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格隆溴铵是一种类似阿托品的季铵类抗胆碱能药物，具有较强的抑制胃液分泌作用及轻微的胃肠道解痉作用。本药可以调节胃肠蠕动，降低胃液分泌量和游离酸浓度以及抑制气管和支气管的过度分泌。另外，本药还具有比阿托品更强的抗唾液分泌作用，且作用维持时间更长。此外，由于本药的季铵基团限制了它通过诸如血-脑脊液屏障这样的脂细胞膜，所以与中枢神经系统相关的不良反应发生极少。本药比等量的阿托品效力强5～6倍；其抗流涎作用较阿托品为佳，镇静作用较东莨菪碱轻；其加速心率、视力模糊，发热等不良反应较阿托品轻；延迟性瞳孔散大在阿托品全身用药时较为显著，但本药仅会引起很小的变化；本药与新斯的明合用纠正竞争性肌肉松弛药过量，与阿托品合用新斯的明相比，心动过速出现较少，止涎作用较佳。
分类名称
一级分类：神经系统药物 二级分类：作用于自主神经系统的药物 三级分类：抗胆碱药
药品英文名
Glycopyrronium Bromide
药品别名
甘罗溴铵、甘罗溴胺、格隆溴胺、胃长宁、溴环扁吡酯、甲比戊痉平、Glycopyrrolate Bromide、Robinul
药物剂型
1.片剂：0.25mg，0.5mg，1mg，2mg；2.胶囊：0.5mg；3.注射剂：0.2mg(1ml)。
药理作用
本药是一种类似阿托品的季铵类抗胆碱能药物，具有较强的抑制胃液分泌作用及轻微的胃肠道解痉作用。本药可以调节胃肠蠕动，降低胃液分泌量和游离酸浓度以及抑制气管和支气管的过度分泌。另外，本药还具有比阿托品更强的抗唾液分泌作用，且作用维持时间更长。此外，由于本药的季铵基团限制了它通过诸如血-脑脊液屏障这样的脂细胞膜，所以与中枢神经系统相关的不良反应发生极少。本药比等量的阿托品效力强5～6倍；其抗流涎作用较阿托品为佳，镇静作用较东莨菪碱轻；其加速心率、视力模糊，发热等不良反应较阿托品轻；延迟性瞳孔散大在阿托品全身用药时较为显著，但本药仅会引起很小的变化；本药与新斯的明合用纠正竞争性肌肉松弛药过量，与阿托品合用新斯的明相比，心动过速出现较少，止涎作用较佳。
药动学
本药口服给药生物利用度低，仅10%～25%吸收。肌注后10min达最大血药浓度，迷走阻滞作用持续2～3h，抑制腺体分泌作用可持续约7h；儿童口服后90min达最大血药浓度。本药不易透过血-脑脊液屏障，在脑脊液和胎盘中浓度低。本药48.5%经肾排泄，少量以原形经胆汁排泄，是否排泄入乳汁尚不清楚。静脉注射后1min内即可起效。
适应证
1.用于胃肠痉挛，胃溃疡及十二指肠溃疡、慢性胃炎、胃液分泌过多等。
2.静注或肌注可用于麻醉前给药以抑制腺体分泌。
3.用于减少抗神经肌肉阻滞剂引起的不良反应。
4.治疗多汗症和支气管痉挛。
禁忌证
1.幽门梗阻。
2.青光眼。
3.前列腺肥大。
4.对本药及其他抗胆碱能药物过敏者。
5.重症肌无力。
6.麻痹性肠梗阻或肠弛缓。
7.反流性食管炎。
8.溃疡性结肠炎或中毒性巨结肠症。
9.急性出血导致的心血管状态不稳定。
10.梗阻性尿路病变。
注意事项
1.慎用：
(1)自主神经功能障碍；
(2)充血性心力衰竭；
(3)冠心病；
(4)高血压；
(5)甲状腺功能亢进；
(6)回肠造口术或结肠造瘘术；
(7)心动过速；
(8)轻度肝、肾疾病；
(9)儿童和老年患者。
2.药物对妊娠的影响：
(1)本药0.004mg/kg的剂量可加快孕妇的心率，但对胎儿的心率无影响。且孕妇的血压和子宫收缩无明显改变。分娩时需用抗胆碱药治疗时，适用本药；
(2)已有研究表明，与未孕妇女相比，本药对孕妇(妊娠头三个月)的胃排空影响更大。
3.药物对哺乳的影响：本药可能引起泌乳的减少。
4.用药前后及用药时应当检查或监测：
(1)注意监测胃内容物量和pH值；
(2)用药过程中应监测心电图以预防心律失常的发生；
(3)观察胃肠疼痛或其他消化性溃疡症状的缓解；
(4)观察唾液、气管、支气管及咽部的分泌减少的情况；
(5)观察本药不良反应出现的情况。
(6)警惕过敏反应的出现。
5.用药期间应避免驾驶或从事具有潜在危险的工作。
6.本药不能与碱性药物混合。
不良反应
1.心血管系统：可引起心律失常。
2.中枢神经系统：可引起头痛、头晕、嗜睡、失眠、精神错乱。由于本药不能通过血-脑脊液屏障，故由其引起的中枢神经系统不良反应比其他抗胆碱能药少。
3.内分泌/代谢系统：本药可能引起泌乳的减少。
4.消化系统：
(1)本药的抗胆碱能特性可使食管下段括约肌松弛，降低食管下端压力，增加胃食管反流的可能性。其作用持续时间比阿托品长，且抗唾液分泌作用比阿托品更强，因此本药引起反流的可能性就更高；
(2)服药初期可出现口干(口苦)现象，在一到两周内可减轻或消失；
(3)本药还可能引起味觉丧失。
5.泌尿生殖系统：本药可能引起勃起功能障碍。
6.眼：国外有资料报道，本药大剂量会引起瞳孔放大，但还未发现本药常用剂量肌内注射或静脉注射会引起散瞳。此外，本药还可能引起睫状肌麻痹。
7.皮肤：本药可引起出汗减少，在环境温度高时可能导致发热和热衰竭。此外本药还可引起荨麻疹。
8.骨骼/肌肉：本药可引起神经肌肉阻滞并导致肌无力或瘫痪。
9.致畸性/对妊娠的影响：美国食品和药品管理局的妊娠危险性分类为B级。
10.其他：本药可引起过敏反应。
用法用量
1.口服给药：每次1～2mg，每天3～4次，饭后及睡前服。维持量为每次1mg，每天2次。单次极量4mg，每天极量12mg。
2.肌内注射：用于麻醉前给药，肌注0.2～0.4mg。
3.静脉注射：用于麻醉前给药，静注0.2～0.4mg。4.术前用药：为了抵消手术期间药物所致或迷走牵引反射伴随的心律失常(如心动过缓)可静脉注射0.1mg。
5.用于消化性溃疡：可口服1～2mg，每天2～3次。
药物相应作用
1.本药与普鲁卡因胺合用时，可对房室结传导产生相加的抗迷走神经效应，其机制可能为两者药理作用的相互叠加。
2.本药与西沙必利合用时，可减弱西沙必利的促胃肠动力作用。
3.本药与利托君合用时，可导致室上性心动过速。
4.本药与环丙烷同时应用于麻醉治疗时可引起室性心律失常。
5.用药期间饮酒可使患者注意力下降。
专家点评
本品为抗胆碱药。临床很少用药。能选择性作用胃肠道，有较强抑制胃液分泌作用。用于溃疡病、胃炎、胃酸过多症等。本品为季铵抗毒蕈碱药。其周围作用类似阿托品。但本品抑制腺体分泌作用较强，临床多用于麻醉前给药，亦可作为消化性溃疡和缓解内脏痉挛的辅助药。
ROBINUL - glycopyrrolate tablet
ROBINUL FORTE - glycopyrrolate tablet
Shionogi Pharma, Inc.
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Robinul and Robinul Forte
Robinul® and Robinul® Forte
(Glycopyrrolate Tablets, USP)
Rx Only
DESCRIPTION
Robinul® and Robinul® Forte tablets contain the synthetic anticholinergic, glycopyrrolate. Glycopyrrolate is a quaternary ammonium compound with the following chemical name: 3-[(cyclopentylhydroxyacetyl)oxy]-1,1-dimethylpyrrolidinium bromide.
Robinul tablets are scored, compressed white tablets engraved HPC 200. Each tablet contains:
Glycopyrrolate, USP………..1 mg
Robinul Forte tablets are scored, compressed white tablets engraved HORIZON 205. Each tablet contains:
Glycopyrrolate, USP……….2 mg
Inactive Ingredients: Dibasic Calcium Phosphate, Lactose, Magnesium Stearate, Povidone, Sodium Starch Glycolate
ACTIONS
Glycopyrrolate, like other anticholinergic (antimuscarinic) agents, inhibits the action of acetylcholine on structures innervated by postganglionic cholinergic nerves and on smooth muscles that respond to acetylcholine by lack cholinergic innervation. These peripheral cholinergic receptors are present in the autonomic effector cells of smooth muscle, cardiac muscle, the sino-atrial node, the atrioventricular node, exocrine glands, and, to a limited degree, in the autonomic ganglia. Thus, it diminishes the volume and free acidity of gastric secretions and controls excessive pharyngeal, tracheal, and bronchial secretions.
Glycopyrrolate antagonizes muscarinic symptoms (e.g., bronchorrhea, bronchospasm, bradycardia, and intestinal hypermotility) induced by cholinergic drugs such as the anticholinesterases.
The highly polar quaternary ammonium group of glycopyrrolate limits its passage across lipid membranes, such as the blood-brain barrier, in contrast to atropine sulfate and scopolamine hydrobromide, which are non-polar tertiary amines which penetrate lipid barriers easily.
INDICATIONS
For use as adjunctive therapy in the treatment of peptic ulcer.
CONTRAINDICATIONS
Glaucoma; obstructive uropathy (for example, bladder neck obstruction due to prostatic hypertrophy); obstructive disease of the gastrointestinal tract (as in achalasia, pyloroduodenal stenosis, etc.); paralytic ileus; intestinal atony of the elderly or debilitated patient; unstable cardiovascular status in acute hemorrhage; severe ulcerative colitis; toxic megacolon complicating ulcerative colitis; myasthenia gravis. Robinul (glycopyrrolate) tablets are contraindicated in those patients with a hypersensitivity to glycopyrrolate.
WARNINGS
In the presence of a high environmental temperature, heal prostration (fever and heat stroke due to decreased sweating) can occur with the use of Robinul.
Diarrhea may be an early symptom of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy. In this instance treatment with this drug would be inappropriate and possibly harmful.
Robinul (glycopyrrolate) may produce drowsiness or blurred vision. In this event, the patient should be warned not to engage in activities requiring mental alertness such as operating a motor vehicle or other machinery, or performing hazardous work while taking this drug.
Theoretically, with overdosage, a curare-like action may occur, i.e., neuro-muscular blockade leading to muscular weakness and possible paralysis.
Pregnancy
The safety of this drug during pregnancy has not been established. The use of any drug during pregnancy requires that the potential benefits of the drug be weighed against possible hazards to mother and child. Reproduction studies in rats revealed no teratogenic effects from glycopyrrolate; however, the potent anticholinergic action of this agent resulted in diminished rates of conception and of survival at weaning, in a dose-related manner. Other studies in dogs suggest that this may be due to diminished seminal secretion which is evident at high doses of glycopyrrolate. Information on possible adverse effects in the pregnant female is limited to uncontrolled data derived from marketing experience. Such experience has revealed no reports of teratogenic or other fetus-damaging potential. No controlled studies to establish the safety of the drug in pregnancy have been performed.
Nursing Mothers
It is not know whether this drug is excreted in human milk. As a general rule, nursing should not be undertaken while a patient is on a drug since many drugs are excreted in human milk.
Pediatric Use
Since there is no adequate experience in pediatric patients who have received this drug, safety and efficacy in pediatric patients have not been established.
PRECAUTIONS
Use Robinul with caution in the elderly and in all patients with:
- Autonomic neuropathy.
- Hepatic or renal disease.
- Ulcerative colitis - large doses may suppress intestinal motility to the point of producing a paralytic ileus and for this reason may precipitate or aggravate the "toxic megacolon," a serious complication of the disease.
- Hyperthyroidism, coronary heart disease, congestive heart failure, cardiac tachyarrhythmias, tachycardia, hypertension and prostatic hypertrophy.
- Hiatal hernia associated with reflux esophagitis, since anticholinergic drugs may aggravate this condition.
ADVERSE REACTIONS
Anticholinergics produce certain effects, most of which are extensions of their fundamental pharmacological actions. Adverse reactions to anticholinergics in general may include xerostomia; decreased sweating; urinary hesitancy and retention; blurred vision; tachycardia; palpitations; dilation of the pupil; cycloplegia; increased ocular tension; loss of taste; headaches; nervousness; mental confusion; drowsiness; weakness; dizziness; insomnia; nausea; vomiting; constipation; bloated feeling; impotence; suppression of lactation; severe allergic reaction or drug idiosyncrasies including anaphylaxis, urticaria and other dermal manifestations.
Robinul (glycopyrrolate) is chemically a quaternary ammonium compound; hence, its passage across lipid membranes, such as the blood-brain barrier, is limited in contrast to atropine sulfate and scopolamine hydrobromide. For this reason the occurrence of CNS related side effects is lower, in comparison to their incidence following administration of anticholinergics which are chemically tertiary amines that can cross this barrier readily.
OVERDOSAGE
The symptoms of overdosage of glycopyrrolate are peripheral in nature rather than central.
- To guard against further absorption of the drug - use gastric lavage, cathartics, and/or enemas.
- To combat peripheral anticholinergic effects (residual mydriasis, dry mouth, etc.) - utilize a quaternary ammonium anticholinesterase, such as neostigmine methylsulfate.
- To combat hypotension - use pressor amines (norepinephrine, metaraminol) i.v.; and supportive care.
- To combat respiratory depression - administer oxygen; utilize a respiratory stimulant such as Dopram® i.v.; artificial respiration.
DOSAGE AND ADMINISTRATION
The dosage of Robinul® or Robinul® Forte should be adjusted to the needs of the individual patient to assure symptomatic control with a minimum of adverse reactions. The presently recommended maximum daily dosage of glycopyrrolate is 8 mg.
Robinul (glycopyrrolate, 1 mg) tablets. The recommended initial dosage of Robinul for adults is one tablet three times daily (in the morning, early afternoon, and at bedtime). Some patients may require two tablets at bedtime to assure overnight control of symptoms. For maintenance, a dosage of one tablet twice a day is frequently adequate.
Robinul Forte (glycopyrrolate, 2 mg) tablets. The recommended dosage of Robinul Forte for adults is one tablet two or three times daily at equally spaced intervals.
Robinul tablets are not recommended for use in pediatric patients under the age of 12 years.
DRUG INTERACTIONS
There are no known drug interactions.
HOW SUPPLIED
Robinul® (glycopyrrolate, 1 mg) tablets in bottles of 100 (NDC 59630-200-10).
Robinul® Forte (glycopyrrolate, 2 mg) tablets in bottles of 100 (NDC 59630-205-10).
Store at controlled room temperature, 20˚C to 25˚C (68˚F to 77˚F); excursions permitted to 15˚C-30˚C (59˚F-86˚F) [See USP Controlled Room Temperature]. Keep out of reach of children.
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