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Drugs uses of uterine relaxation and contraction

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									                                      DONE BY:
                                 Ahmed Al abdaly
                                 Khalid bakheet
                                 Turky al ohadib
                                 Ibrahim al zaben
 Supervised by : Dr . Mahmud ehab
Physiology of Uterine contration and
receptors involved
Drugs used for Uterine Stimulants and
Indication and contraidication of Uterine
Stimulants and Relaxants.
Mechanism of action for Uterine Stimulants
and Relaxants.
Side effect of Uterine Stimulants and
 There is many receptors in uterus:
   • EP1 & EP2 receptors contraction promoting,
  abundant in the fundus
 • EP3 & EP4 receptors relaxation promoting,
  found in lower uterine segment
 • various expression of receptors may be
  responsible for differing sensitivity of
  myometrium throughout gestation and at
  delivery: E.G.
 beta-2   receptors

 Oxytocin   receptors

 PG   receptors
“Positive feedback loop”

              Oxytocin↑         Estradiol
         ⊕      Uterine     Oxytocin receptor
              contraction        ↑x100


  The Myometrium
  Smooth Muscle Contractions
  Contraction                           Relaxation
                Myosin light chain
Myosin light chain kinase
                                        1) Decreased intracellular Ca2+;
    Ca2+ activated
                                           Ca2+ sequestration
                Myosin light chain      2) Dephosphorylation of
                                Actin       myosin light chain

                                        3) Inactivation of myosin light
          Actin-Phosphorylated Myowin
                                        Chain kinase (e.g., by cyclic
                                        AMP- dependent phosphory-
              ATP                ADP
 The Myometrium
Uterine Contractions Characteristic of Labor
  ; muscular contractions, those of uterine smooth
    muscle of labor are painful

 • cause of pain (not known definitely)
   ① hypoxia of contracted myometrium
   ② compression of nerve ganglia in cervix & lower
      uterus by the tightly interlocking muscle bundles
   ③ stretching of cervix during dilatation
   ④ stretching of peritoneum overlying the fundus
  tocolytics           example              uterotonic      example
B2 receptor           Ritodrine             oxytocin        pitocin
  agonist            Terbutaline

Ca+ channel    Nifedipine and Verapamil   Prostaglandin   (Hemabate)

 Oxytocin        i(Atibosan) Atociban      ergotamine     (Methergine)

   Ca+         Magnesium Sulfate
antagonist         (MgSO4(

NSAID          indomethazine and
1- Ritodrine:
 uncomlipcated premature labor

A/E : Poorly controlled thyroid disease and diabetes

2- Nifedipine (not effective oraly)
 temporarily stopping contractions

 Other in treatment of hypertension

A/E: Cardiac disease. It should not be used concomitantly with
  magnesium sulfate
3- Atociban ( as IV)
          premature labor
          cessation of uterus contraction

4- (MgSo4)
 First line of therapy
 decreasing the force of contractions
A/E : Renal failure, atrioventricular block.

   5-NSAID :indomethazone and suldine
       It use in case of uterine tension in young female
   Uterotonic
   1- Oxytocin :
       Induction of labor

       Control of postpartum hemorrage

       Induction of lactation

        , Significant cephalopelvic disproportion

     A/E : Hypertonic uterine patterns, Patients with
      hypersensitivity to the drug

     2- Prostaglandin (PGE1) Mesoprestol
      Induction of labor

      Other like : First line agent for Open Angle Glaucoma

      soften the cervix
3-Ergotamine (Methergine)
 Postpartum Hemorrhage
 routine management after delivery of the

Hypertension; toxemia; hypersensitivity to
 ergots; peripheral ischemia
   tocolytics            example              uterotonic      example

B2 receptor             Ritodrine             oxytocin        pitocin
  agonist              Terbutaline

Ca+ channel      Nifedipine and Verapamil   Prostaglandin   (Hemabate)

  Oxytocin              Atociban             ergotamine     (Methergine)

Ca+ antagonist     Magnesium Sulfate
anti-contraction medications or labour repressants)
  are medications used to suppress premature
  labor (from the Greek tokos, childbirth, and lytic,
  capable of dissolving).
They are given when delivery would result
  in premature birth. The therapy also buys time for
  the administration of betamethasone,
  a glucocorticoid drug which greatly accelerates
  fetal lung maturity, but takes one to two days to
 Ritodrine   and Terbutaline:
Are beta-2 adrenergic receptor agonist - a
  class of medication used for smooth muscle
  relaxation (other similar drugs are used in
  asthma or other pulmonary diseases such
  as salbutamol). Since they have a bulky N-
  substituent, they have high β2-selectivity.
  Since it is β2-selective it is used for
  premature labor.
Nifedipine and Verapamil:
block the inward movement of calcium by binding
  to the L-type calcium channels in the heart and
  in smooth muscle of the peripheral vasculature.
  CCB’s dilate coronary arteries and peripheral
  arterioles, but not veins. They also decrease
  cardiac contractility (negative inotropic effect)
  ,automaticity at the SA node and conduction at
  the AV node. Dilation of the coronary arteries
  increases myocardial oxigen supply.
 nhibit passage of calcium through the voltage
  gated L-type (for Large/Long-lasting current)
  calcium channel on vascular smooth muscle cells
  and cardiac myocytes, reducing calcium
  availability for muscle contraction. Note that an
  inhibitor of the T-type (Transient current)
  cardiac calcium channel, MIBEFRADIL, has
  recently been terminated due to unacceptable
  drug interactions. Ion channel blockade explains
  the observed
 Peripheral vasodilatation
 Negative inotropic and negative chronotropic
   Atosiban:
   competitive inhibitor of oxytocin by blocking oxytocin

  Magnesium sulfate:
is believed to reduce acetylcholine released by nerve
   impulses, resulting in anticonvulsant effects and
   central nervous system depression and blocking
   peripheral neuromuscular transmission. Because
   magnesium antagonizes calcium and blocks calcium
   channels in bronchial and vascular smooth muscle, it
   also has antihypertensive actions.
A uterotonic is an agent used to
induce contraction or greater
tonicity of the uterus. Utertonics
are used both to induce labor, and
to reduce postpartum hemorrhage.
 Piticin:
    important for cervical dilation before birth
    and causes contractions during the second
    and third stages of labor . Oxytocin release
    during breastfeeding causes mild but often
    painful uterine contractions during the first
    few weeks of lactation. This also serves to
    assist the uterus in clotting the placental
    attachment point postpartum. However,
    in knockout mice lacking the oxytocin
    receptor, reproductive behavior
    and parturition is normal
 Hemabate:
 it is produced by the uterus when stimulated
  by oxytocin, in the event that there has been no
  implantation during the follicular phase. It acts
  on the corpus luteum to cause luteolysis,
  forming a corpus albicans and stopping the
  production of progesterone. Action of PGF2α is
  dependent on the number of receptors on the
  corpus luteum membrane.
 The PGF2α isoform 8-iso-PGF2α is significantly
  increased endometriosis, being a potential
  causative links in endometriosis-associated
  oxidative stress.
   The trade name of carboprost tromethamine is Hemabate.
   Carboprost induces contractions and can trigger abortion in early
    pregnancy. It also reduces postpartum bleeding

   arboprost tromethamine administered intramuscularly stimulates
    in the gra viduterus myometrial contractions similar
    to labor contractions at the end of a full term pregnancy.
    Whether or not these contractions result from a direct effect of
    carboprost on the myome-trium has not been determined.
    Nonetheless, they evacuate the products of conception from the
    uterus in most cases.
   Postpartum, the resultant myometrial contractions
    provide hemostasis at the site of placentation.
   Carboprost tromethamine also stimulates the smooth muscle of
    the humangastrointestinal tract. This activity may produce the
    vomiting or diarrhea or both that is common when carbo-prost
    tromethamine is used to terminate pregnancy and for use
    postpartum. In laboratory animals and also in humans carboprost
    tromethamine can elevate body temperature. With the clinical
    doses of carboprost trometh-amine used for the termination of
    pregnancy, and for use postpartum, some patients do experience
    transient temperature increases.
 Methergin:
 itis used medicinally for treatment of
  acute migraine attacks (sometimes in
  combination with caffeine). Its medicinal
  usage to induce childbirth, yet dosage
  uncertainties discouraged the use. It has
  been used to prevent post-
  partum haemorrhage (bleeding after
  childbirth), The molecule shares structural
  similarity with neurotransmitters such
  as serotonin, dopamine, and epinephrine and
  can thus bind to several receptors acting as
  an agonist
  Stimulates uterine
   smooth muscles
 producing sustained
thereby shortens the
 third stage of labor
 Hypotension  or hypertension, chest pain
 Headache, dizziness, fainting
 Nausea, vomiting, diarrhea
 Vaginal pain, cramping
 Leg cramps, joint swelling, chills, fever,
  weakness, blurred vision and hyperstimulation
 (oxytocin) : cardiovascular changes, cyanosis,
  muscle pain, tingling, other symptoms
  associated with decreased blood circulation.
 Palpitations,tachycardia, hypertension.
 Tremors, anxiety, insomnia, headache, dizziness,
 Nausea, vomiting, anorexia, bloating, diarrhea,
 Hyperglycemia, hypokalemia
 Dyspnea, hyperventilation,
      and Clinical Pharmacology, 11th Edition
 Basic
 (LANGE Basic Science)

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