Chapter 42 Drugs for Bowel Disorder and Other Gastrointestinal Conditions Reading Notes PDF

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Chapter 42 Drugs for Bowel Disorder and Other Gastrointestinal Conditions Reading Notes  

Nausea, vomiting, diarrhea, and constipation are the most common adverse effects of oral medications Drugs are used to symptoms that are prolonged

Normal Function of the Lower Digestive Tract  Lower portion of the GI tract consists of the small and large intestine o First part of small intestine -> duodenum -> chyme mixes with bile and digestive enzymes from pancreas o Remainder of small intestine is the jejunum and the ileum  Jejunum is where most nutrient is absorbed  Ileum is empties contents into large intestine

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Activation of the parasympathetic NS will increase peristalsis and speed up materials traveling o Activation on sympathetic NS does the opposite 3 – 6 hours for chyme to get through small intestine The large intestine (colon) receives chyme in a fluid state o Main function is to reabsorb water and rid of waste o This is where bacteria and flora live  Synthesize Vitamin K and B  Disruption of host flora can lead to diarrhea

Pathophysiology of Constipation  If stool remains in the colon for too long, too much water is absorbed resulting in small hard stools  Common side effects of constipation are: abdominal distention, discomfort, and flatulence o It is not a disease, it is a underlying symptom of a disorder  Etiology that related to constipation:

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o Lake of exercise, insufficient food intake (fiber), diminished fluid intake, or medications that reduce intestinal motility:  Opioids  Anticholinergic  Antihistamines  Certain antacids  Iron supplements Diseases that can cause constipation: o Hypothyroidism o Diabetes o Irritable bowel syndrome Elderly experience constipation because of normal aging process -> slowed peristalsis, lowered motility, and chronic disorders Lifestyle modifications should be considered before drug treatment such as: o Dietary fiber intake, fluid intake, and physical activity It its most severe form, constipation can led to: fecal impaction and complete obstruction of bowel

Pharmacotherapy with Laxatives  Laxatives promote bowel movement  Types: o Bulk Forming: methylcellulose, psyllium, calcium polycarbophil  Can cause GI obstruction if not taken with enough water  Contain fiber that increase the size of fecal mass  Preferred for treatment of constipation  Can be taken on regular bases without ill effects  Slow onset -> not used for rapid and immediate relief o Saline and Osmotic: lactulose, magnesium hydroxide, polyethylene glycol, sodium phosphate  Hypermagnesaemia with magnesium hydroxide  Pull water into the fecal mass to create more watery stool  Not to be used on regular basis  Quick onset  Saline is important for colonoscopy o Stimulant: bisacodyl  Fluid and electrolyte lose o Surfactant (stool softener): docusate  More water and fat to be absorbed into stool  PREVENT constipation -> surgery o Herbal Agent: castor oil, senna  Used for self treatment o Opioid Antagonist: alvimopan, methylnaltrexone, naloxegol  MI with LTU, GI perforation, opioid withdrawal  Block opioid receptor in large intestine  Used for SHORT TERM hospital use due to chances of MI

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o Miscellaneous drugs: mineral oil -> coats stools and colon mucosa -> should not be used because of its interference with absorption of fat soluble vitamins Used for prevention or treatment of constipation The goal with treatment of constipation is -> cathartic Prophylactic indications: o Post abdominal surgery o Pregnant women o Patients unable to exercise o Patients who are taking drugs known to cause constipation Most common use is for simple constipation treatment o Sometimes used to accelerate digestion if toxins have been ingested o Used to clean the bowel prior to surgery Most frequent AE are abdominal distention and cramping -> diarrhea from excessive use -> monitor electrolyte and fluid balance EXPECTED outcomes with use are: toxic substances in stool, forceful and frequent bowel movements DO NOT give to a patient that may have an obstruction

Pathophysiology of Diarrhea  Diarrhea occurs when no enough water is absorbed from fecal mass, the frequency and fluidity is also increased o A symptom of a underlying disorder  Acts as a defense response of the body  Can result in loss of fluids, electrolyte imbalance and avid-base disorder  Can be caused by medications, infection of bowel, and substances such as lactose  Underlying causes can be: ulcerative colitis, Crohn’s disease, and IBS  Antibiotics often kill flora in intestines -> causing growth of pathogenic organisms Pharmacotherapy with Antidiarrheal  For chronic or severe diarrhea, opioids care most effective  Types of antidiarrheals: o Opioids:  Ex. Difenoxin with atropine, diphenoxulate with atropine, loperamide, opium tincture  Drowsiness and dry mouth may occur with atropine, respiratory depression, CNS depression paralytic ileus o Miscellaneous Drugs:  Ex. bismuth salts, lactobacillus acidophilus, octreotide, telotristat  Impaction, allergic reactions, changes in serum glucose, severe constipation  If drug is caused by a disease -> antibiotic or antiparasitic

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Opioids are the most effective drug for treatment -> slows peristalsis in the colon -> allowing for more fluid absorption Diphenoxylate is a schedule V drug o Used for short term therapy -> dependence o Can cause CNS depressant @ high doses OTC: o Loperamide (Imodium) -> does not have addictive qualities as the other opioids o Bismuth subsalicylate (Pepto Bismol)-> binds and absorbs toxins o Psyllium -> absorbs more liquid -> bulkier stool o Lactobacillus can be taken to correct the altered flora in the GI tract Antidiarrheal medications should not be used to treat diarrhea caused by poisoning or infection o Do not use antidiarrheal medications if the cause is PMC

Irritable Bowel Syndrome  IBS (spastic colon or mucous colitis) is a disorder of the lower GI tract o Identified by reoccurrence of abdominal pain for 3 days per month over 3 months, accompanied by:  Relieved by defecation  Onset associated with change in stool frequency  Onset associated with change is stool form and appearance  Symptoms: abdominal pain, bloating, excessive gas, and colicky cramping (cramping in the intestines)  Severe mucus may be present in stool, diarrhea and constipation will alternate during IBS as well  “Triggers” from certain foods or substances cause IBS  Medication therapy is difficult due to the alternation between constipation and diarrhea, drugs are used to treat symptoms -> can sometimes worsen the patient’s condition  Most providers will first prescribe a low cost OTC laxative and fiber therapy  Treat the symptom bothering the patient the most  IBS-C (constipation) o Linaclotide and Lubiprostone: reduces bloating and constipation by increasing water secretion -> may cause diarrhea  IBS-D (diarrhea): o Loperamide is sometimes chosen as initial therapy because effective antidiarrheal properties o Eluxadoline acts on opioids receptors to slow peristalsis o Rifaximin: “travelers diarrhea” antibiotic -> changes bacteria composition and reduces gas o Alosetron is contradicted because of AE in the GI tract 

IBS-M (alternation)

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Dicyclomine and hyoscyamine are older anticholinergic drugs that reduce bowel spams Serotonin receptor antagonist ondansetron slow transit through intestine TCAs are used when patient is having pain as a majoy symptom

Inflammatory Bowel Disease  Presence of ulcers in the distal portion of the small intestine (Crohn’s Disease) or mucosal erosions in the large intestine (ulcerative colitis). o Presentation for UC is cramping with frequent bowel movements o Presentation for CD is abdominal cramping, pain, and diarrhea  Crohns disease may appear anyone in the digestive tract o More common in smokers  UC is curable with surgery o More common in non smokers  Defective genes causing hyperactivity of immune responses result in chronic intestinal inflammation (IBD)  Factors the contribute to IBD: o Genetics o Environmental triggers ex. Smoking o Use of NSAIDs o High levels of stress  Goals with Pharm Treatment: o Place disease in remission and reduce acute symptoms o Keep disease in remission o Change natural course or progression of disease  Step 1:5 amino-salicylic are the first step in treatment o Safe and well established  Step 2: if the 5-ASA drugs are ineffective -> oral corticosteroids are used o Budesonide is first line for corticosteroid therapy  Prevents absorption in ileum and proximal colon  Produces a topical anti-inflammatory effect  Step 3: immunosuppressant drugs o Azathioprine and methotrexate o Not used for initial treatment because it takes 3 months for effects  Probiotics can help regain the balance of flora in the intestine thus relieving IBD Pathophysiology of Nausea and Vomiting  Nausea is a sensation accompanied by weakness, diaphoresis, and hyper production of saliva  Intense nausea leads to vomiting or emesis  Medulla controls the defense mechanism of vomiting  Treatment focuses on removal of the cause o Physical or psychological  Morning sickness occurs in first trimester

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Antineoplastic drugs (cancer drugs) cause intense vomiting o Emetogenic potential Vomiting can cause o Fluid and electrolyte imbalance o Blood pH to change -> alkalosis o Weight loss -> vascular collapse o Dehydration Antimetics inhibit dopamine or serotonin receptors in the brain Drug classes that can treat: o Anticholinergic and antihistamine  Used for nausea related to motion sickness  Causes drowsiness in patients (antihistamines) o Benzodiazepine o Cannabinoids o Corticosteroids  Chemotherapy induced and post surgical nausea  Short term only o Neurokinin receptor antagonist  Following surgery or chemo therapy treatment o Phenothiazine and phenothiazine like drugs  Good for nausea associated with antineoplastic therapy o Serotonin (5-HT3) receptor antagonist  First line drug because of effectiveness and safety profile  Given prophylactically o Emetics  Stimulate vomiting reflux  Used when poison or overdose has happened (15 minutes) Simple nausea and vomiting can be relieved by antacids or diphenhydramine Therapy with antineoplastic drugs is a common reason for prescribing a antiemetic

Pharmacotherapy for Pancreatitis  Pancreas secretes essential digestive enzymes  Lipase, amylase, and nuclease are three enzymes secreted that need bile to become activated  Lack of pancreatic secretion can result in mal-absorption disorders  Pancreatitis occurs when enzymes stay in the pancreas and are not secreted o Enzymes escape into surrounding tissue  Symptoms of acute pancreatitis present suddenly often after eating fatty meals or consuming a lot of alcohol  Epigastria region pain is a indicator  Pancreatitis relates heavily to alcoholism  Steatorrhea occurs later with disease  Nutrition replacement may be needed in serious cases

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o Chronic is related to alcoholism  Occlude the pancreatic duct Symptoms include: o Epigastric or left upper quadrant pain o Anorexia o Nausea o Vomiting o Weight loss o Steatorrhea occurs later in the course of the disease Drug classes used to treat pancreatitis: o Opioid analgesics o IV fluids o Insulin o Antemetics

Chapter Review: 1. The small intestine is the location for most nutrient and drug absorption. The large intestine is responsible for the reabsorption of water. 2. Constipation, the infrequent passage of hard, small stools, is a common condition caused by insufficient dietary fiber and slow motility of waste material through the large intestine. 3. Laxatives and cathartics are drugs given to promote emptying of the large intestine by adding more bulk or water to the colon contents, lubricating the fecal mass, or stimulating peristalsis. 4. Diarrhea is an increase in the frequency and fluidity of bowel movements that occurs when the colon fails to reabsorb enough water. 5. For simple diarrhea, OTC medications such as loperamide or bismuth subsalicylate are effective. Opioids are the most effective drugs for controlling severe diarrhea. 6. Drugs for irritable bowel syndrome (IBS) are targeted at symptomatic treatment, depending on whether constipation or diarrhea is the predominant symptom. 7. Treatment for inflammatory bowel disease (IBD) includes 5aminosalicylic acid (5-ASA) drugs, corticosteroids, and immunosuppressants.

8. Nausea and vomiting are common symptoms associated with a wide variety of conditions, such as GI infections, food poisoning, nervousness, emotional imbalances, motion sickness, and extreme pain. Many oral drugs can cause nausea and vomiting as side effects. 9. Symptomatic treatment of nausea and vomiting includes drugs from many different classes, including serotonin receptor antagonists, antihistamines, anticholinergics, phenothiazines, corticosteroids, neurokinin receptor antagonists, benzodiazepines, and cannabinoids. Emetics are used on some occasions to stimulate the vomiting reflex. 10. Pancreatitis results when pancreatic enzymes remain in the

pancreas rather than being released into the duodenum. Pharmacotherapy includes replacement enzymes and supportive drugs for reduction of pain and gastric acid secretion....