Pharmacology Of Drugs Acting On Uterus- Mbbs

Drugs acting on the uterus

Dr.U.P.Rathnakar MD. DIH. PGDHM K.M.C.Mangalore

Drugs Acting on the Uterus • Introduction • Stimulants 1. Oxytocin 2. Desamino-oxytocin 3. Ergometrine, Methyl ergometrine 4. Prostaglandins • Tocolytics (Relaxants) 1. Adr.agonists, Ca++ blockers, Magnesium sulfate, oxytocin antagonist, Misc *

Drugs

• Drugs ---- Endometrium or myometrium • Endometrium--- Estrogen or progesterone, and antagonists • Myometrium1. Indirectly acting-Symp or P.symp [ANS drugs-non selective-other systems+] 2. Directly acting 1. Ut.stimulants (oxytocics) 2. Ut. Relaxants (Tocolytics)*

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)*

Pharmacokinetics • Not absorbed orally • Administerd by i.v, i.m, rarely nasal route. • Not bound to plasma protienst1/2- 2 -5mts • Metabolized in liver and kidney*

Pharmacodynamics • Acts → GPCR • Small doses → Frequency and force • Large doses → Sustained contraction • Mammary alveoli-myoepethelial cells → contraction • Neurotransmitter in brain*

Ph. Actions: • Uterus: • Sensitivity increases as pregnancy progresses9 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*

Clinical uses of Oxytocin • 2. 3. 4. 5.

To induce, augment labor in Premature rupture Isoimmunization Placental insufficiency Toxemia, post maturity, DM Verify fetal lung maturity, Exclude C.IsPosition abnormalities, CPD,distress etc. Monitor fetal HR Look for fetal, maternal distress, ut.scar*

Induction & Augmentation     

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*

Why Oxytocin? Why not Ergometrine?

1. Short t ½ 2. Normal relaxation of uterus allowedGood fetal oxygenation 3. Lower segment not affected-descent free 4. Consistent augmentation in ut.inertia*

Other uses 1. Third stage of labour, puerperium: (Post partum hemorrhage) 5 IU i.m or i.v infusion. Other drugs→Ergometrine, Misoprostol 3. Breast engorgement: Nasal spray before suckling 4. Oxytocin challenge test: To assess placental insufficiency • AD.Effects: Rupture ut. Fetal distress, maternal injury*

Desamino-oxytocin

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

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.*

Ad. Effects: • Methyl ergometrine less toxic Nausea, vomiting, rise in BP. Decreases milk secretion Avoided in  Vascular disease, HTN, toxemia  Sepsis→gangrene  Liver and kidney disease.*  [Safe in ob.doses]

C.I.in pregnancy & early stages of labour

Uses: • PPH→ After anterior shoulder presentation  Prevention → 0.2-0.3 mg i.m  Treatment → 0.5 mg i.v. 4. Prevent uterine atony[cesarian, instrument] 5. To promote involution in multipara → 0.125mg TDS -7days 6. Diagnosis of variant angina during Coronary angio*

•The "Four Ts" for Causes of Postpartum Hemorrhage

•Four Ts Tone Trauma

Tissue Thrombin

Cause Atonic uterus

Approximate incidence (%) 70

Lacerations, 20 hematomas, inversion, rupture Retained tissue, 10 invasive placenta Coagulopathies 1

Ergometrine

Prostaglandins • PGE2 (Dinoprostone)→ Vaginal application → Induce II trimester abortion, missed abortion, ripening of cervix in near term • Preperations Misoprostol → with mifepristone for early abortion 15-Methyl-PGF2α (Carboprost) → II trimester abortions Facilitate labour- Unlabelled use in cardiac, renal disease, eclampsia*

Uterine relaxants[Tocolytics]

• Adrenergic agonists[β2] • Ca++ channel blockers • Magnesium sulfate • Atosiban • Others*

Adrenergic agonists: • 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*

• 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.*

Indications & Contraindications for tocolytics

Ind: Delay preterm labour CI: More than 37 weeks gestation Fetus >2500g Fetus in distress Cx dilation > 4 cm Ruptured membrane Toxemia, Cardiac diseases 