GI symptoms Classification Therapeutic approaches Mechanisms of action Dosage Efficacy Side effects Comments Studies Constipation (1) Use with caution Tricyclic antidepressants Anticholinergic side effects [15 , 52 ] Antimuscarinics Anticholinergic side effects [15 , 52 ] Opioids Anticholinergic side effects [15 , 52 ] (2) Nonpharmacological options Exercise Intestinal stimulation by movements, increased fluids, and muscular mass [6 , 16 , 32 ] Dietary fibers [6 , 16 , 32 ] Increased fluid uptake [6 , 16 , 32 ] (3) Laxatives Macrogol (polyethylene glycol) Passes through the gut without being absorbed and digested by enzymes, causing retention of water in the intestinal tube Oral: 17 g (~1 tablespoon) dissolved in 240 mL of water or juice once daily Abdominal bloating, cramping, diarrhea, flatulence, and nausea Do not use for >1-2 weeks [121 , 189 ] Lactulose Passes through the gut without being absorbed and digested by enzymes, causing retention of water in the intestinal tube Oral or rectal: 10 to 20 g, daily Abdominal discomfort and distention, belching, cramping, diarrhea (excessive dose), flatulence, nausea, and vomiting [190 ] Magnesium sulfate Blocks peripheral muscular contractions and neurotransmission Oral: 2–4 level teaspoons of granules dissolved in 240 mL of water; may repeat in 6 hours Hypermagnesemia, flushing, hypotension, and vasodilatation Do not exceed 2 doses per day [191 ] Bisacodyl Stimulates enteric nerves to cause colonic contractions Oral or rectal: 5–15 mg as single dose <1% : abdominal mild cramps, metabolic acidosis or alkalosis, hypocalcemia, nausea, rectal irritation, vertigo, and vomiting [124 ] Sodium picosulfate Stimulates peristalsis and promotes water and electrolytes accumulation in the colon Oral: 150 mL in the evening before the colonoscopy, followed by a second dose ~5 hours before the procedure Hypermagnesemia (12% ), hypokalemia (7% ), increased serum creatinine (5% ), hypochloremia (4% ), hyponatremia (4% ), headache (3% ), nausea (3% ), and vomiting (1% ) Mainly used for colonoscopy procedure [124 ] Docusate sodium Unclear; may inhibit fluids absorption or stimulate secretion in jejunum Oral: 50 to 360 mg, once daily or in divided doses Throat irritation (1 to 10% ) [192 ] Senna acutifolia Reduces fluid absorption from the faeces and influences fluid secretions by the colon Long-term use is not recommended [126 ] (4) Other pharmacological options Lubiprostone Intestinal ClC-2 chloride channel activator Oral: 24 µ g twice daily 64% Intermittent loose stools (48% ), nausea (29% ), diarrhea (12% ), abdominal pain (8% ), flatulence (6% ), dizziness (3% ), and vomiting (3% ) [126 , 127 ] Methylnaltrexone µ -Opioid antagonistSubcutaneous: 12 mg, once daily 60% Abdominal pain (45% ), flatulence (33% ), diarrhea (30% ), and nausea (24% ) Discontinue all laxatives prior to use; if response is not optimal after 3 days, laxative therapy may be reinitiated [128 ] Linaclotide Guanylate cyclase C agonist Oral: 145 µ g, once daily Abdominal cramping (4% ), discomfort (4% ), and diarrhea (4% ) Contraindicated in pediatric patients (<6 years of age) [129 , 130 , 193 ] Drooling and dysphagia (1) Use with caution Cholinesterase inhibitors [51 ] Clozapine Serotonin antagonist Demonstrated effectiveness against dyskinesias [51 , 161 , 194 ] Yohimbine Presynaptic α 2-adrenergic blocking agent [51 , 162 ] Quetiapine D2 receptors (mesolimbic pathway) and 5HT2A (frontal cortex) antagonist Demonstrated effectiveness against dyskinesias [51 , 195 ] (2) Nonpharmacological options Chewing gum or sucking on hard candy 5 times improved [158 ] Speech and position therapy Self-motivation is an important factor to obtain a positive outcome [159 , 160 ] (3) Pharmacological options Botulinum toxin A/B injections (parotid and submandibular glands) Inhibits the cholinergic parasympathetic and postganglionic sympathetic activity A toxin: A toxin: 6% )Produced by Clostridium botulinum bacterium [163 , 165 , 166 , 168 ] B toxin: B toxin: 40% ), worsened gait (25% ), diarrhea (15 %), neck pain (15% ), and mild transitory swallowing difficulties (16% )[50 , 163 , 167 ] Atropine ophthalmic drops (sublingual administration) Anticholinergic that blocks muscarinic receptor M3 1 drop of 1% atropine solution, twice daily for 1 week Hallucinations (29 %) and delirium (14% ) Lack of clinical evidence for treatments lasting longer than a few weeks [170 ] Glycopyrrolate Anticholinergic that blocks muscarinic receptor M3 Oral: 1 mg 3 times, daily 95 to 100% Dry mouth (52% ), urinary retention (13% ), vision problems (13% ), constipation (13% ), and nausea (4% ) [171 , 172 , 174 , 175 ] Nausea, vomiting and gastroparesis (1) Use with caution High-fat foods [31 ] Metoclopramide Dopamine antagonist Contraindicated for PD patients because it worsens motor symptoms by blocking dopamine receptors in the CNS [31 ] (2) Nonpharmacological options Small and frequent meals [31 ] Drinking during meals [31 ] Walking after meals [31 ] (3) Pharmacological options Domperidone Dopamine antagonist Oral: initiating at 10 mg daily (maximum: 30 mg/day) 100% Xerostomia (2% ) and headache (1% ) Does not readily cross the BBB the lowest effective dose for the shortest duration necessary available in the United States [149 , 196 , 197 ] Trimethobenzamide Unclear; most likely involves the chemoreceptor trigger zone (through which emetic impulses are transported to the vomiting center) Oral: 300 mg;3 or 4 times daily 20% Dizziness, headache, blurred vision, and diarrhea May mask toxicity of other drugs or conditions [198 ]
