Pharmacology of Drugs Acting on Uterus- MBBS
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Transcript of Pharmacology of Drugs Acting on Uterus- MBBS
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