Published on August 18, 2019
slide 1: PHARMACOTHERAPEUTICS-II GASTROENTERITIS PHARM.D 1 GASTROENTERITIS T.SOUJANYA 16DC1T0021 slide 2: PHARMACOTHERAPEUTICS-II GASTROENTERITIS PHARM.D 2 GASTROENTERITIS Definition: Gastroenteritis is defined as inflammation of the lining of gastrointestinal tract particularly stomach and intestines. Infection that remains confined to stomach is referred as gastritis and to intestine is enteritis together it is gastroenteritis. Gastroenteritis is a term commonly used for acute diarrhoea that occurs suddenly and remains for a short time. It is a non-invasive infection the main cause behind which is bacteria and virus. However it may also be caused by parasites and due to adverse reaction to food and medication. Severity of gastroenteritis vary from mild and inconvenient to life threatening depending upon an individuals immunity to resist the infection. Classification: Gastroenteritis is classified as viral or bacterial. Viral Gastroenteritis: The viruses including adenovirus rotavirus astrovirus norovirs and calcivirus are responsible for many of the outbreaks of previously unidentified viral gastroenteritis. Among these rotavirus is the leading cause of gastroenteritis in infants as well as in children and calcivirus in adults. Norovirus causes fifty to seventy percent of gastroenteritis in adults. Gastroenteritis caused by viruses is highly contagious. Most of the patients recover without any complications but it becomes serious when people do not drink enough fluid to replace the fluid lost by dehydration. Bacterial Gastroenteritis: It is an inflammation of the stomach and intestines caused by bacteria or bacterial toxins. It has many causes and can range from mild to severe. slide 3: PHARMACOTHERAPEUTICS-II GASTROENTERITIS PHARM.D 3 Bacterial gastroenteritis unlike viral gastroenteritis lasts for longer period of time. Many different types of bacteria such as Camphylobacter jejuni Clostridium E.coli Salmonella Shigella Staphylococcus Versinia and Vibrio cholerae produce symptoms associated with gastroenteritis. Bacteria like Staphylococcus aureus can release toxins that cause diarrhoea. Escherichia coli can cause significant problems in children especially in developed countries. 1. Salmonella is spread by handling poultry. 2. Camphylobacter jejuni acquired by consumption of undercooked meat and unpasteurized milk is the major cause of traveller’s diarrhoea. 3. Shigella typically spreads via faecal-oral route from person to person. 4. Clostridium difficle may overgrow in the large intestine after the patient has been on certain antibiotics for an infection. Epidemiology: Gastroenteritis is the leading cause of mortality worldwide due to inadequate treatment. Epidemiological factors for gastroenteritis include travelling to countries with poor sanitation consumption of intake of contaminated food and water antibiotics recent camping etc. Children immunocompromised patients and people living in areas with poor sanitation are at a risk of acquiring infectious diarrhoea. Aetiology: It is estimated that almost 50 cases of gastroenteritis are food-borne and non-viral in nature whereas 20 cases which are more severe in nature and affect infants and children are caused by rotavirus. Adenovirus norovirs and astrovirus may also lead to gastroenteritis. slide 4: PHARMACOTHERAPEUTICS-II GASTROENTERITIS PHARM.D 4 Though cases of bacterial infection are not common bacteria like Salmonella Shigella Staphylococcus Camphylobacter jejuni Escherichia coli Clostridium Yersinia etc. usually result in gastroenteritis. Gastroenteritis is a contagious infection and can be transferred through an infected person poor hygiene as well as contaminated food and water. Pathophysiology: Pathophysiology of gastroenteritis depends upon the following two factors a. Pathogens ingested are insufficient in quantity to cause the infection and can survive the hosts defence mechanisms. b. Pathogens causing gastroenteritis possess virulence mechanisms. The host defence mechanisms that decrease the risk of infectious disease are as follows • Gastric acidity: The normal acidic p H of the stomach is an effective antimicrobial defence. Only specific or acid-resistance pathogens e.g. Shigella can survive in gastric medium of the stomach while others are unable to reach the intestine and are killed at gastric p H . Hence lowering the acidity of the stomach either by antacids or ulcer healing drugs increases the incidence of infection. • Peristalsis: Reduced peristalsis and gastrointestinal motility causes reabsorption of water and electrolytes from the gastrointestinal contents causing a decrease in the frequency of passage of stool. On the other hand reduced peristalsis becomes hazardous in patients with infective gastroenteritis as slow intestinal motility increases the duration of contact of pathogens with the intestinal mucosa and allows their colonization. slide 5: PHARMACOTHERAPEUTICS-II GASTROENTERITIS PHARM.D 5 • Immune system: Severity of infectious gastroenteritis depends upon the ability of immune system to resist the infection. Immunocompromised host is more susceptible to the infection. • Gastrointestinal microfilaria: Any alteration in normal gastrointestinal flora results in colonization of pathogens. Broad spectrum antibiotics alter the normal flora of GIT and allow their colonization and overgrowth. Clinical manifestations: Infectious gastroenteritis is generally classified as inflammatory and non-inflammatory gastroenteritis. Depending upon severity of infection clinical manifestations vary from mild to severe ranging from few hours to couple of weeks. 1. Inflammatory gastroenteritis: Inflammatory gastroenteritis is a severe form of gastroenteritis that may result in systemic illness. It is mainly caused by bacterial strains like Shigella causing bacillary dysentery Entamoeba histolytica causing amoebic dysentery Vibrio cholerae E.coli Camphylobacter Chlamydia Yersinia Clostridium difficle. As inflammatory diarrhoea is caused by specific by specific pathogens antibiotic therapy is beneficial in this case. Signs and symptoms of inflammatory gastroenteritis include fever abdominal pain presence of blood and mucus in stool accompanied with tenesmus vasculitic rashes arthritis and bacteraemia. 2. Non- inflammatory gastroenteritis: Non-inflammatory gastroenteritis is less severe form of gastroenteritis. It is generally caused by viruses Cereus perfringens and Staphylococcus aureus. Non-inflammatory gastroenteritis is self-limiting. It gets cured within 2-3 days and does not require antibiotic therapy. slide 6: PHARMACOTHERAPEUTICS-II GASTROENTERITIS PHARM.D 6 Signs and symptoms of non-inflammatory gastroenteritis include low grade fever accompanied with headache nausea vomiting watery diarrhoea and abdominal cramps. Diagnosis: Gastroenteritis is often self-limiting but can cause significant problems with excess dehydration. Investigations are most likely to be done in severe or inflammatory illness. Diagnosis is done by culturing the organisms from faeces if the symptoms persist for a prolonged period of time. Physician may take a thorough history of the patient as a physical examination before sending samples for laboratory testing. It is important to know the details pertaining to the age of the patient family history duration frequency description of the patients bowel movements recent travel recent antibiotic use exposure to poisons and other irritants weight loss diet change and food preparation habits. Blood cultures are usually taken during systemic illness. • Food poisoning pathogens Staphylococcus aureus and Bacillus cereus isolated from vomitus and food is cultured if poisoning is due to food. • Botulism is diagnosed by demonstrating the presence of toxin in serum. • Typhoid pathogens Salmonella typhi and paratyphi are isolated from the cultures of blood urine faeces and bone marrow. • Microscopic evaluation of parasites and their ova is done by performing microscopy of faeces. • Sigmoidoscopy is done for diagnosing pseudomembranous colitis. • Enteric viruses are detected by immunological and molecular based detection techniques. Prognosis: Viral gastroenteritis is usually self-limiting and does not require special treatment. But antibiotic therapy is required in the slide 7: PHARMACOTHERAPEUTICS-II GASTROENTERITIS PHARM.D 7 management of uncomplicated bacterial gastroenteritis so as to reduce the severity of clinical illness and to eradicate the organisms from the faeces. Treatment: Most cases of gastroenteritis are self-limiting and can be treated at home. The most important is to replace the lost fluids and salts to prevent dehydration. 1.Drug treatment: Pharmacological therapy includes treatment with anti diarrhoeal agents antimicrobial agents and with antiemetics. i Anti microbials: Antibiotic therapy is required only in case of bacterial gastroenteritis that lasts for a long duration of time. a. Tetracycline: M.O.A: The tetracyclines are primarily bacteriostatic inhibit protein synthesis by binding to 30s ribosomes in susceptible organism. Uses: Doxycycline and tetracyclines are effective against Vibrio cholerae Shigella and Enterotoxigenic Escherichia coli ETEC. ADRs: GIT disturbances like nausea vomiting diarrhoea and hepatotoxicity renal toxicity phototoxicity hypersensitivity reactions nephrotic diabetes insipidus etc. Dose: Tetracycline-250500mg cap. Doxycycline-100mg cap. b. Penicillins: M.O.A: Penicillins covalently bind to penicillin binding proteins PBPs and inhibit the cross linking of peptidoglycan resulting in the formation of cell wall deficient bacteria. These undergo lysis. Thus penicillins are bactericidal and act on actively multiplying bacteria. slide 8: PHARMACOTHERAPEUTICS-II GASTROENTERITIS PHARM.D 8 Uses: Amoxicillin and ampicillin are effective against salmonella and shigella strains. ADRs: Hypersensitivity reactions like skin rashes urticaria pruritus fever bronchospasm serum sickness and rarely exfoliative dermatitis and anaphylaxis. Dose: Amoxicillin-500mg Ampicillin-500mg c. Trimethoprim/Sulfamethoxazole: M.O.A: Trimethoprim is a diaminopyrimidine which selectively inhibits ‘bacterial dihydrofolate reductase DHFRase’ and thereby inhibits the formation of ‘tetrahydrofolic acidTHFA’ which is essential for the formation of DNA. Sulfamethoxazole competitively inhibit the union of PABA with pteridine residue to ‘dihydropteroic acid DHPA’ which conjugates with glutamic acid to produce dihydrofolic acid. Uses: Trimethoprim/sulphamethoxazole are effective first and second line drugs against ETEC. ADRs: Nausea vomiting and epigastric pain hypersensitivity reactions like skin rashes urticaria and drug fever hepatitis etc are noticed. Dose: Sulphamethoxazole-1g BD for 2 days then 0.5g BD. Trimethoprim-200mg per day d. Macrolides: M.O.A: Macrolides bind to 50s ribosomal subunit and inhibit polypeptide chain elongation which inhibits bacterial protein synthesis. Thus they exhibit the ‘bacteriostatic’ action. Uses: Macrolides Erythromycin or azithromycin are effective first or second line drugs against Clostridium jejuni. slide 9: PHARMACOTHERAPEUTICS-II GASTROENTERITIS PHARM.D 9 ADRs: Hepatitis with cholestatic jaundice nausea vomiting abdominal cramps and allergic reactions like fever skin rashes can occur. Dose: Erythromycin-250500mg cap. Azithromycin-250500mg tab. e. Fluoroquinolones: M.O.A: They are active against typical and atypical mycobacteria. They inhibit the bacterial DNA synthesis by inhibiting bacterial topoisomerase- II DNA gyrase and topoisomerase-IV. They have bactericidal activity. Uses: Fluoroquinolones ofloxacin norfloxacin ciprofloxacin and nalidixic acid are effective against Shigella Salmonella Camphylobacter E.coli Vibrio cholerae and Yersinia. ADRs: Nausea vomiting diarrhoea headache dizziness skin rashes photosensitivity damage growing cartilage tendinitis tendon rupture insomnia etc. Dose: Ofloxacin-400mg OD Norfloxacin-200400mg BD Ciprofloxacin-250500750mg BD Nalidixic acid-1g QID ii Antiemetics: M.O.A: Antiemetics like ondonsetron is a prototype drug. Their antiemetic effect is mainly due to the blockade of 5-HT 3 receptors on vagal afferents in the gut. In addition they also block 5-HT 3 receptors in the CTZ and solitary tract nucleus STN. Ondonsetron and other 5-HT 3 antagonists control vomiting by blocking emetogenic impulses in the gut and their central relay CTZ and STN. slide 10: PHARMACOTHERAPEUTICS-II GASTROENTERITIS PHARM.D 10 Uses: Antiemetics like ondonsetron is helpful in case of severe diarrhoea associated with vomiting. ADRs: Drowsiness dizziness and diarrhoea gynaecomastia galactorrhoea and menstrual irregularities etc. Dose: Ondonsetron-4mg IV BD iii Probiotics: Probiotics are usually recommended to replace normal GI flora that prevent colonization and overgrowth of pathogens. e.g. Lactobacillus and bifidobacterium. 2. Non- drug treatment: a. In mild gastroenteritis usual drinks like water and squash are sufficient. Normal diet can be continued but food containing fats and sugar should be avoided. Oral rehydration therapy is successful in atleast 95 of cases. b. Severely dehydrated patients require rapid intravenous rehydration and hospitalization. 3. Prophylaxis: Preventive measures that can curb gastroenteritis are as follows 1. Prevention from school and work until complete recovery. 2. Consumption of well cooked and unspoiled food. 3. Maintenance of clean and healthy environment. 4. Most of the gastroenteritis infections spread through food and water contaminated by bacterial toxins. Therefore thorough hand washing before eating and handling eatables prevents further transmission of pathogens.