Case reports

Case 1 A 73-year-old lady with primary open-angle glaucoma had therapeutic failure with several antiglaucoma medications. In view of inadequate control of intraocular pressure and undesirable side effects to -blockers, brimonidine and dorzolamide, she was given latanoprost (Xalatan^®Pharmacia) eye drops as monotherapy. She complained of chest tightness following 1 month of Xalatan therapy, which was persistent. Although there was no objective evidence to suggest cardiac ischaemia, the symptoms subsided on discontinuation of the drug.

Case 2 A 67-year-old hypertensive lady with valvular heart disease and bilateral primary open-angle glaucoma was started on Xalatan eye drops. She reported chest tightness for a week following 12 months of uncomplicated use of Xalatan. The symptoms settled after 1 week and she was able to continue Xalatan with no further problems.

Case 3 An 82-year-old male, insulin-dependent diabetic with bilateral primary open-angle glaucoma had respiratory side effects to -blockers. He was switched to Xalatan monotherapy. He developed chest tightness 3 days following commencement of therapy. The symptoms settled after 1 week. He has continued to take Xalatan and has not complained of similar symptoms since then.

Case 4 An 89-year-old hypertensive male with primary open-angle glaucoma was started on Xalatan, after developing side effects with timolol and brimonidine eye drops. He developed chest tightness on and off after commencing Xalatan eye drops, which disappeared after 2 months. He has been on Xalatan eye drops for a further 2 years without chest symptoms.

Case 5 An 81-year-old lady with primary open-angle glaucoma was started on Xalatan after developing respiratory side effects to -blockers. She developed chest tightness 1 week following commencement of therapy. She was seen by her GP and a presumptive diagnosis of angina was made. But the ECG taken on the same day was unremarkable. She was started on isosorbide mononitrate and soluble aspirin. As isosorbide mononitrate produced severe headache, it was stopped the next day and she was continued on soluble aspirin. She continued to develop chest tightness for 4 months while she was on Xalatan drops and symptoms disappeared on discontinuation of the drug.

Comment

Little is known about the systemic side effects following topical use of latanoprost. The patients in our case series reported chest tightness. Two of the five patients developed the symptoms within 1 week of initiation of the drug. Only two patients required withdrawal of Xalatan therapy. It is interesting to note that the symptoms appeared sometime after the start of the therapy and disappeared spontaneously in three of the patients. The mechanism of this is unknown.

All five patients were elderly (67–82 years) with possibly compromised cardiac circulation. Prostaglandin F2 is a known vasoconstrictor. Therefore, these elderly patients could be vulnerable to even small quantities of the drug reaching systemic circulation via topical administration. Systemic use of PGF2 has been implicated in cardiac arrhythmias and vasospastic angina.^4,5 However, the symptoms described by the patients in our series were not typical of cardiac pain. Case numbers 1–4 were not assessed by a physician and no ECG was taken. Case number 5 was assessed by a physician and the ECG did not show any abnormalities to support cardiac ischaemia. Out of five cases, only two patients were hypertensive (case numbers 2 and 4). The symptoms of chest tightness described by these patients were poorly localised, as is the case with pain of visceral origin. Prostaglandins also play a significant role in pain mechanisms.⁶ They sensitise visceral nociceptors,⁶ and PGF2 in particular has been shown to produce allodynia (touch-evoked pain) in mice studies.⁷ The viscerae (heart, lung and gastrointestinal tract) have plenty of visceral nociceptors that are supplied by the visceral afferents. These afferent fibres travel in the vagus nerve that mediates visceral pain.⁸ Hence, it is possible that the chest tightness reported in this series is likely caused by the stimulation of visceral afferents by the systemically absorbed latanoprost. Patients should be encouraged to report such symptoms. The undesirable side effects of PGF2 on the cardiovascular system and the sensory perception should be borne in mind while investigating them. We have reported two of these cases to the manufacturer. Although there is some suggestion of a cause–effect relationship between topical latanoprost and visceral pain, more detailed studies are required to evaluate the systemic side effects of topical latanoprost.

References

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