7. Hormones and agents affecting hormonal mechanisms

Systemic administration


Certain






Clinical significance


Ocular side effects seen secondary to prazosin are uncommon and usually of little clinical significance. Blurred vision occurs in some patients, primarily after the first dosage. Schachat (1981) reported two cases of retrobulbar optic neuritis possibly related to prazosin therapy. The National Registry has received several cases of aggravation of dry eyes following the administration of this agent. This is in conjunction with significant drying of the nose and mouth. The very unusual finding of reddening of the sclera is reported by Carruthers (1994). While there have been various reports of central serous retinopathy to the National Registry, the data are soft and inconclusive.



Generic Names:


1. Rescinnamine; 2. reserpine.



Proprietary Names:


1. Moderil; 2. Serplan.



Primary use


These rauwolfia alkaloids are used in the management of hypertension and agitated psychotic states.






Class: Bronchodilators


Generic Name:


Ipratropium.



Proprietary Names:


Atrovent, Atrovent HFA.



Primary use


An inhaled anticholinergic agent used for its bronchodilating and antisecretory properties in chronic obstructive pulmonary disease and asthmatics.





Generic Name:


Salbutamol (albuterol).



Proprietary Names:


Accuneb, Proventil, Proair, Ventolin, Vospire.



Primary use


This sympathomimetic amine is primarily used as a bronchodilator in the symptomatic relief of bronchospasm.




Clinical significance


Oral salbutamol has no reported adverse ocular effects. This beta-agonist only has significant ocular side effects if delivered via a nebulizer with the drug coming into direct contact with the eye. Methods to prevent ocular contact will completely prevent all ocular effects. Salbutamol can cause mydriasis and may increase intraocular pressure in predisposed narrow angles. This drug is often given also in nebulized form with ipratropium and will induce angle-closure glaucoma by its parasympathetic inhibitory effect. In a study by Kalra et al (1988), both salbutamol and ipratropium were administered simultaneously via nebulizers without eye protection, and all patients with narrow angles had an increase in intraocular pressure. Transient angle closure occurred in 50% of them. This effect was completely prevented when protective eye goggles were worn. Contact of this drug with the eye and eyelids may occasionally cause transitory irritation and/or ocular pain. Visual hallucinations have been reported only in children.


Sami et al (2007) point out that this drug can cause chronic eyelid edema.



Class: Diuretics


Generic Names:


1. Bendroflumethiazide; 2. chlorothiazide; 3. chlortalidone; 4. hydrochlorothiazide; 5. hydroflumethiazide; 6. indapamide; 7. methyclothiazide; 8. metolazone; 9. polythiazide; 10. trichlormethiazide.



Proprietary Names:


1. Naturetin-5; 2. Diuril; 3. Thalitone; 4. Esidrix, Microzide, Oretic; 5. Saluron; 6. Lozol; 7. Enduron; 8. Zaroxolyn; 9. Renese; 10. Metahydrin, Naqua, Trichlorex, Trichlormas.



Primary use


These thiazides and related diuretics are effective in the maintenance therapy of edema associated with chronic congestive heart failure, essential hypertension, renal dysfunction, cirrhosis, pregnancy, premenstrual tension and hormonal imbalance.




Clinical significance


Ocular side effects due to these diuretics occur only occasionally and are usually transitory. It appears that most of these agents can cause transitory myopia. There are many different possible mechanisms involved in causing myopia. One is a change directly related to the crystalline lens and ciliary body, i.e. spasm of accommodation, altered sodium-chloride metabolism, ciliary body edema, inhibition of fluid by the lens or change in lenticular index of refraction. The second mechanism is related to changes in the media or sclera, i.e. changes in the refractive index of the media or stretching of the sclera (Jampolsky et al 1953). Blain et al (2000), using angiography, showed diffuse choroidal thickening during indapamide induced myopia. Some of the mechanisms proposed for inducing myopia are probably causes of inducing angle-closure glaucoma. There are well-documented cases of unilateral or bilateral ciliary body edema or effusions, which produce anterior rotation of the ciliary body at the scleral spur, allowing laxity of the lens zonule and forward displacement of the iris lens diaphragm. This increases the anterioposterior diameter of the lens, allowing for a shallowing of the anterior chamber with a resultant narrow angle. The cause of the ciliary body edema is unknown; however, Geanon et al (1995) described a case they felt was due to a hypersensitivity reaction. Krieg et al (1996) showed that prostaglandins and eicosanoids are involved. The management of this type of glaucoma is the same as with topiramate. Sponsel et al (1992) reported a posterior subcapsular cataract after indapamide therapy but made no statement as to causation. Miller et al (1979) described a case of transient oculomotor nerve palsy associated with thiazide-induced glucose intolerance. Thiazide diuretics can also cause hypercalcemia, which may result in band keratopathy.


When thiazide diuretics are used in combination with carbonic anhydrase inhibitors, one should be alert for signs of hypokalemia. These diuretics are photosensitizers and Hartzer et al (1993) showed that in tissue culture hydrochlorothiazide will interact with UV-A radiation to produce toxic synergistic effects on human RPE cells. In a case control study, de la Mamierre et al (2003) concluded that drug-induced phototoxicity (thiazide diuretics in long-term treatment) may be involved in causing more severe neovascularization in age-related macular degeneration. Costaglioloa et al (2008) reported a case of suspected retinal phototoxicity caused by UV tanning booth in a patient on hydrochlorothiazide. Iacono et al (2011) reported macular edema secondary to hydrochlorothiazide treatment.



Generic Name:


Furosemide.



Proprietary Name:


Lasix.



Primary use


This potent sulfonamide diuretic is effective primarily in the treatment of hypertension complicated by congestive heart failure or renal impairment.





Class: Osmotics


Generic Name:


Glycerol (glycerin).



Proprietary Names:


Colace infant/child, Computer Eye Drops, Eye Lube-A, Fleet Bablax, Osmoglyn, Sani-Supp.






Generic Name:


Mannitol.



Proprietary Names:


Osmitrol, Resectisol.



Primary use


This hyperosmotic agent is used to decrease intraocular pressure in various acute glaucomas and in preoperative intraocular procedures. It is also used in the management of oliguria and anuria.






Class: Vasopressors


Generic Name:


Ephedrine.



Proprietary Names:


Multi-ingredient preparations only.





Clinical significance


Ocular side effects from systemic administration of ephedrine are rare. O’Brien et al (1989) described an acute macular neuroretinopathy, possibly due to ephedrine. Dark red, outer retinal wedge-shaped lesions surrounding all or part of the central macula, with normal vision but permanent paracentral scotomas developed. This may be due to a direct retinal effect of the drug or an acute hypertensive effect. Lee et al (2007) described a case of -8.0 diopter with ciliochoroidal effusion in a 28 year old on ephedrine and phendimetrazine for weight loss. There was positive dechallenge without complication.


Topical ocular ephedrine is not currently used by most ophthalmologists. The currently used concentration is rarely sufficient to cause significant side effects other than the intended response of vasoconstriction. Repeated use of topical ocular ephedrine, however, may cause rebound conjunctival hyperemia or loss of the drug’s vasoconstrictive effect. The FDA gave a warning for drugs containing ephedrine: “Pupils may become dilated. If you have narrow-angle glaucoma, do not use this product.”



Generic Names:


1. Epinephrine; 2. norepinephrine (levaterenol).



Proprietary Names:


1. Adrenaclick, Epipen, Epipen Jr., Twinject, Twinject 0.3; 2. Levophed.




Ocular side effects


Systemic administration – injection


Certain







Clinical significance


Adverse events from systemic administration are heavily dose dependent or additive dependent on associated drug use. All events are rare because dosages used have been tested to be safe over time. O’Brien et al (1989) and Desai et al (1993) have reported cases of intravenous epinephrine causing acute macular neuroretinopathy. Savino et al (1990) described four patients with severe visual loss after intranasal anesthetic with epinephrine injections. The causes of the visual loss included retinal arterial occlusion and optic nerve ischemia, both of which the authors felt were due to secondary vasospasm induced by epinephrine. Patients undergoing ocular surgery with halothane anesthesia may experience tachycardia and arrhythmia from supplemental injection of local anesthetics containing epinephrine, from topical ophthalmic administration or intracameral injection of epinephrine.


Norepinephrine causes few ocular side effects from systemic exposure, and those are transitory and reversible except in overdose situations. Jandrasits et al (2002) reported that high levels of circulating norepinephrine have little impact on retinal vascular tone or retinal blood flow.


In over 20% of patients, topical ocular epinephrine must be stopped after prolonged use because of ocular discomfort and rebound conjunctival hyperemia. Over 50% of patients develop reactive hyperemia with long-term use. Concomitant use of timolol and epinephrine therapy occasionally has an additive effect on reactive hyperemia, cardiac arrhythmia or elevated blood pressure. Long-term topical ocular epinephrine preparations can cause cicatrizing conjunctivitis, which clinically or pathologically may be difficult to distinguish from ocular pemphigoid. This may include shortening of the fornices. Most epinephrine-induced macular edema is reversible, but lack of early detection may cause irreversible cystoid macular changes. Cystoid maculopathy may require more than six months to clear once the medication is discontinued. These changes occur more frequently in aphakic patients. This drug can cause conjunctival epidermalization, loss of eyelashes, blepharitis and meibomianitis. Most ocular adverse reactions due to epinephrine resolve or significantly improve with discontinuation of the drug. However, adrenochrome deposits in the cornea or conjunctiva may be exceedingly slow to absorb. Adrenochrome deposits in the lacrimal ducts may cause obstruction with epiphora. There are data to suggest that long-term topical ocular or intracameral epinephrine may cause significant corneal edema. This primarily occurs in corneas with damaged epithelium, which allows for increased penetration of this drug to reach the endothelium.


Norepinephrine is seldom given topically because epinephrine is much more effective and potent. Ocular side effects from norepinephrine are transitory and minimal. Systemic side effects are less potent then epinephrine, but norepinephrine may have a greater effect on the elevation of blood pressure.



Generic Name:


Phenylephrine.



Proprietary Names:


AH-chew D, Ak-Dilate, Children’s nostril, Children’s Sudafed PE, Mydfrin, Neo-Synephrine, Neofrin, Nostil, Ocu-Phrin, PediaCare Children’s Decongestant, Phenoptic, Prefin, Rectacaine, Relief, Rhinall, Sinex, Sudafed PE.






Clinical significance


Phenylephrine is given systemically primarily as sprays onto mucous membranes, i.e. nasal mucosa; therefore systemic side effects are essentially the same as for topical ocular exposure.


Ocular side effects due to topical ocular phenylephrine are usually of little significance unless the drug is used for prolonged periods of time. Phenylephrine used topically is one of the more toxic commercial drugs to the conjunctival and corneal epithelium. Soparkar et al (1997) have pointed out that even in low concentration in over-the-counter ophthalmic decongestants, acute and chronic conjunctivitis can go unrecognized. Unfortunately, signs and symptoms of these adverse effects of the drug may take 1–24 weeks to resolve. While the drug is used for pupillary dilation it may have a varied response on intraocular pressure. Initially, there may be a transitory decrease, later a transitory increase even with open angles. There may be no pressure change; or, in very rare instances, angle-closure glaucoma may be precipitated. Pupillary dilatation lasting for prolonged periods has been reported, especially in patients on guanethidine. Mydriasis varies with iris pigmentation and depth of the anterior chamber. Blue irides and shallow anterior chambers produce the greatest mydriasis, and dark irides or deep chambers produce the least. A diminished mydriatic response has been seen after repeated use of phenylephrine. A 10% concentration of phenylephrine can cause significant keratitis and a reduction in the conjunctival PO2 , which may result in delayed wound healing by reducing aerobic metabolism of rapidly dividing cells. Blanching of the skin, particularly the lower eyelid, may occur secondary to topical ocular phenylephrine. Following ophthalmic examination with a combination of phenylephrine and cyclopentolate in neonates, an increased risk of feeding intolerance may result, which could be due to the mydriatic drugs, the physical stress applying eye medication or a combination of these factors. Pless et al (2003) described four patients with nonarteritic ischemic optic neuropathy who experienced acute worsening of visual function after instillation of phenylephrine for a dilated fundus exam. Morrison et al (2006) pointed out the effects of topical ocular phenylephrine on hydrogel keratoprosthesis, promoting hydrogel cloudiness and surface deposits. Chronic use of this drug may be one of the more common causes of contact dermatitis of the eyelids as per incidence of use. In fact, Villarreal (1998) reported that 93.5% of acute dermatitis from all eye drops was due to topical mydriatic drugs, primarily phenylephrine.


Over 100 plus articles support the finding that topical ocular phenylephrine can cause, in rare instances, severe stress on the cardiovascular system and marked elevation of blood pressure. This was first reported by Fraunfelder et al (1978), who reported 11 deaths. Numerous additional terminal cases have been reported to the National Registry. Phenylephrine 10% should be used with caution or not at all in patients with cardiac disease, significant hypertension, aneurysms and advanced arteriosclerosis. It also should be used with caution in the elderly and in patients on monoamine oxidase inhibitors, tricyclic antidepressants or atropine. Similar findings were reported in 11 patients (Fraunfelder et al 2002) to whom 10% phenylephrine was applied to the eye in pledget form.


There have been a few reports of topical ocular phenylephrine in concentrations of 10%, 5% and 2.5% causing hypertension with pulmonary edema primarily in infants, but even in young children (Baldwin et al 2002; Venkatakrishnan et al 2011).


Numerous reports in the National Registry and in the literature have associated unilateral and bilateral acute glaucoma, secondary to nasal drops containing phenylephrine (Khan et al 2002; Zenzen et al 2004). In a preterm infant, Berman et al (1994) postulate that 2.5% phenylephrine may have triggered a series of events to cause bilateral spontaneous pigment epithelial detachments. Also in infants, phenylephrine eye drops have been implicated in paralytic ileus (Lim et al 2003) and renal failure (Shinomiya et al 2003).

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Nov 21, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on 7. Hormones and agents affecting hormonal mechanisms
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