Drugs used in obstetrics: Drugs may be used to modify uterine contractions. These include oxytocic drugs to stimulate uterine contractions both in induction of labour and to control postpartum haemorrhage and beta₂-adrenoceptor agonists used to relax the uterus and prevent premature labour.

Postpartum Haemorrhage, Ergometrine and oxytocin differ in their actions on the uterus. In moderate doses oxytocin produces slow generalized contractions with full relaxation in between; ergometrine produces faster contractions superimposed on a tonic contraction. High doses of both substances produce sustained tonic contractions. Oxytocin is now recommended for routine use in postpartum and post - abortion haemorrhage since it is more stable than ergometrine. However, ergometrine may be used if oxytocin is not available or in emergency situations.

Premature labour. Salbutamol is a beta₂-adrenoceptor agonist which relaxes the uterus and can be used to prevent premature labour in uncomplicated cases between 23 and 24 weeks of gestation. Its main purpose is to permit a delay in delivery of at least 48 hours. The greatest benefit is obtained by using this delay to administer corticosteroid therapy or to implement other measures known to improve perinatal health. Prolonged therapy should be avoided since the risk to the mother increase after 48 hours and the response of the myometrium is reduced.

Treatment of vaginal and vulval conditions - Anti - infective drugs: Candidal vulvitis can be treated locally with cream but is almost invariably associated with vaginal infection which should also be treated. Vaginal candidiasis is treated primarily with antifungal pessaries or cream inserted high into the vagina (including during menstruation) local irritation may occur on application of vaginal antifungal products.

Imidazole drugs (clotrimazole, miconazole) are effective in short courses of 3 to 14 days according to the preparation used; single dose preparations after an advantage when compliance is a problem. Vaginal applications may be supplemented with antifungal cream for vulvitis and to treat other superficial sites of infection.

Nystatin is a well established treatment (but stain clothing yellow). One or two pessaries are inserted for 14 to 28 nights; they may be supplemented with cream for vulvitis and to treat other superficial sites of infection.

Trichomonal infections: Commonly involve the lower urinary tract as well as the genital system and need systemic treatment with metronidazole or tinidazole. Bacterial infections with Gram - negative organisms are particularly common in association with gynaecological operations and trauma. Metronidazole is effective against certain Gram - negative organisms, especially Bacteroides spp. and may be used prophylactically in gynaecological surgery. Metronidazole is also indicated for bacterial vaginosis.

Clotrimazole
Tablet (vaginal), 100mg, 500mg
Cream (vaginal), 1%

Indications: - in the local treatment of vulvovaginal candidiasis caused by Candida albicans and other species of candida in pregnant (second and third trimester only) and non-pregnant women.

Note: - It is not effective in the treatment of vulvovaginitis caused by other common pathogens such as Trichomonas vaginitis.

Cautions: - pregnancy and labour and in those patients who are allergic to clotrimazole and its family. Use hygienic measures to cure infection and prevent reinfection by wearing cotton panties instead of synthetic underclothes and wearing only freshly washed under clothes. Sex partners should be advised to use condom.

Contraindications - hypersensitivity to clotrimazole

Side effects: - vaginal burning, itching, discharge, or other irritation not present before therapy, abdominal or stomach cramps or pain, burning or irritation of penis of sexual partner; headache.

Dose and Administration -

Clotrimazole cream - Intravaginal, 50mg (1 applicatorful of 1% vaginal cream, once a day, preferably at bed time, for six to fourteen consecutive day.

Storage: - vaginal cream - store between 2 and 30°C in a collapsible tube or in a tight container. Vaginal tablet - at room temperature in a well-closed container

Metronidazole
Tablet, 250mg
Tablet (vaginal), 500mg
Intravenous infusion, 5mg/ml in 100ml
Syrup, 4% w/v, 250mg/5ml

Indications: - used orally or intravaginally for the treatment of bacterial vaginosis (formerly called, Haemophilus vaginitis, Gardnerella vaginitis, non-specific vaginitis, Carynebacterium vaginitis, or anaerobic vaginosis) which is a non-inflammatory vaginal syndrome characterized by replacement of the normal vaginal flora (predominantly hydrogen producing lactobacillus) with a mixed flora including Gardnerella vaginalis.

It is also used in the treatment of female pelvic infections, including endometritis, endomyometritis, tube-ovarian abscess, and liver abscess, caused by bacteriodes species, including the B. fragilis group, clostridium species, petpococcus species, and peptostreptococcus species. See also section 7.1.2 & 7.4.2 for other uses.

Cautions: - abnormal neurologic symptoms, history of blood dyscrasias. Caution and reduce dosage in patients with such hepatic impairment. Use of the drug during pregnancy with caution when it is clearly needed. Breastfeeding should be interrupted in nursing mothers.

Drug interactions: - alcohol, anticoagulants (cumarin - or indandione - derivatives), cimetidine, disulfiram, phenobarbital, phenytoin.

Contraindications: - history of hypersensitivity to the drug or other nitroimidazole derivative.

Side-effect: - nausea, vomiting, diarrhoea, loss of appetite, dry mouth, sharp unpleasant metallic taste, constipation, abdominal discomfort, numbness, tingling, pain, or weakness in hands or feet, seizures, leucopenia, thrombocytopenia, vaginal candidiasis (any vaginal irritation, discharge, or dryness not present before therapy).

Dose and Administration -

Usual Adult and Adolescent dose:

Vaginosis (bacteria) - by mouth, 500mg (base) two times a day for seven days, or 2gm as single dose; Intravaginal, 500mg placed high into the vagina every night for ten or twenty consecutive days. IV-infusion, 15mg (base) per kg of body weight initially, then 7.5mg per kg of body weight up to a maximum of 1gm, every six hours for seven days or longer

Pelvic inflammatory disease - by mouth, 500mg of metronidazole twice daily with ofloxacin given orally in a dosage of 400mg twice daily. Therapy should be continued for 14 days.

Note: - Metronidazole may cause dizziness patients should be advised to avoid alcoholic beverage and to comply with full time of treatment.

Storage: - at room temperature in a well-closed, light-resistant container.

Miconazole Nitrate
Tablet (vaginal), 200mg, 400mg
Cream (vaginal), 2%

Indications: - treatment of Vulvovaginal candidiasis caused by Candida albicans and other species of candida in pregnant (second and third trimesters only), non-pregnant women.

Cautions, Contraindications, Side effects - Same as clotrimazole

Dose and Administration - usual Adult and Adolescent dose

Vaginal cream - Intravaginal, one applicatorful once a day at bed time for seven or fourteen days. May be repeated if needed.

Vaginal tablets - Intravaginal, 100mg once a day at bed time for seven days. May be repeated for seven days if needed or 200mg or 400mg once a day at bedtime for three days. May be repeated if needed.

Storage: - at room temperature in a tight container.

Nystatin
Cream (vaginal), 100,000 units in 4g
Pessary (ovules), 100,000 units

Indications: - local treatment of vulvovaginal candidiasis caused by Candida (monilia) albicans and other candida species.

Note: - It is not effective against Trichomonas Vaginalis or Gardnerella vaginalis (Haemophilus Vaginalis).

Cautions: - discontinue treatment with nystatin therapy if irritation or sensitization occurs. They are also advised against interrupting or discontinuing, vaginal nystatin therapy during a prescribed regimen, even during menstruation or if symptomatic relief occurs after only a few days of therapy, unless otherwise instructed by their physician.

Contraindications - sensitivity to nystatin

Side effects:- vaginal irritation not present before therapy

Dose and Administration - usual Adult and Adolescent dose

Nystatin vaginal cream - Intravaginal, insert 1-2 applicatorfuls at night for at least 14 nights.

Nystatin vaginal pessary - Intravaginally, insert 1-2 pessaries at night for at least 14 nights.

Storage: - at room temperature in a tight, light-resistant container.

Oxytocin
Injection, 10 units/ml in 0.5 and 1ml ampoules, 1 unit/ml, 5 units/ml in 1ml

Indications: - for nonselective induction of labour for medical reasons and for stimulation or reinforcement of labour in patients with dysfunctional inertia. Parenteral oxytocin is also indicated for management of incomplete or therapeutic abortion, as well as to produce uterine contractions during the third stage of labour. Oxytocin is also indicated to control postpartum bleeding or hemorrhage.

Cautions: - particular caution needed when given for induction or enhancement of labour in presence of borderline cephalopelvic disproportion (avoid if significant), mild or moderate pregnancy-induced hypertension or cardiac disease, women over 35 years or with history of lower-uterine segment caesarean section; if fetal death in utero or meconium-stained amniotic fluid avoid tumultuous labour (may cause amniotic fluid embolism); water intoxication and hyponatraemia-avoid large infusion volumes and restrict fluid intake by mouth; effects enhanced by concomitant prostaglandins (very careful monitoring) caudal block anaesthesia (may enhance hypersensitive effects of sympathomimetic vasopressors), see also interaction.

Drug interactions - hydrocarbon, inhalation anesthetic such as enflurane, halothane, isoflurane, and with vasopressors, other oxytocins.

Contraindications: - significant cephalopelvic disproportion, cold presentation, total placenta previa, vasa previa, where vaginal delivery is contraindicated, fatal distress, hypertonic uterine patterns, obstetrical emergencies requiring surgical intervention, uterine inertia or severe toxemia on prolonged use.

Side effects: - fast or irregular heartbeat, nausea or vomiting

Dose and Administration - usual Adult dose

Induction or stimulation of labour - IV infusion, initially at an initial rate 0.5 to 4 milli units (0.0005 to 0.004 unit) per minute, and then increased gradually at intervals every 20-60 minutes in increments of 1 to 2 milliunits (0.001-0.002 unit) per minute until a contraction pattern similar to that of normal labour is obtained. The rate of up to 6 milli units per minute is reported to produce plasma oxytocin concentrations comparable to those in natural labour but doses of up to 20 milliunits (0.02 unit) or more per minute may be required. The rate may be reduced gradually once labour is induced.

Incomplete or therapeutic abortion - IV infusion, 10 units at a rate of 20 to 40 milliunits (0.02 to 0.04 unit) per minute.

Control of postpartum uterine bleeding - IV infusion, 10 units at a rate of 20 to 40 milliunits per minute following delivery of the infant(s) and preferably placenta(s). A rate of 20-100 milliunits per minute may be used following abortion.

Storage - at room temperature, protect from freezing.

Oxytocin + Ergometrine Maleate
Injection, 5 units + 500mcg in each ml

See notes under ergometrine maleate

Dose: by intramuscular injection, 1 ml; by intravenous injection, no longer recommended

Ergometrine maleate
Tablet, 0.25mg, 0.5mg
Injection, 0.25 mg/ml, 0.5mg/ml in 1ml ampoule

Indications: - for the prevention and treatment of postpartum and postabortion hemorrhage.

Cautions: - cardiovascular diseases, renal and hepatic function impairment, sepsis, or hypersensitivity.

Drug interactions: adrenaline. Smoking tobacco should also be avoided.

Contraindications: coronary artery disease, eclampsia or preeclampsia, or pregnancy.

Side effects: dizziness, mild and transient headache, ringing in the ears, and hypertension may occur rarely. Abdominal pain, nausea, vomiting and uterine cramping may also occur, especially after intravenous injection.

Dose and Administration: Orally, intramuscularly, or intravenously. It should not be administered prior to delivery of the placenta. Intravenous route should be used only for emergencies or cases of excessive uterine bleeding. Intravenous injection should be diluted and administered slowly.

Adults: I.M. or I.V., 0.25 mg repeated in 2-4 hours if necessary, up to five doses. Usually followed by, Oral, 0.25 - 0.5mg every 6-12 hours daily for 2 days or until the danger of uterine hemorrhage has passed.

Storage: Injection: 2-8°C, or as specified by manufacturer. Protect from light and freezing.

Note: Discoloured solution or solutions containing visible particles should not be used.

Tablets - at room temperature, in tight container. Protect from light.

Methylergometrine Maleate
Tablet, 0.12mg
Injection, 0.2mg/ml

Indications: - prevention and treatment of postpartum or postabortal uterine bleeding due to uterine atony or subinvolution. Its use is not recommended prior to delivery of the placenta since placental entrapment may occur. It is also used to lessen expulsion of uterine contents in cases of incomplete abortion.

It is not indicated for induction or augmentation of labor, to induce abortion, or in cases of threatened spontaneous abortion because of its propensity to produce non-physiologic, tetanic contractions and its long duration of action.

Cautions: - hepatic and renal function impairment, hypocalcaemia, mitral valve stenosis, venoatrial shunts and in those patients allergic to methylergometrine or ergot alkaloids.

Drug interactions: - general anaesthetic especially halothane, bromocriptine, other ergot alkaloids, nicotine, smoking tobacco, nitroglycerine, vasoconstrictors and vasopressors.

Contraindications: - pregnancy, labour and delivery, unstable anginal pectoris, recent myocardial infarction, history of cerebrovascular accident, history of transient ischemic attack, cardiovascular disease, coronary artery disease, eclampsia or preeclampsia, (history of) severe hypertension, occlusive peripheral vascular disease, severe raynaud’s phenomenon.

Side effects - nausea, vomiting, abdominal pain, diarrhoea, uterine cramping dizziness, sweating, tinnitus (ringing in the ears)

Dose and administration -

Usual Adult and Adolescent dose - uterine stimulant - Oral, 0.2 to 0.4mg two or four times a day until the danger of uterine atony and hemorrhage has passed.

IV, or IM - 0.2mg repeated in two or four hours if necessary, up to five doses.

Storage: - at room temperature in a tight container (tablets), protect from light and from freezing.

Salbutamol
Injection, 0.5mg/ml in 1ml ampoule

Indications: - to arrest uncomplicated premature labour; see also sec. 2.2.

Cautions: - suspected cardiac disease, hypertension, hyperthyroidism, hypokalaemia, diabetes mellitus, mild to moderate pre-eclampsia. The patient's state of hydration and heart rate should be monitored carefully

Drug interactions: - corticosteroids, diuretics, theophylline.

Side effects: - nausea, vomiting, flushing, sweating, tremor, hypokalemia, tachycardia, muscle cramps, palpitation, and hypotension, increased tendency to uterine bleeding, pulmonary oedema, chest pain or tightness, arrhythmias, headache.

Contraindications: - cardiac disease, eclampsia and severe pre-eclampsia, intra-uterine infection, antepartum haemorrhage (requires immediate delivery), placenta praevia, cord compression, not for use in first or second trimesters.

Dose and Administration:

By intravenous infusion, 10 micrograms/minute gradually increased to maximum of 45 micrograms/minute until contractions have ceased, then gradually reduced; or by intravenous or intramuscular injection, 100 - 250 micrograms repeated according to patient’s response; Subsequently by mouth 4 mg every 6 - 8 hours:

Storage: - Store at room temperature. Protect from light.

Tetracycline + Amphotericin B
Tablet (vaginal), 100mg + 50mg