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🔹 ANALGESICS USED IN OBSTETRICS — LOGIC-BASED MASTER NOTE
(PD → PK → Clinical logic → Exam locks)
🟠 PARACETAMOL (Acetaminophen) — foundation drug
Pharmacodynamics (WHY it works)
- Acts centrally
- Inhibits central COX (not peripheral)
- Raises pain threshold + resets hypothalamic temperature set-point
- No effect on prostaglandins in periphery → no anti-inflammatory action
👉 Hence: analgesic + antipyretic, no gastric / platelet toxicity
Pharmacokinetics (WHY it’s safe)
- Oral / IV
- Hepatic metabolism:
- Mostly glucuronidation + sulfation
- Small fraction → NAPQI (toxic) detoxified by glutathione
- Half-life: 2–3 hours
👉 Liver disease → glutathione depleted → toxicity risk
Clinical logic
- First-line pain control in pregnancy + postpartum
- Safe across all trimesters
- Combine with opioids → opioid-sparing effect
Exam locks
- NOT anti-inflammatory
- Overdose → acute hepatic necrosis
- Safe in pregnancy
🟠 NSAIDs (Ibuprofen, Diclofenac, Indomethacin) — prostaglandin blockers
Pharmacodynamics
- Inhibit COX-1 & COX-2
- ↓ prostaglandins → ↓ pain, inflammation, fever
- ↓ prostaglandins also affect:
- gastric mucosa
- renal blood flow
- uterine tone
- fetal ductus arteriosus
Pharmacokinetics
- Oral
- Hepatic metabolism
- Short half-life (2–4 h) but physiological effects longer
Clinical logic
- Excellent for:
- dysmenorrhoea
- musculoskeletal pain
- postpartum analgesia
- Avoid in:
- renal disease
- peptic ulcer
- aspirin-sensitive asthma
OB logic
- Prostaglandins maintain fetal ductus arteriosus
- Blocking them late → ductus closure + oligohydramnios
Exam locks
- ❌ Avoid after 32 weeks
- Can cause oligohydramnios
- Indomethacin = tocolytic (short-term only)
🔵 INDOMETHACIN (Special NSAID)
Why it is special
- Very potent COX inhibitor
- Strong prostaglandin suppression
OB relevance
- Used as second-line tocolytic
- GA < 32 weeks
- Short duration (<48–72 h)
Fetal risks (logic)
- ↓ fetal renal perfusion → ↓ urine → oligohydramnios
- ↓ ductal prostaglandins → ductus arteriosus constriction
Exam locks
- Avoid prolonged use
- Monitor AFI if used
- Avoid >32 weeks
🔴 TRAMADOL — dual-mechanism weak opioid
Pharmacodynamics
- Weak µ-opioid agonist
- Inhibits serotonin + noradrenaline reuptake
- Enhances descending inhibitory pain pathways
👉 Dual mechanism = less respiratory depression but CNS risk
Pharmacokinetics
- Oral / IV
- Hepatic metabolism via CYP2D6
- Active metabolites
- Half-life ~ 6 hours
Clinical logic
- Moderate pain
- Alternative to pethidine in labour
- Less neonatal respiratory depression than morphine
Risks explained
- ↓ seizure threshold
- ↑ serotonin → serotonin syndrome with SSRIs
Exam locks
- ❌ Epilepsy
- ❌ SSRI / MAOI
- Causes seizures at high dose
🔴 PETHIDINE (Meperidine) — declining labour opioid
Pharmacodynamics
- µ-opioid agonist
- Metabolite normeperidine = neurotoxic
Pharmacokinetics
- IM / IV
- Hepatic metabolism
- Parent half-life ~3 h
- Metabolite half-life long → accumulation
Clinical logic
- Historically used in labour
- Now avoided due to:
- neonatal respiratory depression
- fetal acidosis
- maternal seizures
Exam locks
- Normeperidine causes seizures
- Avoid in renal / hepatic disease
- Avoid with MAOIs
🔴 MORPHINE — prototype strong opioid
Pharmacodynamics
- Pure µ-opioid receptor agonist
- ↓ Ca²⁺ influx presynaptic
- ↑ K⁺ efflux postsynaptic
- ↓ release of substance P & glutamate
System effects (logic)
- CNS: analgesia, sedation, euphoria
- Respiration: ↓ CO₂ responsiveness → depression
- GI: ↓ motility → constipation
- CVS: histamine release → vasodilation
- Eye: pinpoint pupils
Pharmacokinetics
- Poor oral bioavailability
- Hepatic glucuronidation → M3G, M6G
- Renal excretion → accumulation in renal failure
OB logic
- Crosses placenta easily
- Neonatal respiratory depression
- ↓ fetal heart rate variability
Exam locks
- Triad: coma + pinpoint pupils + respiratory depression
- Antidote = naloxone
- Avoid in head injury
🟢 ENTONOX (50% N₂O + 50% O₂) — safest labour analgesic gas
Pharmacodynamics
- Nitrous oxide → CNS depression
- ↑ endogenous endorphins
- Produces analgesia without loss of consciousness
Pharmacokinetics
- Inhaled
- Onset: 30–45 sec
- Offset: 1–2 min
- No metabolism → exhaled unchanged
Clinical logic
- Labour analgesia
- Self-administered
- Minimal maternal & fetal effects
Exam locks
- Contra: pneumothorax, air embolism
- Very rapid recovery
- Does not accumulate
🟣 REMIFENTANIL — ultra-short acting opioid
Pharmacodynamics
- Potent µ-opioid agonist
- Strong analgesia + sedation
Pharmacokinetics (WHY it’s unique)
- Metabolised by non-specific plasma esterases
- Independent of liver & kidney
- Context-insensitive half-life: 3–10 min
👉 No accumulation even with infusion
OB logic
- Used as PCA in labour
- When epidural contraindicated
- Rapid titration + fast recovery
Risks
- Maternal respiratory depression
- Neonatal respiratory depression if near delivery
Exam locks
- Continuous SpO₂ monitoring mandatory
- Avoid background infusion
- Neonatal team must be informed
🔹 ANALGESICS USED IN OBSTETRICS — SINGLE MASTER TABLE (TRANSPOSED)
Parameter | Paracetamol | NSAIDs (Ibuprofen, Diclofenac) | Indomethacin | Tramadol | Pethidine (Meperidine) | Morphine | Remifentanil | Entonox (50% N₂O + 50% O₂) |
Drug class / strength | Non-opioid, mild | Non-opioid, moderate | Potent NSAID | Weak opioid | Opioid | Strong opioid | Ultra-short opioid | Inhalational analgesic |
Primary mechanism (PD) | Central COX inhibition only | COX-1 & COX-2 inhibition | Very strong COX inhibition | Weak µ-agonist + ↓ 5-HT/NA reuptake | µ-opioid agonist | Pure µ-opioid agonist | Potent µ-opioid agonist | CNS depression + ↑ endorphins |
Peripheral anti-inflammatory effect | ❌ Absent | ✅ Present | ✅ Strong | ❌ | ❌ | ❌ | ❌ | ❌ |
Special PD features | Raises pain threshold; antipyretic | ↓ PGs in stomach, kidney, uterus, ductus | Profound PG suppression | Dual mechanism | Neurotoxic metabolite | ↓ Ca²⁺ presynaptic, ↑ K⁺ postsynaptic | Strong analgesia + sedation | Analgesia without LOC |
Route(s) | Oral, IV | Oral | Oral | Oral, IV | IM, IV | Oral (poor), IV | IV (PCA) | Inhaled |
Metabolism | Hepatic | Hepatic | Hepatic | Hepatic (CYP2D6) | Hepatic | Hepatic (glucuronidation) | Plasma esterases | ❌ None |
Key metabolites | NAPQI (toxic) | — | — | Active metabolites | Normeperidine (toxic) | M3G, M6G | Inactive | None |
Half-life / offset | 2–3 h | 2–4 h | Short (effect strong) | ~6 h | Parent ~3 h; metabolite long | Long (↑ in renal failure) | Context-insensitive t½ 3–10 min | Onset 30–45 s; offset 1–2 min |
Placental transfer | Minimal risk | Yes | Yes | Yes | Yes | Yes (easy) | Yes | Minimal |
OB / clinical use | First-line in pregnancy & postpartum | Postpartum pain, dysmenorrhoea | Short-term tocolysis | Moderate pain, labour alternative | Historical labour analgesia | Severe pain | Labour PCA if epidural contraindicated | Labour analgesia |
Gestational limits | Safe all trimesters | ❌ Avoid >32 weeks | ❌ Avoid >32 weeks | Use with caution | Avoid | Avoid if possible | Specialist use | Safe |
Fetal effects (logic) | Safe | Ductus closure, oligohydramnios | ↓ renal perfusion → oligohydramnios; ductal constriction | Less neonatal depression than morphine | Neonatal respiratory depression, acidosis | Neonatal respiratory depression; ↓ FHR variability | Neonatal depression if near delivery | Minimal |
Major maternal risks | Hepatotoxicity | GI bleed, renal injury | Same + fetal risks | Seizures, serotonin syndrome | Seizures | Respiratory depression | Respiratory depression | Gas space expansion |
Key contraindications | Severe liver disease | PUD, renal disease, aspirin-asthma | Prolonged use | Epilepsy, SSRIs, MAOIs | Renal/hepatic disease, MAOIs | Head injury | No background infusion | Pneumothorax, air embolism |
Absolute exam locks | NOT anti-inflammatory; overdose → acute hepatic necrosis | ❌ After 32 weeks; oligohydramnios | Tocolytic <48–72 h only; monitor AFI | ↓ seizure threshold | Normeperidine causes seizures | Triad: coma + pinpoint pupils + resp depression; antidote naloxone | Continuous SpO₂; neonatal team alert | Rapid on/off; no accumulatio |
Morphine vs Pethidine (Meperidine)
Domain | Morphine | Pethidine (Meperidine) |
Opioid class | Strong opioid | Synthetic opioid |
Lipid solubility | Less lipid-soluble | More lipid-soluble |
Onset of action | Slower | Faster |
Duration / Half-life | Longer half-life | Shorter half-life |
Placental transfer | Crosses placenta easily | Crosses placenta easily |
Neonatal respiratory depression | High risk | Lower risk (not zero) |
Primary reason for neonatal depression | Long half-life + strong opioid effect | Still crosses placenta but less prolonged effect |
Maternal sedation / hypnosis | Marked ↑ | Moderate |
Maternal cooperation in labour | Poor | Better |
Constipation | Present | Less prominent |
Urinary retention | Present | Less |
Effect on uterine contractions | Significant ↓ | Mild ↓ |
Mechanism of uterine inhibition | ❌ Not via oxytocin ↓ ✅ CNS depression + direct smooth muscle relaxation | Minimal uterine smooth muscle inhibition |
Effect on labour duration | Prolongs labour | Less effect on labour duration |
Anticholinergic property | Absent | Present (mild) |
Metabolites | No neurotoxic metabolite | Normeperidine (neurotoxic) |
Effect on seizure threshold | Neutral | Lowers seizure threshold |
Use in epilepsy | Can be used cautiously | Contraindicated |
Repeated dosing risk | Accumulation → respiratory depression | Accumulation → seizures |
Typical labour use | ❌ Avoid | ✅ Preferred opioid |
Common combinations | Rarely used | Promethazine / Metoclopramide |
Overall role in labour | Poor choice | Drug of choice among opioids |
🧠 EXAM-LOCK MECHANISM TABLE (VERY HIGH-YIELD)
Concept | Morphine | Pethidine |
Why morphine prolongs labour | Strong CNS depression + uterine relaxation | Minimal uterine effect |
Why neonatal depression is worse | Long half-life | Shorter half-life |
Why pethidine preferred | — | Less uterine inhibition + less neonatal depression |
Key danger | Prolonged labour + fetal depression | Seizures (normeperidine) |
⚠️ CLASSIC EXAM TRAPS (DO NOT FALL)
Statement | Truth |
“Morphine reduces oxytocin production” | ❌ False |
“Pethidine does not cross placenta” | ❌ False |
“Pethidine is safe in epilepsy” | ❌ False |
“Pethidine has no neonatal respiratory effect” | ❌ False (just less than morphine) |
🔑 ONE-LINE EXAM ANSWER
Pethidine is preferred over morphine in labour because it causes less uterine inhibition and less neonatal respiratory depression, despite placental transfer, while morphine significantly prolongs labour.