Substance P/Neurokinin 1 (NK1) Receptor Antagonists
Prototypes include aprepitant (Emend-oral) and rolapitant (Varubi). These are specifically used to reduce or prevent nausea and vomiting associated with chemotherapy and postoperative recovery.
- Side Effects/Adverse Effects: Fatigue, diarrhea, headache, dizziness, neutropenia, angioedema, and respiratory depression.
- Interactions: May interact with opioid drugs.
Phenothiazines
The prototype prochlorperazine (Compazine) reduces nausea and vomiting by blocking dopamine (D2) receptors in the CTZ.
- Side Effects/Adverse Effects: Drowsiness, blurred vision, dry mouth, dizziness, and serious neurological issues like tardive dyskinesia, acute dystonia, or neuroleptic malignant syndrome.
- Interactions: Drugs that affect dopamine.
Cannabinoids
Dronabinol (Marinol) and other THC products bind to cannabinoid receptors in the CTZ and prevent serotonin from binding to its receptors. They are used for severe nausea and vomiting.
- Side Effects: A dose-related "high" (elation, easy laughing, increased awareness), acute confusion, and seizure-like activity.
Promotility Drugs
Metoclopramide (Reglan) is a prototype that blocks D2 receptors in the CTZ and is used for postoperative nausea, chemotherapy-induced nausea, and Gastroesophageal Reflux Disease (GERD).
- Side Effects/Adverse Effects: Drowsiness, fatigue, restlessness, visual impairment, urinary incontinence, insomnia, depression, and suicidal ideation.
- Interactions: Phenothiazines, antipsychotics, and levodopa-carbidopa.
Drugs for Peptic Ulcer Disease and GERD
Managing acid-related issues like peptic ulcers and GERD involves controlling the acidity of the stomach environment.
Antacids
Antacids, such as calcium carbonate or magnesium hydroxide, neutralize hydrochloric acid to decrease gastric pH and inhibit pepsin.
- Side Effects: Weakness, anorexia, diarrhea, frequent burping, constipation, and hypermagnesemia.
- Interactions: Antacids can prevent the absorption of many other drugs.
Histamine H₂-Receptor Antagonists
Famotidine (Pepcid) displaces histamine from receptor sites, preventing the stimulation of secretory cells. This neutralizes acid and promotes ulcer healing.
- Side Effects: Dizziness, headache, somnolence, and mild diarrhea.
- Adverse Effects: Hematologic changes, muscle pain, severe allergic reactions, and dysrhythmias.
Proton-Pump Inhibitors (PPIs)
Omeprazole (Prilosec) is a prototype that stops the acid secretory pump located in the parietal cells.
- Side Effects: Headache, diarrhea, abdominal pain, and nausea.
- Adverse Effects: Pancreatitis, blood disorders, and severe allergic reactions.
Cytoprotective Drugs
Drugs like sucralfate (Carafate) and misoprostol (Cytotec) protect the stomach lining from further damage.
CRITICAL SAFETY NOTE: Misoprostol is CONTRAINDICATED in pregnant women.
Drugs for Constipation (Laxatives)
Laxatives are categorized by their mechanism of action and onset of effect:
| Class | Mechanism | Example | Onset |
|---|
| Stool Softener | Wetting agent to soften fecal mass | Docusate (Colace) | 1–3 days |
| Stimulant | Increases peristalsis via nerve stimulation | Bisacodyl (Dulcolax) | 6–12 hours |
| Lubricant | Coats feces/colon to ease passage | Mineral oil | 6–8 hours |
| Bulk-forming | Absorbs water to increase bulk/distention | Psyllium (Metamucil) | 12 hrs–3 days |
| Combination | Stimulates water content and peristalsis | Magnesium citrate | 1–3 hours |
Exam Tip: Be aware that laxatives can cause electrolyte disturbances, cramping, and diarrhea. They may also reduce the effectiveness of antibiotics, anticoagulants, digitalis, and salicylates.
Drugs for Diarrhea and Irritable Bowel Syndrome (IBS)
Diarrhea management focuses on reducing gastrointestinal motility and fluid content.
Antidiarrheals
Anticholinergics (e.g., diphenoxylate/atropine or dicyclomine) block acetylcholine to reduce motility, while antispasmodics reduce muscle contractions to decrease cramping. Opioid agonists reduce motility and increase water absorption.
- Adverse Effects: These can potentiate the effects of other opioids, sedatives, and tranquilizers.
Irritable Bowel Syndrome (IBS)
Treatment depends on whether the patient presents with constipation (IBS-C) or diarrhea (IBS-D):
- For IBS-C (Constipation):
- Chloride channel activators: Lubiprostone (Amitiza) increases intestinal fluid secretion.
- Guanylate cyclase-C agonists: Linaclotide (Linzess) increases fluid and motility.
- Selective 5HT-4 agonists: Tegaserod (Zelnorm) stimulates peristalsis (Note: removed from US market in 2007).
- For IBS-D (Diarrhea):
- Opioid agonists: Eluxadoline (Viberzi) affects opioid receptors to manage motility.
- Antispasmodics.
