Antidiarrheal Therapy by Dr.Hamed Daghzghzadeh

Diarrhea is loosely defined as passage of abnormally liquid or unformed Stool at an increased frequency. For adults on a typically western Diet, stool weight exceeding 200g/d Can generally be considered diarrheal.

Epidemiology of Acute Diarrhea

Worldwide > 1000,000,000 people/year

5-8 million deaths / year in developing countries in developing countries

► Secretory diarrhea ► Osmotic diarrhea ► Inflammatory ( exudative ) diarrhea ► Motility ( dismotile ) diarrhea ► Anatomic ( absorptive surface) Pathophysiologic classification of diarrhea

Major Causes of Acute Diarrhea 8 ► INFECTIONS (Including Travelers Diarrhea) Bacterial : Campylobactre Species, C.difficile, E.coli, Salmonella eneritides, Shigella Species Parasitic/protozoal : E. histolytica, Giardia lambilia,Cryptosporidium,Cyclospoa Viral : Adenovirus, Norwalk virus, Rotavirus,AIDS, Others Fungal ► FOOD POISONING : B.Cereus, C. Perfringens, Salmonella species, S.aureus, Vibrio species, Shigella species, Camppylobacter.jejuni, E.coli ► MEDICATIONS ► RECENT INGESTION OF LARGE AMOUNT OF POORLY ABSORBABLE SUGARS ► INTESTINAL ISCHEMIA ► FECAL IMPACTION ► PELVIC INFLAMMATION ► GRAFT VS HOST DISEASE

Most acute diarrheas are due to infectious diseases that have limited courses from a few days to a few weeks.

MAJOR CAUSES OF CHRONIC DIARRHEA ► IBS ► IBD ► Ischemic bowel disease ► Chronic bacterial / mycobacterial infection ► Parasitic & fungal infections ► Radiation enteritis ► Malabsorption Syndromes ► Medications, Alcohol ► Colon cancer, Villous Adenoma,intestinal Lymphoma ► Diverticulitis ► Previous Surgery ( gastrectomy, vagatomy, intestinal resection ) ► Endocrine causes ► Fecal impaction ► Heavy metal poisoning ► Epidemic idiopathic chronic diarrhea

NONSPECIFIC Rx OF DIARRHEA

The most important Rx for diarrhea is to ensure that fluid and electrolyte deficits are replenished with IV or oral rehydration solution.

ORS

► ► The rate of replacement should match the clinical presentation.

Empiric Therapy of Acute Diarrhea

Aminoacid & Glucose absorption accelerates sodium and fluid absorption in the jejunum.

Saline solutions containing glucose or amino acids will be absorbed readily

Oral rehydration solutions increase fluid and electrolyte absorption; they are not designed to reduce stool output, so stool weight actually may increase with their use.

Infection is a frequent cause of acute diarrhea.

If the prevalence of bacterial or protozoal infection is high in a community or in a specific situation, empiric use of antibiotics is logical.

as in the treatment of travelers' diarrhea

Even without bacteriologic proof of infection.

Empiric antibiotic therapy is often also logically used for more severely ill patients while awaiting bacterial culture results. Adachi JA, Zeichner LO, DuPont HL, Ericsson CD: Empirical antimicrobial therapy for traveler's diarrhea. Clin Infect Dis 31:1079, 2000.

Ciprofluxacine 500 mg Q12h ( 3 days) Or Azythromycin 1000 mg single dose

Experts also advise against empiric treatment of salmonellosis unless enteric fever is present. Sirinavin S, Garner P: Antibiotics for treating salmonella gut infections. Cochrane Database Syst Rev 30:CD001167, 2000.

Nonspecific antidiarrheal agents can reduce stool frequency and stool weight and can reduce coexisting symptoms, such as abdominal cramps

Opiates, such as loperamide, or diphenoxylate with atropine frequently are employed. Schiller LR: Review article: Anti-diarrhoeal pharmacology and therapeutics. Aliment Pharmacol Ther 9:87, 1995.

Intraluminal agents, such as bismuth subsalicylate and adsorbents (e.g., kaolin) also may help reduce the fluidity of bowel movements. Schiller LR: Review article: Anti-diarrhoeal pharmacology and therapeutics. Aliment Pharmacol Ther 9:87, 1995.

Empiric Therapy of Chronic Diarrhea is used in three situations: (1) Initial treatment before diagnostic testing; (2) After diagnostic testing has failed to confirm a diagnosis (3) When a diagnosis has been made but no specific treatment is available or specific treatment has failed to produce a cure.

Generally, empiric antibiotic therapy is less useful in chronic diarrhea than in acute diarrhea.

In chronic diarrhea an empiric course of metronidazole or a fluoroquinolone before extensive diagnostic testing, before extensive diagnostic testing, is not recommended.

► ► Remember that diarrhea can be a prominent symptom of malaria.

Other drugs

Alosetrone ► 5-HT3-receptorantagonist ► Is indicated for IBS.

► VERAPAMIL ► NIFEDIPENE REDUCE MOTILITY INCREASE ABSORBTION

Travelers' diarrhea

Travelers' diarrhea affects 30% to 50% of travelers to developing countries.

Enterotoxigenic Escherichia coli (ETEC) Enterotoxigenic Escherichia coli (ETEC) is the most common cause of travelers' diarrhea worldwide

Other causes of travelers' diarrhea ► ► Shigella ► ► Campylobacter ► ► Aeromonas, ► ► Plesiomonas, ► ► Vibrio ► ► Rotaviruses ► ► Norwalk virus ► ► Giardia

Most cases of travelers' diarrhea occur between 5 and 15 days after arrival.

► ► Persons with gastric hypoacidity and immunosuppressed patients are probably at greater risk of developing travelers' diarrhea.

► ► Most bouts of travelers' diarrhea are self-limited, with resolution after 4 to 6 days

The illness is heralded by malaise, anorexia, and abdominal cramps, followed by watery, usually nonbloody, diarrhea

► ► In some cases, nausea and vomiting may be a prominent component

How to prevent Travelers' diarrhea?

Bcause travelers' diarrhea is contracted by the ingestion of fecally contaminated food or water.

The first line of defense for the traveler is care in selecting food and beverages.

► ► The first approach is chemoprophylaxis using either antibiotics or bismuth to prevent diarrhea.

 The most widely used approach to travelers' diarrhea is probably the provision of antibiotics to be used by the traveler, if and when diarrhea strikes.

Antibiotic prophylaxis is indicated for travelers (to high risk countries), with 1. Gastric achlorhydria 2. IBD 3. Immunocompromise

  A reasonable current recommendation is to provide a three-day course of a quinolone for travelers to most developing countries.

  The patient is told to begin the antibiotic when diarrhea starts and to continue treatment for 3 days.

A quinolone represents the drug of choice for travelers if antibiotic prophylaxis is used or for the treatment of travelers' diarrhea.

  A single daily dose of ciprofloxacin (500 mg) had a protective efficacy of 94%.

.  Norfloxacin in a daily dose of 400 mg had a protective efficacy of 93%.

► ► Chemoprophylaxis with bismuth is moderately effective (approximately 65%) in preventing diarrhea.

► ► Two bismuth tablets(240mg x 2) taken four times daily.

self-treatment regimens are not appropriate for the traveler with It needs to be emphasized before travel that self-treatment regimens are not appropriate for the traveler with   bloody diarrhea,   severe abdominal pain,   high fever

The disadvantages relate to the possibility of 1-side effects 2-selection of antibiotic-resistant organisms.

The advantage of prophylactic antibiotics is their high efficacy in preventing disease.

Finally, the most important component of self-treatment is the replacement of the fluid and electrolytes lost during diarrhea.

Watery diarrhea that occurs later after return or that persists longer than 10 days despite antibiotic therapy is most commonly Giardia lamblia infection.

If the diarrhea fails to respond to metronidazole, a gastrointestinal evaluation should be performed.

The diagnostic & therapeutic considerations differ somewhat for bloody diarrhea, and the pace of the workup should be accelerated.

Indications of antibiotic coverage wether or not a causative organism is discovered in acute diarrhea 3 1. Immunecompromised patient. 2. Mechanical heart valves or recent vascular graft. 3. Elderly.

Thank you

Constipation

Constipation ► Constipation, or associated symptoms, afflicts many people in the Western world.

The prevalence is greatest among children and the elderly.

► Many people ignore the symptoms or treat themselves by dietary modification or over-the- counter remedies.

PRESENTING SYMPTOMS ► Aperson who says "I am constipated" is either conscious of an unpleasant sensation related to bowel movements or believes that bowel function is abnormal.

► 6% - 23% of subjects said in response to interview that they had experienced constipation during the past 12 months.

► At least 10% of the subjects experienced difficulty in defecation at least once a month.

► More women than men regard themselves as constipated.

CLINICAL DEFINITION AND CLASSIFICATIONA ► Clinical definition of constipation needs to take account of both difficult defecation and infrequent stools.

General Factors ► Sex ► Age ► Nationality ► Diet ► Exercise and Daily Activity

Defecatory Function ► Failure of Relaxation of the Anal Sphincter Complex ► Ineffective Straining ► Diminished Rectal Sensation ► Size and Consistency of Stool

Psychological and Behavioral Factors ► Personality affects stool size and consistency.

CONSTIPATION AS A MANIFESTATION OF SYSTEMIC DISORDERS ► Hypothyroidism ► Diabetes Mellitus ► Hypercalcemia

CONSTIPATION AS A MANIFESTATION OF CENTRAL NERVOUS SYSTEM DISEASE OR EXTRINSIC NERVE SUPPLY TO THE GUT ► Loss of Conscious Control ► Parkinson's Disease ► Multiple Sclerosis ► Spinal Cord Lesions

CONSTIPATION SECONDARY TO STRUCTURAL DISORDERS OF THE COLON, RECTUM, ANUS, AND PELVIC FLOOR ► Disorders of Smooth Muscle ► Enteric Nerves

Disorders of the Anorectum and Pelvic Floor ► Rectocele ► Weakness of the Pelvic Floor — "Descending Perineum Syndrome" ► Full-Thickness Rectal Prolapse, Intrarectal Mucosal Prolapse, and Solitary Rectal Ulcer Syndrome

PSYCHOLOGICAL DISORDERS AS CAUSES OF OR AGGRAVATING FACTORS IN CONSTIPATION ► Depression ► Eating Disorders ► Denied Bowel Movements

CLINICAL ASSESSMENT ► History ► Social History ► Physical Examination ► Prospective Use of a Diary Card