A

B

Fig. 7.5b  A: Limbus necrosis. B: Conjunctival necrosis from subconjunctival injection of atropine.

a hypersensitivity reaction, while a follicular response suggests a toxic or irritative reaction to these agents. However, as with systemic exposure, the effect on the pupil and cillary body with resultant elevation in intraocular pressure with or without the precipitation of angle-closure glaucoma is of greatest concern.

Atropine, but not homatropine, is said to produce a greater pupillary response in patients with Down’s syndrome. Permanent, fixed, dilated pupils may result from chronic atropinization, or large doses of atropine used in resuscitation. Geyer et al (1991) discuss the disagreement of whether or not long-term atropinization post keratoplasty can cause irreversible mydriasis. Unilateral atropinization during visual immaturity may cause amblyopia if used inappropriately (Morrison et al 2005). Seo et al (2002) and cases in the National Registry support the fact that subconjunctival atropine injection may cause necrosis of the sclera and conjunctiva.

Systemic reactions may occur after ocular instillation of these anticholinergic drugs, particularly in children or elderly patients. Symptoms of systemic toxicity include dryness of the mouth and skin, flushing, fever, rash, thirst, tachycardia, irritability, hyperactivity, ataxia, confusion, somnolence, hallucinations and delirium. These reactions have been observed most frequently after the use of atropine. Rarely, convulsions, coma and death have occurred after ocular instillation of atropine in infants and children, primarily if the solution form was used.

Mydriasis due to atropine can be distinguished by applying topical ocular 1.0% pilocarpine, which will not constrict the ­pupil if atropine is present.

References And Further Reading

Arnold RW, Goinet E, Hickel J, et al. Duration and effect of single-dose atropine: Paralysis of accommodation in penalization treatment of functional amblyopia. Binocular Vision Strabismus Quarterly 19: 81–86, 2004.

Chhabra A, Mishra S, Kumar A, et al. Atropine-induced lens extrusion in an open eye surgery. Pediatr Anaesth 16: 59–62, 2006.

Decraene T, Goossens A. Contact allergy to atropine and other mydriatic agents in eye drops. Contact Derm 45: 309–310, 2001.

Geyer O, Rothkoff L, Lazar M. Atropine in keratoplasty for keratoconus. Cornea 10(5): 372–373, 1991.

Gooding JM, Nolcomb MC. Transient blindness following intravenous administration of atropine. Anesth Analg 56: 872, 1977.

Merli GJ, et al. Cardiac dysrhythmias associated with ophthalmic atropine. Arch Intern Med 116: 45, 1986.

Morrison DG, Palmer NJ, Sinatra RB, et al. Severe amblyopia of the sound eye resulting from atropine therapy combined with optical penalization. J Pediatr Ophthalmol Strabismus 42: 52–53, 2005.

O’Brien D, Haake MW, Braid B. Atropine sensitivity and serotonin in mongolism­ . J Dis Child 100: 873–874, 1960.

Sanitato JJ, Burke MJ. Atropine toxicity in identical twins. Ann Ophthalmol 15: 380, 1983.

Seo KY, Kim CY, Lee JH, et al. Amniotic membrane transplantation for necrotizing conjunctival atropine injection. Br J Ophthalmol 86: 1316–1317, 2002.

The Pediatric Eye Disease Investigator Group. A randomized trial of ­atropine vs patching for treatment of moderate amblyopia in children. Arch Ophthalmol 120: 268–278, 2002.

The Pediatric Eye Disease Investigator Group. A randomized trial of atropine regimens for treatment of moderate amblyopia in children. Ophthalmology 111: 2076–2085, 2004.

Verma NP. Drugs as a cause of fixed, dilated pupils after resuscitation. JAMA 255: 3251, 1986.

von Noorden GK. Amblyopia caused by unilateral atropinization. Ophthalmology 88: 131, 1981.

Wark NJ, Overton JH, Marian P. The safety of atropine premedication in children with Down’s syndrome. Anaesthesia 38: 871, 1983.

Wilhelm H, Wilhelm B, Schiefer U. Mydriasis caused by plant content. Fortschritte der Ophthalmologie 88(5): 588–591, 1991.

Wilson FM, II. Adverse external ocular effects of topical ophthalmic medications. Surv Ophthalmol 24: 57, 1979.

Wright BD. Exacerbation of a kinetic seizure by atropine eye drops. Br J Ophthalmol 76(3): 179–180, 1992.

Yung M, Herrema I. Persistent mydriasis following intravenous atropine in a neonate. Paediatr Anaesth 10: 438–440, 2000.

Generic names: 1. Dicycloverine hydrochloride (dicyclomine); 2. glycopyrronium bromide (glycopyrrolate); 3. mepenzolate bromide; 4. propantheline bromide;

5. tolterodine tartrate.

Proprietary names: 1. Antispas, Bentyl; 2. Robinul, Robinul­ Forte; 3. Cantil; 4. Pro-banthine; 5. Detrol, Unidet.

Primary use

Systemic

These anticholinergic agents are effective in the management of gastrointestinal tract spasticity and peptic ulcers.

Ophthalmic

These topical anticholinergic mydriatic and cycloplegic agents are used in refractions and fundus examinations.

Ocular side effects

Systemic administration

Certain

  1. Decreased vision

  2. Mydriasis – may precipitate angle-closure glaucoma

agents Gastrointestinal • 5 Section

effects side ocular induced-Drug • 7 Part

  3. Paralysis of accommodation   4. Photophobia

  5. Diplopia

  6. Problems with color vision

a.Color vision defect

b.Colored flashing lights (propantheline)

 7. Flashing lights

  8. Eyelids or conjunctiva – allergic reactions   9. Visual hallucinations

10. Keratitis sicca (tolterodine)

Possible

1. Eyelids or conjunctiva

a.Exfoliative dermatitis

b.Contact dermatitis

Local ophthalmic use or exposure

Certain

1. Mydriasis may precipitate angle-closure glaucoma

2. Photophobia

3. Paralysis of accommodation

4. Eyelids or conjunctiva

a.Allergic reactions

b.Conjunctivitis – non-specific

c.Contact dermatitis

Possible

5. Increased intraocular pressure

Inadvertent ocular exposure

Certain

1. Pupils (propantheline)

a.Mydriasis

b.Absence of reaction to light

Possible

1. Paralysis of accommodation

Clinical significance

Ocular side effects due to these anticholinergic agents vary ­depending on the drug. Adverse ocular reactions are seldom significant and are reversible. None of the preceding drugs has more than 10–15% of the anticholinergic activity of atropine. The most frequent ocular side effects are decreased vision, mydriasis, decreased accommodation and photophobia. While these effects are not uncommon with some of these agents, rarely are they severe enough to modify the use of the drug. The weak anticholinergic effect of these agents seldom aggravates open-angle glaucoma; however, it has the potential to precipitate narrow- ­angle glaucoma attacks. Varssano et al (1996) showed that ­topical ocular glycopyrronium may be faster, stronger and have a more persistent mydriatic effect than atropine. Some of these agents, especially tolterodine, may increase tear film breakup time and aggravate or cause keratitis sicca. Two cases of unilateral pupillary dilatation were seen in patients who inadvertently got antiperspirants containing propantheline on their fingers and transferred it to their eyes.

References And Further Reading

Altan-Yaycioglu R, Yaycioglu O, Aydin-Akova Y, et al. Ocular side-effects of tolterodine and oxybutynin, a single-blinded prospective randomized trial. Br J Clin Pharmacol 59: 588–592, 2005.

Brown DW, Gilbert GD. Acute glaucoma in patient with peptic ulcer. Am J Ophthalmol 36: 1735–1736, 1953.

Cholst M, Goodstein S, Bernes C. Glaucoma in medical practice, danger of use of systemic antispasmodic drugs in patients predisposed to or ­having glaucoma. JAMA 166: 1276–1280, 1958.

Grant WM. Toxicology of the Eye, 1st edn, Charles C Thomas, Springfield, p 160, 1962.

Henry DA, Langman MJS. Adverse effects of anti-ulcer drugs. Drugs 21: 444, 1981.

Hufford AR. Bentyl hydrochloride: Successful administration of a parasympatholytic antispasmodic in glaucoma patients. Am J Dig Dis 19: 257–258, 1952.

Leung DL, Kwong YY, Lam DS. Ocular side-effects of tolterodine and oxybutynin, a single-blind prospective randomized trial. Br J Clin Pharmacol 60: 668, 2005.

McHardy G, Brown DC. Clinical appraisal of gastrointestinal antispas­ modics. South Med J 45: 1139–1144, 1952.

Mody MV, Keeney AH. Propantheline (Pro-Banthine) bromide in relation to normal and glaucomatous eyes: Effects on intraocular tension and pupillary size. JAMA 159: 113–114, 1955.

Nissen SN, Nielsen PG. Unilateral mydriasis after use of propantheline bromide in an antiperspirant. Lancet 2: 1134, 1977.

Schwartz N, Apt L. Mydriatic effect of anticholinergic drugs used during reversal of nondepolarizing muscle relaxants. Am J Ophthalmol 88: 609, 1979.

Varssano D, Rothman S, Haas K, Lazar M. The mydriatic effect of topical ­glycopyrrolate. Graefes Arch Clin Exp Ophthalmol 234(3): 205–207, 1996.

Class: Gastrointestinal and Urinary

Tract Stimulants

Generic name: Bethanechol chloride.

Proprietary names: Duvoid, Urecholine.

Primary use

This quaternary ammonium parasympathomimetic agent is ­effective in the management of postoperative abdominal distention and non-obstructive urinary retention.

Ocular side effects

Systemic administration

Certain

1. Non-specific ocular irritation

a.Lacrimation

b.Hyperemia

c.Burning sensation

d.Pruritus

2. Decreased accommodation

3. Miosis

Clinical significance

Adverse ocular reactions due to bethanechol are unusual, but they may continue long after use of the drug is discontinued. Some advocate use of this agent in the treatment of Riley Day syndrome and ocular pemphigoid because the drug is associated with an increase in lacrimal secretion.

References And Further Reading

Crandall DC, Leopold IH. The influence of systemic drugs on tear constituents. Ophthalmology 86: 115, 1979.

McEvoy GK (ed). American Hospital Formulary Service Drug information 87, American Society of Hospital Pharmacists, Bethesda, p 521–523, 1987.

Perritt RA. Eye complications resulting from systemic medications. Ill Med J 117: 423, 1960.

Physicians’ Desk Reference, 60th edn, Thomson PDR, Montvale NJ, pp 2349–2350, 2006.

Generic name: Carbachol.

Proprietary names: Carbostat, Miostat.

Primary use

Systemic

This quaternary ammonium parasympathomimetic agent is ­effective in the management of postoperative intestinal atony and urinary retention.

Ophthalmic

This topical or intraocular agent is used for open-angle glaucoma­ .

Ocular side effects

Systemic administration

Certain

1. Decreased accommodation

Local ophthalmic use or exposure – topical application

Certain

 1. Miosis

 2. Decreased vision

 3. Decreased intraocular pressure

 4. Accommodative spasm

 5. Eyelids or conjunctiva

a.Allergic reactions

b.Hyperemia

c.Cojunctivitis – follicular

d.Pemphigoid-like lesion with symblepharon and shortening of the fornices

 6. Irritation

a.Lacrimation

b.Ocular pain

 7. Blepharoclonus

 8. Myopia

 9. Retinal detachment

10.Problems with color vision – objects have yellow tinge 11.Cataract formation

12.Myokymia

Local ophthalmic use or exposure – intracameral ­injection

Certain

1. Miosis

2. Corneal edema

3. Decreased vision

4. Anterior chamber – cells and flare (increased after cataract surgery)

Systemic side effects

Local ophthalmic use or exposure – topical application

Certain

 1. Headaches – frontal

 2. Ocular or periocular pain

 3. Dizziness

 4. Vomiting

 5. Diarrhea

 6. Stomach pain

 7. Intestinal cramps

 8. Bradycardia

 9. Arrhythmia

10.Hypotension

11.Syncope

12.Asthma – may aggravate

13.Salivation increase

14.Perspiration increase

15.Bronchospasm

16.Generalized muscle weakness

Clinical significance

Probably the most frequent ocular side effect due to carbachol is a decrease in vision secondary to miosis or accommodative spasms. In the younger age groups, transient drug-induced myopia also may occur. Follicular conjunctivitis often occurs after long-term therapy, but this in general is of limited clinical significance. Some of the topical ocular side effects may be aggravated or caused by the benzalkonium chloride preservative. Enhancement of cataract formation is probably common to all miotics after many years of exposure. Miotics can induce retinal detachments but probably only in eyes with pre-existing retinal pathology (Beasley and Fraunfelder 1979). This topical ocular medication may be one of the more toxic agents on the corneal epithelium. Roberts (1993) showed increased cells and flare post-cataract surgery due to carbachol by delaying the re-establishment of the blood aqueous barrier after surgery, causing a more prolonged inflammatory pro­ cess. Phillips et al (1997) suggested that intraocular carbachol post surgery did not play a role in increasing postcapsular opacification.

If there are abrasions of the conjunctiva or corneal epithelium, care must be taken not to apply topical ocular carbachol since this enhances absorption and increases the incidences of systemic side effects. In general, systemic reactions to carbachol are rare, usually occurring only after excessive use of the medication.

References And Further Reading

Beasley H, Fraunfelder FT. Retinal detachments and topical ocular miotics. Ophthalmology 86: 95, 1979.

Beasley H, et al. Carbachol in cataract surgery. Arch Ophthalmol 80: 39, 1968.

Crandall DC, Leopold IH. The influence of systemic drugs on tear constituents. Ophthalmology 86: 115, 1979.

Fraunfelder FT. Corneal edema after use of carbachol. Arch Ophthalmol 97: 975, 1979.

Hesse RJ, et al. The effect of carbachol combined with intraoperative visco­ elastic substances on postoperative IOP response. Ophthalmic Surg 19: 224, 1988.

Hung PT, Hsieh JW, Chiou GCY. Ocular hypotensive effects of N-de­ methylated carbachol on open angle glaucoma. Arch Ophthalmol 100: 262, 1982.

Krejci L, Harrison R. Antiglaucoma drug effects on corneal epithelium. A comparative study in tissue culture. Arch Ophthalmol 81: 766, 1970.

Monig H, et al. Kreislaufkollaps durch carbachol-haltige augentropgen. Dtsch Med Wochenschr 114(47): 1860, 1989.

Olson RJ, et al. Commonly used intraocular medications and the corneal endothelium. Arch Ophthalmol 98: 2224–2226, 1980.

Pape LG, Forbes M. Retinal detachment and miotic therapy. Am J Ophthalmol­ 85: 558, 1978.

Phillips B, Crandall AS, Mamalis N, Olson RJ. Intraoperative miotics and posterior capsular opacification following phacoemulsification with ­intraocular lens insertion. Ophthalmic Surg Lasers 28(11): 911–914, 1997.

Roberts CW. Intraocular miotics and postoperative inflammation. J Cat Refractive Surg 19(6): 731–734, 1993.

Vaughn ED, Hull DS, Green K. Effect of intraocular miotics on corneal endothelium. Arch Ophthalmol 96: 1897, 1978.

agents Gastrointestinal • 5 Section