Ординатура / Офтальмология / Английские материалы / Ophthalmic Drugs Diagnostic and Therapeutic Uses 5th edition_Hopkins, Pearson_2007
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218 OPHTHALMIC DRUGS
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A comparison of the relative efficacy and clinical performance of olopatadine hydrochloride 0.1% ophthalmic solution and ketotifen fumarate 0.025% ophthalmic solution in the conjunctival antigen challenge model. Clinical Therapeutics 22:826–833
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miosis during cataract extraction by diclofenac eye drops. New Trends in Ophthalmology 11:513–519
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Cerqueti P M, Ricca V, Tosca M A et al 1994 Lodoxamide treatment in allergic conjunctivitis. International Archives of Allergy and Immunology 105:185–189
Clark A F 1995 Steroids ocular hypertension and glaucoma. Journal of Glaucoma 4:354–369 Debnath S C, Richards A B 1983 Concentration of
clobetasone in aqueous humour. British Journal of Ophthalmology 67:203–205
Drouin M A, Yang W H, Horak F 1995 Faster onset of action with topical levocabastine than with oral cetirizine. Mediators of Inflammation 4 (supplement): s5–sl0
Dunne J A, Travers J P 1979 Double blind clinical trial of topical steroids in anterior uveitis. British Journal of Ophthalmology 63:762–767
Erturk H, Ozcetin H, Avci R 1991 Diclofenac sodium for the prevention of surgically induced miosis. European Journal of Implant Refractive Surgery 3:55–57
Fabian E, Dennfer R, Wertheimer R 1991 Diclofenac eye drops to maintain mydriasis during extracapsular cataract extraction [in German]. Ophhalmo-Chirurgie 3:115–119
Fahy G et al 1988 Double masked efficacy and safety evaluation of lodoxamide 0.1% ophthalmic solution versus opticrom 2% – a multicentre study. Ophthalmology Today 341–342
Ganz M, Koll E, Gausche J et al 2003 Ketotifen fumarate and olopatadine hydrochloride in the treatment of allergic conjunctivitis: a real-world comparison of efficacy and ocular comfort. Advances in Therapy 20:79–91
Hennawi M 1994 A double blind placebo controlled group comparative study of ophthalmic sodium cromoglycate and nedocromil sodium in the treatment of vernal keratoconjunctivitis. British Journal of Ophthalmology 18:365–369
Hersh P S, Rice B A, Baer J C et al 1990 Topical nonsteroidal agents and corneal wound healing. Archives of Ophthalmology 108:577–583
Hodgkins P, Hull R G, Evans A R, Jeffrey M N 1997 Osteoporosis: a survey of consultant ophthalmologists. British Journal of Ophthalmology 81:260
Ilic J, Gigon S, Leuenberger P M 1984 Comparison of the anti-inflammatory effects of dexamethasone and diclofenac eye drops [in German]. Klinische Monatsblatter für Augenheilkunde 184:494–498
Katelaris C H, Ciprandi G, Missotten L et al 2002 comparison of the efficacy and tolerability of olopatadine hydrochloride 0.1% ophthalmic solution and cromolyn sodium 2% ophthalmic solution in seasonal allergic conjunctivitis. Clinical Therapeutics 24:1561–1575
Kishore K, Panda A, Gupta S K 1994 Prospective placebo controlled clinical trial in the management of chronic no-infectious conjunctivitis with indomethacin. Afro-Asian Journal of Ophthalmology 133:69–70
Kjellman N-I M, Stevens M T 1995 Clinical experience with tilavist: An overview of efficacy and safety. Allergy, 50 (supplement), 21, 14-22
Laerum E, Fiskaadal H J, Erdal J E et al (1994) Chloramphenicol eyedrops in acute bacterial conjunctivitis. A comparison of 2 dosage regimes in general practice [in Norwegian]. Tidsskrift for den Norske Laegeforening 114:671–673
Laibowitz H L, Koester J, Schaich L et al 1995 Safety and efficacy of diclofenac sodium 0.1 in acute seasonal allergic conjunctivitis. Journal of Ocular Pharmacology & Therapeutics 11:361–368
Leino S, Ennevaara K, Latvala A L et al 1992 Double blind group comparative study of 2 nedocromil sodium eye drops with 2 sodium cromoglycate and placebo eye drops in the treatment of seasonal allergic conjunctivitis. Clinical and Experimental Allergy 22:929
Melamed J, Schwartz R H, Hirsch S R et al 1994 Evaluation of nedocromil sodium 2% ophthalmic solution for the treatment of seasonal allergic conjunctivitis. Annals of Allergy, Asthma, and Immunology 73:57–66
Miglior M, Scullica L, Secchi A G et al 1993 Nedocromil sodium and astemizole, alone or combined, in the treatment of seasonal allergic conjunctivitis. Acta Ophthalmologica (Kbh) 71:73–78
ANTI-INFLAMMATORY AGENTS 219
Ramsell T G, Bartholomew R S, Walker S R 1980 Clinical evaluation of clobetasone butyrate; a comparative study of its effects in postoperative inflammation and on intraocular pressure. British Journal of Ophthalmology 64:43–45
Ronen S, Rozenman Y, Zylbermann R et al 1985 Treatment of ocular inflammation with diclofenac sodium. Double blind trial following cataract surgery. Annals of Ophthalmology 17:577–581
Sand B B, Krogh E 1991 Topical indomethacin, a prostaglandin inhibitor, in acute anterior uveitis. A controlled clinical trial of nonsteroid versus steroid anti-inflammatory treatment. Acta Ophthalmologica (Kbh) 69:145–148
Sher N A, Barak M, Daya S et al 1992 Excimer laser photorefractive keratectomy in high myopia. Archives of Ophthalmology 194:935–943
Sher N A, Frantz J M, Talley A et al 1993 Topical diclofenac in the treatment of ocular pain after excimer photorefractive keratectomy. Refractive and Corneal Surgery 9:425–436
Spangler D L, Bensch G, Berdy G J 2001. Evaluation of olopatadine hydrochloride 0.1% ophthalmic solution and azelastine hydrochloride 0.05% ophthalmic solution in the conjunctival allergen
challenge model. Clinical Therapeutics 23:1272–1280
Stern G A, Buttross M 1991 Use of corticosteroids in combination with preantimicrobial drugs in the treatment of infectious corneal disease. Ophthalmology 98:847–853
Struck H G et al 1994 Influence of diclofenac and flurbiprofen eye drops on the inflammation after cataract extraction. Ophthalmology 31:482–485
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The effects of topical S(+)-ibuprofen on interleukin-1 induced ocular inflammation on a rabbit model. Journal of Ocular Pharmacology & Therapeutics 6:131–135
van Bijsterveld et al 1994 Nedocromil sodium treats symptoms of perennial allergic conjunctivitis not fully controlled by sodium cromoglycate. Ocular Immunology and Inflammation 2:177–186
Vickers F F, McGuigan L J B, Ford C et al 1991 The effect of diclofenac sodium ophthalmic solution on the treatment of post-operative inflammation. Programme for the Association for Research in Vision and Ophthalmology Meeting, page 793,
poster 616-2
Zuber P, Pecaud A 1988 Effect of levocabastine, a new HI antagonist, in a conjunctival provocation test with allergens. Journal of Allergy & Clinical Immunology 82:590–594
220
Chapter 14
Drugs for the treatment of glaucoma
The range of drugs available for the treatment of glaucoma has expanded and there is some indication that the new ones have helped to contribute to a reduced rate of surgery. One study showed that, between 1994 and 1999, there had been a 45.9% decrease in the rate of operations and that the number of patients treated with topical hypotensive drugs increased significantly. This change in treatment strategy was attributed to the efficacy of carbonic anhydrase inhibitors, alpha-2 agonists and prostaglandin analogues (Bateman et al 2002). However, despite all the new introductions, glaucoma still is a very serious problem, being the major cause of preventable blindness.
In view of increasing life expectancy, the duration of topical treatment of glaucoma is likely to become greater, making it increasingly important to be aware of both the systemic and ocular side-effects of the various drugs used. It is also necessary to keep in mind the possible influences of subsequent adverse changes in the patient’s health and additions or changes to other medication that are used.
Of the primary glaucomas, only open-angle glaucoma is amenable to chronic medical treatment. Although acute closed-angle glaucoma can be relieved by a combined attack of both topical and systemic treatment, its long-term relief will be from surgery. Surgical treatment of open-angle glaucoma is also an option, especially when medical treatments appear to be losing their effect. Secondary glaucomas might respond to medical treatment, depending on the underlying cause.
Whatever its form, an antiglaucoma treatment should satisfy certain criteria:
•Reduction of intraocular pressure: the amount by which intraocular pressure must be reduced so that the glaucoma can be deemed to be ‘controlled’ varies between different studies. Intraocular pressures of below 20 mmHg are often taken to indicate control but it is known that different individuals tolerate different tensions; a level of 20 mmHg is not control for a patient with low-tension glaucoma. It is probably more important that the pressure should remain stable and not vary greatly during the day.
•Duration of effect: there is little doubt that if the treatment is to be effective then the reduction should last for some hours. Drugs that have a longer duration of action will require less frequent administration and will ensure less diurnal variation in intraocular pressure.
DRUGS FOR THE TREATMENT OF GLAUCOMA 221
As stated above, it is important that the pressure remains stable rather than oscillating. It is assumed, but not proven, that there is an inverse relationship between the number of doses per day and patient compliance. In other words, twice-a-day therapy is better than four-times- a-day therapy but not as good as once a day.
•Preservation of visual field: with modern diagnostic techniques, most glaucomas today are diagnosed before serious impairment of vision has occurred and the obvious aim of treatment is that no further loss will occur. As visual field change is a slow insidious effect, it is important that it is monitored.
•No loss of effect with time: once patients have been stabilized on a treatment, it is unfortunate if therapy has to be modified because the original drug is no longer sufficiently effective.
•Compatibility with other treatments: because drugs can lose their effect with time and because some patients require more vigorous therapy, it is often necessary for more than one drug to be administered (adjunct therapy). As the possibility exists of modifying pressure by reducing secretion or by increasing outflow, drugs with antagonistic pharmacological actions (sympathomimetics and parasympathomimetics) may have synergistic therapeutic effects.
•Lack of topical adverse effects: often, due to the diligence of the optometrist, glaucoma is detected before the patient is aware of symptoms and, indeed, the patient does not know that he or she has a problem that will require a lifetime of continuing therapy. Having persuaded the patient that it is necessary to apply the drops every day, it is counterproductive if these drops cause problems that result in a lack of patient compliance. Initial stinging is one of the problems that can occur with many eyedrops. Some drops can cause a local anaesthetic effect (e.g. beta-blockers) and this can lead to corneal problems. Eyedrops contain other ingredients as well as the drug and water and these adjuvants might interfere with the anterior surface of the eye. For example, some of the preservatives used to maintain sterility can adversely affect the tear film and can thus exacerbate dry eye problems.
•Lack of systemic effects: some of the topical antiglaucoma drugs used today produce their action by modifying the effects of the autonomic nervous system. The ANS innervates many other structures in the body, e.g. the cardiovascular system, the respiratory system and the gastrointestinal system, and serious systemic effects can result from the topical use of autonomic drugs if sufficient drug is allowed access to the systemic circulation.
•Patient compliance: treatments must be easy and pleasant to use and this requires attention not only to the active ingredient and its formulation but also to the container in which it is supplied.
Glaucoma treatments can be administered either systemically or topically. Topical treatments greatly outnumber systemic ones even though it is far easier to administer an oral medicine than eyedrops.
222 OPHTHALMIC DRUGS
SYSTEMIC TREATMENTS
Drugs administered in this manner are given by mouth for chronic treatment or by injection for acute use. Beta-blockers will reduce intraocular pressure when given systemically and have been tested for use in this manner (Tutton & Smith 1983). Williamson et al (1985) compared topical treatment with timolol and systemic treatment with nadolol. They found that once-a-day systemic treatment was as efficacious as twice-a-day topical treatment and suggested that systemic treatment would be useful for patients who had difficulty in administering drops. These findings were not confirmed in a later trial by Dowd et al (1991). Of 30 newly diagnosed patients suffering from chronic open-angle glaucoma, only one was controlled throughout the 3-month study and the authors rightly concluded that the drug was ineffective in controlling intraocular pressure in the patients undergoing the trial. The only drugs that have been used routinely as systemic treatments are the carbonic anhydrase inhibitors acetazolamide and dichlorphenamide. Carbonic anhydrase is present in the ciliary epithelium and is necessary for the secretion of bicarbonate ions. If this secretion is reduced there is a concomitant reduction in the secretion of the accompanying sodium ions. To maintain the proper osmotic pressure, the volume of aqueous secreted is less than normal and intraocular pressure falls. The carbonic anhydrase inhibitors have some unfortunate side-effects, including:
•lack of appetite
•paraesthesia
•gut disturbances
•fatigue
•kidney stones
•aplastic anaemia.
Although acetazolamide is still marketed, it is no longer routinely used in the treatment of glaucoma. In fact, it is probably used more for the prevention of altitude sickness than in the treatment of glaucoma.
LOCAL TREATMENTS
Topical treatments consist of the application of drops to the anterior surface of the eye. A number of agents are available for use in the treatment of glaucoma, which fall into several groups: parasympathomimetics, sympathomimetics and beta-blockers. Parasympathomimetics were previously referred to as miotics, which included the anticholinesterases.
PARASYMPATHOMIMETICS
These are the same drugs that can be used to reverse the action of mydriatics. Whereas for the reversal of mydriasis, pupillary constriction is the desired effect, in the treatment of open-angle glaucoma, it is an
DRUGS FOR THE TREATMENT OF GLAUCOMA 223
unwanted side-effect. The contraction of the ciliary muscle, putting tension on the trabecular meshwork, is responsible for the increased outflow and reduced intraocular pressure. In addition, direct effects on the trabecular meshwork have been postulated by Barany (1962). If the filtration angle is narrow, the miosis is an important component of the drug’s action but, for the majority of patients, it is the cyclospasm that produces the fall in intraocular pressure.
Adverse systemic effects Systemic absorption of parasympathomimetic drugs has the potential to produce sweating, bradycardia, intestinal colic, hypersalivation and bronchospasm. These effects are normally theoretical rather than actual and it is notable that asthmatics are more at risk from beta-blockers than from parasympathomimetics.
Adverse ocular effects The miosis impairs vision in low levels of lighting, aggravates the influence of central lens opacities and constricts the visual field. Patients under the age of about 50 years will be troubled by induced myopia caused by the spasm of accommodation that might be associated with a frontal headache. Pilocarpine used in an unusually high concentration (> 4%) has the potential to cause retinal detachment and to precipitate or exacerbate angle-closure glaucoma due to the narrowing of the anterior chamber caused by contraction of the ciliary muscle.
Contraindications Anterior uveitis (iritis) and secondary glaucoma with extensive obstruction of outflow are contraindications to the use of parasympathomimetics.
Pilocarpine The only parasympathomimetic in routine use is pilocarpine, which has been used in ophthalmology for well over 100 years. The concentration employed varies from 0.5% to 8% but the higher strengths are supramaximal as a maximum effect has been reported at 4% (Harris & Galin 1970). It produces a small, biphasic rise followed by a persistent fall (Korczyn et al 1982) that lasts for about 6 hours, requiring the drug to be administered four times a day. Its effect is on outflow rather than secretion and thus the drug restores the aqueous flow to a more physiological status.
The miosis and spasm of accommodation are fundamental to the mode of action of these drugs and little can be done to separate the beneficial effects from the adverse effects. Not only does the spasm of accommodation caused by miotics lead to pseudomyopia, but it also increases the risk of retinal detachment. Kraushar & Steinberg (1991) recommended peripheral retinal examination prior prescribing miotics. Research into miotics has been aimed at the other disadvantages of pilocarpine, namely:
•It is a natural product, which means that:
•it tends to be expensive
•its supplies can be erratic
•there is a greater possibility of allergic reaction.
224 OPHTHALMIC DRUGS
•Its effects only last for 6 hours and therefore:
•patient compliance is reduced
•the intraocular pressure goes up and down four times a day.
To avoid these problems, developments have been made in two directions: (1) more modern presentations of pilocarpine and (2) alternative miotics. Whereas the different presentations of pilocarpine are still in use, the later miotics have mainly disappeared.
Alternative The developments aimed at increasing the contact time of the drug with presentations of the eye have resulted in a greater and more prolonged effect. These
pilocarpine developments have included:
Viscolized solutions Viscolizers such as hydroxyethylcellulose or polyvinyl alcohol have been added to make the drop more viscous and thus stay in the eye for longer (Davies et al 1977). Although a greater and more prolonged fall has been reported following the use of viscolized drops, the duration of effect does not seem to justify a reduction in the number of doses per day.
Gels Polymers have been developed into which the pilocarpine can be incorporated and from which it is slowly released (Ticho et al 1979). Pilogel is the latest formulation to be introduced into which pilocarpine has been incorporated (pilocarpine 4%). It requires treatment only once a day, usually at bedtime. It can be combined with other treatments, such as beta-blockers and carbonic anhydrase inhibitors.
During early studies with pilocarpine-containing gels it was found that the amount of reduction of intraocular pressure, and the duration of effect, were dose dependent up to 4% (Stewart et al 1984). With aqueous solutions, the maximum is reached at a lower concentration in some patients, especially those with light irides.
Although pilocarpine gels produced a reduction for 24 hours, the effect is greater at 12 hours than 24 hours (March et al 1982) and it might be necessary to carry out phasing studies to determine whether the effect is maintained sufficiently towards the end of the interdose period. Similarly, Johnson et al (1984) found higher values in the afternoon than in the morning, but did nor consider the difference significant.
Apart from patient compliance, the principal advantage of a once-a- day therapy should be a reduction in the inconvenience of pseudomyopia induced four times a day. With the gel applied at bedtime, the worst of the myopia should occur at night-time. Mandell et al (1988) found that patients suffered fewer visual problems with the gel than with aqueous solutions. Aldrete et al (1983) compared pilocarpine gel with 0.5% timolol and found the gel as effective as the beta-blocker. Although the pupil diameter was reduced in the morning by the pilocarpine preparation, visual acuity was unaffected. Pilocarpine lacks some of the side-effects linked with beta-blockers, i.e. cardiovascular problems and corneal sensitivity effects, and, taking into consideration that the gel has to be used only once daily, must represent a useful development in the treatment of glaucoma.
DRUGS FOR THE TREATMENT OF GLAUCOMA 225
Oily solutions Not only are oils more viscous than water but the actual alkaloid rather than the water-soluble salt can be incorporated and thus be better absorbed by the corneal epithelium. Unfortunately, oily drops were not as pleasant to use as the aqueous ones and never found favour.
Soft contact lenses Hydrogel lenses can be soaked in pilocarpine solutions and the lens applied to the eye (Marmion & Yurdakul 1977), a method of application that does not seem to have been widely accepted. A significantly enhanced duration of effect was not achieved.
Ocusert This consisted of viscous solution surrounded by a membrane that allowed a slow but constant delivery of pilocarpine into the conjunctival sac (Heilman & Sinz 1975). The duration of treatment lasted for up to 9 days and because the level of pilocarpine was constant, the side-effects were smaller than from drop application. One of the problems encountered was that the unit was sometimes lost and the patient went untreated until the loss was discovered. It is no longer marketed.
ALTERNATIVE MIOTICS
Many other miotics have been tried in the treatment of glaucoma:
•Other parasympathomimetics:
•Aceclidine: this synthetic drug had similar efficacy and duration of action to pilocarpine but did not seem to confer any particular advantage, other than the fact that it could be tolerated when pilocarpine was not (Romano 1970).
•Metachol: a synthetic analogue of acetylcholine.
•Carbachol: similar to metachol but not broken down by cholinesterase. It was poorly absorbed across the cornea. Reichert et al (1988) reviewed patients who had been switched from pilocarpine (four times a day) to carbachol (three times a day) when the former drug failed to produced adequate control. They found little improvement in control and an increased chance of side-effects.
•Short-acting (reversible) anticholinesterases:
•Physostigmine: produces a marked miosis and a reduction of intraocular pressure that last for 12 hours. It was sometimes combined with pilocarpine.
•Neostigmine: a weaker, synthetic analogue of physostigmine.
•Long-acting (irreversible) anticholinesterases:
•Dyflos: DFP was the first organophosphorus compound but it was unstable in water and was administered in arachis oil.
•Ecothiopate: this is similarly susceptible to hydrolysis and was supplied dry, being dissolved in a diluent just before use. Reichert & Shields (1991) replaced pilocarpine or carbachol with ecothiopate and found in 60% of patients an improvement in intraocular pressure. Predictably patients reported decreased vision and ocular irritation and one patient suffered retinal detachment.
226 OPHTHALMIC DRUGS
Clinical note
Due to their intrinsic adverse ocular effects, cholinergic drugs have been superseded by newer drugs in the treatment of primary open glaucoma. Nevertheless pilocarpine retains a role in the management of acute angle-closure glaucoma.
Adrenaline
•Demecarium: this was one of the shorter-acting irreversible agents. The only miotic products in use today are the various presentations of pilocarpine.
Preparations
Product |
Presentation |
Concentrations |
Preservative |
Pilocarpine |
Eyedrops |
0.5, 1.0, 2.0, 3.0, 4.0 |
BAK |
|
|
|
|
Minims |
Single-use drops |
2.0, 4.0 |
|
|
|
|
|
Pilogel |
Ophthalmic gel |
4.0* |
BAK |
|
|
|
|
* With 3.5% carbomer BAK, benzalkonium chloride
SYMPATHOMIMETICS
Adrenergic drugs decrease aqueous production and might increase its outflow. Alpha-agonists can reduce intraocular pressure.
Sympathomimetics drugs have been used in the treatment of glaucoma since the early twentieth century. The ability of adrenaline to reduce intraocular pressure had been known for a long time but its application to the treatment of glaucoma was only possible following the development of the gonioscope lens. Because of the ability of adrenaline to cause a dilation of the pupil, it is vital that open-angle glaucoma is differentiated from closed-angle glaucoma. Sympathomimetics will reduce pressure in the former and increase it in the latter. They produce a triphasic response with a fall, followed by a rise and then a more persistent fall. The effect lasts for at least 12 hours and thus the drops require administration twice a day. The time course of the ocular hypotensive effect is different from the mydriatic effect (Langham et al 1979). Many different sympathomimetics have been tried but their use has declined following the introduction of more clinically useful drugs.
Adrenaline produces its pharmacological effects by stimulating both alphaand beta-receptors and by a variety of biochemical effects, e.g. enhanced liver glycogenolysis, leading to a higher blood sugar level and enhanced production of prostaglandins. Its best known biochemical effect is the enhanced production of cyclic adenosine monophosphate from adenosine triphosphate.
Adrenaline produces a beta-mediated increase in secretion by stimulating chloride transport through cAMP production. However, this increase is more than cancelled out by an alpha-stimulated reduction. Adrenaline also causes an increase in the facility of outflow by acting beta-receptors. Phenylephrine, a predominantly alpha-agonist, shares
DRUGS FOR THE TREATMENT OF GLAUCOMA 227
with timolol and betaxolol the ability to cause a vasoconstriction in the ciliary epithelium in rabbits during short-term treatment (Van Buskirk et al 1990). However, tolerance develops to phenylephrine and betaxolol (but not to timolol) after several weeks of treatment.
An interesting finding is that pretreatment with steroids can increase the ocular hypotensive effect of adrenaline (Bealka & Schwartz 1991). Steroids on their own can cause a rise in intraocular pressure in some patients.
Adrenaline is not without its adverse effects, producing a red eye in some patients, probably as a result of reactive hyperaemia. It will also cause black deposits in the cornea (Madge et al 1971), especially if old solutions are used (Krejci & Harrison 1969). Maculopathy has been reported, especially in aphakic patients (Kolker & Becker 1968; Mackool et al 1977).
To improve its efficacy, adrenaline has in the past been combined with guanethidine, an adrenergic neuron blocker. Initially, it causes a release of noradrenaline from the nerve terminals and thus acts as an indirectly acting sympathomimetic. Mydriasis and a fall in intraocular pressure are the result. As the noradrenaline is not replaced, eventually a chemical denervation syndrome exists. The intraocular pressure returns to normal and the pupil is constricted. The eye is now supersensitive to sympathomimetics and it will respond to a concentration of these agents which would normally have no effect. Crombie (1974) used the combination of guanethidine and adrenaline to control patients who were previously difficult to control. Eltz et al (1978) used a combination of 5% guanethidine and 1% adrenaline and found that the mixture was synergistic.
Adrenaline is no longer used, either on its own or in combination, in the treatment of glaucoma.
Dipivefrin Dipivefrin is a prodrug with enhanced lipid solubility that facilitates its penetration of the cornea. It is converted to active adrenaline by enzymes to produce its hypotensive effect. Onset of action takes place in 30 min, with the peak effect being recorded after 1 hour. Kass et al (1979) reported smaller falls with 0.1% dipivefrin than from 2% adrenaline. It was found to be less effective than timolol (Frumar & McGuinness 1982). In terms of side-effects, the results are disappointing. Reactive hyperaemia (Azuma & Hirano 1981), endothelial damage (Sasamoto et al 1981) and follicular conjunctivitis (Coleiro et al 1988, Theodore & Leibowitz 1979) have been reported.
Preparations
Product |
Presentation |
Concentration |
Preservative |
Propine |
Eyedrops |
0.1% |
BAK |
|
|
|
|
BAK, benzalkonium chloride