Download Ocular side-effects of urological pharmacy

Review
Ocular side-effects of urological
pharmacy
Nikolaos A. Kostakopoulos, Vasileios G. Argyropoulos
Department of Urology, IASO General Hospital, Athens, Greece
Corresponding author:
Nikolaos A. Kostakopoulos Email: '[email protected]'
Περίληψη
Η αυξανόμενη γήρανση του πληθυσμού έχει σαν αποτέλεσμα συχνότερη εμφάνιση
συμπτωμάτων καλοήθους υπερπλασίας του προστάτη, ασταθούς κύστεως και στυτικής
δυσλειτουργίας. Αυτό έχει σαν επακόλουθο ευρεία συνταγογράφηση. φαρμάκων, όπως
αναστολέων της φωσφοδιεστεράσης, αντιμουσκαρινικών παραγόντων και α-αναστολέων
που προκαλούν μερικές φορές σοβαρές παρενέργειες από τους οφθαλμούς. Σ΄αυτή την
ανασκόπηση θα αναφερθούν περιληπτικά οι διάφορες δυνητικές οφθαλμικές
παρενέργειες, η συχνότητά τους, η φυσική τους ιστορία και η σημασία τους για τον κλινικό
γιατρό.
Λέξεις ευρετηριασμού:
ουρολογικά φάρμακα, οφθαλμικές παρενέργειες.
Summary
The increasing rate of aging population worldwide has resulted in a more frequent diagnosis
of aging related urological diseases and conditions such as benign prostatic hyperplasia,
urinary bladder instability and erectile dysfunction. This has subsequently led to the wider
prescription of medications such as phosphodiesterase inhibitors, antimuscarinic agents and
alpha-inhibitors which may induce severe ocular side effects. This review outlines potential
ocular side effects of the above-mentioned drugs, provides information on their frequency
and natural history and highlights their importance to the clinician.
Key words:
urological medications, ocular side effects.
Introduction
Continuous advances in the treatment of several urological diseases and conditions are
associated with the development of novel drugs and the evolution of older agents as well.
The above may have led to a rising number of prescriptions of urological medications by
non-specialized physicians, an evolving incidence of prescriptions with irrational drug
combination and an increasing rate of side effects occurrence. Actually, most of the
medication currently used in the treatment of benign prostatic hyperplasia, urinary bladder
instability and erectile dysfunction is safe for most of the patients, however several of them
may develop ocular side effects. The last may result in a disproportionate concern both for
the patients and the clinicians. In this article, we outline several ocular side effects of the
most commonly prescribing urological medications and we provide information on their
frequency, natural history and clinical importance.
1. 5-Phosphodiesterase inhibitors (5-PDE Inhibitors: Sildenafil, Tadalafil).
The main ocular side effect associated with phosphodiesterase inhibitors use is the nonArteritic Anterior Ischemic Optic Neuropathy (NAION). Actually, few clinicians are aware of
an unusual and yet unpleasant side effect of these agents. NAION is the most common cause
of acute optic neuropathy in adults and it develops in 1.500-1.600 individuals annually in the
USA (1,2,3). Fifty NAION cases associated with phosphodiesterase inhibitors intake have been
reported up-to-date (4,5). NAION develops upon reduced arterial infiltration at the anterior
lamina of the optic disc, causing sparse retinal infarcts (6). Predisposing factors are:

hypertension

hyperlipidemia

diabetes mellitus (DB) and

ischemic heart disease (IHD).
Almost all patients developing NAION, usually manifest optic disc congestion which results in
ischemia of optic nerve axes as they are compressed among them. It has been documented
that the 5-PDE inhibitors may deteriorate the optic nerve ischemia and result in vision loss,
by affecting the nitrogen monoxide levels in the optic nerve vascularisation (5).
It should be mentioned that 5-PDE inhibitors remain the most effective medical treatment
option for the management of erectile dysfunction (7). Recent data do not provide clear
evidence indicating that the 5-PDE inhibitors use constitute an independent predisposition
factor for developing NAION. However, patients should be informed of the possibility to
suffer from vision loss. This should be particularly stressed to IHD or atherosclerosis
predisposed patients. Patients with pre-existing monocular NAION should not be prescribed
phosphodiesterase inhibitors given that the risk of developing NAION in the other eye
exceeds 20%.
2. Antimuscarinic agents (oxybutynin, tolterodine)
The bladder’s detrusor muscle is rich in innervations with muscarinic receptors. Muscarinic
acetylcholine (mACh) receptor antagonists reduce the contractions of detrusor muscle and
usually improve symptoms of overactive bladder syndrome (OAB) such as frequency and
urgency. Intraocularly, there is a stable condition between the formation and the absorption
of the aqueous humor (AqH) which is responsible for the humidification of the basic ocular
structures and the maintenance of the organ’s spherical shape. Normal intraocular pressure
preservation depends on the AqH outflow. Any intraocular pressure increase may be caused
by the increased resistance in the AqH outflow (open-angle glaucoma – OAG) or
stricture/obstruction in the anterior chamber (closed-angle glaucoma – CAG) due to
trabecular meshwork (TM) dysfunction. The iris constantly changes its shape being affected
by the parasympathetic (muscarinic) (PNS) and the sympathetic nervous system (SNS). The
antimuscarinic agents cause mydriasis. In those patients with an anatomical “narrow” angle,
this may result in acute occlusion of the drainage angle. This particular case constitutes an
ocular emergency which, if not treated, may cause permanent vision loss. Vision loss cases
have been reported after angle occlusion episodes induced by oxybutynin (8) and other
anticholinergic agents e.g. propiverine (9). Prognosis is favoured by accurate diagnosis and
early treatment.
CAG should be managed with laser iristomy during or after an acute episode. This prevents
any further acute episodes by creating an alternative path for the AqH outflow and thusly
preventing obstruction. When treated, the risk of an episode anew is zero. Therefore,
anticholinergic treatment in patients with surgically treated CAG is safe.
Regarding clinicians, their poor update on glaucoma creates confusion over the management
of OAB and glaucoma (9). Both may co-exist in the elderly. By definition, OAG bears no
evidence of AqH outflow mechanical obstruction and accordingly the anticholinergic
treatment is safe (10).
Prior to anticholinergic agents administration, taking a detailed history of the glaucoma
patient is of vital importance. Anticholinergic agents must be avoided in patients reporting a
narrow angle not surgically treated. In patients on anticholinergic medication, it must be
recommended emergency medical consultation in case of painful eye redness or acute vision
loss.
3. a- Blockers (e.g. tamsulosin, alfuzosin )
The main ocular side effect associated with a Blockers use is the Intra-operative floppy iris
syndrome- IFIS.
Selective a1-antagonists are widely used in the improvement of lower urinary tract
obstruction symptoms and micturition flow. Pharmacologically, a1-subtype presents the
greatest interest in BPH treatment. On the other hand, both the iris and the protective tissue
present a variety of several a-receptors subtypes (11). Those of a1-subtype have an important
role in the cataract surgical treatment. In fact, safe and successful cataract surgical
treatment requires full and maintainable dilation of the pupil. The insufficient dilation
increases the risk of intra-operative complications given that the surgical site is disturbed (12).
The eye is pharmacologically dilated prior to cataract surgery. In normal conditions, this
dilation lasts throughout the surgery. Intra-operative cataract surgery difficulties have been
reported in patients receiving tamsulosin. It has been found that, in stable intraocular
conditions, the iris is pathologically mobile and tends to prolapse towards the surgical
instruments. During surgery, an iris spasm has also been observed which usually does not
respond to the pharmacological treatment. The spasm in question limits the surgical site and
technically impedes the procedure. These intra-operative findings are known as Intraoperative floppy iris syndrome (IFIS).
Chang and Campbell (12) studied over 500 patients who had been subjected to more than 700
cataract procedures over a 12-month period. They found that the total IFIS impact
accounted for 2%. However, 63% of the patients on a-inhibitors developed IFIS during the
cataract procedure. 94% of IFIS patients had been receiving tamsulosin on a regular basis.
Traditional intra-operative techniques for the iris dilation during ocular surgery, e.g.
mechanical dilation or dissection of the iris sphincter are ineffective in such cases.
Several IFIS-induced complications have been reported including iris atrophy and capsular
rupture. Further studies have also shown increased impact of the complications in IFIS eyes.
The complications in question were more common when on tamsulosin compared to
terazosin (13). Once the surgeon is informed of the tamsulosin intake, s/he may use several
alternative strategies for the improvement of the surgical site (14). To avoid the
aforementioned complications, pre-operative interruption of the a-inhibitors for 1-2 weeks
is advised (15,16,17).
Results
It is a fact that a pool of urological conditions (BPH, undetected prostatic cancer, OAB, atonic
bladder, genital glands infection, erectile dysfunction etc) can nowadays be safely and
effectively treated with applicable pharmacy. Some of these medicines are now widely
prescribed by unqualified clinicians causing great concern about ocular side-effects. It should
be fully understood that the ocular complications induced by urological pharmacy
administration are rare, yet manageable. Nevertheless, the appropriate cooperation and
communication between the urologist and the ophthalmologist is an undoubted
prerequisite.
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