Oxytocics classify uses adverse effect ; enumerate clinical indications of each agents ; Oxytocin and prostaglandin analogues compare and contrast as oxytocics; Oxytocin and ergometrine compare and contrast ; Why is oxytocin used for induction of labor and not methylergometrine; Ergometrine inPPH pharmacological basis, contraindications to use if ergometrine 2nd yr mbbs pharmacology refer kd tripathi answers in details with flowcharts and diagrams as well
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KD Tripathi oxytocics classification ergometrine oxytocin prostaglandins pharmacology 2nd year MBBS
I now have enough information from the library and my own comprehensive pharmacology knowledge to write a complete, detailed answer. Let me now compile everything, including the flowcharts and diagrams (as ASCII/text-based diagrams since the user is a 2nd year MBBS student who needs structured visual aids).Here is the full, structured answer based on KD Tripathi (Essentials of Medical Pharmacology, Chapter 23: Oxytocin and Other Drugs Acting on Uterus) supplemented by Goodman & Gilman and Katzung.
OXYTOCICS - Complete 2nd Year MBBS Pharmacology Guide
(Based on KD Tripathi, Chapter 23)
1. CLASSIFICATION OF OXYTOCICS
┌─────────────────────────────────────────────────────────────────┐
│ OXYTOCICS │
│ (Drugs that stimulate the uterus) │
└──────────────────────────┬──────────────────────────────────────┘
│
┌──────────────────┼──────────────────┐
▼ ▼ ▼
┌──────────────┐ ┌─────────────────┐ ┌──────────────────────┐
│ POSTERIOR │ │ ERGOT │ │ PROSTAGLANDINS │
│ PITUITARY │ │ ALKALOIDS │ │ │
│ HORMONE │ │ │ │ │
│ │ │ │ │ │
│ • Oxytocin │ │ • Ergometrine │ │ PGE2: Dinoprostone │
│ (Syntocinon│ │ (Ergonovine) │ │ PGF2α: Carboprost │
│ Pitocin) │ │ • Methyl- │ │ PGE1: Misoprostol │
│ │ │ ergometrine │ │ (Cytotec) │
│ │ │ (Methergine) │ │ │
└──────────────┘ └─────────────────┘ └──────────────────────┘
2. MECHANISM OF ACTION
OXYTOCIN
─────────────────────────────────────────────────────
Oxytocin → Oxytocin receptor (Gq-coupled, GPCR)
│
▼
Phospholipase C activated
│
▼
IP3 ↑ + DAG ↑
│ │
▼ ▼
Ca²⁺ release PKC activation
from SR
│
└──────────────► Myosin Light Chain Kinase
│
▼
Myosin phosphorylation
│
▼
UTERINE CONTRACTION
Also: stimulates PGF2α and PGE2 production from decidua
─────────────────────────────────────────────────────
ERGOMETRINE
─────────────────────────────────────────────────────
Ergometrine → α-adrenoceptor + Serotonin (5-HT2)
receptor agonist on uterus
│
▼
Sustained tonic contraction (tetanic)
(partial agonist at dopamine receptors)
─────────────────────────────────────────────────────
PROSTAGLANDINS
─────────────────────────────────────────────────────
PGE2 / PGF2α → EP/FP receptors (GPCR)
│
▼
Ca²⁺ mobilization (IP3 pathway)
│
▼
Uterine contraction + cervical ripening
(PGE2 especially softens cervix)
3. USES & CLINICAL INDICATIONS
A. OXYTOCIN
┌──────────────────────────────────────────────────┐
│ CLINICAL USES OF OXYTOCIN │
├──────────────────────────────────────────────────┤
│ OBSTETRIC │
│ 1. Induction of labour (DOC) │
│ - Post-dates pregnancy (>42 weeks) │
│ - Pre-eclampsia / eclampsia │
│ - Diabetes mellitus in pregnancy │
│ - IUFD (intrauterine fetal death) │
│ - PROM (premature rupture of membranes) │
│ 2. Augmentation of dysfunctional labour │
│ 3. 3rd stage management (PPH prevention) │
│ 4. Treatment of PPH (uterine atony) │
│ 5. Oxytocin challenge test (OCT) │
│ - Tests uteroplacental reserve │
├──────────────────────────────────────────────────┤
│ NON-OBSTETRIC │
│ 6. Milk let-down (intranasal spray) │
└──────────────────────────────────────────────────┘
Dose for induction: 2–5 mU/min IV infusion,
titrate up to 20–40 mU/min max
PPH: 10 units IM or 20–40 units in 500 mL saline IV infusion
B. ERGOMETRINE / METHYLERGOMETRINE
┌──────────────────────────────────────────────────┐
│ CLINICAL USES OF ERGOMETRINE │
├──────────────────────────────────────────────────┤
│ 1. PPH (postpartum hemorrhage) - PRIMARY USE │
│ - Atonic PPH after delivery of placenta │
│ 2. Active management of 3rd stage of labour │
│ (combined with oxytocin = Syntometrine) │
│ 3. Subinvolution of uterus (postpartum) │
│ 4. Incomplete/inevitable abortion │
│ 5. Lochia (excessive postpartum bleeding) │
├──────────────────────────────────────────────────┤
│ NOT used for induction of labour │
│ (causes tetanic, sustained contraction) │
└──────────────────────────────────────────────────┘
Dose: Ergometrine 0.2 mg IM/IV (IV only in emergency)
Methylergometrine 0.2 mg IM/oral
C. PROSTAGLANDINS
┌──────────────────────────────────────────────────┐
│ CLINICAL USES OF PROSTAGLANDINS │
├──────────────────────────────────────────────────┤
│ PGE2 (DINOPROSTONE) │
│ 1. Cervical ripening (intravaginal/intracervical│
│ gel or pessary) │
│ 2. Induction of labour (term + late 2nd trim) │
│ 3. Missed abortion / IUFD (2nd trimester) │
│ │
│ PGF2α (CARBOPROST = 15-methyl-PGF2α) │
│ 1. PPH refractory to oxytocin/ergometrine │
│ 2. 2nd trimester abortion (MTP) │
│ 3. Cervical ripening │
│ │
│ PGE1 (MISOPROSTOL) │
│ 1. Induction of labour (cervical ripening) │
│ 2. Medical abortion (with mifepristone) │
│ 3. PPH (sublingual/rectal - when other drugs │
│ not available, e.g., resource-limited areas) │
│ 4. Postpartum bleeding prevention │
│ 5. Gastric cytoprotection (peptic ulcer) │
└──────────────────────────────────────────────────┘
4. ADVERSE EFFECTS
A. Oxytocin - Adverse Effects
┌────────────────────────────────────────────────────────┐
│ ADVERSE EFFECTS - OXYTOCIN │
├────────────────────────────────────────────────────────┤
│ UTERINE │
│ • Uterine hyperstimulation (>5 contractions/10 min) │
│ • Uterine rupture (especially with scarred uterus) │
│ • Fetal distress (FHR decelerations) │
│ • Placental abruption │
│ │
│ CARDIOVASCULAR │
│ • Hypotension (vasodilation - at high doses) │
│ • Reflex tachycardia │
│ (Especially dangerous with rapid IV bolus) │
│ │
│ ANTIDIURETIC (ADH-like effect at high doses) │
│ • Water retention → hyponatremia │
│ • Water intoxication → convulsions, coma │
│ (Activates vasopressin V2 receptor) │
│ │
│ OTHERS │
│ • Nausea, vomiting │
│ • Maternal hypersensitivity (rare) │
└────────────────────────────────────────────────────────┘
B. Ergometrine - Adverse Effects
┌────────────────────────────────────────────────────────┐
│ ADVERSE EFFECTS - ERGOMETRINE │
├────────────────────────────────────────────────────────┤
│ CARDIOVASCULAR (most important) │
│ • Hypertension (vasoconstriction via α-agonism) │
│ • Coronary vasospasm → angina, MI │
│ • Peripheral vasospasm │
│ │
│ CNS │
│ • Nausea, vomiting │
│ • Headache, dizziness │
│ │
│ UTERINE │
│ • Sustained tetanic contraction │
│ (dangerous if given before placental delivery) │
│ → placenta trapping │
│ │
│ OTHERS │
│ • Ergotism (overdose): gangrene, convulsions │
└────────────────────────────────────────────────────────┘
C. Prostaglandins - Adverse Effects
┌────────────────────────────────────────────────────────┐
│ ADVERSE EFFECTS - PROSTAGLANDINS │
├────────────────────────────────────────────────────────┤
│ • Nausea, vomiting, diarrhea (most common) │
│ (GI smooth muscle stimulation) │
│ • Uterine hyperstimulation → fetal distress │
│ • Fever, chills (pyrexia) - esp. carboprost │
│ • Bronchospasm (PGF2α/carboprost) │
│ → contraindicated in asthma │
│ • Headache, flushing │
│ • Uterine rupture (rare, with misoprostol) │
│ • Hypotension (PGE2) │
└────────────────────────────────────────────────────────┘
5. COMPARE & CONTRAST: OXYTOCIN vs PROSTAGLANDIN ANALOGUES
┌────────────────────────┬──────────────────────────┬──────────────────────────┐
│ FEATURE │ OXYTOCIN │ PROSTAGLANDINS │
│ │ │ (PGE2, PGF2α, PGE1) │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Source │ Posterior pituitary │ Synthesized from │
│ │ (hypothalamus) │ arachidonic acid │
│ │ (nonapeptide) │ (eicosanoids) │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Receptor │ Oxytocin receptor (Gq) │ EP / FP receptors (GPCR) │
│ │ │ │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Mechanism │ Gq → PLC → IP3 → Ca²⁺↑ │ Gq → PLC → IP3 → Ca²⁺↑ │
│ │ Also stimulates │ Also Gs → cAMP in some │
│ │ prostaglandin release │ subtypes (EP2/EP4 relax) │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Type of contraction │ Rhythmic, physiological │ Rhythmic but more │
│ │ (like normal labour) │ sustained; also acts on │
│ │ │ all gestational ages │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Cervical ripening │ NO (minimal effect on │ YES - hallmark of PGE2 │
│ │ cervix) │ and misoprostol │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Gestational age │ Effective only near term │ Effective at ALL │
│ dependence │ (requires estrogen- │ gestational ages │
│ │ primed receptors) │ (used in 2nd trimester │
│ │ │ abortion) │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Route │ IV infusion (main) │ Vaginal, intracervical, │
│ │ IM (PPH) │ oral, sublingual, rectal │
│ │ Intranasal (milk letdown)│ (versatile) │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Induction of labour │ DOC (1st line) │ Used for cervical │
│ │ │ ripening first, then │
│ │ │ oxytocin continued │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ PPH management │ 1st line (10U IM/IV) │ 2nd-3rd line │
│ │ │ (carboprost for │
│ │ │ refractory atonic PPH) │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Half-life │ 5–12 min (IV) │ Seconds (natural) │
│ │ │ Minutes–hours (synthetic │
│ │ │ analogues) │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Cardiovascular effect │ Vasodilation → │ Variable: PGE2 vasodil.; │
│ │ hypotension (high dose) │ PGF2α vasoconstriction │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Antidiuretic effect │ YES (V2 receptor │ No │
│ │ cross-activation) │ │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ GI side effects │ Mild │ Prominent (N/V/D) │
│ │ │ │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Bronchospasm │ No │ YES (PGF2α/Carboprost) │
│ │ │ → Contraindicated asthma │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ 2nd trimester MTP │ Not used (ineffective) │ YES - misoprostol + │
│ │ │ mifepristone │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Stability / cost │ Requires refrigeration; │ Misoprostol: stable at │
│ │ expensive │ room temp, very cheap │
└────────────────────────┴──────────────────────────┴──────────────────────────┘
6. COMPARE & CONTRAST: OXYTOCIN vs ERGOMETRINE
┌────────────────────────┬──────────────────────────┬──────────────────────────┐
│ FEATURE │ OXYTOCIN │ ERGOMETRINE │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Source │ Posterior pituitary │ Ergot (Claviceps │
│ │ (synthetic: Syntocinon) │ purpurea) - fungus on rye│
│ │ │ (synthetic: Methergine) │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Chemical nature │ Nonapeptide │ Ergot alkaloid │
│ │ │ (lysergic acid │
│ │ │ derivative) │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Receptor │ Oxytocin receptor │ α-adrenergic + 5-HT2 │
│ │ (Gq-coupled GPCR) │ receptors (partial │
│ │ │ agonist/antagonist) │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Type of contraction │ Rhythmic, phasic │ Sustained TETANIC │
│ │ (like physiological │ contraction │
│ │ labour contractions) │ (tonic, prolonged) │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Action on uterus │ Increases frequency │ Powerful constrictor; │
│ │ and amplitude of │ compresses blood vessels │
│ │ contractions; fundal │ within myometrium │
│ │ predominance │ (ligature of living) │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Gestational age │ Near term only │ Active at ALL stages │
│ │ (needs primed receptors) │ of labour (less gestage- │
│ │ │ age dependent than PGs) │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Induction of labour │ YES - DOC for induction │ NOT used (tetanic │
│ │ │ contraction → fetal │
│ │ │ asphyxia + rupture) │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ 3rd stage of labour │ Used: reduces PPH risk │ Used after placental │
│ │ (10U IM after delivery │ delivery (prevents │
│ │ of baby) │ retained placenta risk │
│ │ │ if given before) │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ PPH treatment │ 1st line │ 2nd line OR concurrent │
│ │ │ │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Blood pressure │ Hypotension (vasodil.) │ HYPERTENSION │
│ │ at high doses │ (vasoconstriction) │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Cardiovascular risk │ Hypotension, │ Hypertension, │
│ │ tachycardia │ coronary vasospasm │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Antidiuretic effect │ YES (at high doses) │ No │
│ │ → water intoxication │ │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Route │ IV infusion, IM │ IM, IV (emergency only), │
│ │ (intranasal for letdown) │ oral (methylergometrine) │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Half-life │ 5–12 min │ 1–2 hours │
│ │ │ (longer duration) │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Contraindicated in │ Fetal malpresentation, │ Hypertension, │
│ │ fetal distress, │ Pre-eclampsia/eclampsia, │
│ │ placenta praevia, │ heart disease, │
│ │ CPD, previous uterine │ peripheral vascular │
│ │ surgery │ disease, 1st/2nd stage │
│ │ │ of labour │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Cervical ripening │ No │ No │
├────────────────────────┼──────────────────────────┼──────────────────────────┤
│ Combined use │ Syntometrine = Oxytocin │ Syntometrine = 5U │
│ │ + Ergometrine │ Oxytocin + 0.5 mg │
│ │ (active management 3rd │ Ergometrine IM │
│ │ stage) │ │
└────────────────────────┴──────────────────────────┴──────────────────────────┘
7. WHY OXYTOCIN IS USED FOR INDUCTION OF LABOUR AND NOT METHYLERGOMETRINE
┌─────────────────────────────────────────────────────────────────────────┐
│ OXYTOCIN vs METHYLERGOMETRINE │
├─────────────────────────────────────────────────────────────────────────┤
│ │
│ CONTRACTION TYPE │
│ │
│ Oxytocin: Methylergometrine: │
│ │
│ ▲ ▲▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬ │
│ │ ╭─╮ ╭─╮ ╭─╮ ╭─╮ │ │
│ │ ╭╯ ╰╮ ╭╯ ╰╮ ╭╯ ╰╮ ╭╯ ╰╮ │ │
│ │──╯ ╰─╯ ╰─╯ ╰─╯ ╰─ │───────────────────────────── │
│ RHYTHMIC PHASIC SUSTAINED TETANIC │
│ (with relaxation) (no relaxation) │
│ │
└─────────────────────────────────────────────────────────────────────────┘
Reasons in detail:
| Reason | Oxytocin (SAFE for induction) | Methylergometrine (UNSAFE) |
|---|---|---|
| Type of contraction | Rhythmic, phasic - allows uterine relaxation between contractions, preserving fetoplacental blood flow | Sustained tetanic contraction - no relaxation phase |
| Fetoplacental blood flow | Maintained during relaxation phase | Severely compromised → fetal hypoxia and asphyxia |
| Uterine rupture risk | Low when properly monitored | High - unrelenting contraction can rupture even a normal uterus |
| Dose titratability | Easily titrated by IV infusion, short t½ (5-12 min) - can stop quickly if hyperstimulation | Long duration of action (1-2 hrs), cannot be quickly reversed |
| Cervical effect | Dilates cervix gradually with contractions | No cervical ripening; may cause cervical laceration |
| BP effect | Vasodilatory (not dangerous in normotensive) | Vasoconstrictive → dangerous hypertension, risk of cerebral hemorrhage, stroke in mother |
| Reversal | Stop infusion → effects dissipate in 15-30 min | Effects persist for 1-2 hours even after stopping IM dose |
| Fetal viability | Allows fetal heart rate monitoring and adjustment | Tetanic contraction makes FHR monitoring difficult and late decelerations common |
Summary (Memory Aid):
Oxytocin = "O" for Oscillating (rhythmic) = safe for labour induction
Ergometrine = "E" for Eternal contraction (tetanic) = only after delivery = safe for PPH
8. ERGOMETRINE IN PPH - PHARMACOLOGICAL BASIS
Flowchart: Why Ergometrine Works in PPH
POSTPARTUM HEMORRHAGE
(After placental delivery)
│
▼
CAUSE: Uterine ATONY
(uterus fails to contract properly
after placental separation)
│
▼
Blood vessels in myometrium
remain open → massive bleeding
│
▼
┌──────────────────────────────────────────────────────┐
│ ERGOMETRINE ACTION │
│ │
│ Ergometrine │
│ │ │
│ ▼ │
│ α-adrenergic receptors + 5-HT2 receptors │
│ on myometrium activated │
│ │ │
│ ▼ │
│ SUSTAINED TETANIC CONTRACTION of uterus │
│ │ │
│ ▼ │
│ Myometrium acts as "LIVING LIGATURE" │
│ (Blood vessels within the myometrium are │
│ physically compressed and occluded) │
│ │ │
│ ▼ │
│ Hemostasis achieved → BLEEDING STOPS │
└──────────────────────────────────────────────────────┘
ADVANTAGE HERE: The tetanic contraction that makes ergometrine
DANGEROUS in labour is BENEFICIAL in PPH - because the baby
and placenta are already OUT, sustained contraction only
compresses bleeding vessels - no risk to fetus!
Why ergometrine is particularly effective in PPH:
- The sustained tonic contraction produces intense compression of the sinusoidal vessels within the myometrium
- This is called the "living ligature" effect - the contracted myometrium physically strangles the blood vessels
- Effect is maintained for 1-2 hours (longer than oxytocin) - providing prolonged hemostasis
- Onset: IM = 2-7 min; IV = 40 seconds (emergency)
9. CONTRAINDICATIONS TO ERGOMETRINE
┌─────────────────────────────────────────────────────────────────────────┐
│ CONTRAINDICATIONS TO ERGOMETRINE │
│ │
│ CARDIOVASCULAR │
│ ┌──────────────────────────────────────────────────────────────────┐ │
│ │ • Hypertension (any cause) - most important CI │ │
│ │ (causes further rise in BP → risk of stroke, CVA) │ │
│ │ • Pre-eclampsia / Eclampsia │ │
│ │ • Heart disease (coronary vasospasm → MI) │ │
│ │ • Peripheral vascular disease │ │
│ │ • Raynaud's phenomenon │ │
│ └──────────────────────────────────────────────────────────────────┘ │
│ │
│ OBSTETRIC (timing-related) │
│ ┌──────────────────────────────────────────────────────────────────┐ │
│ │ • First stage of labour (baby not yet delivered - fetal risk) │ │
│ │ • Second stage of labour (same reason) │ │
│ │ • Before delivery of placenta (retained placenta risk) │ │
│ │ → ONLY give AFTER placental delivery │ │
│ │ • Multiple pregnancy (risk of entrapment of 2nd twin) │ │
│ │ • Malpresentation (fetus not in right position) │ │
│ └──────────────────────────────────────────────────────────────────┘ │
│ │
│ OTHER │
│ ┌──────────────────────────────────────────────────────────────────┐ │
│ │ • Sepsis (unpredictable response) │ │
│ │ • Hepatic / Renal impairment (impaired metabolism) │ │
│ │ • Induction / augmentation of labour (wrong drug!) │ │
│ └──────────────────────────────────────────────────────────────────┘ │
└─────────────────────────────────────────────────────────────────────────┘
MEMORY AID for ergometrine contraindications:
"HIPPER"
H - Hypertension
I - Induction of labour
P - Pre-eclampsia
P - Placenta not yet delivered
E - Eclampsia
R - Raynaud's / cardiac disease
10. MASTER FLOWCHART: OXYTOCICS IN OBSTETRIC PRACTICE
CLINICAL SITUATION
│
├──► INDUCTION OF LABOUR ──────────────────────────────────┐
│ │
│ [Unfavorable cervix?] │
│ │ │
│ ├──YES──► PGE2 (Dinoprostone) / Misoprostol │
│ │ (cervical ripening first) │
│ │ │
│ └──NO───► OXYTOCIN IV infusion (DOC) │
│ │
├──► ACTIVE MANAGEMENT 3RD STAGE ──────────────────────────┤
│ │
│ Oxytocin 10U IM OR │
│ Syntometrine (Oxytocin 5U + Ergometrine 0.5mg) IM │
│ [give AFTER anterior shoulder delivered] │
│ │
├──► POSTPARTUM HEMORRHAGE (PPH) ──────────────────────────┤
│ │
│ STEP 1: Oxytocin 10U IM + uterine massage │
│ │ │
│ └──Not controlled──► │
│ STEP 2: Ergometrine 0.2mg IM (if not hypertensive) │
│ │ │
│ └──Not controlled──► │
│ STEP 3: Carboprost (PGF2α) 250μg IM q15-90 min │
│ (if not asthmatic) │
│ │ │
│ └──Not controlled──► │
│ STEP 4: Misoprostol 600-1000μg sublingual/rectal │
│ │ │
│ └──Not controlled──► Surgical/interventional │
│ │
└──► 2ND TRIMESTER MTP ─────────────────────────────────────
Mifepristone 200mg oral, then 24-48h later
Misoprostol 400-800μg vaginal/sublingual
QUICK SUMMARY TABLE: ALL OXYTOCICS AT A GLANCE
┌──────────────────┬───────────┬────────────┬────────────┬────────────┐
│ DRUG │ RECEPTOR │ CONTRACTION│ MAIN USE │ KEY AE │
├──────────────────┼───────────┼────────────┼────────────┼────────────┤
│ Oxytocin │ OT-R (Gq) │ Rhythmic │ Induction │ Water │
│ │ │ phasic │ Labour/PPH │ intoxica- │
│ │ │ │ │ tion; │
│ │ │ │ │ Hypotension│
├──────────────────┼───────────┼────────────┼────────────┼────────────┤
│ Ergometrine / │ α + 5HT2 │ Sustained │ PPH │ Hyper- │
│ Methylergometrine│ │ TETANIC │ 3rd stage │ tension; │
│ │ │ │ │ Coronary │
│ │ │ │ │ spasm │
├──────────────────┼───────────┼────────────┼────────────┼────────────┤
│ Dinoprostone │ EP (Gq) │ Rhythmic+ │ Cervical │ N/V/D; │
│ (PGE2) │ │ cervix │ ripening │ Hypotension│
│ │ │ ripening │ Induction │ │
├──────────────────┼───────────┼────────────┼────────────┼────────────┤
│ Carboprost │ FP (Gq) │ Sustained │ Refractory │ Broncho- │
│ (15-me-PGF2α) │ │ (all ages) │ PPH; MTP │ spasm; │
│ │ │ │ │ Fever; D/V │
├──────────────────┼───────────┼────────────┼────────────┼────────────┤
│ Misoprostol │ EP1/EP3 │ Rhythmic │ MTP; PPH │ N/D; │
│ (PGE1 analogue) │ │ + cervical │ Induction │ Uterine │
│ │ │ ripening │ (resource- │ hyperstim │
│ │ │ │ limited) │ │
└──────────────────┴───────────┴────────────┴────────────┴────────────┘
Sources:
- KD Tripathi: Essentials of Medical Pharmacology, 8th Edition, Chapter 23 (Oxytocin and Other Drugs Acting on Uterus)
- Goodman & Gilman's Pharmacological Basis of Therapeutics, 14th Ed. - Oxytocin section
- Katzung Basic & Clinical Pharmacology, 16th Ed., Chapter 37
- Creasy & Resnik's Maternal-Fetal Medicine, 9th Ed.Here is your complete, exam-oriented guide to Oxytocics for 2nd year MBBS, aligned with KD Tripathi Chapter 23.
OXYTOCICS - Complete 2nd Year MBBS Pharmacology Guide
(KD Tripathi, Ch. 23: Oxytocin and Other Drugs Acting on Uterus)
1. CLASSIFICATION OF OXYTOCICS
┌─────────────────────────────────────────────────────────────┐
│ OXYTOCICS │
│ (Drugs that stimulate the uterus) │
└────────────────────────┬────────────────────────────────────┘
│
┌─────────────────┼─────────────────┐
▼ ▼ ▼
┌──────────────┐ ┌──────────────┐ ┌─────────────────────┐
│ POSTERIOR │ │ ERGOT │ │ PROSTAGLANDINS │
│ PITUITARY │ │ ALKALOIDS │ │ │
│ HORMONE │ │ │ │ PGE2: Dinoprostone │
│ │ │ Ergometrine │ │ PGF2α: Carboprost │
│ Oxytocin │ │ Methyl- │ │ (15-me-PGF2α) │
│ (Syntocinon │ │ ergometrine │ │ PGE1: Misoprostol │
│ Pitocin) │ │ (Methergine) │ │ (Cytotec) │
└──────────────┘ └──────────────┘ └─────────────────────┘
2. MECHANISM OF ACTION
OXYTOCIN
────────────────────────────────────────────────────────────
Oxytocin → Oxytocin receptor (Gq-coupled GPCR)
│
▼
Phospholipase C activated
│
┌─────┴─────┐
▼ ▼
IP3 ↑ DAG ↑
│ │
▼ ▼
Ca²⁺ release PKC activation
from SR
│
└───────────► Myosin Light Chain Kinase (MLCK)
│
▼
Myosin phosphorylation
│
▼
UTERINE CONTRACTION
Also: stimulates PGF2α / PGE2 production from decidua
────────────────────────────────────────────────────────────
ERGOMETRINE
────────────────────────────────────────────────────────────
Ergometrine → α-adrenoceptor + 5-HT2 receptor agonist
on uterine smooth muscle
│
▼
Sustained TETANIC contraction
(no relaxation phase between contractions)
────────────────────────────────────────────────────────────
PROSTAGLANDINS
────────────────────────────────────────────────────────────
PGE2/PGF2α → EP / FP receptors (Gq-coupled GPCR)
│
▼
Ca²⁺ mobilization (IP3 pathway)
│
▼
Uterine contraction + cervical ripening/softening
(PGE2 = best cervical ripener)
3. CLINICAL INDICATIONS OF EACH AGENT
A. Oxytocin
┌──────────────────────────────────────────────────┐
│ CLINICAL USES OF OXYTOCIN │
├──────────────────────────────────────────────────┤
│ 1. Induction of labour (DOC - drug of choice) │
│ - Post-dates pregnancy (>42 weeks) │
│ - Pre-eclampsia / eclampsia │
│ - Diabetes mellitus in pregnancy │
│ - IUFD (intrauterine fetal death) │
│ - PROM (premature rupture of membranes) │
│ 2. Augmentation of dysfunctional labour │
│ 3. Active management of 3rd stage of labour │
│ (prevents PPH) │
│ 4. Treatment of PPH (uterine atony) - 1st line │
│ 5. Oxytocin challenge test (OCT) │
│ - Tests uteroplacental reserve │
│ 6. Milk let-down (intranasal spray) │
├──────────────────────────────────────────────────┤
│ Dose (induction): 0.5-2 mU/min IV, titrate to │
│ max 20-40 mU/min │
│ Dose (PPH): 10U IM; or 20-40U in 500mL saline │
└──────────────────────────────────────────────────┘
B. Ergometrine / Methylergometrine
┌──────────────────────────────────────────────────┐
│ CLINICAL USES OF ERGOMETRINE │
├──────────────────────────────────────────────────┤
│ 1. PPH - PRIMARY USE (atonic PPH after placental │
│ delivery; 2nd line after oxytocin) │
│ 2. Active management of 3rd stage of labour │
│ (combined with oxytocin = Syntometrine) │
│ 3. Subinvolution of uterus (postpartum) │
│ 4. Incomplete/inevitable abortion (lochia) │
│ 5. To hasten uterine involution │
├──────────────────────────────────────────────────┤
│ NOT used for induction of labour! │
│ Dose: 0.2 mg IM (or IV in emergency only) │
└──────────────────────────────────────────────────┘
C. Prostaglandins
┌──────────────────────────────────────────────────┐
│ CLINICAL USES OF PROSTAGLANDINS │
├──────────────────────────────────────────────────┤
│ PGE2 (DINOPROSTONE) │
│ 1. Cervical ripening (unfavorable cervix) │
│ - Intravaginal gel/pessary/tablet │
│ 2. Induction of labour at term │
│ 3. 2nd trimester abortion / IUFD │
│ │
│ PGF2α (CARBOPROST = 15-methyl-PGF2α) │
│ 1. Refractory PPH (after oxytocin + ergometrine │
│ have failed) │
│ 2. 2nd trimester MTP (abortion) │
│ Dose: 250 mcg IM every 15-90 min, max 8 doses │
│ │
│ PGE1 (MISOPROSTOL - Cytotec) │
│ 1. Medical abortion (+ mifepristone) │
│ 2. Cervical ripening / labour induction │
│ 3. PPH prevention/treatment (when refrigeration │
│ unavailable - resource-limited settings) │
│ 4. Missed/incomplete abortion │
│ 5. Peptic ulcer (gastric cytoprotection) │
│ Dose (PPH): 600-1000 mcg sublingual/rectal │
└──────────────────────────────────────────────────┘
4. ADVERSE EFFECTS
Oxytocin
┌──────────────────────────────────────────────────────────┐
│ ADVERSE EFFECTS - OXYTOCIN │
├──────────────────────────────────────────────────────────┤
│ UTERINE │
│ • Uterine hyperstimulation (>5 contractions/10 min) │
│ • Uterine rupture (esp. scarred/multipara uterus) │
│ • Fetal distress (late decelerations on CTG) │
│ • Placental abruption │
│ │
│ CARDIOVASCULAR (at high doses) │
│ • Hypotension (vasodilation) │
│ • Reflex tachycardia │
│ • Especially dangerous with rapid IV bolus │
│ │
│ ANTIDIURETIC (ADH-like cross-activation at high doses) │
│ • Water retention → hyponatremia │
│ • Water intoxication → convulsions, coma, death │
│ (particularly with excess hypotonic IV fluids) │
│ │
│ OTHERS │
│ • Nausea, vomiting │
│ • Hypersensitivity (rare) │
└──────────────────────────────────────────────────────────┘
Ergometrine
┌──────────────────────────────────────────────────────────┐
│ ADVERSE EFFECTS - ERGOMETRINE │
├──────────────────────────────────────────────────────────┤
│ CARDIOVASCULAR │
│ • Hypertension (vasoconstriction via α-agonism) │
│ • Coronary vasospasm → angina, MI │
│ • Peripheral vasospasm → gangrene (overdose) │
│ │
│ GI │
│ • Nausea, vomiting (prominent) │
│ │
│ CNS │
│ • Headache, dizziness │
│ • Seizures (ergotism - overdose) │
│ │
│ UTERINE (if given at wrong time) │
│ • Sustained tetanic contraction → fetal asphyxia │
│ • Retained placenta (if given before delivery) │
│ │
│ ERGOTISM (chronic/overdose) │
│ • Gangrene of extremities (vasoconstriction) │
│ • Convulsions │
└──────────────────────────────────────────────────────────┘
Prostaglandins
┌──────────────────────────────────────────────────────────┐
│ ADVERSE EFFECTS - PROSTAGLANDINS │
├──────────────────────────────────────────────────────────┤
│ • Nausea, vomiting, diarrhea (most common - GI smooth │
│ muscle stimulation) │
│ • Uterine hyperstimulation → fetal distress │
│ • Fever, chills, rigors (esp. carboprost) │
│ • BRONCHOSPASM (PGF2α / Carboprost) │
│ → Contraindicated in asthma │
│ • Headache, flushing (vasodilation) │
│ • Hypotension (PGE2 dinoprostone) │
│ • Uterine rupture (rare, misoprostol in scarred uterus)│
└──────────────────────────────────────────────────────────┘
5. COMPARE: OXYTOCIN vs PROSTAGLANDIN ANALOGUES
| Feature | Oxytocin | Prostaglandins (PGE2, PGF2α, PGE1) |
|---|---|---|
| Source | Posterior pituitary (nonapeptide) | Synthesized from arachidonic acid (eicosanoids) |
| Receptor | Oxytocin receptor (Gq-coupled) | EP/FP receptors (GPCR) |
| Mechanism | Gq → PLC → IP3 → Ca²⁺ | Gq → PLC → IP3 → Ca²⁺ (also cAMP via EP2/EP4) |
| Type of contraction | Rhythmic, phasic (like physiological labour) | Rhythmic but also sustained; acts at all gestational ages |
| Cervical ripening | NO (minimal) | YES - hallmark of PGE2 and misoprostol |
| Gestational age dependence | Near term only (needs estrogen-primed receptors; receptor density increases 200-300x during pregnancy) | Effective at ALL gestational ages |
| Route | IV infusion, IM, intranasal | Vaginal, intracervical, oral, sublingual, rectal |
| Induction of labour | DOC - 1st line | Used for cervical ripening first, then oxytocin continues |
| PPH management | 1st line (10U IM) | 2nd-3rd line (carboprost for refractory PPH) |
| Half-life | 5-12 min (IV) | Seconds (natural); minutes-hours (synthetic analogues) |
| BP effect | Vasodilation → hypotension (high dose) | Variable: PGE2 vasodilates; PGF2α vasoconstricts |
| Antidiuretic effect | YES (V2 receptor cross-activation) | No |
| GI side effects | Mild | Prominent (N/V/D) |
| Bronchospasm | No | YES (PGF2α/Carboprost) - CI in asthma |
| 2nd trimester MTP | Not effective | YES - misoprostol + mifepristone (DOC) |
| Storage | Requires cold chain (refrigeration) | Misoprostol stable at room temperature - advantage in field settings |
| Cost | Moderate | Misoprostol - very cheap; dinoprostone - expensive |
6. COMPARE: OXYTOCIN vs ERGOMETRINE
| Feature | Oxytocin | Ergometrine / Methylergometrine |
|---|---|---|
| Source | Posterior pituitary (peptide hormone) | Ergot fungus (Claviceps purpurea) - alkaloid |
| Chemical nature | Nonapeptide | Ergot alkaloid (lysergic acid derivative) |
| Receptor | Oxytocin receptor (Gq-GPCR) | α-adrenergic + 5-HT2 receptors |
| Type of contraction | Rhythmic, PHASIC (with relaxation between contractions) | Sustained TETANIC (no relaxation) |
| Analogy | Like normal uterine contractions | Like a clenched fist that never opens |
| BP effect | Vasodilation → hypotension | Vasoconstriction → HYPERTENSION |
| Induction of labour | YES - DOC | NEVER (tetanic = fetal asphyxia + rupture) |
| PPH | 1st line | 2nd line (or concurrent) |
| 3rd stage | 10U IM after anterior shoulder | ONLY after placental delivery |
| Antidiuretic effect | YES (at high doses) | No |
| Half-life | 5-12 min | 1-2 hours (much longer) |
| Onset (IM) | 3-5 min | 2-7 min |
| Route | IV infusion, IM | IM, oral (methylergometrine); IV only in emergency |
| Titratable | YES (IV infusion easily adjusted) | NO (fixed IM dose; cannot be quickly reversed) |
| Cardiac risk | Hypotension, reflex tachycardia | Coronary vasospasm → angina/MI |
| Key CI | Fetal malpresentation, fetal distress, placenta praevia | Hypertension, pre-eclampsia, heart disease |
| Combined form | Syntometrine = 5U Oxytocin + 0.5 mg Ergometrine IM | (same) |
7. WHY OXYTOCIN FOR INDUCTION - NOT METHYLERGOMETRINE
CONTRACTION PATTERN COMPARISON:
OXYTOCIN (SAFE for induction):
Uterine
tone ▲
│ ╭──╮ ╭──╮ ╭──╮ ╭──╮
│ ╭╯ ╰╮ ╭╯ ╰╮ ╭╯ ╰╮ ╭╯ ╰╮
─────┼──╯ ╰───╯ ╰───╯ ╰───╯ ╰──
└──────────────────────────────────────► time
Rhythmic phasic contractions
(with relaxation phase between them)
↑ Blood flow restored during relaxation
↑ Fetus oxygenated between contractions
METHYLERGOMETRINE (DANGEROUS for induction):
Uterine
tone ▲▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬▬
│
─────┼──────────────────────────────────────► time
Sustained tetanic contraction
(NO relaxation = NO blood flow restoration)
↓ Fetoplacental blood flow → fetal hypoxia
↓ Risk of uterine rupture
| Reason | Oxytocin (safe) | Methylergometrine (unsafe) |
|---|---|---|
| Contraction type | Phasic with relaxation - preserves fetoplacental blood flow | Tetanic, no relaxation - blood flow cut off |
| Fetal oxygenation | Maintained during relaxation | Severely compromised → fetal asphyxia |
| Uterine rupture | Low risk with monitoring | High risk - unrelenting contraction |
| Titratable/reversible | Short t½ (5-12 min) - stop infusion to reverse | Duration 1-2 hrs; cannot be quickly reversed |
| BP effect | Vasodilation - manageable | Hypertension - dangerous in preeclampsia |
| Cervical effect | Gradual cervical dilation with contractions | May cause cervical laceration |
Memory key: "Oxytocin = Oscillating (rhythmic) = safe for labour. Ergometrine = Eternal contraction (tetanic) = only AFTER delivery."
8. ERGOMETRINE IN PPH: PHARMACOLOGICAL BASIS
Why Does PPH Occur? Why Does Ergometrine Help?
POSTPARTUM - Normal hemostasis:
Placenta delivered
│
▼
Uterus must CONTRACT
│
▼
Myometrial fibers compress sinusoidal vessels
│
▼
"LIVING LIGATURE" effect = hemostasis
──────────────────────────────────────────────────
IN ATONIC PPH:
Uterus FAILS to contract (uterine atony)
│
▼
Sinusoidal vessels remain OPEN
│
▼
Massive hemorrhage from placental bed
(can lose 500-1000+ mL/minute)
──────────────────────────────────────────────────
HOW ERGOMETRINE TREATS PPH:
Ergometrine 0.2 mg IM
│
▼
α-adrenergic + 5-HT2 receptor activation
on myometrium
│
▼
SUSTAINED TETANIC CONTRACTION of entire uterus
│
▼
Myometrium physically COMPRESSES intramural vessels
│
▼
"LIVING LIGATURE" restored
│
▼
BLEEDING STOPS
KEY: The tetanic contraction that is DANGEROUS during
labour (risks fetus + rupture) is BENEFICIAL in PPH
because: fetus is delivered, placenta is out -
sustained contraction = maximum hemostasis
Pharmacological basis summary:
- Ergometrine acts on α-adrenergic and 5-HT2 receptors to cause sustained, powerful uterine contraction
- The contraction physically occludes the open sinusoidal/spiral arteries at the placental bed
- This is called the "living ligature" - contracted myometrial fibers act like ties around the bleeding vessels
- Onset is rapid (IM 2-7 min, IV 40 seconds) and effect lasts 1-2 hours - sustained hemostasis
- The longer duration vs oxytocin (5-12 min) means less chance of rebleeding
9. CONTRAINDICATIONS TO ERGOMETRINE
┌─────────────────────────────────────────────────────────┐
│ CONTRAINDICATIONS TO ERGOMETRINE │
├─────────────────────────────────────────────────────────┤
│ │
│ CARDIOVASCULAR (ergometrine raises BP) │
│ • Hypertension - ANY cause (most important CI) │
│ (causes further dangerous BP rise → stroke) │
│ • Pre-eclampsia / Eclampsia │
│ • Heart disease (ischemic, valve disease) │
│ (coronary vasospasm → MI) │
│ • Peripheral vascular disease │
│ • Raynaud's phenomenon │
│ │
│ OBSTETRIC (wrong timing = catastrophe) │
│ • First stage of labour (baby in utero - fetal risk) │
│ • Second stage of labour (same reason) │
│ • Before placental delivery │
│ (tetanic contraction traps placenta │
│ → retained placenta → worse PPH!) │
│ • Multiple pregnancy (2nd twin may be trapped) │
│ • Malpresentation │
│ │
│ OTHER │
│ • Hepatic impairment (impaired metabolism) │
│ • Renal impairment │
│ • Sepsis │
│ • Induction/augmentation of labour (wrong indication) │
│ │
└─────────────────────────────────────────────────────────┘
MEMORY AID - "HIPPER MC":
H - Hypertension
I - Induction of labour (contraindicated)
P - Pre-eclampsia
P - Placenta not yet delivered
E - Eclampsia
R - Raynaud's / cardiac/peripheral vascular disease
M - Multiple pregnancy
C - Coronary artery disease
10. MASTER FLOWCHART: OXYTOCICS IN OBSTETRIC PRACTICE
CLINICAL SITUATION
│
├──► INDUCTION OF LABOUR ─────────────────────────┐
│ │
│ Is cervix favorable (Bishop score >6)? │
│ │ │
│ NO ├──► PGE2 (Dinoprostone) / │
│ │ Misoprostol (PGE1) │
│ │ → Cervical ripening first │
│ │ │ │
│ │ ▼ │
│ YES └──► OXYTOCIN IV infusion (DOC) │
│ 0.5-2 mU/min, titrate │
│ up to 20 mU/min max │
│ │
├──► ACTIVE MANAGEMENT 3RD STAGE ─────────────────┤
│ │
│ After delivery of anterior shoulder: │
│ Oxytocin 10U IM OR │
│ Syntometrine (Oxytocin 5U + │
│ Ergometrine 0.5mg) IM │
│ → ONLY after placenta delivered for ergom. │
│ │
└──► POSTPARTUM HEMORRHAGE (PPH) ─────────────────┘
PPH STEPWISE MANAGEMENT:
┌─────────────────────────────────────────────────────────┐
│ STEP 1: Oxytocin 10U IM + uterine massage │
│ (+20-40U in IV infusion) 1st line │
│ │ │
│ ▼ (not controlled) │
│ STEP 2: Ergometrine 0.2mg IM 2nd line │
│ (IF not hypertensive, no eclampsia) │
│ │ │
│ ▼ (not controlled) │
│ STEP 3: Carboprost (PGF2α) 250mcg IM 3rd line │
│ repeat q15-90 min (max 8 doses) │
│ (IF not asthmatic) │
│ │ │
│ ▼ (not controlled) │
│ STEP 4: Misoprostol 600-1000mcg sublingual/rectal │
│ │ │
│ ▼ (not controlled) │
│ STEP 5: Surgical/interventional (B-Lynch suture, │
│ uterine artery ligation, hysterectomy) │
└─────────────────────────────────────────────────────────┘
QUICK EXAM SUMMARY TABLE
| Drug | Receptor | Contraction | Key Use | Key AE |
|---|---|---|---|---|
| Oxytocin | OT-R (Gq) | Rhythmic phasic | Labour induction (DOC); PPH 1st line | Water intoxication; Hypotension |
| Ergometrine | α + 5-HT2 | Sustained TETANIC | PPH 2nd line; 3rd stage | Hypertension; Coronary spasm |
| Dinoprostone (PGE2) | EP (Gq) | Rhythmic + cervix ripening | Cervical ripening; Induction | N/V/D; Hypotension |
| Carboprost (PGF2α) | FP (Gq) | Sustained; all ages | Refractory PPH; 2nd trim MTP | Bronchospasm (CI asthma); Fever |
| Misoprostol (PGE1) | EP1/EP3 | Rhythmic + cervix | MTP; PPH (resource-limited); Induction | N/D; Uterine hyperstim |
References:
- KD Tripathi: Essentials of Medical Pharmacology, 8th Ed., Ch. 23 (Oxytocin and Other Drugs Acting on Uterus)
- Goodman & Gilman's Pharmacological Basis of Therapeutics, 14th Ed.
- Katzung Basic & Clinical Pharmacology, 16th Ed., Ch. 37
- Creasy & Resnik's Maternal-Fetal Medicine, 9th Ed.
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