Ординатура / Офтальмология / Английские материалы / Ophthalmic Drugs Diagnostic and Therapeutic Uses 5th edition_Hopkins, Pearson_2007

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administered by inhalation – are associated with the increase risk of the development of cataract.

The effect on wound healing is brought about by changes in the relationship of collagen and cells. Corticosteroids impair fibroblastic and keratocytic activity. They normally inhibit collagenase activity but, on some occasions, this can be potentiated, leading to a rapid destruction of the stroma-melting cornea. Wounds have reduced tensile strength as a result of the actions of steroids.

Another adverse reaction to topical therapy is a rise in intraocular pressure in a small number of individuals (1%). Termed steroid glaucoma, this is caused by an increased resistance to the outflow of aqueous humour by causing morphological and biochemical changes (Clark 1995). This effect is not limited to humans and can be demonstrated in other animals, such as rabbits, cats, dogs and primates. Patients vary in their responsiveness to this effect of corticosteroids but they are more likely to exhibit a rise in intraocular pressure with prolonged treatment with higher doses. There are many similarities between the development of steroid-induced ocular hypertension and primary open-angle glaucoma, and it has been postulated that there is a causal relationship between the higher than normal cortisone levels sometimes noted in such patients. Unfortunately, if the situation is allowed to continue, steroid glaucoma will develop, which will not respond to a cessation of treatment.

Agents such as clobetasone, rimexolone and fluorometholone are claimed to produce fewer adverse effects on the intraocular pressure, possibly due to differences in absorption.

Another adverse effect of long-term use of corticosteroids is thinning of the cornea, known as ‘corneal melt’ or even corneal perforation.

PREDNISOLONE

Prednisolone, in comparison with cortisone and hydrocortisone, has marked anti-inflammatory activity with low mineralocorticoid effects. The half-life in blood plasma is intermediate between that of the natural corticosteroids and the long-acting dexamethasone, betamethasone and triamcinolone. It is extensively used in the treatment of bronchial asthma and other respiratory diseases and is regarded as the preferred corticosteroid for oral administration.

Preparations

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BETAMETHASONE

Betamethasone is a synthetic corticosteroid has minimal mineralocorticoid activity along with marked anti-inflammatory action. This allows its use at a relatively low dose, which reduces the risk of sideeffects. The half-life is much longer than that of prednisolone.

Preparations

BAK, benzalkonium chloride

CLOBETASONE

Clobetasone is a steroid with the advantage of causing less of a rise in intraocular pressure than other topical steroids. Dunne & Travers (1979) found it less effective in reducing the ocular signs of uveitis than dexamethasone, although it was as effective in reducing the subjects’ symptoms. The beneficial lower rise in intraocular pressure was demonstrated in known steroid responders and ocular hypertensive patients. Following cataract surgery it was found to be equally effective as prednisolone and as effective as betamethasone in treating patients with ocular inflammation (Ramsell et al 1980).

The difference in the effects on intraocular pressure is probably not due to any pharmacological difference but a pharmacokinetic one. Clobetasone is absorbed into the aqueous humour at a much lower level than other steroids such as betamethasone (Debnath & Richards 1983).

DEXAMETHASONE

Dexamethasone is a synthetic glucocorticoid with no wateror electrolyteretaining properties. It is seven times as potent as prednisolone and has the greatest propensity of all steroids to raise intraocular pressure.

Preparations

BAK, benzalkonium chloride

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FLUOROMETHOLONE

A synthetic glucocorticoid with fewer ocular hypertensive effects than dexamethasone.

Preparations

HYDROCORTISONE

One of the first corticosteroids to be used in medicine, hydrocortisone has both mineralocorticoid and glucocorticoid properties.

Preparations

NS – generic product, preservative not stated

RIMEXOLONE

Only used short term for acute inflammations but is claimed to have similar ocular hypertensive effects to fluoromethalone.

Preparations

Clinical note

Because topical corticosteroids reduce local tissue immunity, they are capable of aggravating an eye infection, particularly if it is viral or fungal in origin. They can also facilitate opportunistic infection, especially by bacteria. If a steroid were used to treat the inflammation accompanying a herpes simplex ulcer, viral replication would be encourage leading to a much larger area of ulceration. Accordingly, steroids should not be used in the treatment of a ‘red eye’ if the exact aetiology has not been established.

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LEVOCABASTINE

Levocabastine is a new potent H1 receptor blocker that has been tested for its effect on allergic conjunctivitis (Laerum et al 1994, Zuber & Pecaud 1988). Eyedrops containing this agent were well tolerated and have a faster onset than some antihistamines taken orally in the treatment of allergic conjunctivitis (Drouin et al 1995). It is active in 10 min and its effects can last up to 12 h.

A preparation licensed for use in seasonal allergic conjunctivitis is available over the counter.

AZELASTINE

As well as having selective H1 blocking activity, azelastine also has some mast-cell-stabilizing action, preventing the release of chemicals mediators such as the leukotrienes, histamine and serotonin. It has a quick onset of action and its duration of action is sufficient to allow a three times a day dosing.

Preparations

EMEDASTINE

Emedastine produces its effect by selective inhibition of H1 receptors and is indicated for the relief of seasonal allergic conjunctivitis.

Preparations

BAK, benzalkonium chloride

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KETOTIFEN

Ketotifen is similar to azelastine in having mast-cell-stabilizing properties as well selective non-competitive inhibition of H1 receptors. It has a quick onset of action. Systemically, it is used in the treatment of bronchial asthma. One study has found that ketotifen was superior to olopatadine in the relief of signs and symptoms of allergic conjunctivitis (Ganz et al 2003), whereas another investigation demonstrated that olopatadine was more effective than ketotifen in reducing the itching associated with allergic conjunctivitis and caused less ocular discomfort (Berdy et al 2000).

Preparations

OLOPATADINE

Olopatadine is a very specific H1 inhibitor and, unlike many antihistamines, has no antimuscarinic activity. It has, however, mast-cell- stabilizing action. Olopatadine has a rapid onset of action and, as the duration of its anti-allergic action is at least 8 hours, twice daily administration is sufficient compared with the four times daily administration required for levocabastine, lodoxamide and ketorolac (Abelson & Spitalny 1998). Olopatadine has been found to be more effective than azelastine (Spangler et al 2001), nedocromil (Butrus et al 2000) and sodium cromoglicate (Katelaris et al 2002).

Preparations

EPINASTINE

This is a highly selective H1 blocker with little antimuscarinic effect but some antiserotonin effect.

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Preparations

Clinical note

It is relatively common for patients to require simultaneous antibiotic and

steroid therapy. The products shown in Table 13.1 address this need.

Table 13.1 Table of antibiotic/steroid combination products

References