses of oxytocin and preparations of prostaglandins also
induce
tonic contractions of the myometrium and can be used in postpartum bleeding.
Drugs that Inhibit Contractions of Myometrium (Tocolytics)
> > selective beta-2 adrenergic receptor agonists
Antagonist of oxytocin receptors. Atosiban
Ca++ channel blocker - Nifedipine
(Drugs that inhibit contractions of the myometrium are used to prevent premature labor or spontaneous abortion.
>After systemic administration. (per os or IV)
Selective beta-2 adrenergic receptor agonist?
●can cause some cardiovascular adverse effects:
the decrease of the blood pressure
(through beta-2 adrenergic receptors in the vessels),
●the increase of the heart rate,
arrhythmias
(due to the activation of some beta-1 adrenergic receptors).
●Due to the risk of dangerous cardiovascular adverse effects in the USA, these drugs are now not recommended for use to prevent preterm labor.
Antagogonist of oxytocin receptors. Atosiban
●causes
relaxation of the myometrium
by blocking the oxytocin receptors.
●It is safer in comparison with the adrenergic receptor agonists,
has fewer adverse effects
(sometimes causes nausea, vomiting, dizziness, headache)
Ca++ channel blocker. Nifedipine
> Induces the relaxation of the myometrium
by blocking the Ca++ flow into the cell through the
L-type Ca++ channels.
> also causes vasodilation and is used
in arterial hypertension
and coronary artery diseases
(see “Antihypertensive drugs”, “Drugs used
for the treatment of coronary artery disease”).
Nifedipine can cause adverse effects related to vasodilation
(dizziness, reflex tachycardia)
