Effects of pilocarpine on salivary flow in patients with Sjo¨gren's syndrome

Rhodus, Nelson L.; Schuh, Maximilian

doi:10.1016/0030-4220(91)90491-t

Cited by 55 publications

(21 citation statements)

References 6 publications

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“…Similar levels of salivary increase have been previously reported in other groups of patients following head and neck irradiation and in patients suffering from Sjögren's syndrome. [19][20][21]23,24 It is noteworthy that we found a similar response to the medication under both resting and stimulated conditions, and for both major salivary glands and whole saliva. Similarly, under resting and stimulated conditions, whole saliva, parotid and SM/SL flow rates increased by 284%, 230% and 200%, and by 242%, 268% and 248%, respectively (P Ͻ 0.01).…”

Section: Discussionsupporting

confidence: 68%

“…[16][17][18] Some encouraging studies published in recent years have demonstrated the efficacy of oral pilocarpine hydrochloride in partially relieving xerostomia in post-head and neck radiotherapy patients. [19][20][21][22][23][24][25][26][27][28][29] Therefore, we investigated the efficacy of pilocarpine hydrochloride on xerostomia in cGVHD patients. The effect was evaluated by both objective parameters, including sialometric studies, measuring whole saliva and parotid and submandibular flow rates at both resting and stimulated conditions, and by subjective parameters.…”

mentioning

confidence: 99%

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Pilocarpine hydrochloride relieves xerostomia in chronic graft-versus-host disease: a sialometrical study

Nagler

1999

Bone Marrow Transplant

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Summary:Bone marrow transplantation is considered to be the treatment of choice for various hematological and solid malignancies, as well as for bone marrow failure syndromes and some genetic diseases. Unfortunately, a great number of patients who receive allogeneic BMT suffer from graft-versus-host disease (GVHD) following the procedure. Xerostomia is considered to be one of the most annoying complications of chronic GVHD (cGVHD), and the rapidly growing number of BMT patients with prolonged survival renders GVHD-related xerostomia a major clinical problem. As pilocarpine hydrochloride has been shown to relieve xerostomia in other disease categories, we administered pilocarpine hydrochloride 30 mg/day to six cGVHD patients and measured their whole saliva, parotid and submandibular-sublingual flow rates in both resting and stimulated conditions. Mean values of flow rates of whole saliva in resting conditions at 2 weeks, 2 months and 6 months following administration of pilocarpine hydrochloride 30 mg/day were 0.71 ؎ 0.12 ml/min, 0.59 ؎ 0.07 ml/min and 0.56 ؎ 0.11 ml/min, respectively. In stimulated conditions, mean values were 1.7 ؎ 0.3 ml/min, 1.0 ؎ 0.17 ml/min and 0.94 ؎ 0.21 ml/min, respectively. The mean values of whole saliva flow rates under both conditions represented an increase of 224-284% and 134-247%, respectively (P Ͻ 0.01). The pattern and magnitude of parotid and submandibular-sublingual flow rate increases following pilocarpine hydrochloride administration were similar. Patients were followed for 6 months and demonstrated increased levels of secretion, with some reduction after the initial peak values. The medication was discontinued at 2 months and reinstated after 2 weeks in three patients. This resulted in rapid flow rate reduction followed by another profound increase. Contrary to the sialometrical analysis, the subjective scoring showed no fluctuations during the study period. We discuss these results in the context of the clinical experience of xerostomic patients in whom even a minute increase in secretion may be significant. Our results demonstrate that objective and subjective relief from xerostomia in cGVHD patients can be achieved with the routine oral administration of pilocarpine hydrochloride.

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Section: Discussionsupporting

confidence: 68%

mentioning

confidence: 99%

Pilocarpine hydrochloride relieves xerostomia in chronic graft-versus-host disease: a sialometrical study

Nagler

1999

Bone Marrow Transplant

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“…Decreased saliva production caused by Sjö gren's Syndrome and head and neck g-irradiation therapy, among other causes, leads to severe damage within the oral cavity that significantly reduces the quality of life for afflicted patients. Treatments for hyposalivation are limited to medications (e.g., the muscarinic receptor agonists, pilocarpine and cevimeline) that induce saliva secretion from residual acinar cells [1][2][3] and the introduction of artificial saliva. 4 Currently, there are no therapies that can provide permanent relief for afflicted patients.…”

mentioning

confidence: 99%

Growth Factors Polymerized Within Fibrin Hydrogel Promote Amylase Production in Parotid Cells

McCall

Nelson

Leigh

et al. 2013

Tissue Engineering Part A

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Salivary gland cell differentiation has been a recurring challenge for researchers as primary salivary cells show a loss of phenotype in culture. Particularly, parotid cells show a marked decrease in amylase expression, the loss of tight junction organization and proper cell function. Previously, Matrigel has been used successfully as an extracellular matrix; however, it is not practical for in vivo applications as it is tumorigenic. An alternative method could rely on the use of fibrin hydrogel (FH), which has been used extensively in biomedical engineering applications ranging from cardiovascular tissue engineering to wound-healing experiments. Although several groups have examined the effects of a three-dimensional (3D) environment on salivary cell cultures, little is known about the effects of FH on salivary cell cultures. The current study developed a 3D cell culture model to support parotid gland cell differentiation using a combination of FH and growth factor-reduced Matrigel (GFR-MG). Furthermore, FH polymerized with a combination of EGF and IGF-1 induced formation of 3D spheroids capable of amylase expression and an agonist-induced increase in the intracellular Ca 2 + concentration ([Ca 2 + ] i ) in salivary cells. These studies represent an initial step toward the construction of an artificial salivary gland to restore salivary gland dysfunction. This is necessary to reduce xerostomia in patients with compromised salivary function.

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“…They are generally intended to be administered orally. Pilocarpine, a cholinomimetic agent, has shown promise as a salivary stimulant when administered to normal volunteers (Dawes, 1966;Mandel et al, 1968), to patients with xerostomia secondary to radiation therapy (Greenspan and Daniels, 1987;Schuller et al, 1989), and to patients with salivary gland dysfunction and/or Sjogren's syndrome (Fox et al, 1986(Fox et al, , 1991Rhodus and Schuh, 1991).…”

Section: Introductionmentioning

confidence: 97%

Salivary Flow Induction by Buccal Permucosal Pilocarpine in Anesthetized Beagle Dogs

1992

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We tested whether permucosal delivery of pilocarpine nitrate could be used to elicit significant salivary secretion. Pilocarpine (pKa 6.6 at 37 degrees C) was applied as solutions (pHs 5.6, 6.6, 7.6; 15 mg/mL) to the buccal mucosa (2.8 cm2) of 6 anesthetized dogs. Saliva was collected continuously from cannulated submandibular and parotid ducts and blood sampled during and after drug administration. Plasma pilocarpine levels were determined by reversed-phase HPLC. Absorption rates were determined by use of data from separate zero-order intravenous infusions to the same dogs. Pilocarpine was buccally absorbed at a constant rate of 72.9 +/- 38.5 micrograms/kg/h following its application at pH 7.6. At this pH of the drug solution, the time to appearance of pilocarpine in blood plasma was 0.31 +/- 0.08 h, and the time to appearance of salivary flow was 0.86 +/- 0.32 h. A threshold dose of 32.9 +/- 7.5 micrograms/kg was required to induce secretion with the pH 7.6 drug, the steady-state submandibular flow rate was 0.14 +/- 0.11 mL/min/gland pair. Salivary flow induction was symmetrical and reached levels as high as 0.35 mL/min/submandibular gland pair without apparent tachyphylaxis. Results at pHs 5.6, 6.6, and 7.6 were consistent with the hypothesis that pilocarpine is primarily absorbed as un-ionized drug. The data indicate that transmucosal delivery of pilocarpine, avoiding "first pass" hepatic loss, may hold promise for the treatment of xerostomia.

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Effects of pilocarpine on salivary flow in patients with Sjo¨gren's syndrome

Cited by 55 publications

References 6 publications

Pilocarpine hydrochloride relieves xerostomia in chronic graft-versus-host disease: a sialometrical study

Pilocarpine hydrochloride relieves xerostomia in chronic graft-versus-host disease: a sialometrical study

Growth Factors Polymerized Within Fibrin Hydrogel Promote Amylase Production in Parotid Cells

Salivary Flow Induction by Buccal Permucosal Pilocarpine in Anesthetized Beagle Dogs

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