Ophthalmologica. Basel 171: 157-164 (1975)
Pump Infusion of Pilocarpine L aurence S. H arris and Y affa K ahanowicz Department of Ophthalmology, New York Hospital/Cornell Medical Center, New York, N.Y.
Introduction Attempts to increase the efficacy and/or duration of action of pilo carpine have involved either increasing the concentration of the drug, alteration of the pH of the dispensing medium and/or changes in the viscosity of the vehicle [8], Increasing pilocarpine concentration beyond 4°/o produces no additional ocular hypertensive response [4]. An alter native approach to enhancing therapeutic efficacy and duration of action is by the use of drug delivery systems [1, 7]. The present study describes preliminary results with an ocular pump infusion method of delivering pilocarpine. The initial results disclose significant increases, both in the ocular hypotensive response of glauco matous eyes and the duration of action of this drug.
The 13 patients utilized in this study had documented open angle glaucoma diagnosed by the criteria of elevated intraocular pressure when off medications, open angle on gonioscopy characteristic visual field changes and cupping of the optic nerveheads. All ocular medications were discontinued one week prior to study. Patients were hospitalized for the duration of the study. Diurnal curves of intraocular pressure were performed by repeating applanation tonometry with the Goldmann instrument at 4-hour intervals around the clock. After measurements for 24 h without medication, one eye only received 0.05 ml of 4-percent pilocarpine hydrochloride and the diurnal measurements were repeated. 48 h later, the same eye was treated with pilocarpine pump infusion and the diurnal measurements repeated in an identical fashion.
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Methods and Materials
158
H arris/K ahanowicz
F ig .l. Sage Model 216 infusion pump opened to demonstrate syringe containing medication.
The Sage Model 216 infusion pump is a pocket-sized, battery operated commer cially available apparatus (fig. 1). It can be preset to deliver fluid at a constant rate of from 1 ml/24 h up to 1 ml in 15 min. The fluid to be delivered is contained in a 10-ml syringe within the unit (fig. 1). An electric current is passed from a battery through an electrolyte solution in the upper part of the syringe barrel, generating a gas which causes the piston barrel to eject fluid at the preset rate. In each case, the rate of electrolysis and, thus, the rate of pumping, is controlled by a resistor between the battery and electrodes. PE No. 50 tubing is connected to the pump syringe and run through spectacle frames as indicated in figure 2. With proper adjustment, the distal end of the tubing rest on or near the caruncle where the fluid is discharged and then distributed in the tear film. The drug used in the present study was the commercially available pilocarpine hydrochloride in hydroxpropyl methylcellulose (0.33 °/o).
The tip of the polyethylene tubing resting on or near the caruncle, in most subjects, produced a sensation which was described as 'tickling' but not in any case painful (fig. 2). Preliminary studies demonstrated that most
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 4:45:12 PM
Results
Pump Infusion of Pilocarpine
159
patients could tolerate fluid delivery to the conjunctival sac at a rate of 1 ml/h without developing overflow on the cheek. In an initial group of patients, the pump was used to apply a balanced salt solution and methylcellulose to the conjunctival sac of one eye for 30 min. At the conclusion, patients were examined with the biomicroscope and their intraocular pressures measured. No conjunctival irritation or effect on the intraocular pressure was noted as a result of this procedure. Patients were found to tolerate infusions of pilocarpine up to 40 mg in a 30-min interval without the development of systemic toxicity or ocular side-effects. Doses above this level were not utilized. The change in intraocular pressure of 13 glaucomatous eyes 1 h after a single pump infusion of 40 mg of pilocarpine hydrochloride in a volume of 0.50 ml in 30 min is shown in table I. Striking decline in both the percentage pressure change and the absolute intraocular pressure is noted in 12 of the 13 eyes (table I). In slightly more than half of this group, the intraocular pressure was decreased by 50°/« or more. Maximum efficacy of the pilocarpine is greatly enhanced over single drop administration, or the use of the drug four times daily (table II).
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 4:45:12 PM
Fig. 2. Tip of polyethylene-tubing resting in region of coruncle. Note absence on conjunctival injection and/or irritation.
H arris/K ahanowicz
160
Table I. Initial pressure, fall in pressure, and percentage change in pressure of
13 glaucomatous after pump infusion of 40 mg of pilocarpine Baseline lOP, mm Hg
Fall in absolute lOP, mm Hg
Fall in lOP, «/«
20 34 43 30 40
9 24 31 19 25
45 70 72 63 63
28 40 28 26 38
13 2 11 16 20
46 5 39 62 53
24 25 46 30.25 ± 1.47
6 7 23 15.85 ± 4.33
25 28 50 47.21 ± 7.24
lOP — Intraocular pressure.
Table II. Mean untreated (± SEM) intraocular pressure and fall in ocular pressure and in percentage after single drop of 4-percent pilocarpine, single drop of pilocarpine 4 times daily and after pump infusion of 40 mg of pilocarpine in 30 min
Pilocarpine 4°/o, 1 drop, n 22 Pilocarpine 4 u/o, q.i.d., n = 22 Pilocarpine 4 %, pump, n = 13
Baseline IOP, mm Hg
Fall in IOP, mm Hg
Fall in IOP, °/o
28.45 ± 1.33 26.50 ± 1.90 32.46 ± 2.30
5.39 ± 1.78 6.42 ± 2.19 15.84 ± 2.41
18.78 ± 0.94 26.76 ± 4.12 47.77 ± 14.83
Representative time-action curves for pump infusion of pilocarpine are depicted in figures 3 and 4. Complete dissipation of the ocular hypotensive effect of a single instillation of 4-percent pilocarpine occurred with a mean of 9.31 h in the present study. The marked drop in intraocular pres sure noted after a single pump infusion persisted well beyond 20 h. After
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 4:45:12 PM
IOP = Intraocular pressure.
Pump Infusion of Pilocarpine
4
161
Time, h
Fig. 3. Representative diurnal studies comparing the effects of no treatment (0 )
(X) and to infusion of 40mg of pilocarpine in in the same eye. studies comparing the effects of no treatment < •) (X) and to infusion of 40 mg of pilocarpine in in the same eye.
pump infusion, the mean time to maximal response was 2.17 h and the mean time to return to baseline intraocular pressures was 33.9 h. The mean fall in intraocular pressure after a single instillation of one drop of 4-percent pilocarpine approaches 20% (table II). When this drug is used four times daily, an alteration in intraocular pressure of almost
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 4:45:12 PM
to 0.05 ml 4-percent pilocarpine 30 min (□). All studies performed Fig. 4. Representative diurnal to 0.05 ml 4-percent pilocarpine 30 min (Q)- All studies performed
162
H arris/K ahanowicz
25% is noted (table II). The fall in intraocular pressure seen after a single pump infusion, however, is double that noted by the previous routes of administration (table II).
There have been no meaningful advances in the medical therapy of open angle glaucoma in the almost two decades since the inception of carbonic anhydrase inhibitors. During the ensuing interval, attempts albeit largely unsuccessful, have been made to improve the efficacy and/or duration of action of commonly used anti-glaucomatous medications [8], It would now seem that it is feasible to achieve both of these goals through the usage of newer drug delivery systems [1, 7]. Clinical dose-response patterns have been obtained for cchothiophate iodide, 1-epinephrine and pilocarpine under circumstances of routine clinical usage [5, 7 ]. The mean maximal ocular hypotensive response for each of these drugs is in the range of 25-30%. With each drug a dose exists beyond which no further therapeutic response is achieved [5, 7]. Increasing the drug beyond these ceiling levels, in at least one instance, produced side-effects at a much greater rate than therapeutic efficacy [5]. No experimental evidence exists to explain the augmentation in both magnitude of response and duration of action of pilocarpine after pump infusion. Theoretically, absorption of most drugs proceeds at a varying rate that is proportional to the amount of drug remaining to be absorbed; exponential or first-order kinetics [2]. Under these circumstances, a con stant fraction of the total drug present is absorbed in each time interval. Usually there is a rapid decrease in the amount of drug in the tear film. Therefore, the total amount of drug absorbed per unit time decreases even though the percentage of absorption of the remaining drug is constant. When conditions are altered, drug absorption may be made to proceed at a constant rate independent of the amount of drug to be absorbed (zeroorder kinetics) [2], This mode of absorption may be seen with continuous intravenous infusion or with sustained-release dosage forms. It would be expected that pump infusion of drugs would yield zero-order kinetics of absorption. Most drugs are eliminated by first-order kinetics mechanisms Therefore, the duration of a therapeutically effective dose increases with the logarithm of the dose. It would be expected that getting large amounts of drug into the eye would increase the duration of action.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 4:45:12 PM
Discussion
Pump Infusion of Pilocarpine
163
Using Bionite soft contact lenses, P odos et al. [7J were able to deliver approximately 1 mg of pilocarpine in a 3()-min interval. Pressure control comparable to pilocarpine drops was attained for 23 h. The present study would suggest that increasing the dose may considerably augment not only the duration of action but also the hypotensive effect of this drug. Con tinuous release of pilocarpine with an Ocusert at a rate of 50 //g/h would seem to produce an ocular hypotensive effect comparable to that seen with a single pump infusion at high dosage [1]. Tn the present study, rather striking increases in both the duration of action and efficacy of pilocarpine were obtained by the acute introduction of rather large doses into the conjunctival sac. The dosage of 20 mg of pilocarpine applied in 30-min contrasts with the approximately 8 mg that an eye would receive when one drop of 4-percent pilocarpine was used four times daily. Surprisingly, no evidence of systemic or ocular toxicity was noted at these dose levels. Although patients can readily adjust the tip of the polyethylene tubing into proper position for delivery of drugs, it is unlikely that the ocular pump infusion technique will achieve wide spread clinical utilization. It is far more likely that this technique will find utility as a clinical investigative tool to determine the precise dosages and routes of delivery required for other drug delivery systems, such as soil contact lenses. Summary Pilocarpine was infused into the conjunctival sac of glaucoma patients with the Sage Model 216 pump. Doses as high as 20 mg were given in 30 min without ocular or systemic toxicity. The ocular hypotension effect, in the same group of patients, was doubled over 4-percent pilocarpine drops given four times daily. In addition to increased efficacy the duration of the ocular hypotensive effect was markedly pro longed. Return of ocular pressure to baseline values after a single pump infusion of 20 mg required an average of 33.9 h.
Pilocarpin wurde in den Conjunctivalsack von Patienten mit einem Glaukom mit Hilfe einer Modellpumpe verabreicht. Eine Dosis von 20 mg wurde in 30 Minuten ohne Augen- oder allgemeine Toxizität verabreicht. Der Senkungseffekt in der selben Gruppe der Patienten war doppelt so hoch wie bei 4°/oiger Verabreichung von Tropfen 4x täglich. Zusätzlich zu dieser deutlichen Wirksamkeit dauerte der hypertone Effekt wesentlich länger an. Die Rückkehr des intraokularen Druckes auf die Basiswerte nach einer einfachen Pumpinfusion von 20 mg betrug im Durchschnitt 33,9 Stunden.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 4:45:12 PM
Zusammenfassung
164
H arris/K ahanowicz
Résumé De la pilocarpine a été infusée dans le cul-de-Sac conjonctival de glaucomateux avec la pompe de Sage model 216. Des doses aussi fortes que 20 mg ont été données en 30 minutes sans manifestations oculaires ou systémiques. L'effet hypotensif, sur le même groupe de patients, doubla celui d’un collyre de pilocarpine 4% donné 4 fois par jour. En plus de cette augmentation de l’efficacité, la durée de l’effet hypotenseur oculaire en fut remarquablement prolongé. Le retour aux pressions de base demande en moyenne 33,9 heures après une seule infusion à la pompe.
References 1 A rmaly, M. F. and Rao, K. R.: Effects of pilocarpine ocusert with different
L. S. H arris, MD, Department of Ophthalmology, New York Hospital, Cornell Medical Center, 12E, 68th Street, New York, N Y 10021 (USA)
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 4:45:12 PM
release roles on ocular pressure. Invest. Ophthal. 12: 491-496 (1973). 2 G oldstein , A.; A ronow , L., and K alman, S. M.: Principles of drug action (Harper & Row, London 1969). 3 H aas, J. and M erril , D. L.: The effect of methylccllulose on responses to solution of pilocarpine. Amer. J. Ophthal. 54: 21 (1962). 4 H arris, L. S.; Dose response analysis of pilocarpine-induced ocular hypotension. Arch. Ophthal., Chicago 84: 605-608 (1970). 5 H arris, L. S.: Dose response analysis of echothiophate iodide. Arch. Ophthal., Chicago 86: 502-505 (1971). 6 H avener, W. H.: Ocular pharmacology, p. 404 (Mosby, St. Louis 1970). 7 P odos, S.; Becker , B.; A sseff , C., and H artsetin, J.: Pilocarpine therapy with soft contact lenses. Amer. J. Ophthal. 73: 336-341 (1972). 8 G oldstein , A.; A ronow , L., and K alman, S. M.: Principles of drug action (Harper & Row, London 1968).
Pump Infusion of Pilocarpine L aurence S. H arris and Y affa K ahanowicz Department of Ophthalmology, New York Hospital/Cornell Medical Center, New York, N.Y.
Introduction Attempts to increase the efficacy and/or duration of action of pilo carpine have involved either increasing the concentration of the drug, alteration of the pH of the dispensing medium and/or changes in the viscosity of the vehicle [8], Increasing pilocarpine concentration beyond 4°/o produces no additional ocular hypertensive response [4]. An alter native approach to enhancing therapeutic efficacy and duration of action is by the use of drug delivery systems [1, 7]. The present study describes preliminary results with an ocular pump infusion method of delivering pilocarpine. The initial results disclose significant increases, both in the ocular hypotensive response of glauco matous eyes and the duration of action of this drug.
The 13 patients utilized in this study had documented open angle glaucoma diagnosed by the criteria of elevated intraocular pressure when off medications, open angle on gonioscopy characteristic visual field changes and cupping of the optic nerveheads. All ocular medications were discontinued one week prior to study. Patients were hospitalized for the duration of the study. Diurnal curves of intraocular pressure were performed by repeating applanation tonometry with the Goldmann instrument at 4-hour intervals around the clock. After measurements for 24 h without medication, one eye only received 0.05 ml of 4-percent pilocarpine hydrochloride and the diurnal measurements were repeated. 48 h later, the same eye was treated with pilocarpine pump infusion and the diurnal measurements repeated in an identical fashion.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 4:45:12 PM
Methods and Materials
158
H arris/K ahanowicz
F ig .l. Sage Model 216 infusion pump opened to demonstrate syringe containing medication.
The Sage Model 216 infusion pump is a pocket-sized, battery operated commer cially available apparatus (fig. 1). It can be preset to deliver fluid at a constant rate of from 1 ml/24 h up to 1 ml in 15 min. The fluid to be delivered is contained in a 10-ml syringe within the unit (fig. 1). An electric current is passed from a battery through an electrolyte solution in the upper part of the syringe barrel, generating a gas which causes the piston barrel to eject fluid at the preset rate. In each case, the rate of electrolysis and, thus, the rate of pumping, is controlled by a resistor between the battery and electrodes. PE No. 50 tubing is connected to the pump syringe and run through spectacle frames as indicated in figure 2. With proper adjustment, the distal end of the tubing rest on or near the caruncle where the fluid is discharged and then distributed in the tear film. The drug used in the present study was the commercially available pilocarpine hydrochloride in hydroxpropyl methylcellulose (0.33 °/o).
The tip of the polyethylene tubing resting on or near the caruncle, in most subjects, produced a sensation which was described as 'tickling' but not in any case painful (fig. 2). Preliminary studies demonstrated that most
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 4:45:12 PM
Results
Pump Infusion of Pilocarpine
159
patients could tolerate fluid delivery to the conjunctival sac at a rate of 1 ml/h without developing overflow on the cheek. In an initial group of patients, the pump was used to apply a balanced salt solution and methylcellulose to the conjunctival sac of one eye for 30 min. At the conclusion, patients were examined with the biomicroscope and their intraocular pressures measured. No conjunctival irritation or effect on the intraocular pressure was noted as a result of this procedure. Patients were found to tolerate infusions of pilocarpine up to 40 mg in a 30-min interval without the development of systemic toxicity or ocular side-effects. Doses above this level were not utilized. The change in intraocular pressure of 13 glaucomatous eyes 1 h after a single pump infusion of 40 mg of pilocarpine hydrochloride in a volume of 0.50 ml in 30 min is shown in table I. Striking decline in both the percentage pressure change and the absolute intraocular pressure is noted in 12 of the 13 eyes (table I). In slightly more than half of this group, the intraocular pressure was decreased by 50°/« or more. Maximum efficacy of the pilocarpine is greatly enhanced over single drop administration, or the use of the drug four times daily (table II).
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 4:45:12 PM
Fig. 2. Tip of polyethylene-tubing resting in region of coruncle. Note absence on conjunctival injection and/or irritation.
H arris/K ahanowicz
160
Table I. Initial pressure, fall in pressure, and percentage change in pressure of
13 glaucomatous after pump infusion of 40 mg of pilocarpine Baseline lOP, mm Hg
Fall in absolute lOP, mm Hg
Fall in lOP, «/«
20 34 43 30 40
9 24 31 19 25
45 70 72 63 63
28 40 28 26 38
13 2 11 16 20
46 5 39 62 53
24 25 46 30.25 ± 1.47
6 7 23 15.85 ± 4.33
25 28 50 47.21 ± 7.24
lOP — Intraocular pressure.
Table II. Mean untreated (± SEM) intraocular pressure and fall in ocular pressure and in percentage after single drop of 4-percent pilocarpine, single drop of pilocarpine 4 times daily and after pump infusion of 40 mg of pilocarpine in 30 min
Pilocarpine 4°/o, 1 drop, n 22 Pilocarpine 4 u/o, q.i.d., n = 22 Pilocarpine 4 %, pump, n = 13
Baseline IOP, mm Hg
Fall in IOP, mm Hg
Fall in IOP, °/o
28.45 ± 1.33 26.50 ± 1.90 32.46 ± 2.30
5.39 ± 1.78 6.42 ± 2.19 15.84 ± 2.41
18.78 ± 0.94 26.76 ± 4.12 47.77 ± 14.83
Representative time-action curves for pump infusion of pilocarpine are depicted in figures 3 and 4. Complete dissipation of the ocular hypotensive effect of a single instillation of 4-percent pilocarpine occurred with a mean of 9.31 h in the present study. The marked drop in intraocular pres sure noted after a single pump infusion persisted well beyond 20 h. After
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 4:45:12 PM
IOP = Intraocular pressure.
Pump Infusion of Pilocarpine
4
161
Time, h
Fig. 3. Representative diurnal studies comparing the effects of no treatment (0 )
(X) and to infusion of 40mg of pilocarpine in in the same eye. studies comparing the effects of no treatment < •) (X) and to infusion of 40 mg of pilocarpine in in the same eye.
pump infusion, the mean time to maximal response was 2.17 h and the mean time to return to baseline intraocular pressures was 33.9 h. The mean fall in intraocular pressure after a single instillation of one drop of 4-percent pilocarpine approaches 20% (table II). When this drug is used four times daily, an alteration in intraocular pressure of almost
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 4:45:12 PM
to 0.05 ml 4-percent pilocarpine 30 min (□). All studies performed Fig. 4. Representative diurnal to 0.05 ml 4-percent pilocarpine 30 min (Q)- All studies performed
162
H arris/K ahanowicz
25% is noted (table II). The fall in intraocular pressure seen after a single pump infusion, however, is double that noted by the previous routes of administration (table II).
There have been no meaningful advances in the medical therapy of open angle glaucoma in the almost two decades since the inception of carbonic anhydrase inhibitors. During the ensuing interval, attempts albeit largely unsuccessful, have been made to improve the efficacy and/or duration of action of commonly used anti-glaucomatous medications [8], It would now seem that it is feasible to achieve both of these goals through the usage of newer drug delivery systems [1, 7]. Clinical dose-response patterns have been obtained for cchothiophate iodide, 1-epinephrine and pilocarpine under circumstances of routine clinical usage [5, 7 ]. The mean maximal ocular hypotensive response for each of these drugs is in the range of 25-30%. With each drug a dose exists beyond which no further therapeutic response is achieved [5, 7]. Increasing the drug beyond these ceiling levels, in at least one instance, produced side-effects at a much greater rate than therapeutic efficacy [5]. No experimental evidence exists to explain the augmentation in both magnitude of response and duration of action of pilocarpine after pump infusion. Theoretically, absorption of most drugs proceeds at a varying rate that is proportional to the amount of drug remaining to be absorbed; exponential or first-order kinetics [2]. Under these circumstances, a con stant fraction of the total drug present is absorbed in each time interval. Usually there is a rapid decrease in the amount of drug in the tear film. Therefore, the total amount of drug absorbed per unit time decreases even though the percentage of absorption of the remaining drug is constant. When conditions are altered, drug absorption may be made to proceed at a constant rate independent of the amount of drug to be absorbed (zeroorder kinetics) [2], This mode of absorption may be seen with continuous intravenous infusion or with sustained-release dosage forms. It would be expected that pump infusion of drugs would yield zero-order kinetics of absorption. Most drugs are eliminated by first-order kinetics mechanisms Therefore, the duration of a therapeutically effective dose increases with the logarithm of the dose. It would be expected that getting large amounts of drug into the eye would increase the duration of action.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 4:45:12 PM
Discussion
Pump Infusion of Pilocarpine
163
Using Bionite soft contact lenses, P odos et al. [7J were able to deliver approximately 1 mg of pilocarpine in a 3()-min interval. Pressure control comparable to pilocarpine drops was attained for 23 h. The present study would suggest that increasing the dose may considerably augment not only the duration of action but also the hypotensive effect of this drug. Con tinuous release of pilocarpine with an Ocusert at a rate of 50 //g/h would seem to produce an ocular hypotensive effect comparable to that seen with a single pump infusion at high dosage [1]. Tn the present study, rather striking increases in both the duration of action and efficacy of pilocarpine were obtained by the acute introduction of rather large doses into the conjunctival sac. The dosage of 20 mg of pilocarpine applied in 30-min contrasts with the approximately 8 mg that an eye would receive when one drop of 4-percent pilocarpine was used four times daily. Surprisingly, no evidence of systemic or ocular toxicity was noted at these dose levels. Although patients can readily adjust the tip of the polyethylene tubing into proper position for delivery of drugs, it is unlikely that the ocular pump infusion technique will achieve wide spread clinical utilization. It is far more likely that this technique will find utility as a clinical investigative tool to determine the precise dosages and routes of delivery required for other drug delivery systems, such as soil contact lenses. Summary Pilocarpine was infused into the conjunctival sac of glaucoma patients with the Sage Model 216 pump. Doses as high as 20 mg were given in 30 min without ocular or systemic toxicity. The ocular hypotension effect, in the same group of patients, was doubled over 4-percent pilocarpine drops given four times daily. In addition to increased efficacy the duration of the ocular hypotensive effect was markedly pro longed. Return of ocular pressure to baseline values after a single pump infusion of 20 mg required an average of 33.9 h.
Pilocarpin wurde in den Conjunctivalsack von Patienten mit einem Glaukom mit Hilfe einer Modellpumpe verabreicht. Eine Dosis von 20 mg wurde in 30 Minuten ohne Augen- oder allgemeine Toxizität verabreicht. Der Senkungseffekt in der selben Gruppe der Patienten war doppelt so hoch wie bei 4°/oiger Verabreichung von Tropfen 4x täglich. Zusätzlich zu dieser deutlichen Wirksamkeit dauerte der hypertone Effekt wesentlich länger an. Die Rückkehr des intraokularen Druckes auf die Basiswerte nach einer einfachen Pumpinfusion von 20 mg betrug im Durchschnitt 33,9 Stunden.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 4:45:12 PM
Zusammenfassung
164
H arris/K ahanowicz
Résumé De la pilocarpine a été infusée dans le cul-de-Sac conjonctival de glaucomateux avec la pompe de Sage model 216. Des doses aussi fortes que 20 mg ont été données en 30 minutes sans manifestations oculaires ou systémiques. L'effet hypotensif, sur le même groupe de patients, doubla celui d’un collyre de pilocarpine 4% donné 4 fois par jour. En plus de cette augmentation de l’efficacité, la durée de l’effet hypotenseur oculaire en fut remarquablement prolongé. Le retour aux pressions de base demande en moyenne 33,9 heures après une seule infusion à la pompe.
References 1 A rmaly, M. F. and Rao, K. R.: Effects of pilocarpine ocusert with different
L. S. H arris, MD, Department of Ophthalmology, New York Hospital, Cornell Medical Center, 12E, 68th Street, New York, N Y 10021 (USA)
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 4:45:12 PM
release roles on ocular pressure. Invest. Ophthal. 12: 491-496 (1973). 2 G oldstein , A.; A ronow , L., and K alman, S. M.: Principles of drug action (Harper & Row, London 1969). 3 H aas, J. and M erril , D. L.: The effect of methylccllulose on responses to solution of pilocarpine. Amer. J. Ophthal. 54: 21 (1962). 4 H arris, L. S.; Dose response analysis of pilocarpine-induced ocular hypotension. Arch. Ophthal., Chicago 84: 605-608 (1970). 5 H arris, L. S.: Dose response analysis of echothiophate iodide. Arch. Ophthal., Chicago 86: 502-505 (1971). 6 H avener, W. H.: Ocular pharmacology, p. 404 (Mosby, St. Louis 1970). 7 P odos, S.; Becker , B.; A sseff , C., and H artsetin, J.: Pilocarpine therapy with soft contact lenses. Amer. J. Ophthal. 73: 336-341 (1972). 8 G oldstein , A.; A ronow , L., and K alman, S. M.: Principles of drug action (Harper & Row, London 1968).
