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College of Pharmacy Fourth year. Clinical Pharmacy. 2016-2017 Diarrhea: - It is an increase in the bowel movement with the production of soft watery stools. - It can be defined by the passage of 300 ml of liquid feaces within 24 hours. - It results in fluid and electrolytes loss. - It is not a disease but a sign of underlying illness such as infections or GI disorders. - It is more common in persons with poor level of hygiene, high mortality rate between children under 5 years old, it also increased between tourists visiting foreign countries. 1 A/ Acute diarrhea : ( self-limiting simple diarrhea): Causes 1- Infectious diarrhea - It is the commonest type of diarrhea caused by virus such as (rota virus) that cause infantile diarrhea, or bacteria such as E.coli , staph. , clostridium that produces toxins, or salmonella and shigella that cause damage to epithelial mucosa and prevent the absorption . E.coli is the major cause of traveller's diarrhea. - Protozoal gastroenteritis e.g: amebiasis and giardia. 2- Food induced diarrhea: - Food poisoning occurs mainly with frozen meat and other contaminated food. - The incidence is more in elderly patients. - In children milk, banana and chocklet may induce diarrhea. 3- Drug induced diarrhea: - Many broad spectrum AB such as ampicillin, erythromycin and neomycin may induce secondary infections. - The primary cause is the growth of AB resistant bacteria and fungi in large bowel. 2 - It is generally are self-limiting except the over growth of clostridium difficil that cause PMC which is life-threating one. - Other drugs such as Mg containing antacid, alcohol, frusemide, digoxin, mefenamic acid, and caffeine may induce simple diarrhea. B/ Chronic diarrhea: Diarrhea for more than 4 weeks. It occurs secondary to a disease such as IBS or DM, ulcerative colitis and thyrotoxicosis. Diagnosis: For acute diarrhea stool examination and culture is performed but for chronic barium enema or endoscopy are performed. Symptoms: The symptoms of acute diarrhea are mild abdomen cramps, flatulence and general weakness due to electrolyte loss by vomiting and diarrhea. These symptoms can be resolved spontaneously with several days. Fever occurs with infectious &food poisoning diarrhea. For chronic diarrhea blood and mucus may appear in stool secondary to ulcerative colitis or chronic disease in GIT. For PMC diarrhea,the symptoms are more severe and occur 4-10 days after AB initiation of therapy , its associated with fever and high volume of mucus, (erythromycin & clindamycin) 3 Treatment: 1-Basic approach: - To determine the cause of diarrhea we should take history from the patients about drugs, diseases or unusual dietary habits. - The food and the drinks should be stopped 4-6 hr. followed by fluid only (glucose and electrolytes mixture, ORS for 18-24 hr.) - The same treatment is preferred in children and infants with small amounts of soft foods given for 1-2 days. - Milk should not be stopped in infants, but avoid artificial milk and drink that contain disaccharides since disaccharidase enzyme (lactase) is deficient in inflamed bowel leading to accumulation of lactose, that cause osmotic diarrhea. 2- Rehydration: - ORS (glucose-electrolyte mixture) is used to treat diarrhea according to WHO recommendations, it contains glucose, potassium, sodium, and chloride in isotonic solutions. The level of glucose is 80-120 mmol/L, to optimize the absorption in small bowel, when the amount of glucose is more than 160 mmol/L will cause osmotic gradient and worsen the condition. 4 - Sodium should not exceed 90 mmol/liter to avoid hypernatremia in children specially. - Potassium level is given to avoid hypokalemia in elderly patients on diuretics with digoxin therapy. - In adults, ORS can be substrates by tea spoonful of table salt and one table spoonful of sugar will be enough to replace electrolyte loss. - The volume of ORS required in adults in 400 ml of each loss, children 100 ml, and infant 50 ml. - In severe diarrhea the patient should be hospitalized and I.V electrolytes like ringer lactate solution also for patients can not taking oral therapy because of vomiting, when electrolyte is replaced vomiting will be stopped. 3-Medical therapy: Treatment of acute diarrhea: Infectious diarrhea: stool examination is necessary to determine type of causing microorganism, acute viral or bacterial diarrhea are self-limiting and do not require antimicrobial agent, but patients with severe symptoms like fever and bloody stool, AB is recommended and the DOC is flouroquinolones e.g: ciprofloxacin (500 mg po bid for 3 days) the alternative is co-trimoxazol (2*2 po bid for 5 days) but resistance are common in some areas. - Parasitic infections such as amebiasis (traveller's diarrhea) occurs in areas with poor sanitation. 5 The causative m.o. is entamebahistolytica that are treated by metronidazole (750 mg po tid for 10 days). - Other cause of traveler's diarrhea is giardiasis that may cause acute or chronic diarrhea, treated by quinacrine (100 mg po tid for 5-7 days) or metronidazole (250 mg po tid for 7 days). - Diloxamide for dysentery and giardiasis. Pseudomembranous colitis (PMC): It is other type of infectious diarrhea following AB therapy. The colon may become colonized with C. difficil that suppress the normal flora and cause severe diarrhea. Clindamycin, lincomycin and cephalosporins are the major problem, this is treated by metronidazole (500 mg oral or IV for 7-14 days), initial relapse is treated with larger course of metronidazole and refractory cases is treated by vancomycin (125 mg po q 6). Food poisoning /gastroenteritis: - It is characterized by diarrhea associated with vomiting and fever. - There are many causes of food poisoning either bacteria, chemicals or food allergy. - The onset of symptoms is a guide to the cause, when the onset is within 30 minutes,it is likely to be due to chemical poisoning, vomiting within 2-6 hr associated with diarrhea and abdominal pain is caused by staph. or bacillus toxins. While salmonella infection produce these symptoms within 12-48 hr of ingesting contaminated food. 6 Non-specific anti-diarrheal: - In most cases of acute diarrhea, anti-diarrheal are not necessary although they are over used. They should be avoided in invasive bacterial infections since they precipitate megacolon, specially with those decrease peristalsis, they are not recommended for children under 12 y.o. when rehydration fluid is the important treatment, the anti-motility drugs should also be avoided in chronic diarrhea such as ulcerative colitis to avoid megacolon. 1- Opioid agents: they should be used with caution in patients with asthma, chronic lung disease, prostatic hypertrophy and narrow angle glaucoma. Drug abuse for these opioids should be recognized. - Lopramide it is synthetic opioid that is incompletely absorbed from GIT and does not cross BBB , so has no CNS s.e,it increase the tone of anal sphincter and given in a dose of 2-4 mg po after each loss.(max 8mg/day). - Diphenoxylate it is a synthetic opioid that is given in combination with subclinical dose of atropine (lomotil) to avoid drug abuse. They are readily absorbed from GIT causing systemic effect like respiratory depression and can cross CNS causing abuse s.e, it also should be avoided in advanced liver disease. It is given in a dose of (5 mg po qid) followed by lowest effective dose. Children are susceptible to over doses, 10 tablets may be fatal. It does not have effect on anal sphincter, so it cause some leakage. - Codeine and morphinethe constipating effect of narcoting analgesic is used to treat diarrhea, morphine has GIT selective effect, dependence and tolerance may occur that limit their use, they are contained in some preparations of antidiarrheal agents. 7 2- Adsorbents like kaolin and pectin (60-120 ml po after each loss bowel) they adsorb fluid and bulk the stool, but they are not recommended for acute diarrhea, although they provide some relief with chronic diarrhea, they are given in infectious diarrhea and food poisoning to adsorb bacterial toxins. 3- Bulk forming agents they are mostly used in chronic diarrhea, and after ileostomy and colostomy to normalize bowel consistency. 8 Constipation: - It is the passage of hard stool, painful or incomplete evacuation with abdominal discomfort. - Normal bowel habits range from the passage of several stools a day to passage of one stool every 2-3 days (3 /week). - The patient is constipated when stools are passed < three times a week in adults, two or less /week in children. - The incidence is more in elderly patients due to diminish colonic activity and chronic illness and receiving constipating drugs. - The incidence is also increased in bedridden children and pregnant females, also in laxative abuse. Causes: 1- diet : low fiber diet and dehydration 2- disease: - Metabolic disorderse.g: hypokalemia, DM, hypercalcemia, and hypothyroidism. - Neurologic e.g: parkinsons, cerebral tumor. - Functional e.g: irritable bowel, hemorrhoid, hernia, - Psychological e.g: depression, stress. - Surgical e.g: GIT surgery. 9 3- Drugs: - Opioid analgesics, cough suppressants, anticholinergic, antihistamine, TCA, diuretics, MAOI, AL-containing antacid, PPI. - Polypharmacy Rx may cause constipation e.g: diuretics in dehydrated patients, e.g: antihistamines with TCA. Treatment: 1- Basic approach: - Mild form of constipationmay be treated by increasing the amount of high fiber diet, increasing fluid intake, and encouraging for regular exercise (normal person should take 6 glasses of water/ day. - We should educate the patient about normal body physiology; take history to know the cause of constipation. 2- Medications: (laxative drugs) The passage of stool is speeded by: a. Increase volume of non-absorbable solids with bulking agents. b. Stimulation of gastrointestinal mucosa and initiate to peristalsis c. Increase water contents of GIT contents. d. Change the consistency of the feaces. So laxatives are grouped into 4 main groups:1) Bulk forming laxatives: (methyl cellulose, ispagulla, streculia& bran) 10 - These agents increase the volume of intestinal content and stimulate peristalsis. - They are safe and used to treat simple constipation. - They should be taken with plenty of water to be swallowed and form gel that increase stool bulk, also to avoid intestinal obstruction. - The onset of action is 12 – 72 hr. - They are safe in elderly patients, pregnant and lactating women, in abdominal surgery (ileostomy and colostomy), chronic bowel disease. 2) Stimulant laxatives: (bisacodyl, senna, glycerin, castor oil) - They stimulate nerve ending effect (peristalsis). - They also inhibit Na-K ATPase and decrease fluid reabsorption. - The onset of action is 8 – 12 hr. and given at night. - They may cause S.E. like abdominal cramps, fluid loss and electrolyte imbalance so they should be given with caution in elderly and pregnant patients. - Cascara and phenophthaline are no longer use, since they color the urine with pink or red and cause skin rash, cardiovascular and respiratory collapse. 11 - Glycerine suppository has irritating and lubricating effect and used mainly in children and elderly patients. They have rapid onset of 30 min-1hr. 3) Osmotic laxatives: salts) (MG salts, lactulose, phosphate & sod. - They have rapid onset about 2-8 hrs. - They are poorly absorbed from GIT, so they retain fluid by their osmotic action. - They should be taken on empty stomach, before breakfast. - They should be taken with sufficient fluid to ensure a hypotonic solution is produced. - Lactulose is widely used in elderly patients, it need 2-3 days to exert its laxative action. - Mg (OH or sulfate) and lactilol are less expensive, has rapid action, but over doses is avoided , taken on need only. They are C.I in H.T. - Lactulose (fructose + galactose) is given with caution in patient with DM. 12 - Osmotic laxatives also may cause cramps flatulence, &electrolyte disturbance. 4) Fecal softener / Lubricants: (Liquid paraffin, docusate sodium) - They reduce the surface tension of hard stool, so act as a wetting agent like (detergents) - They are used when defecation is difficult like in hemorrhoid or anal fissures, also indicated in elderly and patients with M.I. or stroke where straining is dangerous. - The major S.E. of liquid paraffin is their interaction with absorption of lipid soluble vitamins (A, K, D, E) causing vit. A deficiency mainly. - It also may be absorbed in mesenteric lymph node in children, or it may be aspirated during sleeping causing lipoid pneumonia. - Prolong use may cause anal leakage and seepage (used for short term 7 days). - Rectal (docusate sod.) has rapid onset of action but should not be used for patients with hemorrhoid & anal fissure. Adverse reaction, C.I., and warnings: - They are safe, but chronic use should be avoided mainly with stimulant laxatives. 13 - They are all C.I. in intestinal absorption, fecal impaction and abdominal pain of unknown cause. - Bulking agent should be taken with cold water and avoided immediately before bed time. - Stimulant laxatives may cause sever abdominal cramps so avoided in children, most of them may color the urine. Danthrone & caster oil best avoided in pregnancy and lactation since they are excreted by milk. - Sodium containing laxatives should be avoided in HT, CHF & impaired renal function. - Patients on X-ray or endoscopy or pre-operatively should use laxatives for 3 days only, since longer time may worsen the condition and cause misdiagnosis. - Laxative abuse may cause abdominal pain, steatorrhea, nausea, vomiting and electrolyte imbalance. - To avoid laxative abuse, we can start with stimulant & osmotic laxative, and then continue with balking agents. Dr. Mohammed M. Mohammed Good Luck 14