Laxatives & Antidiarrhoeals Flashcards
(23 cards)
What are the primary mechanisms of stimulant laxatives such as bisacodyl in treating constipation?
Stimulant laxatives act by:
- Directly stimulating the enteric nervous system
- Producing migrating colonic contractions
- Enhancing electrolyte and water secretion in the colon
Bisacodyl, a diphenylmethane derivative, results in bowel movements usually within 6-10 hours (oral) or 30-60 minutes (rectal). Their efficacy makes them useful for colonic cleansing procedures, though they must be used cautiously due to potential adverse effects like abdominal cramping.
How do osmotic laxatives like lactulose and macrogol act to alleviate constipation?
Osmotic laxatives work by:
- Drawing water into the bowel lumen via osmotic gradients
- Increasing stool liquidity and volume
- Stimulating peristalsis due to increased stool mass
Lactulose, a nonabsorbable sugar, and macrogol, a balanced isotonic solution, both facilitate bowel movements by hydrating the stool, making it softer and easier to pass. High doses can lead to rapid purgation, hence careful dosing is necessary.
Describe the mechanism of action of serotonin 5-HT4 receptor agonists in treating constipation and name two examples.
Serotonin 5-HT4 receptor agonists work by:
- Stimulating 5-HT4 receptors on gastrointestinal nerve terminals
- Increasing neurotransmitter release and smooth muscle motor activity
- Enhancing gastrointestinal motility (prokinetic effect)
Examples include cisapride and prucalopride. These drugs enhance peristalsis and transit, improving stool passage, but are contraindicated in cases of complete intestinal obstruction due to the risk of exacerbating blockage.
What are the common gastrointestinal adverse effects associated with osmotic laxatives and what is their underlying cause?
Common gastrointestinal side effects include severe flatus and abdominal cramps. These effects are primarily due to colonic bacteria fermenting the nonabsorbable sugars present in osmotic laxatives. The fermentation process produces gas, leading to bloating and discomfort. Awareness of this mechanism helps in managing and counseling patients who experience these symptoms.
What are some major adverse effects associated with prolonged use of somatostatin-like peptides?
Major adverse effects include:
- Impaired pancreatic secretion leading to steatorrhoea and potential fat-soluble vitamin deficiency.
- Gastrointestinal symptoms such as nausea, abdominal pain, flatulence, and diarrhea.
- Increased risk of gallbladder issues like the formation of sludge or gallstones, sometimes progressing to acute cholecystitis.
- Additional effects may include hypothyroidism and bradycardia due to broader hormonal suppression.
What is the therapeutic mechanism of colloidal bismuth compounds in managing diarrhoea?
Colloidal bismuth compounds, including bismuth subcitrate and bismuth subsalicylate, have antimicrobial properties and bind enterotoxins, which is beneficial in traveller’s diarrhoea. They also function as mucosal protective agents in acid-peptic conditions such as peptic ulcers. In the case of bismuth subsalicylate, rapid dissociation in the stomach allows absorption of salicylate that inhibits intestinal prostaglandin production and chloride secretion. This dual action helps reduce stool frequency and liquidity in acute infectious diarrhoea.
What is the mechanism of action of opioid agonists used in the treatment of diarrhoea?
Opioid agonists, such as loperamide and diphenoxylate, work by acting on the enteric nervous system to increase colonic transit time. This slows down intestinal motility, allowing more time for fluid and electrolyte absorption. They reduce stool frequency and liquidity. Loperamide, notably, does not cross the blood-brain barrier, minimizing central nervous system effects, while diphenoxylate may cause CNS effects at higher doses.
How do opioid receptor antagonists help alleviate constipation, and what is a key example in this class?
Opioid receptor antagonists alleviate constipation by:
- Blocking μ-opioid receptors in the gastrointestinal tract
- Counteracting opioid-induced slowing of GI transit
- Improving bowel motility without affecting central analgesia
Methylnaltrexone bromide is a key example; it targets peripheral receptors, reversing opioid-induced constipation while preserving pain management. It is especially beneficial in patients on chronic opioid therapy who develop significant constipation.
Describe the mechanism and clinical utility of intestinal adsorbents in the treatment of diarrhoea.
Intestinal adsorbents like kaolin and diosmectite work by adsorbing bacteria, toxins, and excess fluid from the gastrointestinal tract. This reduces stool liquidity and frequency, making them effective in acute diarrhoea. They are not systemically absorbed, which minimizes significant adverse effects, though constipation is a possible side effect. Additionally, caution is needed as they can bind to other medications, warranting a 2-hour gap between dosing.
How do bile salt-binding resins alleviate diarrhoea caused by excess fecal bile salts?
Bile salt-binding resins, such as colestyramine, bind to unabsorbed bile salts in the colon. This prevents the osmotic laxative effect that free bile salts exert, thus reducing diarrhoea. They are particularly useful in conditions where bile salt malabsorption occurs, such as Crohn’s disease or after ileal resection. However, they may cause bloating, flatulence, constipation, and interfere with the absorption of other oral medications.
What is octreotide and how does it differ from natural somatostatin?
Octreotide is a synthetic peptide that mimics the action of natural somatostatin but with a longer half-life.
- It is administered via subcutaneous injection or intramuscular depot formulations.
- Like somatostatin, it inhibits the release of gastrointestinal hormones (e.g., gastrin, VIP, 5-HT) and reduces secretions, but its prolonged duration makes it more practical for therapeutic use.
- Its extended activity allows for sustained control of symptoms such as secretory diarrhea in gastrointestinal and neuroendocrine tumors.
How does octreotide help in managing secretory diarrhea caused by gastrointestinal and neuroendocrine tumors?
Octreotide manages secretory diarrhea by imitating somatostatin and inhibiting excessive hormone secretion.
- It suppresses the release of vasoactive intestinal peptide (VIP) and other secretagogues.
- This leads to decreased intestinal and pancreatic secretions and slows gastrointestinal motility.
- These combined effects reduce fluid secretion in the intestines, thereby alleviating diarrhea symptoms, particularly in carcinoid and VIP-secreting tumors.
What are the primary concerns and adverse effects associated with opioid agonists in antidiarrhoeal therapy?
The major concerns include potential CNS effects, dependency, and side effects such as anticholinergic effects when combined with atropine. Loperamide has a low risk of CNS penetration, but diphenoxylate can cause central effects and lead to dependence with long-term use. Overdose of loperamide carries a risk of cardiac abnormalities. The addition of atropine aims to discourage overdose by inducing anticholinergic adverse effects like dry mouth.
Which class of laxatives works by reducing fecal surface tension to facilitate water penetration, and what are common examples?
Stool surfactant agents (or stool softeners) reduce fecal surface tension.
- Examples include glycerin (used in enemas) and mineral oil (taken orally).
These agents work by facilitating the interaction between water and stool, thereby softening the fecal mass. They are particularly useful in patients where increasing stool bulk might be contraindicated or insufficient, ensuring easier passage of stools.
List the key physiological mechanisms by which somatostatin-like peptides exert their effects.
Somatostatin-like peptides act through several key mechanisms:
1. Inhibition of hormone and neurotransmitter release (e.g., gastrin, VIP, 5-HT).
2. Reduction of intestinal and pancreatic secretions.
3. Slowing gastrointestinal motility and inhibiting gallbladder contraction.
4. They mimic the endogenous hormone somatostatin, leading to a broad reduction in secretory and motor activities in the GI tract.
What is the mechanism of action of bulk-forming laxatives such as psyllium?
Bulk-forming laxatives work by:
- Absorbing water to form a viscous, emollient gel
- Increasing stool bulk and mass
- Stimulating peristalsis through colonic wall distension
This mechanism enhances bowel motility by increasing the volumetric load within the colon, which triggers natural peristaltic movements. Adequate water intake is necessary to prevent obstruction and ensure efficacy.
Why is it important to maintain adequate hydration when using osmotic laxatives?
Adequate hydration is crucial because osmotic laxatives work by drawing water into the intestine. Without sufficient fluid intake, there is a risk of dehydration and electrolyte imbalances. Maintaining hydration ensures the osmotic gradient is effective in softening stools and facilitating peristalsis. This is particularly important in vulnerable populations such as the elderly or those with renal insufficiency or cardiac disease.
Why is octreotide particularly useful in the treatment of diarrhea in patients with neuroendocrine tumors?
Octreotide is useful because it targets the excessive hormone secretion from neuroendocrine tumors.
- It reduces the release of hormones such as VIP and serotonin, which are responsible for the secretory diarrhea seen in these conditions.
- By decreasing gastrointestinal secretions and motility, it helps control the severe watery diarrhea.
- This targeted approach improves the quality of life and helps manage the clinical complications associated with neuroendocrine tumors.
What is the primary mechanism of action for osmotic laxatives in treating constipation?
Osmotic laxatives work by pulling water into the bowel lumen via an osmotic gradient, thereby increasing stool liquidity and volume. The increased water content stimulates peristalsis. This process helps soften stools and facilitates bowel evacuation. The efficacy of osmotic laxatives depends on their ability to maintain an osmotic load in the colon.
What is the role of chloride channel activators in constipation management, and which drug is a typical example?
Chloride channel activators work by:
- Activating chloride channels in the gastrointestinal epithelium
- Promoting chloride and water secretion into the bowel lumen
- Increasing stool liquidity and volume to facilitate bowel movements
Lubiprostone is a common chloride channel activator. Its mechanism leads to improved intestinal fluid secretion and enhanced motility, making it particularly useful for chronic idiopathic constipation. Side effects may include nausea and headache.
What role do products of Lactobacillus acidophilus and somatostatin-like peptides play in the management of diarrhoea?
Products of Lactobacillus acidophilus help restore normal intestinal flora and enhance the gut’s immune function, providing a probiotic benefit. Somatostatin-like peptides, such as octreotide, are used to suppress gastrointestinal secretions and reduce motility, thereby alleviating diarrhoea. Octreotide decreases intestinal fluid secretion, which is particularly useful in refractory and severe cases of diarrhoea. Both interventions address different aspects of diarrhoeal pathophysiology, one by microbial balance restoration and the other by modulating intestinal secretions.
List the specific electrolyte abnormalities that can occur with sodium phosphate use in osmotic laxatives.
Sodium phosphate can cause the following electrolyte abnormalities:
1. Hyperphosphataemia
2. Hypernatraemia
3. Hypocalcaemia
4. Hypokalaemia
These abnormalities result from the phosphate and sodium loads inherent in sodium phosphate formulations, which can disrupt normal serum electrolyte balances. Although these changes are often not clinically significant in healthy individuals, they may lead to severe complications in vulnerable populations.
What makes balanced macrogol a safer alternative compared to sodium phosphate formulations?
Balanced macrogol formulations contain polyethylene glycol along with a defined mixture of electrolytes (e.g., potassium chloride, sodium chloride, sodium hydrogen carbonate, and sodium sulphate) to avoid significant electrolyte shifts. This balance minimizes the risk of hypernatraemia, hyperphosphataemia, and other electrolyte derangements that can occur with sodium phosphate. Additionally, macrogol is less likely to cause severe cramps or flatus. These properties make it a safer option, especially for patients with renal or cardiac concerns.
