Constipation Pathophysiology Lecture 2024 PDF

Constipation PHM101 Foundations and General Medicine February 2, 2024 S. Yamashita BScPhm, Pharm.D., FCSHP Clinical Coordinator, Critical Care Sunnybrook Health Sciences Centre Constipation – Learning Objectives Understand the epidemiology,...

Constipation PHM101 Foundations and General Medicine February 2, 2024 S. Yamashita BScPhm, Pharm.D., FCSHP Clinical Coordinator, Critical Care Sunnybrook Health Sciences Centre Constipation – Learning Objectives Understand the epidemiology, pathophysiology, clinical presentation and risk factors for constipation Identify common drug-induced causes of constipation and how these drugs cause or worsen constipation Discuss nonpharmacologic options used in the prevention and treatment of constipation State the main laxative classes and list examples Compare and contrast each class of laxatives with respect to pharmacology, indications, efficacy, onset, adverse effects, contraindications, drug interactions, convenience and cost  Why do I need to know this? A patient walks into the pharmacy during your EPE rotation and asks for your recommendation on a laxative – What would you recommend? – Are there any questions you would ask before making your recommendation? A patient walks in with a prescription for hydromorphone 2 mg po q4h and 1-2 mg q2h prn – What counselling information would you provide the patient? – What prophylactic therapy would you recommend for this patient? What is considered to be a “normal” frequency for bowel movements? A. One per day B. One per week C. Once per month D. Variable from person to person  Constipation - Definition “ A bowel disorder characterized by difficult, infrequent, or seemingly incomplete defecation that does not meet the criteria for irritable bowel syndrome” – Fewer than 3 BM’s/week – > 3 days without a BM – Straining > 25% of the time  Constipation Common – North America: 1.9 – 27% (12-19%) – More common in females, elderly Can be associated with serious complications Our obsession with bowel function can lead to laxative abuse  Constipation Primary – No identifiable cause Secondary – Due to lifestyle, medical disorders, drugs  Constipation subtypes Normal transit (functional constipation) – Most common – Difficulty evacuating, hard stool, abdominal discomfort Slow transit – ↑ GI transit time Disorders of defecation – Pelvic floor muscle or anal sphincter dysfunction  Normal Colonic physiology Smooth Muscle Parasympathetic activity responsible for peristalsis which propels colonic contents forward Colon absorbs 90% of fluid presented to it (1.5- 2L) Defecation regulated by pelvic floor muscles and anal sphincters Parasympathetic tone is mediated by A. Acetylcholine B. Histamine C. Epinephrine D. Somatostatin Risk factors for constipation include which of the following? A. Lack of fluid in diet B. Lack of fibre in diet C. Lack of exercise D. All of the above  Risk Factors for/ Causes of constipation Lifestyle Neurogenic – ↓ dietary fibre – Spinal cord injury (SCI) – inadequate fluid intake – CNS trauma, tumours – inactivity – Strokes GI disorders – Multiple sclerosis, Parkinson’s disease – Irritable bowel syndrome – Diverticulitis Endocrine disorders – Anal/rectal diseases – Hypothyroidism – Tumours – Diabetes (autonomic dysfunction) Pregnancy – Hypercalcemia Drugs  Constipation – risk factors Elderly (age > 65 years) – 30-40% in community – > 50% nursing home residents – Contributing factors: ↓ dietary fibre (“tea and toast”) ↓ physical activity Medications Co-morbidities (e.g., diabetes, hypothyroidism) Pregnancy – Hormonal changes in colonic motility – Pressure of enlarged uterus on colon – Use of iron and calcium supplements  Constipation – risk factors Children – Transition to solid food – Toilet training – Entry to school Neurogenic – Diabetic autonomic gastroparesis – Sacral nerve damage (innervate rectum) – SCI: ↓ rectal tone; ↓ sensation of rectal fullness, inability to relax external anal sphincter All of the following drug classes can cause constipation EXCEPT A. Anticholinergics B. Misoprostil C. Opioids D. Iron  All of the following drugs have anticholinergic properties EXCEPT: A. Diazepam (benzodiazepine) B. Imipramine (tricylic antidepressant) C. Dimenhydrinate (antihistamine) D. Oxybutynin (antispasmodic)  Drug –induced constipation Anticholinergics – First generation Opioids Antihistamines (diphenhydramine, Aluminum or calcium dimenhydrinate, antacids hydroxyzine) Iron preparations – Tricyclic antidepressants Calcium channel (amitriptyline, imipramine) blockers (verapamil) – Antiparkinson drugs Diuretics benztropine – Others: oxybutynin  Constipation Clinical presentation – Hard stool, difficulty defecating, sensation of incomplete defecation – Bloating, distention, abdominal pain Diagnosis (see Rome criteria) Complications – Hemorrhoids, rectal prolapse, anal fissures – Bowel obstruction/impaction – Fecal incontinence (overflow diarrhea)  Diagnostic Criteria for Functional Constipation (Rome IV criteria) At least 2 of the following in previous 3 months (with symptom onset at least 6 months prior) – Straining > 25% of defecations – Lumpy or hard stool > 25% of defecations – Sensation of incomplete defecation > 25% of defecations – Sensation of blockage > 25% of defecations – Manual manoeuvres to facilitate >25% of defecations – < 3 defecations per week Loose stools rare without use of laxatives Insufficient evidence for IBS  Constipation Clinical presentation – Hard stool, difficulty defecating, sensation of incomplete defecation – Bloating, distention, abdominal pain Diagnosis (see Rome criteria) Complications – Hemorrhoids, rectal prolapse, anal fissures – Bowel obstruction/impaction – Fecal incontinence (overflow diarrhea)  Constipation – diagnosis – History and physical exam – Response to empiric therapy – Routine labs and diagnostic imaging not recommended unless alarm symptoms Labs based on suspicion of underlying cause (eg TSH for hypothyroidism, Ca for hypercalcemia of malignancy) Flat plate abdomen: structural causes – Barium enema, colonoscopy – Alarm symptoms: Unintended weight loss, hematochezia, family history of colorectal ca or IBD, anemia Flat plate (X-ray) abdomen From MedBroadcast  Constipation History – 2 week bowel diary – Other medical conditions – Drugs – Alarm symptoms Physical Exam – Rectal exam Rectal tone, structural abnormalities  Constipation - Management Prevention – ↑ dietary fibre, fluid intake, exercise – Choice of medication Eg SNRI instead of TCA, non-opioid analgesic – Prophylactic laxatives in high-risk individuals (e.g. bedridden, drug-induced) Treatment – Correct underlying cause – Laxatives – Manual disimpaction  Nonpharmacologic strategies ↑ dietary fibre – ↑ stool bulk, retention of stool water and transit time – 20-25g/day (increase gradually, otherwise bloating, flatus) – May take a few weeks to see effect ↑ fluid intake – Especially if eating soluble fibre/ using bulk-forming laxatives (otherwise constipating) ↑ exercise – walking Bowel training – Not inhibiting urge to defecate  Laxatives Bulk-forming laxatives (eg psyllium, methylcellulose) Stool softeners/ Emollients (eg docusate) Lubricants (eg mineral oil) Stimulants (eg senna, bisacodyl, cascara) Osmotic laxatives / Saline cathartics (eg PEG, lactulose, sorbitol, magnesium) Opioid receptor antagonists (naloxegol, methylnaltrexone) Serotonin5-HT4 receptor agonist (prucalopride) Guanylate cyclase C receptor agonist (linaclotide) Be prepared to compare the efficacy, onset, adverse effects, drug interactions, cost and convenience of these agents!  Laxatives Oral Rectal – Suppositories method of drug delivery (bisacodyl) Lubricant (glycerin) – Enemas Tap water Fleet (sodium phosphate)  Constipation - treatment Acute – Periodic use of laxatives – Seek medical attention if no response in ~ 1 week Chronic – Prophylactic laxatives  Laxatives How to assess efficacy? – Acute treatment vs chronic prophylaxis Relevance of onset of effect in disease – Acute treatment vs chronic prophylaxis  Laxative Abuse Misperceptions about normal bowel movement frequency – Psychological dependency – ?physical dependency (“lazy colon”) – Fluid and electrolyte disturbances Weight loss strategy  Case Helen is a 73 year old female with hard, lumpy stools PMH: – Hypothyroidism (levothyroxine) – Hypertension (candesartan) – Type 2 Diabetes (metformin, empagliflozin) – Diabetic neuropathy (amitriptyline) Could this be caused by drug therapy? Can this be treated with drug therapy? – If so, what would be effective and safe alternatives for Helen?  Workshop - constipation Using the Pharmacotherapy Work-up, determine the drug therapy problem(s) related to constipation – Current Medication Record – Be prepared to compare therapeutic alternatives for constipation Develop a Care Plan for constipation – Be prepared to make specific recommendations and justify your plan – Be prepared to discuss the “What if?” scenarios  Assigned Readings Case to be posted DiPiro 12th ed: Chapter 54: Constipation section eCPS – Minor Ailments: Constipation chapter Recommended Readings: – Leung L, Riutta T, Kotecha J, Rosser W. Chronic constipation: an evidence-based review. J Am Board Fam Med 2011; 24: 436- 51. – Battistella M. Current and future therapies for the management of chronic constipation. Pharmacy Practice CE Lesson, February/March 2012.  Constipation workshops (Feb 14th) Groups A and B: – 0900 – 1030 h – 1030 – quiz feedback Groups C and D: – 1310 – 1440 h – 1440 – quiz feedback 1 group will lead the Pharmacotherapy Work-up discussion 1 group will lead the Care Plan discussion  PHM101 – See Schedule!! Wed Feb 7th Brennan Hall (2-5pm): – Pediatric Lectures (whole class) instead of workshops Fri Feb 9th (PB B150): – Lecture (11am – 1pm): COPD/Asthma pathophysiology (Assignment #1 to be posted) – Lecture (3-4pm): Pharmacology of GI and respiratory drugs Wed Feb 14th – Constipation workshop Fri Feb 16th (PB B150): – Pharmaceutics of Inhalers Fri Feb 16th (3 – 5 PM): MIDTERM EX200