Community Pharmacy Lecture 3 - PDF

Lecture 3 Dr.Sahar Badr Associate prof. of Clinical Pharmacy  Diarrhea ▪ Diarrhea is defined as an increased frequency of bowel evacuation, with the passage of abnormally soft or watery feces/stool (more than three times a day). ▪ It is a common and debili...

Lecture 3 Dr.Sahar Badr Associate prof. of Clinical Pharmacy  Diarrhea ▪ Diarrhea is defined as an increased frequency of bowel evacuation, with the passage of abnormally soft or watery feces/stool (more than three times a day). ▪ It is a common and debilitating (i.e. making someone very weak) condition, and in extreme condition can be life-threatening, with some 5 million deaths annually worldwide due to dehydration. ▪ Prolonged diarrhea, altered bowel habits or the passing of blood should all warrant referral. ▪ Diarrhea may be acute, e.g. due to infection, or chronic, e.g. associated with other gastrointestinal pathologies. Significance of questions and answers Age ▪ Particular care is needed in the very young and the very old. ▪ Infants (younger than 1 year) and elderly patients are especially at risk of becoming dehydrated. Duration ▪ Most cases of diarrhea will be acute and self-limiting. ▪ Because of the dangers of dehydration it would be wise to refer infants with diarrhea of longer than 1 day duration to the physician.  Classification of diarrhea by Mechanism ▪ Osmotic diarrhea: occurs when excess water is pulled into the intestinal tract. This may be the result of hypermagnesemia, undigested lactose or fructose or celiac disease. ▪ Secretory diarrhea: occurs when the intestinal wall is damaged, resulting in an increased secretion rather than absorption of electrolytes into the intestinal tract. This can occur with the ingestion of bacterial enteropathogens (Escherichia coli, Salmonella, Shigella). ▪ Motility-related diarrhea: occurs when food moves through the intestines at such a rapid rate (hypermotility) that insufficient time is allowed for water and nutrient absorption. Medications that can also cause hypermotility include parasympathomimetic agents (metoclopramide), digitalis, quinidine and antibiotics. ▪ Inflammatory diarrhea: occurs when there is damage to the mucosal lining which leads to a passive loss of protein-rich fluids and a decreased ability to absorb these lost fluids. ▪ It is characterized by frequent, small-volume, bloody stools and may be accompanied by tenesmus, fever, or severe abdominal pain. It can be caused by bacterial infections, viral infections, parasitic infections, or autoimmune problems such as inflammatory bowel diseases (Crohn’s disease or ulcerative colitis).  Classification of diarrhea by Origin (causes) Viral gastroenteritis ▪ Viral gastroenteritis is caused by the noroviruses, which are transmitted by contaminated water or food, resulting in a watery stool. ▪ Other viruses include rotaviruses, adenoviruses, hepatitis A virus. ▪ Associated symptoms are those of a cold and perhaps a cough. The infection starts suddenly and vomiting often precedes diarrhea. ▪ Diarrhea associated with viral gastroenteritis is usually self- limiting for 2 to 3 days but may last up to 2 weeks.  Bacterial gastroenteritis ▪ Bacterial gastroenteritis results from consumption of contaminated water or food. ▪ Common organisms include E. coli, Staphylococcus aureus, Vibrio cholerae, Shigella, Salmonella, Campylobacter and Clostridium difficile. ▪ Invasive bacteria affect the large intestines, resulting in dysentery-like stools (extreme urgency to defecate, tenesmus, and small-volume stools that contain blood or pus). ▪ Onset of diarrhea may range between 1 and 72 hrs, depending on the infecting bacteria and require treatment with antibiotic. Tenesmus: it is the sensation of inability or difficulty to empty the bowel at defecation. ▪ Two commonly seen infections are Campylobacter and Salmonella, which are often associated with contaminated poultry. ▪ Contaminated eggs have also been found to be a source of Salmonella. ▪ E. coli is a common bacteria that causes diarrhea. E. coli infection is related to improper food preparation. ▪ Infection during pregnancy can cause miscarriage, still birth or an infection of the newborn. ▪ Foods to be avoided during pregnancy include unpasteurized cheese, cold meat and smoked fish. ▪ Pregnant women with diarrhea or fever should be referred to GP.  Parasitic gastroenteritis ▪ Protozoal diarrhea results from fecal–oral route, contaminated water or food. ▪ It is caused by Giardia lamblia, Entamoeba histolytica, or Cryptosporidium, may be described as profuse (i.e. excessive) watery diarrhea, which may be accompanied by flatulence and/or abdominal pain. ▪ This type of diarrhea is self-limiting, but may persist for several weeks. Therefore, individuals with protozoal-induced diarrhea are at risk for dehydration. ▪ Self-care is inappropriate for this type of diarrhea; infected persons should be referred to a medical provider as it may require treatment with Metronidazole or Diloxanide furoate (not OTC medication).  Cryptosporidium Entamoeba histolytica Giardia lamblia Diet-Induced Diarrhea ▪ Diarrhea induced by foods results from food allergies, high fiber diets, fatty or spicy foods, large amounts of caffeine, or lactose intolerance. ▪ The best treatment is prevention by avoiding these types of foods. Traveller's Diarrhea ▪ It is the most common form of bacterial diarrhea caused by contaminated water or food in foreign country where sanitary conditions are inadequate (most commonly by E.coli). ▪ This is due to extensive alteration in the bacteria flora of the gut. It is usually self-limited (3-5days). However supplement therapy with minerals & electrolyte replacement is usually required. ▪ General precautions to avoid traveller's diarrhoea:  Eat well cooked food.  Recently peeled fresh fruit is usually safe.  Bread is usually safe.  Always avoid fresh fruit juice or fresh salad because the moist nature is the prime environment for bacterial growth.  Drink boiled or bottled water. Drug-Induced Diarrhea Broad-spectrum antibiotics may alter the natural gut flora, leading to superinfection (pseudomembranous colitis, which is serious complication of treatment with broad spectrum antibiotics, especially clindamycin). Orlistat, an anti-obesity drug, inhibits pancreatic lipases to prevent the breakdown of fat and this may lead to steatorrhoea (fatty diarrhoea). Misoprostol activates prostanoid receptors in the intestines, which may lead to secretory diarrhea. Antacids: Magnesium salts, PPIs (achlorhydria) Antihypertensives: methyldopa; beta-blockers Digoxin Diuretics (furosemide) Laxatives Non-steroidal anti-inflammatory drugs.  Symptoms ▪ Acute diarrhea is rapid in onset and produces watery stools that are passed frequently. ▪ Abdominal cramps, flatulence and weakness or malaise may also occur. ▪ Nausea and vomiting may be associated with diarrhea, as may fever. ▪ The pharmacist should always ask about vomiting and fever in infants; both will increase the likelihood that severe dehydration will develop. ▪ Another important question to ask about diarrhea in infants is whether the baby has been taking milk feeds and other drinks as normal. ▪ Loss of body fluids will lead to dehydration specially in children and elderly. Since most fluids contain important electrolytes the patient may suffer from hypokalemia, hyponatrimia and electrolyte imbalance which may lead to death.  Pharmacological Basis of Management ▪ The first step in the management of acute diarrhea is to remove the cause and the condition may resolve. ▪ The patient should continue normal feeding with simple foods such as boiled rice, and infants should continue with breast or formula milk feeds. ▪ The basis of treatment is electrolyte and fluid replacement; in addition, antidiarrheals are useful in adults and older children. ▪ The first measure is oral rehydration therapy (ORT).  Oral Rehydration Therapy ▪ The risk of dehydration from diarrhea is greatest in babies, and rehydration therapy is considered to be the standard treatment for acute diarrhea in babies and young children and for who are over the age of 60. ▪ Oral rehydration sachets may be used with antidiarrheals in older children and adults. ▪ Sachets of powder for reconstitution are available; these contain sodium as chloride and bicarbonate, glucose and potassium. ▪ The absorption of sodium is facilitated in the presence of glucose. ▪ Patients should be reminded that only water should be used to make the solution (never fruit or fizzy drinks) and that boiled and cooled water should be used for children younger than 1 year. ▪ Fizzy, sugary drinks should never be used to make rehydration fluids, as they will produce a hyperosmolar solution that may exacerbate the problem. The sodium content of such drinks, as well as the glucose content, may be high. ▪ Boiling water should not be used, as it would cause the liberation of carbon dioxide. ▪ The solution can be kept for 24 h if stored in a refrigerator. ▪ Home-made salt and sugar solutions are not recommended, especially in infants, young children and elderly patient. They are commonly used in developing countries where access to preformulated products is limited. ▪ In infants, breastfeeding or formula feeds should be offered between ORS drinks. ▪ Give ORS by mouth to correct continuing losses in the following volumes: For Children of 1–11 months 1–1½ times usual feed volume For Children of 1–11 years 200 ml, after every loose motion For Children of 12–17 years 200–400 ml, after every loose motion, dose according to fluid loss For Adults 200–400 mL, after every loose motion, dose according to fluid loss  Antimotility Agents ▪ These agents provide symptomatic relief by reducing the motility of the lower gastrointestinal tract, allowing reabsorption of fluid and reducing the passage of watery stools. ▪ The relief allows bowel control and prevents diarrhea from interfering with daily activities. ▪ They should be used in addition to ORT. ▪ Antimotility agents should not be used in children or in adults with severe inflammatory bowel disease where they may cause obstruction, leading to megacolon.  Loperamide ▪ Opioid antiperistaltic agent, is approved as a nonprescription treatment for acute, nonspecific diarrhea, including traveler’s diarrhea. ▪ Loperamide (Imodium) provides effective control of diarrhea as quickly as 1 hr after administration. ▪ Mechanism of action: Loperamide stimulates micro-opioid receptors on the circular and longitudinal musculature of the small and large intestines. ▪ They slow intestinal motility and affect water and electrolyte movement through the bowel, thus, the consistency of stools is increased. ▪ Adverse effects: constipation, dizziness, headaches, flatulence and nausea. ▪ Loperamide should not be recommended with symptoms of bloody acute bacterial diarrhea as expulsion of the toxin is necessary. ▪ It should not be recommended in patients with colitis (megacolon). ▪ The pharmacist should remind patients to drink plenty of extra fluids. Oral rehydration sachets may be recommended. ▪ Loperamide may not be recommended for use in children under 12 years. Atropin/Diphenoxylate (Co-phenotrope) ▪ Atropine is present in combination with diphenoxylate (co-phenotrope) and will reduce peristalsis through inhibition of muscarinic receptors on the gastrointestinal muscle. ▪ Co-phenotrope can be used as an adjunct to rehydration to treat diarrhea in those aged 16 years and over. ▪ Diphenoxylate is a centrally active opioid drug.  Kaolin ▪ Kaolin has been used as a traditional remedy for diarrhea for many years. ▪ It would absorb water in the GI tract and would adsorb toxins and bacteria onto its surface, thus removing them from the gut. ▪ The use of kaolin-based preparations has largely been replaced by oral rehydration therapy, although patients continue to ask for various products containing kaolin.  Bismuth Subsalicylate ▪ Bismuth preparations have moderate effectiveness against the prevention and treatment of traveler’s diarrhea and nonspecific diarrhea. ▪ The doses required for relief are large and must be administered frequently, so these preparations may be inconvenient. ▪ Mechanism of action: Bismuth salts work as adsorbents but also are believed to decrease secretion of water into the bowel. ▪ It is effective and can reduce the number of stools by 50%. ▪ Adverse effects: The most remarkable adverse effect is darkening of the tongue and stools. In excessive doses, BSS may cause ringing in the ears (Tinnitus) or neurotoxicity. ▪ Contraindications: BSS is not appropriate to recommend to individuals with hematological diseases, active GI or peptic ulcer disease, documented allergies to salicylates, children ˂12 years of age or within a 6-week period following varicella vaccination (The chickenpox vaccine), and those taking warfarin therapy.  Lactase ▪ Lactase is indicated for individuals who have insufficient amounts of lactase in the small intestine. Thus, this agent is not appropriate to treat any cause of diarrhea other than a lactase deficiency. ▪ In the body, lactose (a disaccharide present in dairy products) must be broken down to glucose and galactose to be fully digested. If the lactase enzyme is unable to break down the lactose, water is drawn into the gastrointestinal tract and results in diarrhea.  Probiotics ▪ Antibiotic-associated diarrhea is due to alterations in gastrointestinal flora, allowing the outgrowth of pathogenic bacteria. ▪ Lactobacillus are living organisms that colonize in the GIT to promote health benefits (L. acidophilus, L. bulgaricus). can only be recommended for maintenance of normal gastrointestinal tract function. ▪ Mechanism of action: probiotics is a means by which an exogenous species of bacteria is introduced into the gut to reestablish normal gut flora. Lactobacillus produces lactic acid, thus creating an acidic environment that is unfavorable for pathogenic microorganisms. ▪ Contraindications: Lactobacillus is not appropriate in individuals with immunosuppression or valvular heart disease due to the risk of bacteremia, those with a milk allergy/sensitivity because the product is dairy based, and those younger than the age of 3 years.  Practical Points 1. Patients with diarrhea should be advised to drink plenty of clear, non-milky fluids, such as water. 2. The patient can be advised to continue their usual diet but that fatty foods and foods with high sugar content might be best avoided as they may not be well tolerated. 3. Breast or bottle feeding should be continued in infants. 4. Avoid spicy foods, fruits, alcohol, and caffeine until 48 hours after all symptoms have disappeared. 5. Avoid chewing gum that contains sorbitol. 6. Avoid dairy product for 3 days after symptoms disappear. 7. Patients taking diuretics are at increased risk of dehydration and electrolyte disturbances, and may be advised to consult their GP or omit doses.  Counselling Oral rehydration therapy ▪ This should be made up with the correct amount of freshly boiled and cooled water. The amount required depends on the number of watery stools passed. Once reconstituted, ORT may be stored refrigerated for 24 h. Antibiotics ▪ Many cases of diarrhea are viral, so antibiotics are unlikely to be effective. ▪ Patients who are taking antibiotics (clindamycin) and then develop diarrhea that is severe or bloody should consult their GP immediately. Opioids ▪ These are effective at symptomatic relief but will not shorten the course of the diarrhea.