Dr.U.P.Rathnakar MD. DIH. PGDHM

K.M.C.Mangalore

Drugs acting on the uterus

Drugs Acting on the Uterus

• Introduction• Stimulants

1. Oxytocin2. Desamino-oxytocin3. Ergometrine, Methyl ergometrine4. Prostaglandins

• Tocolytics (Relaxants)1. Adr.agonists, Ca++ blockers,

Magnesium sulfate, oxytocin antagonist, Misc *

• Drugs ---- Endometrium or myometrium

• Endometrium--- Estrogen or progesterone, and antagonists

• Myometrium-1. Indirectly acting-Symp or P.symp

[ANS drugs-non selective-other systems+]

2. Directly acting1. Ut.stimulants (oxytocics)2. Ut. Relaxants (Tocolytics)*

Drugs

UTERINE STIMULANTS

• Post. Pit. Hormone- Oxytocin

• Ergot alkaloids- Ergometrine (Ergonovine), Methylergometrine

• Prostaglandins- PGE2, PGF2a, 15-Methyl PGF2a, Misoprostol

• Miscellaneous- Alcohol, Ethacridine, Quinine*

Oxytocin (Quick birth) • Post Pit Oxytocin and Vasopressin• Synth. In hypothalumus Transported

and stored in post. Pitutary• Released after distension of the cervix

and vagina birth• Stimulation of the nipples

breastfeeding, (Letdown or milk ejection reflex)*

•Not absorbed orally•Administerd by i.v, i.m, rarely nasal route.

•Not bound to plasma protiens-t1/2- 2 -5mts

•Metabolized in liver and kidney*

Pharmacokinetics

•Acts GPCR•Small doses Frequency and

force•Large doses Sustained

contraction•Mammary alveoli-myoepethelial

cells contraction•Neurotransmitter in brain*

Pharmacodynamics

• Uterus:

• Sensitivity increases as pregnancy progresses-9 fold [early&nonpregnant-resistant]

• Receptors increase- 30 times

• Estrogen facilitates, progesterone inhibits

• Lower segment not contracted

• Breast- Milk ejection

• CVS- Hypotension

• Kidney- ADH like

• CNS*

Ph. Actions:

• To induce, augment labor in1. Premature rupture2. Isoimmunization3. Placental insufficiency4. Toxemia, post maturity, DM

Verify fetal lung maturity, Exclude C.Is-Position abnormalities, CPD,distress etc.Monitor fetal HRLook for fetal, maternal distress, ut.scar*

Clinical uses of Oxytocin

Oxytocin DOC i.v. infusion pump Dilution-5 IU in 500ml

NS/Glucose 0.2-2ml/mt. depending on

response Precautions Monitor mother

and fetus. Over stimulation Discontinue*

Induction & Augmentation

1. Short t ½2. Normal relaxation of uterus

allowed-Good fetal oxygenation3. Lower segment not affected-

descent free4. Consistent augmentation in

ut.inertia*

Why Oxytocin? Why not Ergometrine?

3. Third stage of labour, puerperium: (Post partum hemorrhage) 5 IU i.m or i.v infusion.

Other drugsErgometrine, Misoprostol4. Breast engorgement: Nasal spray before

suckling5. Oxytocin challenge test: To assess

placental insufficiency• AD.Effects: Rupture ut. Fetal distress,

maternal injury*

Other uses

•Buccal formulation, uses same as oxytocin, less consistent action*

Desamino-oxytocin

Ergometrine and Methyl ergometrine

• Amine ergot alkaloid and methyl derivative.

• Increase force, frequency, duration of ut.contractions

• Moderate increase of dose Basal tone increased

• Lower segment also contracts.

• 5HT2, α Adre.agonist

• Methyl ergometrine more potent action on uterus and less on CVS, CNS, GIT etc.*

• Methyl ergometrine less toxicNausea, vomiting, rise in BP.Decreases milk secretionAvoided in Vascular disease, HTN, toxemia Sepsisgangrene Liver and kidney disease.*

[Safe in ob.doses]C.I.in pregnancy & early stages of labour

Ad. Effects:

1. PPH After anterior shoulder presentation

Prevention 0.2-0.3 mg i.m Treatment 0.5 mg i.v.2. Prevent uterine atony[cesarian,

instrument]3. To promote involution in multipara

0.125mg TDS -7days4. Diagnosis of variant angina during

Coronary angio*

Uses:

•The "Four Ts" for Causes of Postpartum Hemorrhage

•Four Ts CauseApproximate incidence (%)

Tone Atonic uterus 70

Trauma Lacerations, hematomas, inversion, rupture

20

Tissue Retained tissue, invasive placenta

10

Thrombin Coagulopathies 1

Ergometrine

• PGE2 (Dinoprostone) Vaginal application Induce II trimester abortion, missed abortion, ripening of cervix in near term

• Preperations- Misoprostol with mifepristone for early

abortion15-Methyl-PGF2α (Carboprost) II

trimester abortionsFacilitate labour- Unlabelled use in

cardiac, renal disease, eclampsia*

Prostaglandins

Uterine relaxants[Tocolytics]

•Adrenergic agonists[β2]

•Ca++ channel blockers •Magnesium sulfate•Atosiban•Others*

• Ritodrine:Ritodrine is a Beta-2 agonist

ADE: CVS- Metaboloic- Use: To delay labour I.v infusion 50μg/mt CI: Heart disease, diabetes, on beta

blockers.• Others: Isoxsuprine*

Adrenergic agonists:

• Magnesium sulfate:• Not routinely used because of toxicity.

[eclampsia-for siezures]Ca++ channel blockers: Reduced Ca entry Reduced tone Nifedipine 10mg every 30 mts

Atosiban: Antagonist of oxytocin receptors

Others: Ethyl alcohol, nitrates, Halothane etc.*

Ind: Delay preterm labourCI:More than 37 weeks gestationFetus >2500g Fetus in distress Cx dilation > 4 cmRuptured membraneToxemia, Cardiac diseasesPPH*

Indications & Contraindications for tocolytics