User:Slalop/Antidiarrhoeal

An anti-diarrhoeal drug (or anti-diarrheal drug in American English) is any medication which provides symptomatic relief for diarrhea. There are many classes and types of medications indicated for the treatment of diarrhea. The antidiarrheal agent chosen depends on the cause and severity of the diarrhea, as well as other patient-specific factors. Often, diarrhea is self-resolving with treatment consisting of symptom management and rehydration. Most cases of diarrhea are acute, and do not necessitate the use of antidiarrheal agents. A proper medical history and patient examination is necessary to initiate proper antidiarrheal use. Care is primarily focused on symptom management, with certain cases of infectious bacteria requiring further treatment. For all cases of diarrhea, oral rehydration therapy and the treatment and prevention of dehydration is important.

Electrolyte solutions
Also known as oral rehydration therapy (ORT), these solutions are considered to be the treatment of choice for acute cases of dehydration caused by diarrhea. ORT consists of replenishing fluids and electrolyes that have been lost. Oral Rehydration Solutions (ORS) optimize the absorption of the sodium-dependent hexose transporter-1 co-transporter along the intestinal epithelium. ORT was developed in the 1970’s as a safe, inexpensive replacement of intravenous rehydration. Studies show fewer side effects and shorter hospital stays when using ORT as compared to intravenous therapy. Common ORS consist of a dextrose, sodium, and bicarbonate solution that replaces electrolytes without being causing gastrointestinal side effects from hyperosmolarity. Monitoring for electrolyte levels, renal function, and signs of organ failure must occur with both oral and intravenous rehydration therapy. A patient’s clinical signs, symptoms, and level of dehydration are all considered when managing diarrheal illness.

Common electrolyte solutions available for children include Pedialyte, Gatorade, Infalyte, or the World Health Organization (WHO) ORS. These are considered to be the ORS of choice in children. Drinks with high sugar content, such as juices, can worsen diarrhea and dehydration and should be avoided. undefined Clear liquids such as water, sodas and broth are not considered replacements for ORS. These solutions are hypo-osmolar and do not replace potassium, bicarbonate, and sodium levels enough, possibly resulting in hyponatremia.

Opioid agonists
An opioid agonist commonly used for the treatment of diarrhea is loperamide, or Imodium. This product is approved to treat diarrhea in those aged 12 and older. Opioid agonists activate μ receptor, this causes an inhibition of acetylcholine release that subsequently decreases peristaltic activity. Inhibiting acetylcholine also has an antisecretory effect on gut epithelial cells. This mechanism of action makes loperamide effective in preventing fluid and electrolyte loss, decreasing fecal volume, and increasing stool consistency. Loperamide is made to specifically activate μ receptors in the myenteric plexus of the intestinal wall.

Loperamide’s max dose is 16 mg daily. It has a wide dose range, with an increased dose needed if diarrhea is not being controlled. Loperamide should not be used in inflammatory bowel conditions, and caution should be taken when using loperamide for the treatment of infectious diarrhea. Loperamide should not be used if blood is visible in the stool.

Absorbents
Diosmectite is a common example of an absorbent used in diarrhea. It is made of natural aluminium and magnesium silicate clay. Diosmectite absorbs and removes toxins, bacteria, and viruses that contribute to diarrhea. It has the added benefit of decreasing the amount of antigen s able to pass through the intestinal mucous layer, thus reducing inflammation. This additionally helps to improve stool consistency. Diosmectite is indicated for use in both acute and chronic diarrhea. It is also used in infectious and non-infectious diarrhea, acquired immune deficiency syndrome (AIDS) associated chronic diarrhea, and in diarrhea caused by radiation and chemotherapy. In patients with chronic functional diarrhea, diosmectite has shown to reduce the frequency of bowl movements and improve stool consistency.

Another common absorbent is bismuth subsalicylate (BSS). It is prepared as an insoluble salt of bismuth and salicylic acid, with preparations commonly containing 58% bismuth and 42% salicylate by weight. The mechanism of action of BSS is not entirely known. It is hydrolyzed to form bismuth oxychloride and salicylic acid in the stomach. Studies have suggested BSS works by decreasing fluid flow into the bowels, and therefore inflammation. BSS may have some antimicrobial activity. There is no evidence to suggest that BSS is unsafe in the stomach or gastrointestinal tract. BSS is the active ingredient Pepto-Bismol, and is available in various dosage forms around the world without the need of a prescription. Oral BSS has been successfully used for the treatment of diarrhea for over a century, and for Helicobacter pylori (H. pylori) infections and their associated ulcers. While studies show BSS to be successful in the treatment of diarrhea, it’s efficacy in shortening the duration and frequency of diarrhea appears to be lower than that of loperamide. BSS has also been used as an antacid, and for the treatment of nausea, indigestion and stomach upset.

Antispasmodics/anticholinergics/antimuscarinics
These agents work to relieve symptoms of diarrhea by reducing gastrointestinal motility and secretions. This is done through blockage of acetylcholine receptor binding. This drug class includes medications like butylscopolamine, scopolamine, cimetropium bromide, pirenzepine, dicycloverine and prifinium bromide.

Adrenergic α2 receptor agonists
The only drug of this class used in diarrhea is clonidine. Clonidine is an effective treatment for diarrhea, and works by activating alpha-2 adrenergic receptors on enterocytes. This decreases bowel transit time and secretion and increases fluid and electrolyte absorption. It is used as an alternative treatment for refractory diarrhea. The use of this agent is only used when other, more traditional antidiarrheals have failed.

Bile acid sequestrants
Common agents in this class are colestyramine and colestipol. These bile acid sequestrants (BAS) are positively charged resins that are unable to be digested by the body. They bind to bile acids in the intestine, forming an insoluble complex which is then excreted through the feces. These agents were more commonly used to lower cholesterol, but show promise in being effective treatments for diarrhea caused by bile acid malabsorption (BAM). Bile acids have secretory actions on the colon, and these resins can bind to and eliminate this effect. Their use as cholesterol-lowing agents have been largely supplanted by statins. Colestyramine is the most studied BAS for its use in treating BAM-associated diarrhea, and has shown to be effective.

Antibiotics
Most often, diarrhea is viral and self-limiting. This makes the use of antibiotics in treating diarrhea not indicated in most adults with non-severe, watery diarrhea. Their use in the treatment of diarrhea is also limited due to antimicrobial stewardship, a program geared to the proper use of antibiotics in order to prevent antibiotic resistance. The use of antibiotics can also set the normal gut microbiota out of balance and can counterintuitively cause diarrhea and prolong illness. Some few instances where the use of antibiotics in diarrhea would be effective are in shigellosis, campylobacteriosis, C. difficile infection, travelers' diarrhea, and in protozoal infections. A case for the use of antibiotics in diarrhea may be made for those who are Immunocompromised, septic, severely ill or older than 65 years of age.

In traveler’s diarrhea, the antibiotic treatment is based on where one is travelling, and any patterns of resistance or common pathogens noted. The two antibiotics most commonly used in traveler’s diarrhea are ciprofloxacin and rifaximin. For South and Southeast Asia specifically, azithromycin is indicated instead.

Diarrhea caused by Shiga toxin-producing E. coli should not be treated with antibiotics due to the increased risk in hemolytic–uremic syndrome. This type of diarrhea is diagnosed based on a patient’s clinical presentation. It commonly presents as bloody diarrhea, a history of eating uncooked ground beef, or proximity to an outbreak.

Antibiotics are also indicated in diarrhea that was not managed with more common treatments and is still persisting past 10 to 14 days. At this stage, testing and treating for bacterial and protozoal infections should be considered and treated for.

Probiotics
The evidence behind the use of probiotics in diarrhea varies considerably from study to study. Probiotics consist of bacteria that are not harmful or infectious. It is thought that they support the normal gut microbiota, thus helping these microbes outcompete infectious bacteria for space and nutrients needed. Probiotics are also thought to produce chemicals and immune responses that may be helpful in treating diarrhea. Oral rehydration therapy remains the staple in the treatment of diarrhea. However, studies show the use of probiotics is safe and may shorten the duration of diarrhea and reduce the frequency of stools in acute infections diarrhea. Where studies vary is which probiotic to use, and which would be the most safe and effective in acute infectious diarrhea. The probiotic regimen of choice is still up for debate. Studies find that probiotics are not associated with any adverse events, and all seemed to show a shortened duration of diarrhea and improved stool frequency. While study results seem promising, the use of probiotics in the treatment of acute infectious diarrhea still requires further research to determine the best probiotic and treatment regimen. Different probiotics also may be useful for different people and for different causes of diarrhea. This is also an area of study that needs to be improved upon. The cost of probiotics must also be considered when determining the cost-benefit analysis of their use.

Somatostatin
Somatostatin works by inhibiting gastrointestinal motility and secretion, thereby reducing the symptoms of diarrhea. Studies show the use of a somatostatin analog lanreotide improved stool frequency, consistency, and quality of life. Sandostatin is a synthetic somatostatin analogue consisting of octreotide, octreotide acetate and SMS 201-995. It is Sandostatin’s effects on multiple receptors in the gastrointestinal tract that rationalizes its use in refractory diarrhea. It has a high affinity for the somatostatin receptor 2 (SST2), and moderate/weak affinities for the SST5 and SST3 receptors. Sandostatin’s interaction with these receptors inactivates adenylyl cyclase, and inhibits Ca2+and K+ flux through the use of inhibitory G-proteins. Ultimately, this results in decreasing the amount of pancreatic and gastrointestinal hormones and secretions. Increased absorption of water and electrolytes can also be seen, which is key in counteracting the pathogenic effects of diarrhea.

Acute viral diarrhea
The vast majority of acute diarrhea cases are viral in nature. Norovirus, rotavirus and adenovirus remain common causes of diarrhea. Most viral diarrhea is self-limiting and acute, meaning diarrhea lasting less than 14 days. Antidiarrheal treatment consists mainly of rehydration and ORT. Other antidiarrheals such as loperamide may be used for symptom management. Antibiotics should be avoided and would add no benefit.

Acute bacterial diarrhea
Only 1-5% of diarrhea cases are associated with bacterial infection. Bacterial diarrhea is diagnosed based on signs, symptoms and other factors such as diet history. More severe, prolonged symptoms would indicate bacterial diarrhea. Signs that diarrhea may be bacterial in nature include bloody diarrhea, recent antibiotic use, high-risk food ingestions, and severe dehydration. Severe cases may warrant blood, urine and stool analysis for diagnosis. Bacterial cases of diarrhea include Shigella, Salmonella species, Campylobacter jejuni, Cholera, Yersinia, Escherichia coli and Listeria. All bacterial causes of diarrhea are treated with antibiotics. Antibiotic choice is made based on the symptoms presented, patient history, and/or the suspected bacterial cause. Often, empiric therapy is used as finding the specific causal agent is not always feasible. The use of ORT is of importance in bacterial diarrhea for dehydration treatment and prevention.

Traveler's diarrhea
This classification of diarrhea can be considered when one has a recent history of travel. The risk for traveler's diarrhea is highest when travelling to low-moderate income countries. Travelers should be aware of this possibility, and should be informed of safety measures when travelling to high risk areas. Instances of traveler's diarrhea also increase in hot, wet climates. Common pathogens in traveler's diarrhea include enterotoxigenic, enteroaggregative and diffusely adherent E coli, Norovirus, Rotavirus, Salmonella species, Campylobacter jejuni, Shigella , Aeromonas species, Bacteroides fragilis, and Vibrio species. The use of antibiotics in traveler's diarrhea is supported, including prophylactic quinolone antibiotic use before travelling. Azithromycin may be prescribed for travelers to South East Asia. Bismuth subsalicylate also may help protect travelers. Other antidiarrheals and ORT may be used.

C. difficile diarrhea
C. difficile infection is a serious cause of diarrhea. Hospitalization and previous antibiotic use, being the most common cause of antibiotic-associated diarrhea. As antibiotics remove the natural flora of the gut, this gives C. difficile an opportunity to colonize the intestine. Signs of C. difficile diarrhea are more severe, with 10-15 loose stools a day and abdominal cramping and discomfort. Other systemic symptoms such as fever and high white blood cell count are possible. Symptoms commonly appear around a week after antibiotic therapy, but can still occur up to 3 months after. Antibiotics vancomycin and metronidazole are used to treat C. difficile infection.

Parasitic diarrhea
Common parasitic causes of diarrhea include Cryptosporidium, Cyclospora, Entamoeba, Microsporidia and Strongyloides. Parasitic diarrhea should be considered in people with HIV/AIDS, children in daycare centers, or in certain cases of travel. Stool samples need to be collected for 3 days and analyzed for potential parasites. Treatment depends on the type of parasite encountered. Giardia duodenalis, a common parasitic pathogen that can cause diarrhea, is treated with the antibiotic metronidazole. Parasites can be highly infections, and treatment also includes proper prevention of transmission of the parasite through hygiene.