UTERUS :-Drugs acting on uterus either to be a stimulant (
contractor )or relaxant .
UTERINE STIMULANT AGENT include :-
Myometrial stimulants used for induce or facilitate labor & in
post partum hemorrhage to reduce incidence & extent of blood
, also of a role in inducing abortion , include following agents :-
A-OXYTOCIN : it is a peptide secreted via posterior pituitary
gland , it is a nine-amino acid peptide (six amino acid disulfide
bridge + three tail amino acid ) , use as IV infusion to stimulate
labor , also available as nasal spray to induce lactation post
partum ally, circulating half life 5 min. not use orally since it
destroyedby stomach .
Their mode of action via alteration of trans-membrane ionic
current in myometrial smooth muscle cells to produce uterine
contraction . sensitivity of uterus to oxytocin increase during
pregnancy .Their effects can be inhibit via [1- beta-adrenergic
agents , 2- inhaled anesthesia , 3- magnesium sulfate .] Their
effects in inducing lactation : it cause milk ejection via
contracting myo-epithelial cells that surrounding mammary
alveoli .It is of weak anti-diuretic effect .
Their clinical uses include :-
1- diagnostic uses to detect any intra-uterine growth retardation
(it cause uterine contraction that affect fetal blood supply that
affect fetal heart rate response , if no response mean growth
retardation ) .
2- therapeutic uses that include induce labor , augment
dysfunction labor for [ 1- condition required early vaginal
delivery like in case of Rh incompatibility or maternal DM , 2-
uterine inertia ,
3- incompleteabortion ] , also use to control post-partum
hemorrhage , for milk ejection in postpartum ally .their dosage :
give as IV infusion by pump & required fetal & maternal
monitoring , initially infuse 1 mU /min & gradually increase upto
5-20 mU/min till establish uterine contraction that for induction
of labor , for postpartum hemorrhage 10-40 U + 1L of dextrose
solution as 15 drop/min or 10 U IM after delivery of placenta ,
for milk ejection one puff in each nostril in setting position 2-3
min before nursing .their adverse effects include [ maternal
death by causing hypertension episode , uterine rapture , fetal
death , water intoxication ] .their caution include [multi-para ,
multi-pregnancy , hypertension , previous caesarean section ] ,
while their contraindication are hypertonic uterine inertia /
toxemia / placenta praevia / fetal distress . B-PROSTAGLANDIN
(PGE2 – Dinoprost , PG F2α- Dinoprosttone )
Both consider as a potent oxytocic effect for termination of
pregnancy at any age , their rate of successive about 80% , as
potent labor inducer agent either as initiation or stimulation ,
both super to oxytocin as labor inducer in woman with
preclampsia , clampsia , renal disease , cardian disease because
they are of no anti- diuretic effects , both useful to control
postpartum hemorrhage if oxytocin or ergot fail to control it ,
both pass feto-placental barrier, may be use alone or
incombination with oxytocin to induce delivery . their aderse
effects include [ dyspnea , cervical laceration , nausea , vomiting
, diarrhea , headache , MI , syncope , uterine rapture , hypo-
hypertension , flushing , chill & shivering] , while their
contraindication include [vaginal bleeding , seizure , renal
&hepatic & cardiac disease , jaundice , placent previa ,
multiparity , herpes infection , fetal distress , DM , caesarean
section , abnormal fetal position , asthma , anemia ] .
------PG F2α not available longerly for clinical use as intra-
amniotic (cause 100% successive rate of abortion & pregnancy
termination , of less side effects , may cause CV collapse if it
escape into circulation ) / use in second trimester in dose of 40
mg abort after 20 hours , other rout of administration are IM ,
intra-vaginally , available agent called CARBOPROST
TROMETHAMINE , it is one-tenth as potent as PGE2 , of more
GIT toxicity , of broncho-constriction effects so use caution ally
in asthmatic patient .
------PGE2 can be administrate as intra-vaginally for [1-as
oxytocin uses / 2- abortion in second trimester / 3- missed
abortion / 4- benign hydatiform mole / 5- softening of cervix at
term for labor ] , for labor as intra- vaginally 0.5 mg as gel or
control release formulation of PGE2 containing 10 mg , for
abortion 20 mg intra- vaginally suppository to be repeated after
3-5 hours , for softening of cervix at term as single vaginal insert
containing 10 mg PGE2 or vaginal get of 0.5 mg X4 /day , their
mean time of abortion 17 hours . , if administrated at rate of 20
times faster than that to induce labor cause reduction in blood
pressure & increase heart rate . , may be give orally in dose 0.5-
1.5 mg/hour & it is superior to oral oxytocin derivates ( as IV
oxytocin potency ).
C-METHYLERGOMETRINE MALEATE :-Ergot alkaloid either
amine or peptide alkaloid , amine alkaloid include [6-
methylergoline , lysergic acid , lysergic acid diethylamide ,
ergotamine , methylsergide ] , peptide one include [ergotamine
, ergocryptine , bromocriptine ] .Ergot alkaloid of variable
absorption properties via GIT , oral dose more than IM dose in
ten times , their absorption via GIT increase if give with caffeine
, amine alkaloid also absorbed via rectum , buccal cavity , aerosol
inhalation , bromocriptine well absorbed via GIT .
their mode of action by acting on many receptors like alfa-
adrenergic & serotonine receptors + CNS dopamine receptors as
agonist , partial agonist & antagonist .Their effects on uterus
include [its effects appear to combine alfa-adrenergic &
serotonine & other effects , sensitivity of uterus change during
pregnancy to ergots (increase dominance of alfa-1 receptor as
pregnancy progress ) , uterus at the term more sensitive than
early pregnancy & more than non-pregnant female , very small
dose of ergot cause evoke rhythm contraction & relaxation of
uterus , on high dose cause powerful prolong contraction ,
ergonovine a more selective than other alkaloid ergots in
affecting of uterus & it is a drug of choice for obstetric
application, it use as IV or IM for treatment of coronary artery
disease diagnosis –postpartum bleeding-incomplete abortion-
migraine- to accelerate expulsion of uterine contentafter infant
delivery in of 0.2 mg IM response within 5 min. not repeated
more often than every 2-4 hours while IV as infusion of 0.2 mg
over 1 min. required monitoring of blood pressure & uterine
contraction closely to avoid overdosing their oral maintenance
dose 0.2-0.4 mg every 6-12 hours up to a week may cause sinus
tachy-or brady-cardia – chest pain –pruritus –tinnitus –
weakness – if use for prolong time may cause elevated blood
pressure –gangrene –ischemia etc ] , clinically use for
postpartum hemorrhage , if use before delivery cause increasing
of fetal & maternal mortality rate , so only use to control uterine
bleeding postpartum ally in dose 0.2 mg IM its effect within 1-5
minutes .it is give at time of placenta delivery if the bleeding is
significant , their side effects include :
1-GIT disturbance as diarrhea , nausea , vomiting –
2- on prolong uses cause gangrene that may end in amputation
of arm-leg-bowel infarction as this state it is refractory to most
of vasodilators agent but infusion of large dose of
NITROPRUSSIDE or NITROGLYCERIN has been successful in
some cases .
3-drawsness & hallucination .
4-fibroplastic changes in retroperitoneal space , plural cavity &
endocardial tissues .their contraindication obstructive vascular
disease & collagen disease .
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UTERINE RELAXANT AGENTS :-Include following :-
1- uterine relaxant used in treatment of dysmenorrhea like :-
a- PG synthesis inhibitors especially ASPIRIN( non-selective COX
inhibitors ) , MEFENAMIC ACID(inhibitor of both COX &
phospholipase A2 ) , NAPROXEN (non-selective COX inhibitors )
. Arachidonic acid converted via effect of enzyme into many
other products like via COX which influence PG synthesis +
thromboxane , while via lipooxygenase into leukotriene , lipoxin
, hydroxyeicosa-tetraenoic acid . via epoxygenase-P450 into
epoxides , via free radicles into isoprostanes .
b- anti-cholinergic agents like hyoscine butyl- bromide
.2- uterine relaxant use in treatment of premature labor like
[isoxuprine hydrochloride , orciprenalinesulphate , salbutamol ,
terbutaline sulphate ] .
3- general anesthesia inhaled form like that nitrous oxide appear
to have little effect on uterine musculatures , but halogenated
hydrocarbon one are potent uterine relaxant this make it to be
use when uterine relaxation be required as for intra-uterine fetal
manipulation during delivery [agents like halothane ,
enfluraneisoflurane ..etc ] .
4- opioid analgesia :- this may prolong labor by unclear
mechanism but both central & peripheral effects reduce uterine
tone .
5- progesterone by decreasing the sensitivity of uterus to
oxytoncin action , used in treatment of botrh threaten abortion
& habitual abortion .
6- other low efficacy agents like [tramadol , atropine , nitritis ,
phenothiazine …etc] .