Ординатура / Офтальмология / Английские материалы / Ophthalmic Drugs Diagnostic and Therapeutic Uses 5th edition_Hopkins, Pearson_2007
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308 OPHTHALMIC DRUGS
DRUGS USED TO TREAT DIABETES
The best-known agent for treating diabetes is insulin, but one particular type of diabetes can be treated with drugs given by mouth rather than injected – the oral hypoglycaemic agents.
Examples • Glibenclamide (Daonil, Euglucon).
•Chlorpropamide (Diabinese).
•Pioglitazone (Actos).
•Repaglinide (NovoNorm).
•Tolbutamide (Rastinon).
•Metformin (Glucophage).
Ocular adverse effects Diabetes itself has well-known ophthalmic complications and it is important to differentiate any ocular adverse effect of the drug from the problems caused by the condition. Chlorpropamide can produce toxic amblyopia (Davidson 1971). Overdosage can produce hypoglycaemic attacks, with ocular effects of diplopia and loss of visual acuity.
Visual disturbances are common in patients using pioglitazone, whether on its own or in combination, whereas reports from patients taking repaglinide are rare.
CORTICOSTEROIDS
Corticosteroids can be used either physiologically or pharmacologically. In the former manner they are employed for replacement therapy in Addison’s disease or after adrenalectomy. For this use, both mineralocorticoid and glucocorticoid activity is required.
The suppression of disease processes such as inflammation is termed pharmacological use, and corticosteroids are used in this manner in the treatment of rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis, polyarteritis and chronic hepatitis.
Examples • Betamethasone (Betnelan).
•Cortisone (Cortelan).
•Dexamethasone (Decadron).
•Prednisolone (Deltacortril).
•Fludrocortisone (Florinef).
•Triamcinolone (Ledercort).
•Methylprednisolone (Medrone).
Ocular adverse effects Corticosteroids are notorious for the adverse effects they produce. Systemic use of these agents can result in a cataract, which is situated below the posterior capsule and normally occurs after a year’s treatment.
ADVERSE OCULAR REACTIONS TO SYSTEMIC DRUG TREATMENT 309
It affects up to 30% of patients receiving these agents, especially children. Topical use rarely leads to cataract (David & Berkowitz 1969).
Topical ophthalmic use of steroids can lead to a rise in intraocular pressure in a percentage of patients (steroid responders). This effect can also occur with systemic use, albeit less frequently and after a greater duration of treatment (David & Berkowitz 1969, McDonnell & Kerr Muir 1985). Patients who exhibit this reaction are not necessarily in early glaucoma, although like glaucoma there is a familial tendency for the reaction to occur. The increase is due to a reduction in outflow, which itself is thought to be due to an accumulation of insoluble, polymerized, acid mucopolysaccharides (Francois 1984). Newer corticosteroids have been developed and have less of a tendency to produce a rise in intraocular pressure (Morrison & Archer 1984).
The list of other reported adverse reactions from steroids is long and they would appear to have the ability to produce any and every effect on the eye.
ORAL CONTRACEPTIVES
The contraceptive pill has been in use in the UK for many years and it is now the most common method of birth control. A large number of pills is available today but they can be divided into just two groups – the combined pills and the progestagen-only pills. Many of the unwanted side-effects reported following the use of combined pills are from the oestrogen component and the other type is often recommended for individuals who are most at risk from side-effects.
Examples • Combined pills:
•ethinyloestradiol/norethisterone (Brevinor, Gynovlar)
•ethinyloestradiol/levonorgestrel (Microgynon, Eugynon).
•Progestogen only:
•norethisterone (Micronor)
•levonorgestrel (Microval).
Ocular adverse effects The contraceptive pill has been taken by millions of women for several years and with all this patient experience it is surprising that better cause–effect relationships with ocular effects cannot be established. There have been many publications about the possible incompatibility between the pill and the wearing of contact lenses. Goldberg (1970) reviewed the problems of fitting contact lenses to patients taking the pill and suggested that sometimes there is a problem, but his findings are based on ‘observation and conjecture’. Chizek & Franceschetti (1969) considered that the signs and symptoms that were reportedly due to the contraceptive pill could be due to overwear, humidity changes and infection. Petursson et al (1981) reviewed the evidence for the relationship between contact lens intolerance and oral contraceptives. A
310 OPHTHALMIC DRUGS
prospective study of 517 patients failed to show any difference in contact lens tolerance between patients taking the pill and those who were not. A similar study by Frankel & Ellis (1978) found no significant difference in tear production or tear break-up time between women taking oral contraceptives and women who did not. There is some suggestion that the quality and quantity of tears might be adversely affected, especially during the early stages of their use. Davidson (1971) reviewed the reported ocular adverse effects of oral contraceptives. The Committee on Safety of Medicines recorded effects secondary to cerebral vascular and neurological events as well as localized vascular problems and visual disturbances. A very small number of patients reported contact lens intolerance. Faust & Tyler (1966) examined 212 patients taking various pills and considered that no pathology existed which would not normally exist in a healthy random sample. Connell & Kelman (1969), in carrying out a similar study, were surprised at the occurrence of abnormalities in the control group but also found no difference between therapy and control groups.
ANTI-INFLAMMATORY DRUGS
These agents have been developed as alternatives to steroids for the treatment of conditions such as rheumatoid arthritis to avoid the undesirable effects of steroids. They produce their effect in a slightly different manner to steroids and are not as potent. They are referred to as the non-steroidal anti-inflammatory drugs (NSAIDs).
Examples • Diclofenac (Voltarol).
•Ibuprofen (Brufen).
•Indometacin (Indocid).
•Ketoprofen (Orudis).
•Naproxen (Naprosyn).
•Sulindac (Clinoril).
Ocular adverse effects Reduced colour vision and visual acuity have been reported following the use of ibuprofen and indometacin. Retinopathy (similar to that produced by chloroquine) has been reported following the use of indometacin (Bernstein 1977). This involves visual field restrictions, depressed EOGs and a granular appearance of the fundus. These effects are transitory, as is the diplopia that has also been recorded. Fraunfelder (1980) considered most of the ibuprofen-related effects to be unimportant and consistent with ‘blurred vision’. Cataract and optic neuritis are serious adverse reactions that have been linked with naproxen, but the actual causal relationship is yet to be established. Benaxaprofen (Opren) has had to be withdrawn because of very serious photoallergic reactions. Optic neuropathy has been reported following the use of this particular compound.
ADVERSE OCULAR REACTIONS TO SYSTEMIC DRUG TREATMENT 311
DRUGS ACTING ON THE BLOOD
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CHELATING AGENTS |
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Patients with some conditions require regular blood transfusions. As the |
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donated corpuscles are broken down, the iron is stored and iron |
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overload can develop. To remove this excess iron, a compound that will |
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chelate the iron has to be given regularly. This compound is known as |
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desferrioxamine. When it reacts with iron it changes to ferrioxamine, |
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which can be excreted in the bile and urine. |
Examples |
• Desferrioxamine (Desferal). |
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Ocular adverse effects |
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Arden et al (1984) reported minor alterations in the retinal function as |
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evidenced by alterations in the pattern ERG. |
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ANTIFIBRINOLYTIC AGENTS |
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These agents slow the dissolution of fibrin and help prevent blood loss |
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in conditions such as menorrhagia and epistaxis. |
Examples |
• Tranexamic acid. |
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Ocular adverse effects |
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Disturbances in colour vision that were severe enough to cause a |
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discontinuation of treatment have been reported. |
DRUGS FOR THE TREATMENT OF ERECTILE DYSFUNCTION
These drugs inhibit the enzyme phosphodiesterase type-5, enhancing the relaxing effects of nitric oxide on the corpus cavernosum, leading to greater blood flow and enhancement of erection.
Examples • Sildenafil (Viagra).
•Tadalafil (Cilialis).
•Vardenafil (Levitra).
Ocular adverse effects These drugs commonly cause visual side-effects, which are reported as blurred vision and chromatopsia (a coloured tinge to vision). Marmor & Kessler (1999) reported a perception of bluish haze or increased light sensitivity following the drug’s use.
312 OPHTHALMIC DRUGS
There have been reports of non-arteritic ischaemic optic neuropathy (NAION) following the use sildenafil. The numbers quoted are low and, considering the widespread use of this type of agent, do not necessarily demonstrate a causal link. Seven patients developed this problem 36 hours after taking sildenafil, but all had pre-existing conditions such as hypertension, diabetes or hyperlipidaemia (Boshier et al 2002). However, in another report of five patients who developed NAION (Pomeranz et al 2002), none had pre-existing risk factors.
References
Arden G B, Wonke B, Kennedy C, Huehns E R 1984 Ocular changes in patients undergoing long term desferrioxamine treatment. British Journal of Ophthalmology 68:873–877
Aucamp A 1980 Drug excretion in human tears and its meaning for contact lens wearers. Die Suid Afrikaanse Oogkundige 39:128–136
Bernstein H N 1977 Ocular side effects of drugs. In: Drugs and ocular tissues. 2nd meeting of International Society for Eye Research, 1976
Boshier A, Pambakian N, Shakir S A 2002 A case of nonarteritic ischemic optic neuropathy (NAION) in a male patient taking sildenafil. International Journal of Clinical Pharmacology & Therapeutics 40:422–423
British National Formulary 2005 50th edition. Pharmaceutical Press, London
Canning C R, Hague S 1988 Ocular quinine toxicity. British Journal of Ophthalmology 72:23–26
Chaplin S 1984 Adverse reactions to sympathomimetics in cold remedies. Adverse Drug Reaction Bulletins 107:369–399
Chizek D J, Franceschetti A T 1969 Oral contraceptives. Their side effects and ophthalmological manifestations. Survey of Ophthalmology 14:90–105
Connell E B, Kelman C D 1969 Eye examination in patients taking oral contraceptives. Fertility and Sterility 20:67–74
David D S, Berkowitz J S 1969 Ocular effects of topical and systemic corticosteroids. Lancet 2:149–151
Davidson S I 1971 Reported adverse effects of oral contraceptives on the eye. Transactions of the Ophthalmogical Societies of the United Kingdom 91:561–574
Davidson S I 1980 Drug-induced disorders of the eye. British Journal of Hospital Medicine 1:24–25, 27–28
Davidson S I, Rennie I G 1986 Ocular toxicity from systemic drug therapy. Medical Toxicology 1:217–224
Doherty M, Maddison P J, Grey R H B 1985 Hydrazaline induced lupus syndrome with eye disease. British Medical Journal 290:675
Dyson E H, Proudfoot A T, Prescott L F, Heyworth R 1985 Death and blindness due to overdose of quinine. British Medical Journal (Clinical research ed.) 291:31–33
Ehrenfeld M, Nesher R, Merin S 1986 Delayed onset chloroquine retinopathy. British Journal of Ophthalmology 70:281–283
Faust J M, Tyier E T 1966 Ophthalmic findings in patients using oral contraceptives. Fertility and Sterility 17:1–6 Francois J 1984 Corticosteroid glaucoma. Ophthalmologica
188:76–81
Frankel S H, Ellis P P 1978 Effect of oral contraceptives on tear production. Annals of Ophthalmology 10:1585–1588
Fraunfelder F T 1980 Interim reports. National Registry of possible drug induced ocular side effects. Ophthalmology 87:87–90
Frucht J, Freimann I, Merin S 1984 Ocular side effects of disopyramide. British Journal of Ophthalmology 68:890–891
Goldberg J B 1970 A commentary on oral contraceptive therapy and contact lens wear. Journal of the American Optometric Association 41:237–241
Greenberg L M, Mauriello D A, Cinattia A A, Burton J N 1971 Erythema multiforme exudativum (Stevens–Johnson syndrome) following sodium diphenylhydantoin therapy. Annals of Ophthalmology 3:137–139
Honda Y, Podos S M, Becker B 1973 The effect of diphenylhydantoin on the electroretinogram of rabbits. Investigative Ophthalmology & Visual Science 12:567–572
Ingram D V 1986 Spoiled soft contact lenses. British Medical Journal (Clinical research ed.) 292:(6536)1619
Kofoed L L 1986 OTC drugs: a third of the elderly are at risk. Geriatric Medicine February:37–42
Marmor M F, Kessler R 1999 Sildenafil (Viagra) and ophthalmology. Survey of Ophthalmology 44:153–162
McDonnell P J, Kerr Muir M G 1985 Glaucoma associated with systemic corticosteroid therapy. Lancet 2:386–387
ADVERSE OCULAR REACTIONS TO SYSTEMIC DRUG TREATMENT 313
Morrison E, Archer D B 1984 Effect of fluoromethalone (FML) on the intraocular pressure of corticosteroid responders. British Journal of Ophthalmology 168:581–584
Petursson G J, Fraunfelder F T, Meyer B M 1981 Oral contraceptives. Ophthalmology 88:368–371
Pomeranz H D, Smith K H, Hart W M Jr et al 2002 Sildenafil-associated nonarteritic anterior ischemic optic neuropathy. Ophthalmology 109:584–587
Sinabulya P M 1977 Chloroquine retinopathy. Case report. East African Journal of Ophthalmology 2:29–30
Slatter D H, Blogg J R 1978 Keratoconjunctivitis sicca in dogs associated with sulphonamide administration. Australian Veterinary Journal 54:444–447
Spiteri M A, Geraint James D 1983 Adverse ocular reactions to drugs. Post-graduate Medical Journal 59:343–349
Wright P 1978 Effect of drug toxicity on the cornea. Transactions of the Ophthalmogical Societies of the United Kingdom 98:377–378
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Appendix: UK law
In the UK, the use of drugs by optometrists is subject to control and regulation by Acts of Parliament in the same manner as the use of drugs by other health professionals or by patients. Much of the sale and supply of drugs is covered by the Medicines Act 1968, which is set out in eight parts and deals not only with sale and supply but also with the licensing of medicinal products, their manufacture or import and other matters such as advertising. Although this Act is still at the basis of most of the control of the sale and supply of medicines, more recent legislation has produced significant changes in the use of drugs by optometrists:
•Part I: Administration of the Act and setting up of Medicines Commission
•Part II: Licensing:
•manufacture
•product licenses
•import and export
•clinical trial
•Part III: Sale and supply (see below)
•Part IV: Pharmacies
•Part V: Containers, labelling
•Part VI: Promotion and advertising
•Part VII: Publications, e.g. British Pharmacopoeia
•Part VIII: Miscellaneous provisions
A medicinal product is a product intended for one or more of the following purposes:
•treating medical conditions
•preventing medical conditions
•diagnosing medical conditions
•contraception
•otherwise modifying the physiological state of the body.
In addition, orders might be made to include products and devices not falling into one of the groups above. For example, an order made in 1976 brought contact lenses and contact lens solutions under some of the provisions of the Medicines Act.
Sale and supply of medicinal products is covered by Part III of the Act, which categorizes products into three groups:
•General sale list
•Pharmacy medicines
•Prescription-only medicines.
APPENDIX 315
GENERAL SALE LIST (GSL): SECTION 51
Medicines that are considered to be sufficiently safe that they can be supplied to the general public without supervision of a pharmacist are incorporated into a list of medicines called the General sale list (SI 1980/1922). This list is very detailed and can, for instance, limit the quantity supplied in a container. The list is constantly being updated and amended. Any retailer can sell a GSL medicine providing the retail premises are permanent and lockable. An optometric practice will certainly satisfy this criterion.
PHARMACY (P) MEDICINES: SECTION 52
Pharmacy medicines are only available to the general public from a person who is lawfully conducting the business of a retail pharmacy, and the sale must be under the supervision of a registered pharmacist. Whereas there are legal lists of GSL and prescription-only medicines (POM), there is no legal list of Pharmacy medicines. Optometrists can supply any pharmacy medicine that is an eye drop or an eye ointment, providing that the supply is: (1) in line with the optometrist’s professional practice; and (2) is an emergency. This ability to supply P drugs is due to an amendment order made in 1978 (SI 1978/988).
PRESCRIPTION-ONLY MEDICINES (POM): SECTION 58
As the name suggests, these products are available to the public on only the prescription of a doctor, dentist or veterinary surgeon. The Prescription-only medicine List (SI 1983/1212) is very detailed. For many agents there are exemptions from the requirements for a prescription if a maximum dose is specified or if the drug is presented in a particular form. A number of products are exempted, becoming pharmacy medicines if they are intended for external use, providing the external use is not ophthalmic; eyedrops and eye ointments of such compounds remain POM products.
Like the General sales list, the POM list is subject to constant revision, with products being moved from one list to another. For example, chloramphenicol eye drops have changed from being POM to a P medicine and can now be sold over-the-counter by pharmacists. The general trend of movement of products is towards less stringent control, i.e. POM to P to GSL. However, occasionally it is thought desirable to impose tighter restrictions, e.g. insulin and large packs of paracetamol tablets.
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Clinical note
Although chloramphenicol is now available over-the-counter, it still appears on the list of POM products that are available for use by optometrists. This apparent anomaly is due to the fact that apparently identical products can have different legal classifications. The legal classification is specified in the product’s license and is determined not only by drug and concentra-
tion but on the pack size, presentation and patient information leaflet. Another example is sodium cromoglicate, which is P up to 10 mL then
POM. Many other examples exist in general medicines, paracetamol tablets in packs of 16 are GSL, in packs of 32 they are P and in packs of 100 they are POM, even though the strength of the tablet is the same.
SALE AND SUPPLY OF MEDICINES BY OPTOMETRISTS
1. Sale and supply by all optometrists
Legislation that came into force on 30 June 2005 has done much to clear away many of the anomalies that existed before this date relating to the use and supply of medicinal products by optometrists. It has also confined many products that are no longer commercially available to the waste bin.
GENERAL SALES LIST PRODUCTS
Optometrists can sell or supply any GSL product to a patient; the situation does not need to be an ‘Emergency’. This includes all GSL products and not just those which are ophthalmic products.
PHARMACY MEDICINES
The same rules now apply to pharmacy medicines.
PRESCRIPTION-ONLY MEDICINES
Many of the mydriatics/cycloplegics, miotics, local anaesthetics and antimicrobial agents that the optometrist might want to use are POM drugs. To allow access to these drugs, specific exemptions are made for registered optometrists. The products can be divided into three groups:
Registered optometrists can, provided that it is in the course of their business and in an emergency, sell or supply the following:
•chloramphenicol 0.5% eye drops
•chloramphenicol 1.0% eye ointment
APPENDIX 317
•cyclopentolate eye drops
•fusidic acid eye drops
•tropicamide eye drops.
Concentrations are not specified for the last three. These products can also be supplied by a community pharmacist against a signed order (see below). A common question is ‘What constitutes an emergency?’ There is no strict legal definition and it is up to the optometrist to use his or her professional judgement.
2. Administration by Registered optometrists can obtain for use in their practice (but not sell all optometrists or supply) a range of local anaesthetic drops containing the following
substances:
•amethocaine hydrochloride
•lidocaine hydrochloride
•oxybuprocaine
•proxymetacaine.
Thus it would seem that a registered optometrist without further qualification will no longer have access to a miotic. Pupils can be dilated but not constricted!
3. Sale and supply by Optometrists can undertake additional training to obtain accreditation additional supply by the General Optical Council, which allows them to have access to an
optometrists additional range of POM products. These include:
•acetylcysteine
•atropine
•azelastine
•diclofenac
•emedastine
•homatropine
•ketotifen
•levocabastine
•lodoxamide
•nedocromil
•olopatadine
•pilocarpine
•polymixin B/bacitracin
•polymixin B/trimethoprim
•sodium cromoglicate.
These products can also be supplied against a signed order. The effect is to place in a special category drugs to which optometrists have in the past had access. Atropine and homatropine used as diagnostic cycloplegics are no longer routinely available and the inference is that their therapeutic use in the treatment of inflammation is more important. The miotic pilocarpine is included but not the out-of-date physostigmine or