Table 2.

Effective therapeutic approaches. Classification and mechanisms of action of the various effective options for treating GI symptoms experienced by PD patients, depending on efficacy and side effects.

GI symptoms	Classification	Therapeutic approaches	Mechanisms of action	Dosage (adult)	Efficacy (on patients)	Side effects (% of patients)	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 (alone or in combination with psyllium)	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 µg 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 antagonist	Subcutaneous: 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 µg, 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 α2-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:  500 units divided among affected glands		A toxin:  dryness of mouth and mild transitory swallowing difficulties (6%)	Produced by Clostridium botulinum bacterium	[163, 165, 166, 168]
				B toxin:  1,000 units into each parotid gland and 250 units into each submandibular gland		B toxin:  dryness of mouth (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  Use with caution in the elderly; increased risk for anticholinergic effects, confusion, and hallucinations	[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 3 times, daily (maximum: 30 mg/day)	100%	Xerostomia (2%) and headache (1%)	Does not readily cross the BBB ∗ Use the lowest effective dose for the shortest duration necessary  ∗ Not 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; intramuscular: 200 mg,  3 or 4 times daily	20%	Dizziness, headache, blurred vision, and diarrhea	May mask toxicity of other drugs or conditions	[198]

^∗: note.