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

298 OPHTHALMIC DRUGS

Examples • Chlorphenamine (Piriton).

•Promethazine (Phenergan).

•Terfenadine (Triludan).

•Trimeprazine (Vallergan).

Ocular adverse effects Many drugs in this group have antimuscarinic actions as well as antihistaminic and, as would be predicted, a slight mydriasis and cycloplegia are the most common adverse reactions. In addition, the lacrimal gland might be affected, leading to depressed secretion of tears. Contact lens wearers can be particularly affected but sometimes the tears flow is so reduced that the signs and symptoms of keratoconjunctivitis sicca appear.

BRONCHODILATORS

Bronchoconstriction is brought about by the contraction of the smooth muscle, which is innervated by the parasympathetic nervous system. This effect can be reversed by antimuscarinic drugs or by sympathomimetic amines. The tendency today is to use sympathomimetic agents because their effects are less. Sympathomimetics are also used in some common cold remedies which are purchased over-the-counter.

Examples • Ephedrine.

•Orciprenaline (Alupent).

•Pseudoephedrine (Sudafed).

•Salbutamol (Ventolin).

•Terbutaline (Bricanyl).

Ocular adverse effects A slight mydriasis is the principal adverse effect arising from their use. Large doses of ephedrine can lead to visual hallucinations (Chaplin 1984).

DRUGS ACTING ON THE CENTRAL NERVOUS SYSTEM

There are many different types of central nervous system agents and together they represent a large proportion of the prescriptions issued in the UK. Many of the tissues in the eye, particularly the retina, have neural origins and it is therefore likely that these agents will have effects on the eye. They can also affect the centres in the brain which are responsible for controlling eye movements, producing such effects as diplopia.

CNS drugs can be divided into the following groups:

•hypnotics and sedatives

•antiparkinsonism agents

300 OPHTHALMIC DRUGS

•Orphenadrine (Disipal).

•Pergolide (Celance).

•Pramipexole (Mirapexin).

•Trihexyphenidyl (Artane).

Ocular adverse effects Amantadine produces few adverse effects apart from visual hallucinations. Antimuscarinic agents include trihexyphenidyl and orphenadrine, and their effects include a loss of accommodation and a mydriasis that can be sufficient to cause a closed-angle glaucoma in patients whose angle is narrow.

Levodopa produces variable effects. On the pupil, an initial mydriasis is followed by a more persistent miosis. Effects on the lid include ptosis in some patients and intense blepharospasm in others. Involuntary eye movements have also been reported (Davidson & Rennie 1986).

ANTIPSYCHOTIC AGENTS

This group is sometimes called the major tranquillizers or neuroleptics. The term ‘tranquillizer’ is confusing as often this effect is secondary to the principal, antipsychotic action. They do not have a hypnotic effect and are used to relieve conditions such as schizophrenia and severe anxiety.

Examples • Chlorpromazine (Largactil).

•Haloperidol (Serenace).

•Promazine (Sparine).

•Thioridazine (Melleril).

•Trifluoroperazine (Stelazine).

Ocular adverse effects Most of the drugs listed above (with the exception of haloperidol) belong to the group known as the phenothiazines, of which the best known is chlorpromazine. The use of these agents is relatively safe in the short term but with longer use, the possibility of adverse effects increases. Like many other classes of drugs, phenothiazines have varying degrees of antimuscarinic effects and these can affect the iris and ciliary muscles, producing mydriasis and cycloplegia.

Chlorpromazine, in chronic therapy, produces pigmentary deposits in the eye. These appear first on the lens surface, usually in the pupillary area; then Desçemet’s membrane becomes affected. The deposits are rarely found in the corneal epithelium. This effect can continue even after the drug is discontinued. Skin pigmentation can also occur and this affects up to 1% of patients who have received large doses for long periods. Corneal deposits occur in 15% of such patients. As the total dosage increases, so does the percentage of patients affected (Bernstein 1977). The deposits do not appear to interfere with vision and the lens

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Ocular adverse effects Nystagmus and diplopia are more commonly the result of overdose than normal side-effects, and will often regress if the dosage is reduced. Phenytoin had a transient effect on the ERG when the drug was perfused through the retinae of rabbits (Honda et al 1973). A case of Stevens–Johnson syndrome following phenytoin therapy has been reported (Greenberg et al 1971). Blurred vision and diplopia is a reported side-effect to most drugs in this group.

Visual field defects have been reported following the use of vigabratin; these range from the mild to the severe. The manufacturers report a bilateral concentric constriction that is more marked nasally and is often irreversible even after discontinuation. Central visual acuity is unaffected. It is recommended that patients have perimetric tests after the beginning of treatment and at 6-month intervals.

ANTIDEPRESSANTS

The more modern tricyclic antidepressants have, to a large extent, superseded the use of monoamine oxidase inhibitors (MAOIs) because of the latter’s potentially dangerous interactions with some drugs and particular foods (e.g. cheese). Antidepressants are used to treat depressive illnesses and, like the anticonvulsants, it is vital that the dosage is carefully controlled. Some of these drugs have marked sedative properties (e.g. amitriptyline), whereas in others this effect is much less (e.g. imipramine).

Examples • Amitriptyline (Tryptizol).

•Fluoxetine (Prozac).

•Imipramine (Tofranil).

•Nortriptyline (Aventyl).

•Paroxetine (Seroxat).

•Sertraline (Lustral).

•Tranylcypromine (Parnate).

•Trimipramine (Surmontil).

•Venlafaxine (Efexor).

Ocular adverse effects All tricyclic antidepressants have anticholinergic effects to some extent and, because they can produce mydriasis and cycloplegia, they are contraindicated in glaucoma. The effects are reversible and will subside even with continuation of therapy. The lacrimal gland can become affected and the tear flow embarrassed, leading to problems for contact lens wearers.

Monoamine oxidase inhibitors potentiate the effects of sympathomimetics and anticholinergics and care should be taken with the use of mydriatics.

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DRUGS USED IN THE TREATMENT OF INFECTIONS

Many different types of organism can cause infections and a whole range of different compounds can be used to treat them. Although antiinfective drugs are widely prescribed, side-effects are relatively rare. The course of treatment tends to be short and cumulative effects do not have time to develop. Also, anti-infective agents, because of their normally high specificity for the invading micro-organism, have a high therapeutic index. However, some anti-infectives do require long-term therapy and ocular adverse reactions can appear. The following groups will be considered:

•Antibiotics.

•Urinary antiseptics.

•Antitubercular drugs.

•Antifungal drugs.

•Anthelminthics.

•Antimalarials.

ANTIBIOTICS

Agents in this class are used for the treatment of bacterial infections and are some of the most widely prescribed compounds in medicine. For most indications (e.g. upper respiratory tract infections), the treatment lasts for a few days but in the treatment of acne, antibiotics are prescribed for months rather than days. Ideally, the organism should be tested for sensitivity before an antibiotic is prescribed but in practice, therapy is started and modified if necessary.

Examples These are groups rather than individual drugs:

•Penicillins (e.g. penicillin, ampicillin, amoxicillin).

•Cephalosporins (e.g. cephaloridine, cephalexin, cefuroxime).

•Tetracyclines (e.g. chlortetracycline, tetracycline, oxytetracycline).

•Aminoglycosides (e.g. gentamicin, neomycin).

•Macrolides (e.g. erythromycin).

•4-quinolones (e.g. ciprofloxacin).

•Metronidazole.

•Others (e.g. clindamycin, colistin, linezolid).

•Sulphonamides.

Ocular adverse effects Tetracyclines have been reported to cause ocular adverse reactions. As well as transient myopia and colour vision defects, ocular effects secondary to the penetration of the drug into the cerebrospinal fluid,

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Ethambutol is well known for producing optic neuritis, which is slowly reversible in some patients but permanent in others. The optic neuritis has two forms: an axial and a paraxial form. The axial form affects the central fibres of the optic nerve, producing changes in colour vision. Loss of central visual acuity and macular degeneration are often the result. The paraxial form produces visual field defects, with central acuity and colour vision remaining unaffected.

Toxic effects on the optic nerve can also develop from the use of isoniazid and streptomycin (Spiteri & Geraint James 1983).

ANTIFUNGALS

Systemic fungal infections are very rare but systemic treatments are often used to treat local fungal infections, e.g. of the skin, nails and genital tract. The site of the infection will determine the duration of treatment. Treatment of genital candidiasis is usually one capsule, whereas treatment of a infected toenail can be in excess of 3 months. The long duration of treatment gives greater opportunity for side-effects.

Examples • Amphotericin (Fungilin).

• Terbinafine (Lamisil).

Ocular adverse effects Amphotericin has been reported to cause diplopia.

ANTIMALARIALS

Probably the majority of use of these compounds is for the prophylaxis of malaria by travellers to malaria-endemic regions, rather than in the treatment of the condition. There are also other uses for some of the antimalarials, e.g. quinine can be used for the relief of night cramps and chloroquine and hydroxychloroquine can be used in the treatment of rheumatoid arthritis.

Examples • Chloroquine (Avloclor, Nivaquine).

•Hydroxychloroquine (Plaquenil).

•Mefloquine (Lariam).

•Quinine.

Ocular adverse effects The adverse effects of these drugs are well known. Both retina and cornea can be affected, although the two effects are unrelated and can appear independently of one another. Effects on the cornea include