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Ocular Side Effects of Systemic Drugs.Cdr ERA’S JOURNAL OF MEDICAL RESEARCH VOL.6 NO.1 Review Article OCULAR SIDE EFFECTS OF SYSTEMIC DRUGS Pragati Garg, Swati Yadav Department of Ophthalmology Era's Lucknow Medical College & Hospital, Sarfarazganj Lucknow, U.P., India-226003 Received on : 06-03-2019 Accepted on : 28-06-2019 ABSTRACT Systemic drugs are frequently administered in persons of all age group Address for correspondence ranging from children to the elderly for various disorders. There has been Dr. Pragati Garg increased reporting of ocular side effects of various systemic drugs in the Department of Ophthalmology past two decades. Some offenders well known are α -2-adrenergic agonists, Era’s Lucknow Medical College & quinine derivatives, β- adrenergic antagonists and antituberculosis drugs. Hospital, Lucknow-226003 Newer systemic drugs causing ocular side effects are being reported in Email: [email protected] available literature. Knowledge regarding these is expected to aid Contact no: +91-9415396506 clinicians in identifying these side effects and the offending drug, thereby, prescribing the appropriate treatment for the condition the patient maybe suffering from without any ocular disturbances. KEYWORDS: Ocular side effects, Systemic drugs. Introduction This article will briefly cover how systemic drugs can Many common systemic medications can affect ocular affect the various ocular structures. tissues and visual function to varying degrees. When a Factors Affecting The Production Of Ocular Side systemic medication is taken to treat another part of the Effects By A Drug body, the eyes frequently are affected. Systemic A) Drug related factors medications can have adverse effects on the eyes that range from dry eye syndrome, keratitis and cataract to (1) The nature of the drug: Absorption of drug in blinding complications of toxic retinopathy and optic body and its pharmacological effects on the body's neuropathy (1). Some of these side-effects, though metabolism is effected by nature of drug. The ease undesirable, have to be accepted as unavoidable. The with which a drug passes into the general circulation discovery of serious ocular defects arising in and into the eye determines the ability of systemically association with the long-term use in high dosage of administered drugs to affect the eye directly. certain drugs has indicated the need for all prescribers (2) The amount of the drug consumed: The daily to be aware of the risks involved. Particularly this is consumption of high doses of drugs reaches toxic important since some of the toxic effects have seriously levels to effect the eye. In addition, prolonged impaired vision and proved to be irreversible. consumption of drugs whose detoxification and When patients present with ocular symptoms that have excretion is low determines the effect on eyes. no apparent cause, it is important to consider whether (3) The route of its administration:Drugs the condition could be caused by a systemic areadministered locally, orally or through parenteral medication they are taking. Patients often neglect to route. Topical application of drugs, allows sufficient mention the maintenance drugs that they take every absorption to risk ocular side effects. day, so ophthalmologists may need to ask specifically (4) Pathological condition of patient: Liver and about theseEJMR types of medication. One of the most renal diseases frequently affect the detoxication and important aspect is obtaining a thorough medical excretion of drugs, allowing them to accumulate to history which includes specific medication dosage and toxic levels. In some instances, it is difficult to duration of treatment (2). Patient safety is essential determine whether an ocular defect has arisen as a during treatment for a particular disorder. result of involvement with the general disease or as a There is much awareness of systemic effects of ocular toxic manifestation of a drug used in therapy. eye drops due to absorption through nasal mucosa. It is (5) Effect of drug combination: Certain drugs much needed to be aware of the ocular side effects of consumed in combination with other substances have systemic drugs also for better patient compliance and potentiated toxic effects. satisfaction . ERA’S JOURNAL OF MEDICAL RESEARCH, VOL.6 NO.1 Page: 1 OCULAR SIDE EFFECTS OF SYSTEMIC DRUGS (6) Previous exposure to the drug: The ability of the non pigmentedciliary epithelium, which causes non-protein drugs to act as haptens sensitize the reduction in aqueous formation by the ciliary body (5). patient and are thus, responsible for iatrogenic disease, Topical β2 blockers produce little additional IOP particularly where drugs are applied topically over reduction with concomitant administration of a non- long periods. selective (β1 and β2) systemic beta-blocker. Some (7) Drug metabolism: The body's ability to patients may be misdiagnosed as normal tension metabolize a drug directly correlates with toxicity. In glaucoma because the IOP is artificially reduced, patients with liver and kidney disease, there is a appearing within normal limits. decreased rate of excretion, which allows drug 2. Diuretics molecules to accumulate to toxic levels (3). Also, toxic Hydrochlorothiazide (HCTZ) is a diuretic metabolites formed elsewhere like the liver, can reach commonly used to treat congestive heart failure, and the eye through systemic circulation or can be sometimes causes dry eye by changing the tear film. It produced locally in ocular tissues. reduces lysozyme levels and immunoglobulin A, and B) Ocular factors also causes a decrease in aqueous production and. The The eyes are generally affected when a systemic tear potassium is found decreased significantly in medication is taken to treat some other part of the body. subjects taking hydrochlorothiazide (6). Myopic shift Following systemic administration, the and band keratopathyhave been reported, however, blood–aqueous barrier and blood–retinal barrier are occurrence is not common (6). Exact mechanism the major barriers for anterior segment and posterior producing acute myopia is not very clear even though segment ocular drug delivery, respectively4. The it has been postulated to be due to ciliary body effusion, (7) peripheral uveal effusion (8) and ciliary choroid, sclera and ciliary body have thin, fenestrated 9 walls for drug molecules to pass through. Small, lipid spasm and lens swelling. Oral sulphonamides cause soluble molecules, which pass freely into the aqueous transient myopia as a result of forward displacement of humor,can further diffuse into a circulation .The drug the lens due to allergic ciliary body oedema and molecules can enter the eye and contact various ocular rotation (9-10). tissues, and eventually accumulate in ocular tissues or 3. Angiotensin Converting Enzyme (ACE) exit the eye. There are three major accumulation sites Inhibitors including the cornea, lens and vitreous. The duration These are commonly used as antihypertensive drugs of action of drug in the eye is prolonged if it is which can cause decreased vision, photosensitivity, deposited, increasing chances for toxicity (4). conjunctivitis, lid edema and discoloration and The cornea has a permeable endothelium, and blepharitis. Enzyme activities of ACE have been thestomaglycosaminoglycans (GAGs) which can reported further in production of aqueous humour, bindto drug molecules, leading to edema and vitreous humour and tear fluid, also in retina, and decreased transparency. Drug molecules can also bind ciliary body, which are inhibited by these drugs (11). to lens proteins and photosensitize the lens to 4. Antiarrhythmics ultraviolet (UV) radiation. Lastly, drug molecules tend to accumulate in the vitreous due to the slow rate of a) Amiodarone: It is used to treat various cardiac fluid exchange in the lens, cornea, and trabecular arrhythmias like atrial fibrillation and meshwork (2). ventriculartachycardia, which causes certain ocular side effects. Studies have found the presence of List Of Ocular Side Effects Of Some Common amiodarone in all ocular tissues when systematically Systemic Drugs administered. Keratopathy is the mostcommon ocular A) Antihypertensive drugs adverse effect of amiodarone found in almost all 1. Beta-blockers: Beta- blockers,used to treat patients (70-100%) (12). It most commonly appears EJMRafter 1-4 months of therapy. Involvement is bilateral hypertension, reduce tear lysozyme levels and immunoglobulin A(IgA) which leads to reduction in but is often asymmetric. Toxicityincreases with higher tear secretion, and patients complain of ocular doses and longer therapy. irritation, dry eye symptoms, and contact lens Amiodarone tends to cause whorl-like corneal intolerance (5). deposits in as early as six days of treatment butmore Artificial tear supplementation and refitting the patient commonly in one to three months of treatment. The with softcontact lenses should be done as deposits appear whorl-like because epithelial cells management. Beta blockers also decrease intraocular migrate centripetally from limbus. pressure (IOP) by blocking the beta-2 (β2) receptors on ERA’S JOURNAL OF MEDICAL RESEARCH, VOL.6 NO.1 Page: 2 Jan - Jun 2019 ERA’S JOURNAL OF MEDICAL RESEARCH VOL.6 NO.1 sodium, necessary for aqueous secretion. It inhibits the transport of Na+necessary for aqueous secretion and thus causes reduced aqueous secretion and IOP2. Along with the ocular side effects, there are numerous systemic side effects associated with this drug precluding its use in a b c glaucoma treatments (15). Other ocular side effects
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