10.02.3.4 Agonists at Prostaglandin Receptors

A number of agonists, showing selectivity for one or other of the prostaglandin receptors, are used clinically. Firstly, misoprostol is a selective EP₁ receptor agonist. Misoprostol was developed for use to provide gastric cytoprotection, and it does suppress gastric ulceration. Indeed, misoprostol is as effective as the H₂-receptor antagonists at preventing gastric ulceration. However, misoprostol alone is not commonly used to provide gastric cytoprotection, as the proton pump inhibitors are preferred, probably because they have a greater efficacy. Misoprostol is used as a gastric cytoprotective with diclofenac, to prevent gastric ulceration with the diclofenac. When misoprostol is used for gastric cytoprotection, it is contraindicated in pregnant women as is a powerful uterine stimulant, and may cause premature labour. This was originally considered as a detrimental effect of misoprostol when it was being used as a gastroprotective agent. However, this detrimental effect, lead to the clinical development of misoprostol for another use.

One use for a uterine stimulant is to induce abortions. However, the pharmaceutical companies have mainly steered clear of the abortion controversy. Thus, the pharmaceutical company that developed misoprostol, as a cytoprotective agent, did not go on to develop misoprostol as a uterine stimulant. This development was done by others, mainly University clinical academics, and represents the off-label development of misoprostol as a uterine stimulant. When pregnancy is complicated by early death, misoprostol is used to remove the remnants. Misoprostol is not used alone for abortion but misoprostol is used with the progesterone antagonist mifepristone for early abortion. The main adverse effect, when using misoprostol as a uterine stimulant, is gastrointestinal (diarrhoea).

Dinoprostone is a selective EP₂ receptor agonist, which increases contractions of uterus. Dinoprostone also relaxes the cervix. This combination of effects makes dinoprostone useful in the induction or augmentation (increasing) of labour, especially when the cervix is not dilating.

Selective agonists are also available for the prostacyclin (PGI₂) IP receptors. Prostacyclin inhibits platelet aggregation and is a potent vasodilator. PGI₂ is not active after oral administration, and is rapidly broken down. Thus to use prostacyclin clinically, a continuous infusion is required, and this is not always convenient. Iloprost is a synthetic analog of PGI₂, which stimulates the IP receptors with a longer half-life than PGI₂. Iloprost is used in the treatment of pulmonary hypertension, a condition in which the hypertension is limited to the pulmonary circulation. Iloprost is delivered by nebuliser, which gives a high local pulmonary concentration of iloprost, which is localised to the pulmonary vessel to cause dilation of the pulmonary vessels only.

The ciliary muscle of the eye has FP receptors. Stimulation of these receptors increases the aqueous humour outflow from the eye. Latanoprost is an ester analog of PGF2α, and selective agonist of FP receptors. Latanoprost is used in the treatment of ocular hypertension (glaucoma). When ocular pressure is high, the optic nerve can be damaged, which can lead to irreversible. By promoting aqueous humour outflow from the eye, latanoprost reduces intraocular pressure.