GI Meds - Laxatives PDF

GI MEDICATIONS LAXATIVES DEBRA FORZESE, PHARM. D. L A X AT I V E S Bulk forming Psyllium (Metamucil) Methylcellulose (Citrucel) Stool softener Docusate (Colace) Osmotic Magnesium citrate Lactulose Stimulant Senna Bisacodyl L A X AT I V E S Act directly on the gut to increase stool frequency or ease...

GI MEDICATIONS LAXATIVES DEBRA FORZESE, PHARM. D. L A X AT I V E S Bulk forming Psyllium (Metamucil) Methylcellulose (Citrucel) Stool softener Docusate (Colace) Osmotic Magnesium citrate Lactulose Stimulant Senna Bisacodyl L A X AT I V E S Act directly on the gut to increase stool frequency or ease stool passage Used to treat chronic constipation (difficult/infrequent stool passage, symptoms > 3 months) Different types of laxatives act by different mechanisms T R E AT M E N T G U I D E L I N E S F O R C O N ST I PAT I O N American Gastroenterological Association (2013) Stop medications causing/contributing to constipation Gradual increase in fiber intake o Foods, supplements Osmotic agents – milk of magnesia, polyethylene glycol BULK FORMING L A X AT I V E S B U L K F O R M I N G L A X AT I V E S Psyllium (Metamucil) Methylcellulose (Citrucel) Calcium polycarbophil (Fibercon) Wheat dextrin (Benefiber) B U L K F O R M I N G L A X AT I V E S Absorb water and increase fecal mass Stimulates natural contractions of the intestine Bulkier stools with more water easier to pass Important to drink plenty of fluids to optimize effects, lack of water can increase bloating and cause bowel obstruction B U L K F O R M I N G L A X AT I V E S Indications o Treatment of occasional constipation o Dietary fiber supplement PSYLLIUM Pharmacokinetic/pharmacodynamic factors o Not absorbed in GI tract o Not metabolized o Onset of action 12-72 hours Undergoes bacterial fermentation in the colon, producing gas and bloating Powder formulations are gritty even when mixed in liquids, not always well tolerated PSYLLIUM Dosing – increase dose gradually, ensure adequate water intake Renal impairment – no dose reduction Hepatic impairment – no dose reduction Adverse Effects GI – abdominal cramps, constipation, diarrhea Hypersensitivity - anaphylaxis PSYLLIUM Warnings Should be taken with at least 8 oz of fluid to prevent choking Drug Interactions No significant interactions known Pregnancy Use considered safe, not absorbed systemically STOOL SOFTENERS ( S U R FA C TA N T S ) STO O L S O F T E N E R S - D O C U S AT E Indication Prevention of straining during defecation associated with hard dry stools, Relief of occasional constipation Mechanism of Action Lowers surface tension of the stool, allows water to easily enter the stool Marginal efficacy D O C U S AT E Pharmacokinetics/Pharmacodynamic Factors No absorption, no metabolism Onset of action 12-72 hours Available in 2 different salt formulations – docusate sodium, docusate calcium Formulations – tablet, capsule, oral solution, enema D O C U S AT E No dose adjustment with renal or hepatic impairment Adverse effects o Abdominal cramping o Diarrhea o Throat irritation (from liquid) Drug interactions – no significant interactions D O C U S AT E Pregnancy – category C Breastfeeding – considered acceptable OSMOTIC L A X AT I V E S O S M OT I C L A X AT I V E AG E N T S Polyethylene Glycol 3350 (Miralax) Lactulose (Enulose) Magnesium Citrate, Milk of Magnesia P O LY E T H Y L E N E G LY C O L 3 3 5 0 Indication Treatment of occasional constipation Dosing 17 grams – powder measured using cap that comes with powder Do not use in children less than 17 years without provider (FDA approval for 17 years and older) Renal/Hepatic impairment – no dose reduction P O LY E T H Y L E N E G LY C O L 3 3 5 0 Mechanism of Action Draws water into the stool, resulting in softer stools and more frequent stools, easier to pass Pharmacokinetic/Pharmacodynamic Factors Onset of action 24-96 hours Minimal absorption Powder formulation – mix in liquid (4-8 oz), dose measured using dosing cap that comes with powder P O LY E T H Y L E N E G LY C O L 3 3 5 0 Adverse reactions Abdominal cramps, abdominal distention, bloating, diarrhea Hypersensitivity – anaphylaxis Contraindications Known or suspected bowel obstruction P O LY E T H Y L E N E G LY C O L 3 3 5 0 Warnings Electrolyte imbalance – from prolonged, excessive use It may take up to 2-4 days to produce bowel movement Pediatric concerns – FDA has received reports of metabolic acidosis and neuropsychiatric events (seizures, anxiety, obsessive-compulsive behaviors) – not enough data to establish direct causality with drug Drug Interactions Digoxin – propylene glycol can reduce digoxin levels P O LY E T H Y L E N E G LY C O L 3 3 5 0 Pregnancy – minimal systemic absorption, considered safe Breastfeeding - safe LACTULOSE Indication Treatment of constipation Dosing No dose reduction in renal or hepatic impairment LACTULOSE Mechanism of Action Non-absorbable synthetic disaccharide composed of galactose and fructose Metabolized in the colon by bacteria, producing osmotic effect, causes distention resulting in peristalsis Pharmacokinetic/Pharmacodynamic Factors Can take up to 24 – 48 hours to produce a normal bowel movement Poorly absorbed, effects localized in the gut Can be diluted and used via rectal route LACTULOSE Adverse reactions Diarrhea Flatus Bloating Contraindications Patients that need low galactose diet LACTULOSE Warnings Electrolyte imbalance – monitor electrolytes periodically, hepatic disease may increase risk Use caution in diabetics – galactose and lactose may increase blood sugar Chronic use may lead to electrolyte imbalances in infants LACTULOSE Pregnancy – may be used when an osmotic laxative is needed Breastfeeding – manufacturer recommends use cautiously Monitoring BP Electrolytes Frequency of bowel movements Fluid status Serum ammonia STIMULANT L A X AT I V E S ST I M U L A N T L A X AT I V E S Anthraquinones - Senna Diphenylmethanes - Bisacodyl ST I M U L A N T L A X AT I V E S Increase both intestinal motility and intestinal secretion – affects electrolyte transport across intestinal mucosa, decrease absorption of water from the lumen of the bowel Work within hours and frequently associated with abdominal cramps Dose dependent effects Sometimes abused in patients with eating disorder Well tolerated if used in recommended doses for temporary constipation SENNA Indication Occasional constipation Dosing Other agents are preferred for maintenance therapy May be used for additional or second line therapy for short term use Pediatric issues – several formulations exist and not all are equivalent, pay attention to product concentration; approved ages for generic products may vary (see product labeling) SENNA Pharmacokinetic/Pharmacodynamic Factors Onset of action – within 6 to 24 hours Metabolized in the liver Adverse Effects Abdominal cramps, diarrhea, nausea, vomiting SENNA Warnings Failure to have bowel movement or rectal bleeding should be reported to health care provider Not recommended for use inpatient with stomach pain, nausea/vomiting, or sudden change in bowel movements lasting longer than 2 weeks OTC use not recommended in children less than 2 years of age SENNA Pregnancy – other agents recommended for use in pregnancy due to increased risk of adverse effects such as electrolyte abnormalities Breastfeeding – acceptable when used in recommended doses M I S C E L L A N E O U S L A X AT I V E S M I S C E L L A N E O U S L A X AT I V E S Chloride secretion activator Opiod receptor antagonist (peripheral) Seratonin 5-HT4-receptor agonist C H LO R I D E S E C R E T I O N AC T I VATO R LUBIPROSTONE(AMITZA) Chloride channels in the GI tract play an important role in fluid transport, cell volume, intracellular pH Lubiprostone – prostone derived from prostaglandin E1 Metabolized within GI tract Acts locally within GI tract LUBIPROSTONE Indication Chronic idiopathic constipation Irritable bowel syndrome with constipation (females 18 years and older) Opiod induced constipation No dose adjustment in renal or hepatic impairment LUBIPROSTONE Pharmacokinetic/Pharmacodynamic Factors Poorly absorbed Minimal distribution beyond GI tract Rapid and extensive metabolism within GI tract Adverse Effects Diarrhea Nausea Headache LUBIPROSTONE Contraindication Known or suspected mechanical GI obstruction Warnings Dyspnea Nausea – administer with food Syncope/hypotension LUBIPROSTONE Pregnancy – studies suggest adverse effects Breastfeeding – according to manufacturer, decision to continue or discontinue breastfeeding during therapy should take into account the risk of infant exposure, benefits of breastfeeding to the infant, and benefits of treatment to the mother PERIPHERAL ACTING MU RECEPTOR A N TAG O N I ST S Methylnatrexone (Relistor) Naloxegol (Movantik) Naldemedine (Symproic) M E T H Y L N A LT R E X O N E Indications Opiod-induced constipation with advanced illness (injection only) Opiod-induced constipation with chronic non-cancer pain (tablets, injection) Dosing - Adults Renal impairment – dose reduction Hepatic impairment – no dose adjustments per manufacturer, consider dose reduction with severe impairment M E T H Y L N A LT R E X O N E Mechanism of Action Blocks opiod binding at the mu receptor, derivative of naltrexone with limited ability to cross BBB Peripheral acting opiod antagonist, inhibits opiod induced decrease in GI motility and delays GI transit time, reducing opiod induced constipation M E T H Y L N A LT R E X O N E Pharmacokinetic/Pharmacodynamic Factors Half life 15 hours Excreted mostly in urine as unchanged drug Adverse Effects Dizziness, headache Diarrhea, abdominal distention M E T H Y L N A LT R E X O N E Contraindications GI obstruction Warnings Diarrhea – discontinue treatment for severe or persistent diarrhea GI perforation – monitor for persistent, worsening abdominal pain Opiod withdrawal – may precipitate symptoms of opiod withdrawal S E R ATO N I N 5 - H T 4 - R E C E P TO R AGONISTS Cisapride (Propulsid) Tegaserod (Zelnorm) – emergency use Prucalopride (Motegrity) PRUCALOPRIDE Highly selective for seratonin type 4 receptor Minimal activity against other seratonin receptors (different from cisapride, tegaserod) PRUCALOPRIDE Indications Opiod induced constipation in patients with noncancer chronic pain in adults Dosing Consider adjunctive laxative therapy if no bowel movement within 3 or more consecutive days PRUCALOPRIDE Mechanism of Action Selective 5-HT4 receptor agonist causes stimulation of the peristaltic reflex, intestinal secretions, and GI motility PRUCALOPRIDE Pharmacokinetic/Pharmacodynamic Factors Rapid absorption Half life 24 hours Time to peak 2-3 hours PRUCALOPRIDE Adverse effects Abdominal pain, nausea, diarrhea Headache , dizziness Contraindications Intestinal perforation or obstruction, obstructive ileus, severe inflammatory conditions of GI tract such as Crohn disease, ulcerative colitis PRUCALOPRIDE Warnings CNS effects – caution patients about driving, etc. Diarrhea – sometimes severe Suicidal ideation – suicide, suicide attempts reported; watch for worsening depression within first few weeks of therapy, discontinue drug if any symptoms PRUCALOPRIDE Pregnancy Data is limited, spontaneous abortions observed in clinical trials Breastfeeding Present in breastmilk Per manufacturer, decision to breastfeed during therapy should consider the risk of infant exposure, benefits of breastfeeding to the infant, benefits of treatment to the mother