GC160 The Woman Needs That Drug Oral Contraceptives Drugs Affecting Uterine Motility
Oral contraceptives are estrogen-progestin or progestin-only formulations that prevent ovulation, alter the endometrium, and thicken cervical mucus, while uterine motility drugs such as oxytocin, ergot alkaloids, prostaglandins, and tocolytics either stimulate or inhibit uterine contractions to manage labor, postpartum hemorrhage, or preterm labor.
Oral Contraceptives & Drugs Affecting Uterine Motility
Big Idea: This lecture bridges reproductive endocrinology and clinical pharmacology. It covers (1) how gonadotropins and gonadal hormones regulate the menstrual cycle, (2) how exogenous estrogen and progestin exploit these feedback loops for contraception, (3) the pharmacology and adverse-effect profiles of COCs vs POPs, (4) drug interactions that reduce OCP efficacy, (5) the physiology of labour onset, and (6) drugs that either promote (uterotonics) or suppress (tocolytics) uterine contractions.
Learning Objectives (from the slide deck) [1]:
| # | Objective |
|---|---|
| I | Describe functional relationships of gonadotropins (FSH, LH) and gonadal hormones (estrogen, progestin) in ovaries and uterus |
| II | Describe contraceptive actions of estrogen and progestin |
| III | Compare COCs and POPs — composition, dosing regimens, unwanted effects, drug-drug interactions |
| IV | Recognise resources available to guide patient counselling on contraception |
| V | Describe events underlying onset of labour and mediators (PG, OT) involved |
| VI | Describe uses of uterotonic drugs |
| VII | List examples of tocolytic drugs |
How it fits: This is a clinical pharmacology lecture that directly underpins O&G clinical practice — fertility regulation, induction of labour, management of postpartum haemorrhage, and emergency tocolysis for preterm labour. Expect MCQs on COC/POP differences, estrogen-related thromboembolic risk, progestin generations, mechanisms of uterotonics/tocolytics, and drug interactions.
Current-practice safety frame
The deck is useful for mechanisms, but prescribing must use a current contraceptive eligibility framework and a local obstetric protocol. Pregnancy is not a toxic-exposure “contraindication” to oral contraception: contraception is simply unnecessary, and inadvertent early exposure is not known to harm the pregnancy. Conversely, current breast cancer is a true category 4 contraindication to both combined and progestin-only hormonal methods. [14]
1. Menstrual Cycle Hormonal Physiology (Review for Contraception)
High Yield: The lecture walks through a numbered 10-step feedback loop that you must understand to explain why contraceptives work. This is labelled "for your own review" but the contraceptive mechanism slides directly reference it. [1]
| Phase | Ovarian Event | Endometrial Event | Dominant Hormones |
|---|---|---|---|
| Menstrual | — | Shedding | Falling E & P |
| Follicular | Follicle development (FSH early, then LH & E late) | Proliferative (supported by E) | Rising FSH → rising E |
| Ovulatory | Ovulation | — | LH surge (triggered by very high E via +ve feedback) |
| Luteal | Corpus luteum | Secretory (supported by P) | High P & E from corpus luteum |
Critical feedback concepts from slides [1]:
- Rising E has little effect (via −ve feedback) on LH — this is why LH keeps rising in the follicular phase even as E rises.
- Continuous increase in E to reach above a threshold exerts +ve feedback to cause LH & FSH surge — the switch from negative to positive feedback is dose-dependent.
- Very high P level offsets E-mediated +ve feedback, causing FSH & LH to decrease — this is the basis of progestin-based contraception.
- FSH & LH begin to rise again as E & P levels fall — the trigger for a new cycle, and what happens during the hormone-free interval of COCs.
- Inhibin (from granulosa cells) also contributes to FSH suppression.
2. Contraceptive Actions of Estrogen and Progestin
High Yield: Sustained E & P inhibits follicular development (via inhibiting FSH & LH), but no +ve feedback to increase FSH & LH → no LH surge → no ovulation → no corpus luteum. [1]
| Mechanism | Hormone Responsible | Why It Works |
|---|---|---|
| Suppression of ovulation | E + P together suppress FSH & LH; P prevents LH surge | No follicular maturation, no ovulation |
| Impaired endometrial development | Asynchronous P & E → thinner lining, altered secretions | Less favourable for implantation |
| Thickened cervical mucus | P | Impedes sperm penetration |
| Altered ovum transport | P & E alter tubal motility | Lower chance of fertilisation |
Why Sustained E Doesn't Cause an LH Surge in COC Users
In the normal cycle, the LH surge requires E to rise continuously past a threshold. In COC users, E is provided at a constant low dose — it never builds up enough for positive feedback. Additionally, the progestin component actively suppresses the LH surge by exerting negative feedback. The combination is therefore synergistic: estrogen suppresses FSH (preventing follicle development), while progestin suppresses LH (preventing ovulation even if some follicular development occurs).
Slide 10 arranges methods by typical-use pregnancy rate, which is as much a measure of user dependence as pharmacology: [1][15]
| Slide tier | Examples shown | Practical meaning |
|---|---|---|
| Tier 1: < 1 pregnancy per 100 users in the first year | Implant, intrauterine contraception, vasectomy, tubal surgery | Little or no repeated user action; highest real-world effectiveness |
| Tier 2: about 4–7 per 100 | Injectable, pill, patch, ring | Effective, but timely repeat dosing or daily adherence matters |
| Tier 3: generally > 13 per 100 | Condoms, fertility-awareness methods, diaphragm, sponge, withdrawal, spermicides | Effectiveness is highly technique- and use-dependent |
Exact typical-use estimates vary by method and dataset, so learn the ordering, not a single immutable percentage. Except for condoms, these methods do not protect against sexually transmitted infections.
3. Combined Oral Contraceptives (COCs)
Each COC pill contains an estrogen (E) + a progestin (P). [1]
The slide's phrase “pregnancy, breast cancer and other conditions” is too compressed for clinical use. Apply a current medical eligibility chart rather than memorising a short list. Important combined hormonal contraception (CHC) category 4 examples include current breast cancer, migraine with aura, severe hypertension (≥160/100 mmHg), current/high-risk DVT or PE or thrombophilia, smoking at age ≥35 years at ≥15 cigarettes/day, and the first 21 days postpartum. Some related states are category 3 rather than 4 and need individualised assessment. Pregnancy is “not applicable,” not an adverse-exposure category. [14]
Do not substitute POP automatically
Removing estrogen often makes a progestin-only method safer for vascular risk, but it does not make every method suitable for every patient. Check the method-specific category, current disease, interacting medicines, postpartum timing, liver/renal disease and patient preference. [14]
3.3 Dosing Regimens
Each hormone-containing pill (containing same E & P dose) taken continuously for 21 or 24 days; one hormone-free pill for each of remaining 7 (of 21) days or 4 (of 24) days of cycle [1]
Purpose of hormone-free interval: to allow a predictable withdrawal bleed, as preferred by some patients; monthly bleeding has no demonstrated medical necessity [1].
What happens during hormone-free days [1]:
- No exogenous estrogen → reduced negative feedback → FSH may stimulate some follicular development → endogenous estradiol secretion → endometrial growth → endometrial atrophy follows (similar to end of menstrual period) & bleeding.
| Feature | 21-day active + 7-day HFI | 24-day active + 4-day HFI |
|---|---|---|
| Example | Yasmin® (EE 0.03 mg + drospirenone 3 mg) | Yaz® (EE 0.02 mg + drospirenone 3 mg) |
| HFI length | 7 days | 4 days |
| Follicular development | More (longer HFI) | Less (shorter HFI) |
| Follicular suppression margin | Less forgiving if the HFI is inadvertently extended | Greater ovarian suppression in comparative studies |
| Unscheduled bleeding | Less | More (less endometrial development from lower E dose & shorter cycle) |
A shorter hormone-free interval reduces follicular “escape,” but do not infer a universal real-world superiority of every 24/4 product over every 21/7 product: effectiveness also depends on formulation, adherence and correct start/restart. The bleeding pattern is formulation-specific. [1][16]
Other regimen options [1]:
- Extended-cycle (e.g. 84 active pills + 7 inert pills → bleeding every 3 months)
- Continuous (no scheduled bleeding at all)
Biphasic and triphasic COCs: lower total hormone dose taken in a cycle, aiming to mimic more closely changing ratios of E & P in a natural menstrual cycle [1]
- Contraceptive efficacy is broadly comparable when pills are taken correctly.
- The proposed advantages in bleeding control or mood are not universal class effects; evidence and regimens vary. A monophasic pill is often easier to use because every active tablet has the same dose.
- Missing or mixing up tablets in a multiphasic pack is more consequential because phases are not interchangeable.
High-dose (50 μg) no longer common for contraceptive use — more thromboembolic effects [1] Low-dose (20 to 35 μg) [1]
| EE Dose | Thromboembolic Risk | Unscheduled Bleeding |
|---|---|---|
| 50 μg (high) | Higher | Lower |
| 35 μg (low) | Lower | Lower |
| 20 μg (ultra-low) | Lower estrogen-dose contribution; total risk still depends on formulation and patient | Higher |
The slide's 'net estrogenic effect' is a teaching model
The deck explains thrombosis by balancing estrogenic against androgenic activity. Retain that as a historical mechanistic model, not a validated bedside calculator. VTE risk is influenced by estrogen dose and route, the progestin, duration of use and—most importantly—individual risk factors. [14][17]
The slide presents generations as a conceptual framework. Contemporary regulatory data support a lower average VTE risk with levonorgestrel-, norethisterone- or norgestimate-containing CHCs than with desogestrel-, gestodene- or drospirenone-containing CHCs, but “generation” and androgenicity do not prove the mechanism or rank every product. [17]
| Generation | Example | Androgenicity | Anti-androgenicity | Net Estrogenic Effect | Thromboembolic Risk |
|---|---|---|---|---|---|
| 1G | Norethindrone (norethisterone) | Moderate | None | Older-generation example | Lower-risk reference group in EMA estimates |
| 2G | Levonorgestrel (L-norgestrel) | Higher | None | Older-generation example | Lower average VTE risk among CHCs |
| 3G | Desogestrel | Lower | Weak | Newer-generation example | Higher average VTE risk than levonorgestrel CHCs |
| 4G | Drospirenone | None | Strong | Anti-androgenic example | Higher average VTE risk than levonorgestrel CHCs |
More progestogenic & androgenic (1G: norethindrone, 2G: levonorgestrel) = less estrogenic = less thromboembolic [1] More anti-androgenic (4G: drospirenone) or less androgenic (3G: desogestrel) = more estrogenic = more thromboembolic [1]
EMA's approximate annual estimates are about 5–7 VTEs per 10,000 CHC users for levonorgestrel/norethisterone/norgestimate products and 9–12 per 10,000 for drospirenone/gestodene/desogestrel products, compared with about 2 per 10,000 in non-pregnant non-users. These population estimates do not replace individual eligibility assessment. [17]
| Action | Mechanism |
|---|---|
| Suppress ovulation | Sustained E & P → −ve feedback → ↓ FSH & LH → no LH surge |
| Impair implantation | Asynchronous E & P → thin, atrophic endometrium with altered secretions |
| Impede sperm | P → thick cervical mucus |
| Alter transport | P & E → altered tubal motility → ↓ fertilisation chance |
4. Progestin-Only Pills (POPs)
The lecture correctly emphasizes the importance of cervical-mucus effects, but “POPs are less effective because they do not always inhibit ovulation” overgeneralises across formulations. Traditional norethindrone/norgestrel POPs do not suppress ovulation consistently and have a narrow late-pill window; desogestrel and drospirenone POPs suppress ovulation more consistently and have different missed-pill rules. In typical use, the CDC quotes a 7% first-year failure rate for both combined and progestin-only pills, reflecting adherence more than theoretical potency. [15][16]
| Feature | COC | POP |
|---|---|---|
| Components | E + P | P only |
| Ovulation suppression | Reliable with correct use | Formulation-dependent; not consistent with traditional POPs |
| Dosing schedule | 21+7 or 24+4 | 28-day continuous (no pill-free period) — except drospirenone (24+4) |
| Eligibility | Estrogen-related vascular restrictions plus method-specific conditions | Fewer vascular restrictions, but not “pregnancy & breast cancer only”; check method-specific MEC |
| VTE risk | Increased | Not significantly increased |
Used by those contraindicated to COCs, usually due to estrogenic (or "estrogenic-like") effects on vascular conditions [1]
The slide details three mechanisms of estrogen-related vascular harm:
| Vascular Effect | Mechanism | Clinical Consequence |
|---|---|---|
| Endothelial dysfunction | Pro-thrombotic state enhanced by smoking | DVT/PE |
| Increased coagulation | Increased synthesis of clotting factors | Thrombotic disorders |
| Hypertension | More activated RAAS | Promotes thrombosis |
COC Contraindications — The Vascular Triad
Students often forget why estrogen-containing contraception becomes unsafe with major arterial or venous risk. POPs avoid the estrogen component, but eligibility still depends on the exact condition and product; current breast cancer remains category 4 for POPs. [14]
Correction: POP eligibility
Current breast cancer is category 4 for POPs; previous breast cancer without disease for 5 years is category 3. Pregnancy is not applicable because contraception is unnecessary, and inadvertent POP exposure is not known to harm the pregnancy. Other conditions and medicines can also affect suitability. Drospirenone has antimineralocorticoid activity, so renal/adrenal disease and potassium-raising drugs require product-specific review. [14]
Most POPs are taken every day without a hormone-free interval; drospirenone packs use 24 active plus 4 inactive tablets. The schedule reflects each product's pharmacology—not a general rule based on androgenicity—and missed-pill instructions are formulation-specific. [16]
The slide (p. 20) categorizes adverse effects [1]:
| Category | Effect | Explanation |
|---|---|---|
| Estrogenic | Thromboembolic events (DVT/PE/stroke) | ↑ clotting factor synthesis, endothelial dysfunction, ↑ RAAS |
| Progestogenic/Androgenic | Acne or other androgenic symptoms can occur | Effects differ by molecule and person; substantial weight gain is not a universal pill effect |
| Breakthrough bleeding | Unscheduled bleeding | Most common with POP use; also common with low-dose COCs |
| Warning signs (ACHES) | Abdominal pain, Chest pain, Headache, Eye problems, Severe leg pain | May be indicative of stroke or other thrombotic conditions |
Breakthrough Bleeding Explained [1]
| Type | Cause | Mechanism |
|---|---|---|
| Progesterone breakthrough | High P:E ratio (POP, or late COC cycle) | Endometrium atrophic & ulcerated from lack of E → prone to frequent, irregular bleeding |
| Estrogen breakthrough | Excess E without adequate P | Endometrium proliferates in undifferentiated manner → portions slough irregularly → profuse bleeding |
"Progesterone breakthrough bleeding occurs when the progesterone-to-estrogen ratio is high... The endometrium becomes atrophic and ulcerated because of a lack of estrogen" [1]
ACHES Mnemonic for Danger Signs on OCP
ACHES = severe Abdominal pain, Chest pain or breathlessness, new severe Headache, Eye/visual symptoms, Severe unilateral leg pain or swelling. These symptoms require urgent medical assessment for thromboembolism or another emergency; the mnemonic is a triage prompt, not a self-diagnosis.
P450 inducers, e.g. certain anti-epileptics, St. John's wort → increased OCP metabolism [1] Historical slide claim: ordinary beta-lactams and tetracyclines reduce efficacy by interrupting enterohepatic recycling. Current evidence does not support this as a clinically important interaction. [14]
Mechanism of Interaction
CYP450 inducers: EE (and some progestins) are metabolised by hepatic CYP3A4. Enzyme inducers accelerate metabolism → reduced plasma levels → reduced efficacy.
Antibiotics & enterohepatic recycling: this is the proposed mechanism shown on the slide, but most broad-spectrum antibiotics do not reduce pill, patch or ring effectiveness. Backup is needed when vomiting or severe diarrhoea compromises oral absorption, or when the antimicrobial is an enzyme inducer such as rifampicin/rifabutin. [14][16]
| Interacting Drug | Mechanism | Clinical Consequence |
|---|---|---|
| Rifampicin (most potent) | CYP3A4 induction | Dramatically ↓ OCP efficacy; advise alternative contraception [3] |
| Carbamazepine, phenytoin, phenobarbital | CYP induction | ↓ OCP efficacy |
| St. John's wort | CYP3A4 induction | ↓ OCP efficacy (commonly tested!) |
| Most beta-lactams and tetracyclines | No clinically important interaction demonstrated | No routine extra contraceptive precautions solely for the antibiotic [14] |
| Lamotrigine | CHC estrogen increases lamotrigine clearance | Lamotrigine level may fall and seizure control may worsen; coordinate with prescriber [14] |
The slide explicitly notes that the enterohepatic recycling diagram "also applies to progestin" [1]
Rifampicin and OCP
Rifampicin/rifabutin induction can reduce CHC and POP effectiveness. Encourage a method unaffected by enzyme induction (for example, an intrauterine method; DMPA is also unaffected in CDC MEC) and follow current interaction guidance rather than simply adding condoms for an indefinite period. [14]
The lecture includes a 13-year-old with six months of long, heavy periods that are disrupting school. The visual case makes the quality-of-life impact central, not merely the measured volume of blood loss. [1][18]
Assessment priorities in an adolescent: speak confidentially as developmentally appropriate, assess haemodynamic stability, obtain a full blood count, consider pregnancy testing where relevant, and consider a coagulation disorder when HMB began at menarche or there is a personal/family bleeding history. Acute severe bleeding needs urgent specialist care. [18]
Progesterone withdrawal increases endometrial COX-2 enzyme → PGE2 and PGF2α synthesis. Women with HMB have increased prostaglandin synthesis and COX-2 enzymes. PGE2 may contribute to excessive bleeding by enhancing vasodilatation of spiral arteries [1]
Therefore: NSAIDs (which inhibit COX → ↓ PG synthesis) can reduce menstrual loss and dysmenorrhoea; tranexamic acid reduces fibrinolysis. If an LNG-IUS is declined or unsuitable, NICE lists tranexamic acid, NSAIDs, CHC and cyclical oral progestogens as options. Choice depends on contraindications, the suspected cause, need for contraception and patient preference. The slide's blanket statement that luteal progestogens “increase blood loss” should not override current regimen-specific guidance. [18]
The age of the case changes the priorities
Endometrial ablation and hysterectomy are not routine answers for a 13-year-old. Stabilise if needed, identify anaemia or a bleeding disorder, use medical treatment first, protect confidentiality and fertility, and involve paediatric/adolescent gynaecology or haematology when indicated.
Family planning care should not have a singular focus of preventing unintended pregnancy... focus on people reaching their desired reproductive outcomes by supporting them to make informed decisions about their fertility and contraceptive use that are aligned with their preferences and reproductive goals [1]
Key counselling principles [1][4]:
- Informed choice — respect patient preferences
- Dual protection (condoms + hormonal methods)
- Compliance support
- Discussion of side effects, warning signs (ACHES)
- Drug interactions (especially enzyme-inducing antiseizure drugs, rifamycins and St John's wort—not ordinary broad-spectrum antibiotics)
- Fertility return after discontinuation
What the Hong Kong Survey Figure Adds
Slide 24 presents a 2016 Hong Kong survey. Among 842 respondents who had never tried COCs, fear of side effects (72.1%) was the commonest selected reason; satisfaction with a current method (32.1%) and inconvenience (18.5%) followed. Among 276 respondents who had stopped COCs, reported reasons included fear of side effects (39.1%), experienced side effects (27.9%) and forgetting pills (19.9%). Respondents could select more than one answer, so percentages do not sum to 100%. [1]
The teaching point is not that reluctance should be “overcome.” It is to ask what the patient has heard, distinguish expected effects from red flags, offer adherence-independent alternatives where desired, and support an informed, non-coercive choice. [14]
9. Onset of Labour & Mediators
Labour = physiologic process to expel foetus from uterus as it contracts [1]
| State | Contractility |
|---|---|
| Non-pregnant | Spontaneous, weak, un-coordinated contractions |
| Early pregnancy | Contractions suppressed by both estrogen & progestin |
| Late pregnancy | Stronger, more coordinated contractions with increasing frequency |
| At parturition | Fully coordinated and forceful contractions |
Ripening state of cervix becomes critical in onset of labour [1]
9.2 Key Mediators
Increased PG synthesis & receptor expression under influence of estrogen
| PG | Receptor | Effect | Location |
|---|---|---|---|
| PGE1 & PGE2 | EP2 | Cervical ripening (softening) and dilation | More EP2 at cervix |
| PGE1 & PGE2 | EP3 (& EP1) | Uterine contraction | More EP3 at top of uterus |
| PGF2α | FP | Uterine contraction | Throughout myometrium |
Signalling: EP1, FP, OT receptor → PLC → IP3 → ↑ cytosolic Ca²⁺ (from SR release & extracellular Ca²⁺ entry via voltage-gated & store-operated Ca²⁺ channels) → contraction [1]
EP3 additional mechanism: EP3 receptor activation reduces cAMP production, thus suppressing uterine relaxation (i.e. promoting contraction) [1]
Increased OT receptor expression under influence of estrogen & PG → more prevalent in later stage of pregnancy Increased OT release from foetal stimulation (i.e. stretching) of cervix → uterine contraction OT also enhances PG release, thus promoting cervical ripening
This creates a positive feedback loop: cervical stretch → OT release → uterine contraction → more cervical stretch → more OT (Ferguson reflex).
10. Uterotonic Drugs
| Drug | PG Analogue | Primary Use | Key Points |
|---|---|---|---|
| Misoprostol | PGE1 | Medical abortion with mifepristone; selected labour-induction regimens; PPH when indicated | Causes cervical ripening and contraction; route/dose/uterine-scar restrictions are indication-specific |
| Dinoprostone | PGE2 | Cervical ripening and labour induction | Vaginal preparations can be removed in some formulations if hyperstimulation occurs |
| Carboprost | PGF2α | Refractory uterine-atony PPH | FP → PLC → ↑ Ca²⁺; avoid in asthma and use caution with major cardiac, pulmonary, hepatic or renal disease |
The deck's “misoprostol is not preferred for induction” is not universal current guidance. NICE offers either vaginal dinoprostone or low-dose oral misoprostol for an unfavourable cervix, with monitoring because either can cause hyperstimulation; a mechanical method is considered when pharmacological methods are unsuitable, including after previous caesarean birth. [19]
The two-panel medical-abortion diagram shows the sequence: mifepristone blocks progesterone action, destabilising decidua and softening the cervix; misoprostol then promotes cervical change and uterine contraction to expel the pregnancy. This is protocol-based care: gestation, location of pregnancy, contraindications, analgesia, follow-up and emergency access must be addressed under local law and guidance.
For PPH, uterotonics primarily contract the myometrium so it compresses vessels at the placental bed—the “living ligature” effect—not merely direct constriction of myometrial blood vessels.
For induction or augmentation, oxytocin is given as a titrated intravenous infusion under a local protocol, with uterine-contraction and fetal-heart monitoring. The slide's physiological observation about pulsatile endogenous release is not an instruction to use unsupervised “pulsatile dosing.” Excess stimulation can cause tachysystole, fetal compromise and rarely uterine rupture; prolonged/high-dose exposure may cause water intoxication and hyponatraemia because oxytocin has vasopressin-like activity. [19]
For an unfavourable cervix, cervical ripening usually precedes oxytocin; with a Bishop score > 6, NICE offers amniotomy plus IV oxytocin. [19]
Signalling: OT receptor → PLC → IP3 → ↑ Ca²⁺ → contraction
Naturally derived compounds from fungi on plants (e.g. rye grass) [1] Effect depends on contracted state of uterus — cause more forceful contraction in relaxed than contracted uterus [1] Can be used for prevention or treatment of postpartum haemorrhage in selected protocols [1][20]
Signalling: Activate α1-adrenergic & 5-HT receptors → PLC → IP3 → ↑ Ca²⁺ [1]
Ergometrine produces sustained uterine and vascular smooth-muscle contraction. Nausea/vomiting and hypertension are important adverse effects; avoid it in hypertensive disorders and significant cardiovascular disease. The deck's D₂ explanation for vomiting is a simplified receptor model, not the main prescribing discriminator.
| Drug | Main place in care | Key limitation |
|---|---|---|
| Oxytocin | WHO-preferred uterotonic for PPH prevention when quality-assured oxytocin and skilled administration are available | Cold-chain/administration needs; hyponatraemia with prolonged high exposure |
| Misoprostol | Alternative where injectable uterotonics are unavailable; also used in treatment protocols | Fever, shivering, diarrhoea; route and dose matter |
| Ergometrine/methylergometrine | Alternative or add-on in selected PPH protocols | Hypertension and vasoconstriction; avoid in hypertensive disease |
| Carboprost | Additional uterotonic for ongoing uterine-atony PPH | Bronchospasm; avoid in asthma |
PPH is an emergency bundle, not a single-drug question
Current WHO guidance uses the MOTIVE first-response bundle: uterine Massage, Oxytocic drug, Tranexamic acid, IV fluids, Vaginal/genital-tract examination and Escalation if bleeding persists. Objective blood-loss measurement and early action matter; continue cause-directed assessment (tone, trauma, tissue, thrombin) and follow the local PPH protocol. [20]
"toco-" = childbirth; "-lytic" = to loosen, break [1]
Acute tocolysis does not “arrest” preterm labour indefinitely. In a suitable patient it aims to gain a short window—commonly up to about 48 hours—for antenatal corticosteroids and/or transfer to an appropriate neonatal unit. Do not delay indicated delivery for infection, significant bleeding/abruption, fetal compromise or another contraindication to prolonging pregnancy. [21]
| Drug | Mechanism | Key Points |
|---|---|---|
| Nifedipine | Blocks L-type Ca²⁺ entry → reduces contraction | Preferred first-line option in many guidelines when suitable; monitor blood pressure and avoid where hypotension/cardiac status makes it unsafe [21] |
| Atosiban | Oxytocin/vasopressin-receptor antagonist → reduces contraction | Alternative when nifedipine is contraindicated; the slide's “partial agonist paradox” is not the useful clinical description [21] |
| COX inhibitor (e.g. indometacin) | ↓ PG synthesis → reduces contraction and cervical ripening | Gestational-age- and duration-limited; fetal renal dysfunction/oligohydramnios risk from about 20 weeks and ductal constriction risk later [22] |
| β₂ agonist (e.g. ritodrine/terbutaline) | ↑ cAMP/PKA → relaxation | Maternal tachycardia, hypotension, hyperglycaemia and pulmonary oedema; not routine first-line therapy |
| Progesterone | Modulates inflammatory/cervical pathways | Prevention in selected patients with previous spontaneous preterm birth/short cervix, not acute rescue tocolysis [21] |
| MgSO₄ | Multiple membrane/Ca²⁺ effects | Given for fetal neuroprotection before anticipated early preterm birth (and for pre-eclampsia/eclampsia when indicated), not taught as routine acute tocolysis [21] |
Why NSAIDs Cannot Be Used at Term
Indometacin inhibits PG synthesis. This can constrict the fetal ductus arteriosus later in gestation. NSAIDs from around 20 weeks can also cause fetal renal dysfunction and oligohydramnios; if a specialist judges use necessary between 20 and 30 weeks, use the lowest effective dose for the shortest time with appropriate monitoring, and avoid at about 30 weeks or later. [22]
Keep three different goals separate
Vaginal progesterone can prevent preterm birth in selected at-risk pregnancies; nifedipine or atosiban may briefly delay established/suspected preterm labour; magnesium sulfate is used for fetal neuroprotection when early preterm birth is imminent. They are not interchangeable entries in one generic “tocolytic” list. [21]
Exam Intelligence
| Trap | Correct Understanding |
|---|---|
| "COCs increase ovarian cancer risk" | Wrong — COCs DECREASE ovarian and endometrial cancer risk (protective effect of suppressing ovulation) |
| "All CHCs have the same VTE risk" | Wrong — average VTE risk differs by formulation, but generation/androgenicity is not a complete causal model; individual risk assessment is decisive [14][17] |
| "POPs reliably suppress ovulation" | Formulation-dependent — traditional POPs do not do so consistently; newer desogestrel/drospirenone formulations suppress ovulation more reliably |
| "Misoprostol should never be used for labour induction" | Wrong — low-dose oral misoprostol and vaginal dinoprostone are both guideline-supported options in selected patients; scar status and monitoring matter [19] |
| "Oxytocin is the cervical-ripening drug" | Wrong — ripen an unfavourable cervix first; with a favourable cervix, amniotomy plus titrated IV oxytocin is a standard induction approach [19] |
| "NSAIDs are safe tocolytics at term" | Wrong — risk of premature closure of ductus arteriosus |
| "Ergometrine is safe in hypertensive patients" | Wrong — ergometrine causes vasoconstriction (via α1) → dangerous in hypertension |
| "Hormone-free interval in COCs has medical benefit" | The slide explicitly says "no demonstrated medical benefit" — it is for patient preference |
- Gallstones: OC pills are a risk factor for gallstones (estrogen increases cholesterol saturation in bile) [5][6]
- Pre-operative assessment: do not apply a blanket “stop all OCPs” rule. The decision depends on estrogen exposure, surgery/immobility and thrombosis risk, timing, and availability of effective alternative contraception; follow current perioperative guidance.
- Rifampicin interaction: A commonly examined drug interaction — recommend alternative contraception [3]
- Hyperprolactinaemia: Estrogen-containing medications can stimulate lactotrophs → hyperprolactinaemia [8]
High Yield Summary
-
Oral Contraceptives
- COCs contain EE + progestin; suppress ovulation (↓FSH/LH), thin endometrium, thicken cervical mucus.
- Lower EE dose generally reduces the estrogen-dose contribution to VTE risk but can increase unscheduled bleeding; formulation and patient risk still matter.
- Levonorgestrel/norethisterone/norgestimate CHCs have lower average VTE risk than desogestrel/gestodene/drospirenone CHCs, but assess the individual—not “generation” alone.
- POP ovulation suppression and missed-pill rules are formulation-specific; current breast cancer remains a contraindication, while pregnancy is “not applicable.”
- ACHES = symptoms requiring urgent assessment, not proof of thrombosis.
- Enzyme inducers (rifamycins, some antiseizure drugs, St John's wort) reduce efficacy; ordinary broad-spectrum antibiotics generally do not.
-
Uterotonics
- Misoprostol (PGE1): medical abortion with mifepristone, selected induction regimens and PPH protocols; route/dose/context matter.
- Dinoprostone (PGE2): cervical ripening and labour induction.
- Oxytocin: titrated monitored infusion for induction/augmentation; usual first-choice uterotonic for PPH prevention.
- Ergometrine: sustained contraction via α1/5-HT pathways; avoid in hypertension/cardiovascular disease.
- Carboprost: additional drug for atonic PPH; avoid in asthma.
-
Tocolytics
- Tocolysis is short-term to allow steroids/transfer when prolonging pregnancy is appropriate.
- Nifedipine is a common first-line option; atosiban is an OTR antagonist alternative.
- Indometacin is gestation- and duration-limited because of fetal renal/oligohydramnios and ductal risks.
- Progesterone is preventive in selected high-risk patients; MgSO₄ is for fetal neuroprotection, not routine acute tocolysis.
Active Recall - Lecture Notes
[1] GC 160. The woman needs that drug Oral contraceptives Drugs affecting uterine motility.pdf (all slides) [2] CFB (OG03) Fertility Regulation.pdf (mechanisms, methods, injectable contraceptives) [3] MBBS Final MB (Medicine) (Felix PY Lai).pdf (p.178 — rifampicin drug interactions) [4] MBBS_SRH_2025.8.10.pdf (p.25, p.27 — teenage contraception, counselling principles) [5] Block A - Upper abdominal pain_ peptic ulcer; pancreatitis and gallstone.pdf (OCP as gallstone risk factor) [6] MBBS Final MB (Surgery) (Felix PY Lai).pdf (p.508 — gallstone risk factors including OCP) [7] GC 002 - Is he fit for surgery - Pre-operative assessment.pdf (p.32 — stopping OCPs pre-op) [8] Block A - I keep on bumping into people on my side_ pituitary tumours; hypopituitarism.pdf (p.9 — estrogen-containing medications and hyperprolactinaemia) [9] 2025 Fourth Summative MCQ.pdf (Q74, Q80) [10] 2021 Fourth Summative Assessment MCQ.pdf (Q10, Q11) [11] 2023 Fourth Summative MCQ.pdf (Q12) [12] 2022 Fourth Summative MCQ.pdf (Q14) [13] 2018 Fourth Summative SAQ.pdf (Q11) [14] CDC — U.S. Medical Eligibility Criteria for Contraceptive Use, 2024 and method-specific appendices [15] CDC — Contraception and Birth Control Methods [16] CDC — U.S. Selected Practice Recommendations: Progestin-Only Pills (2024) [17] European Medicines Agency — Combined hormonal contraceptives and VTE risk [18] NICE NG88 — Heavy menstrual bleeding: recommendations [19] NICE NG207 — Inducing labour: recommendations [20] WHO/FIGO/ICM — Consolidated guidelines for prevention, diagnosis and treatment of postpartum haemorrhage (2025) [21] NICE NG25 — Preterm labour and birth: recommendations [22] FDA — NSAIDs at 20 weeks of pregnancy or later: oligohydramnios and ductal risk
GC159 Research Ethics (notes)
Research ethics is the framework of principles and regulatory guidelines—including informed consent, beneficence, non-maleficence, justice, and institutional review—that govern the conduct of biomedical and clinical research involving human subjects.
GC161 Alcohol And The Brain From Psychiatric To Neuropsychiatric Perspectives
An integrated clinical framework examining alcohol's effects on the brain across both psychiatric manifestations (such as mood disorders, psychosis, and dependence) and neuropsychiatric consequences (including cognitive impairment, Wernicke-Korsakoff syndrome, and alcohol-related brain damage).