Uses and Side Effects of PGs and their Analogues

USES

Clinical use of PGs and their analogues is rather restricted because of limited availability, short lasting action, cost, side effects and other practical considerations. Their approved indications are:

1. Abortion

During first trimester, termination of pregnancy by transcervical suction is the procedure of choice. Intravaginal PGE₂ pessary inserted 3 hours before attempting dilatation can minimise trauma to the cervix by reducing resistance to dilatation.

Medical termination of pregnancy of upto 7 weeks has been achieved with high success rate by administering mefepristone (antiprogestin) 600 mg orally 2 days before a single oral dose of misoprostol 400 μg. Uterine contractions are provoked and the conceptus is expelled within the next few hours. Ectopic pregnancy should be ruled out beforehand and complete expulsion should be confirmed afterwards. Uterine cramps, vaginal bleeding, nausea, vomiting and diarrhoea are the possible complications. Methotrexate administered along with misoprostol is also highly successful in inducing abortion in the first few weeks of pregnancy.

PGs have a place in midterm abortion, missed abortion and molar gestation, though delayed and erratic action and incomplete abortion are a problem. The initial enthusiasm has given way to more considered use. PGs convert the oxytocin resistant midterm uterus to oxytocin responsive one: a single extraamniotic injection (PGE₂) followed by i.v. infusion of oxytocin or intraamniotic (PGF_2α) with hypertonic solution produces 2nd trimester abortion in a high percentage without undue side effects. Pretreatment with mifepristone improves the efficacy of PGE as abortifacient.

2. Induction/Augmentation Of Labour

PGs do not offer any advantage over oxytocin for induction of labour at term. They are less reliable and show wider individual variation in action. PGE₂ and PGF_2α (rarely) have been used in place of oxytocin in toxaemic and renal failure patients, because they do not cause fluid retention. PGE₂ may also be used to augment labour, if it is slow, in primipara. Intravaginal route is preferred now: side effects are milder; extra/intra amniotic route is infrequently used.

3. Cervical Priming

Applied intravaginally or in the cervical canal, low doses of PGE₂ which do not affect uterine motility make the cervix soft and compliant. This procedure has yielded good results in cases with unfavourable cervix. If needed labour may be induced 12 hours later with oxytocin: chances of failure are reduced.

4. Postpartum Haemorrhage (PPH)

Carboprost (15methyl PGF_2α) injected i.m. is an alternative for control of PPH due to uterine atony, especially in patients unresponsive to ergometrine and oxytocin.

PGE₂ (Dinoprostone) PROSTINE₂ for induction/ augmentation of labour, midterm abortion.

Vaginal gel (1 mg or 2 mg in 2.5 ml) 1 mg inserted into posterior fornix, followed by 1–2 mg after 6 hour if required.

Vaginal tab (3 mg) 3 mg inserted into posterior fornix, followed by another 3 mg if labour does not start within 6 hour.

Extraamniotic solution (10 mg/ml in 0.5 ml amp.) infrequently used.

Intravenous solution (1 mg/ml in 0.75 ml amp., 10 mg/ml in 0.5 ml amp) rarely used.

Oral tablet PRIMIPROST 0.5 mg tab, one tab. hourly till induction, max 1.5 mg per hr; rarely used.

Cervical gel CERVIPRIME (0.5 mg in 2.5 ml prefilled syringe) 0.5 mg inserted into cervical canal for preinduction cervical softening and dilatation in patients with poor Bishop’s score.

Gemeprost CERVAGEM 1 mg vaginal pessary: for softening of cervix in first trimester—1 mg 3 hr before attempting dilatation; for 2nd trimester abortion/molar gestation—1 mg every 3 hours, max. 5 doses.

PGF_2α (Dinoprost) PROSTIN F₂ ALPHA intraamniotic injection 5 mg/ml in 4 ml amp. for midterm abortion/ induction of labour (rarely used).

15methyl PGF_2α (Carboprost) PROSTODIN 0.25 mg in 1 ml amp; 0.25 mg i.m. every 30–120 min for PPH, midterm abortion, missed abortion.

TPILL + MISO Mifepristone 200 mg tab (3 tabs) + misoprostol 200 μg (2 tabs); mifepristone 3 tab orally followed 2 days later by misoprostol 2 tab orally, for termination of pregnancy of upto 49 days.

5. Peptic Ulcer

Stable analogue of PGE₁ (misoprostol) is occasionally used for healing peptic ulcer, especially in patients who need continued NSAID therapy or who continue to smoke (see Ch. No. 46).

6. Glaucoma

Topical PGF_2α analogues like latanoprost and isopropyl unoprostone are one of the first choice drugs in wide angle glaucoma.

7. To Maintain Patency Of Ductus Arteriosus in neonates with congenital heart defects, till surgery is undertaken. PGE₁ (Alprostadil) is used; apnoea occurs in few cases.

PROSTIN VR 0.5 mg in 1 ml amp; dilute and infuse i.v.

8. To Avoid Platelet Damage

PGI₂ (Epoprostenol) can be used to prevent platelet aggregation and damage during haemodialysis or cardiopulmonary bypass. It also improves harvest of platelets for transfusion. Few cases of primary pulmonary hypertension have been successfully maintained on epoprostenol infusion.

FLOLAN 0.5 mg vial for reconstitution.

The other suggested uses of PGs are:

1. Peripheral vascular diseases PGI₂ (or PGE₁) infused i.v. can relieve rest pain and promote ulcer healing in severe cases of intermittent claudication and in Raynaud’s disease.

2. Impotence Alprostadil (PGE₁) injected into the penis causes erection lasting 1–2 hours. However, oral sildenafil/ tadalafil is now preferred for erectile dysfunction.

SIDE EFFECTS

Side effects are common in the use of PGs, but their intensity varies with the PG, the dose and the route. These are: nausea, vomiting, watery diarrhoea, uterine cramps, unduly forceful uterine contractions, vaginal bleeding, flushing, shivering, fever, malaise, fall in BP, tachycardia, chest pain.