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Here is a comprehensive reference covering all key areas of Midwifery Pharmacology.

Midwifery Pharmacology - Complete Reference

1. UTEROTONIC (OXYTOCIC) AGENTS

Uterotonics are the most commonly administered drugs in labour and delivery. They promote uterine contraction by increasing intracellular calcium concentrations. All act via different pathways and carry significant side-effect profiles.

1.1 Oxytocin (Syntocinon)

Feature	Detail
Class	Endogenous posterior pituitary hormone (synthetic form)
Mechanism	Binds oxytocin receptors on myometrium → activates phospholipase C → IP3 → intracellular Ca²⁺ release → uterine contraction
Uses	Induction/augmentation of labour; active management of 3rd stage; prevention and treatment of PPH
Route/Dose	IV infusion (titrated for induction); 10 IU IM or IV bolus for 3rd stage
Onset	IV: immediate; IM: 3-5 minutes
Side effects	Hypotension (IV bolus), tachycardia, fluid retention/hyponatraemia (antidiuretic effect at high doses), uterine hyperstimulation, fetal distress
Contraindications	Mechanical obstruction to delivery, fetal malpresentation, cephalopelvic disproportion, placenta praevia
Monitoring	Continuous CTG during induction; fluid balance; uterine activity

1.2 Ergometrine (Ergot Alkaloid)

Feature	Detail
Class	Ergot alkaloid (derived from Claviceps purpurea fungus on rye)
Mechanism	Binds alpha-adrenergic receptors → alters transmembrane Ca²⁺ channel activity → sustained tonic contraction; also acts on 5-HT receptors
Uses	Prevention and treatment of PPH (3rd stage); uterine atony
Route/Dose	0.5 mg IM or IV (slow); combined as Syntometrine (oxytocin 5 IU + ergometrine 0.5 mg)
Onset	IM: 2-5 minutes; IV: 45 seconds
Half-life	30-120 minutes
Side effects	Hypertension, nausea, vomiting, vasoconstriction, coronary artery spasm, MI (rare)
Contraindications	Hypertension, pre-eclampsia/eclampsia, cardiac disease, vascular disease, Raynaud's; NOT for use before delivery of placenta if multiple pregnancy
Storage	Unstable in heat and light - must be refrigerated

1.3 Misoprostol (Prostaglandin E1 Analogue)

Feature	Detail
Class	Prostaglandin E1 (PGE1) analogue
Mechanism	Binds prostaglandin E receptors on myometrium → smooth muscle contraction; also cervical ripening
Uses	Cervical ripening/induction of labour; prevention and treatment of PPH; management of missed miscarriage
Route/Dose	Oral/sublingual/vaginal/rectal: 25-600 mcg depending on indication
Onset	Sublingual/oral: 9-15 minutes; vaginal/rectal: slower onset, prolonged effect
Half-life	20-40 minutes
Advantages	Water soluble, heat stable, oral administration possible - ideal for low-resource settings
Side effects	Diarrhoea, abdominal cramps, nausea/vomiting, shivering, pyrexia, uterine hyperstimulation
Contraindications	Previous uterine scar (caution for induction - risk of rupture), not licensed for obstetric use (used off-label)

1.4 Carbetocin (Pabal)

Feature	Detail
Class	Long-acting oxytocin analogue
Mechanism	Oxytocin receptor agonist with prolonged activity
Uses	Prevention of PPH after caesarean section
Route/Dose	100 mcg IV single bolus (elective CS); 100 mcg IM (WHO recommended in resource-limited settings)
Advantage over oxytocin	Single dose sufficient (vs infusion); longer duration of action (~1 hour)
Side effects	Facial flushing, headache, nausea, hypotension

1.5 Dinoprostone (PGE2 - Prostin E2)

Used for cervical ripening and induction of labour
Available as vaginal gel, pessary (Cervidil - slow-release)
Side effects: uterine hyperstimulation, GI disturbance, fever
Remove Cervidil pessary if hyperstimulation occurs

2. TOCOLYTIC AGENTS (Preterm Labour)

Used to inhibit uterine contractions and delay preterm birth (to allow corticosteroid administration and/or transfer to a higher-level centre).

Drug	Class	Mechanism	Notes
Nifedipine	Calcium channel blocker	Blocks Ca²⁺ influx into myometrial cells	First-line in most guidelines; oral, well tolerated
Atosiban (Tractocile)	Oxytocin receptor antagonist	Competitive antagonist at oxytocin/vasopressin receptors	IV infusion; fewer systemic side effects; expensive
Salbutamol / Ritodrine	Beta-2 agonist	↑ cAMP → inactivates MLCK → relaxation	Second-line; significant CV side effects (tachycardia, palpitations, pulmonary oedema)
Indomethacin	NSAID/COX inhibitor	Reduces prostaglandin synthesis	Used before 32 weeks only; risk of premature closure of ductus arteriosus
Magnesium sulfate	Mineral	Reduces neuronal excitability; competes with Ca²⁺	Used primarily for neuroprotection <32 weeks + eclampsia; monitoring of reflexes and urine output essential

3. PAIN MANAGEMENT IN LABOUR

3.1 Non-Pharmacological Methods

Water immersion (hydrotherapy)
TENS (transcutaneous electrical nerve stimulation)
Hypnobirthing, massage, breathing techniques
Birthing positions and mobility

3.2 Pharmacological Options

Entonox (Nitrous Oxide + Oxygen 50:50)

Inhaled self-administered analgesic
Onset: 20-30 seconds; wears off quickly (20 seconds)
Mechanism: exact mechanism unclear; likely endorphin release and NMDA receptor modulation
Side effects: light-headedness, nausea, vomiting, disorientation, hyperventilation
Safe for fetus; no accumulation
Midwife must ensure deep breathing before each contraction

Opioids

Drug	Route	Dose	Notes
Pethidine (Meperidine)	IM/IV	100-150 mg IM	Most commonly used opioid in labour in many countries; causes neonatal respiratory depression if given close to delivery; metabolite (norpethidine) accumulates
Diamorphine	IM	5-7.5 mg	Greater lipid solubility; better analgesia and maternal sedation than pethidine
Morphine	IV/IM	2-10 mg	Less commonly used in active labour; used postnatally
Remifentanil	IV PCA	Titrated	Ultra-short-acting; patient-controlled; requires 1:1 midwifery care and O₂ saturation monitoring

Key concern with all opioids: Neonatal respiratory depression - Antidote: Naloxone (Narcan) 0.1 mg/kg IM/IV to neonate

Regional Analgesia

Epidural:

Gold standard for labour analgesia
Combined low-dose local anaesthetic (bupivacaine 0.1%) + opioid (fentanyl)
Continuous infusion or PCEA (patient-controlled epidural analgesia)
Side effects: hypotension (most common), motor block, urinary retention, dural puncture headache, limited mobility, prolonged 2nd stage, increased instrumental delivery rate
Midwife role: IV access first, position (lateral/sitting), BP monitoring q5-15 min after top-up, bladder care

Spinal (Intrathecal):

Single-shot for caesarean section, instrumental delivery, or perineal repair
Faster onset, denser block, shorter duration than epidural
Risk: spinal headache, hypotension, total spinal

Combined Spinal-Epidural (CSE):

"Walking epidural" - lower doses allow mobility
Faster onset than epidural alone

4. ANTENATAL PHARMACOLOGY

4.1 Corticosteroids (Fetal Lung Maturation)

Drug	Dose	Notes
Betamethasone	2 x 12 mg IM 24 hrs apart	Preferred agent (crosses placenta effectively)
Dexamethasone	4 x 6 mg IM 12 hrs apart	Alternative
Indication	Threatened preterm labour 24-34 weeks (up to 36+6 weeks in some guidelines)	Reduces RDS, IVH, NEC, mortality

4.2 Antihypertensives in Pregnancy

Drug	Use	Notes
Labetalol	Hypertension in pregnancy, pre-eclampsia	Alpha + beta blocker; oral or IV; first-line IV for severe hypertension
Nifedipine	Hypertension, tocolysis	Calcium channel blocker; oral; avoid sublingual (precipitous hypotension)
Methyldopa	Chronic hypertension	Alpha-2 agonist; oldest agent; safe profile in pregnancy
Hydralazine	Severe hypertension	IV/IM; causes reflex tachycardia; use with opioid or beta-blocker

AVOID in pregnancy: ACE inhibitors (fetotoxic), ARBs, direct renin inhibitors - cause fetal renal failure, oligohydramnios, skull defects

4.3 Magnesium Sulfate

Indication	Dose	Monitoring
Eclampsia treatment	4 g IV loading over 20 min, then 1-2 g/hr maintenance
Eclampsia prevention	Same regime in severe pre-eclampsia	Urine output >25 ml/hr, respiratory rate >12/min, patellar reflexes present
Neuroprotection	4 g IV before preterm birth <32 weeks
Antidote for toxicity	Calcium gluconate 1 g IV (10 ml of 10%)	Signs of toxicity: loss of reflexes, respiratory depression, cardiac arrest

4.4 Anticoagulation in Pregnancy

Drug	Use	Notes
LMWH (e.g. Enoxaparin)	VTE prophylaxis/treatment	Does NOT cross placenta; safe in pregnancy; stop 12-24 hrs before delivery
Unfractionated heparin	VTE, prosthetic heart valves	Does not cross placenta; reversible with protamine sulfate
Warfarin	AVOID in 1st trimester (weeks 6-12)	Teratogenic (warfarin embryopathy); can be used 2nd trimester with strict monitoring; switch to heparin at 36 weeks
Aspirin (75-150 mg)	Pre-eclampsia prevention (high-risk)	Start at 12 weeks; antiplatelet

4.5 Supplements / Vitamins

Drug	Dose	Indication
Folic acid	400 mcg/day (5 mg if high risk)	From pre-conception to 12 weeks; prevents neural tube defects
Vitamin D	400 IU/day	All pregnant women
Iron (Ferrous sulfate)	200 mg BD-TDS	Iron deficiency anaemia; side effects: constipation, dark stools
Calcium	1.5-2 g/day	Pre-eclampsia prevention in low calcium intake populations

4.6 Anti-emetics (Nausea and Vomiting of Pregnancy)

Drug	Class	Notes
Cyclizine	Antihistamine (H1 antagonist)	Oral or IV/IM; safe first-line in pregnancy
Promethazine	Phenothiazine antihistamine	Oral or IM; sedating
Metoclopramide	Dopamine antagonist	Prokinetic; use cautiously (extrapyramidal effects)
Ondansetron	5-HT3 antagonist	Used for severe/refractory NVP or hyperemesis gravidarum; some concerns about congenital defects with 1st trimester use
Doxylamine + B6	Antihistamine + pyridoxine	First-line in many international guidelines (e.g. USA)

5. INTRAPARTUM PHARMACOLOGY

5.1 Group B Streptococcus (GBS) Prophylaxis

Benzylpenicillin (Penicillin G) 3 g IV loading, then 1.5 g IV 4-hourly during labour
If penicillin allergy (non-anaphylactic): Cefazolin 2 g loading, then 1 g 8-hourly
If high anaphylaxis risk: Clindamycin or Vancomycin (based on sensitivities)

5.2 Cervical Ripening

Method	Drug	Route
Pharmacological	Dinoprostone (PGE2)	Vaginal gel or pessary
Pharmacological	Misoprostol (PGE1)	Vaginal/oral
Mechanical	Foley catheter balloon	Transcervical

6. POSTNATAL PHARMACOLOGY

6.1 Analgesia after Birth

Pain Level	Drug	Dose
Mild	Paracetamol	1 g 4-6 hourly (max 4 g/day)
Mild-Moderate	NSAIDs (Ibuprofen, Diclofenac)	Ibuprofen 400 mg TDS with food; Diclofenac 50 mg TDS
Moderate-Severe	Codeine / Co-codamol	30/500 mg 4-6 hourly; caution in breastfeeding (ultra-rapid metabolisers)
Severe (post-CS)	Morphine / Opioid PCA	5-15 mg IM; multimodal analgesia with paracetamol + NSAID reduces opioid requirements

6.2 Postpartum Haemorrhage (PPH) Treatment Protocol

Oxytocin 10 IU IV/IM - first-line
Ergometrine 0.5 mg IV/IM (avoid if hypertension)
Syntometrine (oxytocin + ergometrine) - widely used in 3rd stage
Carboprost (Hemabate) - PGF2-alpha analogue - 0.25 mg IM every 15 min, max 8 doses; causes bronchospasm - AVOID in asthma
Tranexamic acid - 1 g IV within 3 hours of PPH onset (WOMAN trial evidence); antifibrinolytic
Misoprostol 800 mcg sublingual - if IV access unavailable

6.3 Breastfeeding and Medications

Safe in breastfeeding	Use with caution	Avoid
Paracetamol	Codeine (ultra-rapid metabolisers)	Aspirin (Reye's syndrome risk)
Ibuprofen	Opioids (monitor infant)	Combined OCP (suppresses milk supply)
Most antibiotics	Metronidazole (taste change in milk)	Tetracyclines
LMWH, Warfarin	SSRIs (paroxetine preferred)	Lithium
Labetalol, Nifedipine		Ergotamine (vasoconstriction)

6.4 Postnatal Depression / Mental Health

Drug	Notes
Sertraline	First-line SSRI for postnatal depression; low transfer into breast milk
Paroxetine	Alternative; lowest levels in breast milk of SSRIs
Fluoxetine	Long half-life; use with caution in breastfeeding

6.5 Lactation Suppressants

Cabergoline 1 mg single oral dose (dopamine agonist; suppresses prolactin)
Bromocriptine - older alternative; more side effects

6.6 Contraception Postnatal

Method	Timing	Notes
Progestogen-only pill (POP)	From day 21	Safe while breastfeeding
Combined OCP	After 6 weeks (non-breastfeeding)	Avoid while breastfeeding (oestrogen suppresses milk)
DMPA (Depo-Provera)	From day 21	Can start immediately postpartum
IUD/IUS	Within 48 hrs or after 4 weeks	Mirena IUS - also treats heavy lochia

7. DRUG SAFETY CATEGORIES IN PREGNANCY

Category	Meaning (FDA old system)	Examples
A	Adequate studies - no risk	Folic acid, Vitamin D
B	Animal studies - no risk; no adequate human studies	Metronidazole, Penicillin
C	Animal studies show risk; no adequate human studies	Labetalol, Nifedipine, Aspirin
D	Evidence of risk - benefit may outweigh	Tetracyclines, phenytoin
X	Contraindicated in pregnancy	Warfarin (1st trimester), Retinoids, Statins, Thalidomide

8. KEY DRUG INTERACTIONS AND WARNINGS

Interaction/Concern	Details
Oxytocin + Ergometrine	Combined as Syntometrine; avoid if maternal hypertension
Magnesium + Calcium channel blockers	Enhanced hypotension and neuromuscular blockade
NSAIDs in pregnancy	Avoid after 32 weeks - risk of premature closure of ductus arteriosus and oligohydramnios
Pethidine + MAOIs	Potentially fatal serotonin syndrome
Warfarin in pregnancy	Teratogenic weeks 6-12; use LMWH instead
ACE inhibitors/ARBs	Absolutely contraindicated throughout pregnancy

9. QUICK REFERENCE - EMERGENCY DRUGS

Emergency	Drug	Dose
Eclamptic seizure	Magnesium sulfate	4 g IV over 20 min
Mg toxicity	Calcium gluconate	10 ml of 10% IV
Anaphylaxis	Adrenaline (epinephrine)	0.5 mg IM (1:1000)
Opioid OD / Neonatal apnoea	Naloxone	0.4 mg IV adult; 0.1 mg/kg neonate
PPH unresponsive to oxytocics	Tranexamic acid	1 g IV (repeat if needed at 30 min)
Severe hypertension (>160/110)	Labetalol / Hydralazine	Labetalol 20 mg IV; repeat or switch
Uterine hyperstimulation	Stop oxytocin; Terbutaline	0.25 mg SC (tocolysis)
GBS prophylaxis	Benzylpenicillin	3 g IV, then 1.5 g 4-hourly

10. MIDWIFE PRESCRIBING PRINCIPLES

Always check gestational age - many drugs are trimester-specific in safety
Renal and hepatic function - both alter in pregnancy; drug clearance changes
Check breastfeeding compatibility - use LactMed database (NIH) for current evidence
Document and monitor - uterine activity, fetal heart rate, maternal BP/HR, fluid balance
Informed consent - especially for off-label drugs (misoprostol, tranexamic acid)
PPH kit - know your unit's protocol; have oxytocin and tranexamic acid available at all births
MEOWS/NEWS - escalate early; pharmacology is part of a wider clinical picture

Sources: Creasy & Resnik's Maternal-Fetal Medicine, Katzung's Basic & Clinical Pharmacology 16e, WHO/NCBI uterotonic meta-analysis, UKZN Uterotonics & Tocolytics reference, LSTM Antenatal/Postnatal Care Manual

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