Drug Therapy for Nausea, Vomiting, Constipation, and Diarrhea

Where is the vomiting center located in the brain?

The medulla oblongata

What is the prototype for Phenothiazines?

Prochlorperazine (Compro)

What is the prototype for Antihistamines?

Hydroxyzine (Vistaril)

What is the prototype for 5HT3 or Serotonin Receptor Antagonists?

Ondansteron (Zofran)

What is the prototype for Substance P/Neurokinin 1 Anatgonists?

Aprepitant (Emend)

Phenothiazines (Prochlorperazine/Compro)

Originally used as an antipsychotic. Antagonizes D2 (Dopamine) receptors in the midbrain. Also has muscarinic (M1) and histamine (H1) blocking effects. Used to prevent chemo-induced emesis, as well as to prevent psychosis and schizophrenia.

What are adverse effects of Phenothiazines (Prochlorperazine/Compro)?

Orthostatic hypotension, anticholinergic effects, QT changes on EKGs, Extrapyramidal Symptoms (EPS)

What is the black box warning for Phenothiazines (Prochlorperazine/Compro)

Older adults with dementia related psychosis are at an increased risk for death

Extrapyramidal Symptoms (EPS)

Pseudo-parkinsonism, Actue dystonie, Akathisia, and Tardive Dyskinesia

Antihistamines (Hydroxyzine/Vistaril)

Block H1 receptors and acton of acetylcholine in the brain. Variable half-life. Used for motion sickness/vertigo (meclizine)

What are some adverse effects of Antihistamines (Hydroxyzine/Vistaril)?

Drowsiness, dizziness, confusion, dry mouth, thick respiratory secretions, blurred vision, urinary retention, and tachycardia

5HT3 or Serotonin Receptor Antagonists (Ondansetron/Zofran)

Drug of choice for chemo and post-op nausea and vomiting. Can be used in early pregnancy. Antagonizes serotonin receptors, preventing activation by emetogenic drugs or toxins. Oral dissolving works within 30-60 minutes.

What are the adverse effects of 5HT3 or Serotonin Receptor Antagonists?

Diarrhea, headache, dizziness, constipation, fatigue, transient elevation of liver enzymes, and prolonged QT interval

Substance P/Neurokinin 1 Antagonists (Aprepitant/Emend)

Blocks activity of substance P at NK 1 receptors in brain, inhibiting signal to brain that causes nausea. Highly protein bound. Used for chemo related N/V.

What is an important teaching for patients on Substance P/Neurokinin 1 Antagonists?

It decreases the effectiveness of oral contraceptives

What are examples of synthetic cannabinoids?

Dronabinol and Nabilone

Constipation

Infrequent and pain expulsion of hard, dry stools

What is the prototype for bulk-forming laxatives?

Psyllium

What is the prototype for Surfactant Laxatives?

Docusate Sodium (Colace)

What is the prototype for Lubricant Laxatives?

Mineral oil

Bulk-Forming Laxatives

Adds mass to the feces, stimulating peristalsis and defecation. They must be taken with water to avoid obstruction. Generally, bulk-forming drugs are the most desirable laxative for long term use

Lubricant Laxatives

Lubricate the fecal mass and slow colonic absorption of water from the fecal mass. It may interfere with the absorption of fat-soluble vitamins and if aspirated may result in a liquid aspiration pneumonia.

Surfactants (Stool Softeners)

Decrease the surface tension of the fecal mass to allow water to penetrate stool, making it softer and easier to expel. Avoid straining.

What are the contraindications of Psyllium?

Undiagnosed abdominal pain, obstruction, and fecal impaction

What is an important patient teaching of Psyllium?

Take with a full glass of water and it may inhibit the absorption of some drugs

Docusate Sodium Action

Mixes fat and water in stool. Softens stool, does not actively expel. Main goal is to reduce strain. Should be taken daily

What is the prototype for Stimulant Cathartics?

Bisacodyl

What are the prototypes of Saline Laxatives?

Magnesium Citrate and Polyethylene Glycol

Stimulant Cathartics

The strongest and most abused laxative products. They irritate the GI mucosa, pull water into the colon, and stimulate peristalsis. They produce a watery stool and may lead to fluid, electrolyte, and acid-base balance.

Saline Cathartics

Increases the osmotic pressure in the intestinal lumen, resulting in the retention of water, which distends the bowel and stimulates peristalsis. They produce a semifluid stool and may lead to fluid and electrolyte imbalances.

What are the administration instructions for Bisacodyl?

Do not take with milk, and take on an empty stomach or at bedtime

What are other indications for the use of cathartics?

Obtain a stool specimen for parasitologic examination, accelerate excretion of parasites after anthelmintic drugs have been administered, and reduce serum cholesterol levels.

Guanylate Cyclase-C Agonist (Linaclotide)

Increases secretion of chloride and water and water in intestines. Used to treat IBS-C and idiopathic constipation

What is the black box warning for Guanylate Cyclase-C Agonists?

Huge risk of severe risk of dehydration in children

Lactulose

Exerts an osmotic effect, pulling water into the colon and stimulating peristalsis. It is also useful in treating hepatic encephalopathy by decreasing the production of the waste product ammonia

Sorbitol

Is often given with sodium polystyrene sulfonate (Kayexalate) in the treatment of hyperkalemia to aid in the expulsion of the potassium-resin complex

Lubiprostone

Aids in treating chronic idiopathic constipation by increasing intestinal fluid secretion, stimulating intestinal motility and defecation

Diarrhea

Symptom, not a disease. Increased bowel motility. Frequent liquid or semi liquid stool

Crohn’s Disease

Chronic, recurrent inflammation. Can affect any area of GI tract with patchy lesions. Pain often in RLQ. Symptoms include fever, bleeding, diarrhea, anorexia, and weight loss

Ulcerative Colitis

Chronic, recurrent inflammation. Most often affects the colon and rectum in one continuous section. Pain often in LLQ. Symptoms include blood and mucous in stool, severe pain, severe diarrhea, anorexia, and weight loss.

Diphenoxylate with Atropine (Lomotil)

Prototype used to treat moderate to severe diarrhea. Slows peristalsis by acting on the smooth muscles in the intestine. Hypotension and respiratory depression have occurred with larger doses than ordered

Loperamide (Imodium)

Another opiate-related antidiarrheal. Decreases GI motility by acting in intestinal muscles.

What is the black box warning for Loperamide?

May cause torsades de pointes (no consistent heart rate or rhythm)

Alosetron (Lotronex)

Adjuvant antidiarrheal. Can cause serious GI AEs, like severe constipation, onstruction, perforation, hemorrhage, and ischemic colitis. (Black Box warning)

Bismuth Salts

Have antibacterial and antiviral activity. Also has antisecretory and possibly anti-inflammatory effects because of its salicylate component

Octreotide Acetate

Synethetic form of somatostatin, a hormone produced in the anterior pituitary gland and in the pancreas. The drug may be effective in diarrhea because it decreases GI secretion and motility

Where are the Histamine and Muscarinic receptors located?

The inner ear