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1. RATIONAL DRUG THERAPY 1.1. Definition: In simplest words rational use means “prescribing right drug, in adequate dose for thesufficient duration & appropriate to the clinicalneeds of the patient at lowest cost. The concept of rational drug use is, as evident by the statement made by theAlexandrian physician Herophilus 300 B.C that is “Medicines are nothing in themselves but are thevery hands of god if employed with reason &prudence”. Rational drug use attained more significancenowadays in terms of medical, socio economicaland legal aspect. Factors that have led suddenrealization for rational drug use are. [8]

1.	Drug explosion: Increase in the number of drugs available has incredibly complicated the choice of appropriate drug for particular indication. 2.	Efforts to prevent the development of resistance: Irrational use of drugs may lead to the premature demise of highly efficacious &lifesaving new antimicrobial drug due to development of resistance. 3.	Growing awareness: Today, the information about drug development, its uses & adverse effects travel from one end of the planet to the other end with amazing speed through various media. 4.	Increased cost of the treatment: Increase in cost of the drug increases economic burden on the public as well as on the government. This can be reduced by rational drug use. 5.	Consumer protection Act. (CPA): Extension of CPA in medical profession may restrict the irrational use of drugs.[8]

2. GASTROENTERITIS 2.1. Definition: Gastroenteritis is a condition that causes irritation and inflammation of the Gastric mucosa and intestines (GIT), Also known as "stomach flu." The symptoms of gastroenteritis are vomiting, fever, headache, abdominal pain, diarrhea, and mild chills.Most patient recover by itself without any medication treatment. [2]		2.2. Etiology Viral infections aremaincause of gastroenteritis but bacteria, parasites, contaminated food &water is alsoa causative factor. The intensity of this disease depends upon the immunity of the victim individual that how much they resist to infection. Essential electrolytes like sodium, potassium may be decreased in body as the affected personexperiences diarrhea and vomiting for long time.[2] Most patients recover itself by maintaining amount of fluids in body and taking normal diet.However children and old age people may suffer from dehydration due to loss of fluid with gastroenteritis which is a life-threatening condition until the condition is treated and fluids isrecovered. The basic treatment is sufficientrehydration. In moderate condition the rehydration can be restore by oral route. While in case of severe condition, intravenous therapy is required.[1] The agents that cause infections may be foreign bodies or may be internally from some abnormal condition of the body. For example, intestinal bacteria can grow when certain drugs such as antacids or other medication change the acidity of stomach. Bacteria and Viruses are commonly very contagious and spread disease easily through contaminated food or water. No specific agents are found for 50% of diarrheal cases. Poor hygiene and malnutrition allow the spread of infective organism. [19] Gastroenteritis caused by viruses, may be eliminated within 1-2 days. While caused by bacteria, may be eliminated within week or more. [6] 2.2.1 Bacteria: Bacteria causes Gastroenteritis are following: 	Escherichia coli :Can cause colitis, food poisoning, uremic syndrome,Traveler’s diarrhea, and dysentery 	Salmonella - Can cause Typhoid fever 	Campylobacter - Found in unpasteurized milk ,Undercooked meat, that cause diarrhea 	Shigella – are the cause of Dysentery[19] 2.2.2 Viruses: Diarrhea cause by viruses transferimmediately by the close contact betweenindividuals. Poor hand washing habits can also cause to transfer viruses and cause viral diarrhea. Various viral pathogens that cause viral infection are given.[19] 	Adenoviruses 	Rotaviruses 	Caliciviruses 	Astroviruses 2.2.3. Parasites and protozoans: Some organisms like parasites and protozoans are also causative agent of gastroenteritis but these are less commonly responsible for intestinal irritation. Mostly these organism are found in impure water and as well as in swimming pools. Some such small organisms that cause gastroenteritis are given below. 	Giardialamblia: Giardiasis in human is caused by Giardia which produce waterborne diarrhea. 	Cryptosporidium: Such type organisms cause watery diarrhea in these people having poorimmune systems. 2.2.4.Other Common Causes: Some substance like toxic toxins that are present inantibiotics (disturb the normal flora), and some medications, seafood, food allergies, heavy metals, can also cause gastroenteritis but these are not communicable from one to others humans. 2.2.5.Medications that causes diarrhea: 	Salicylic acid 	NSAID 	Antibiotics 	Steroids – Use in high dose are frequently. 	Laxatives [16] 2.3. Symptoms Various symptoms that appear due to Gastroenteritis are mention below. 2.3.1. Common symptoms 	In abdomen Crimpy painful bloating. 	Low grade fever 	Mild-to-moderate diarrhea: In adolescents and adults 2-4 loose stools in a day. 	Vomiting: In diarrhea vomiting may or may not be present. But in case of vomiting dehydration rate may be increased and which lead to loss of significant amounts of electrolytes and can possibly result shock. 	Nausea with or without vomiting or both. 2.3.2. Some other serious symptom due to gastroenteritis is following 	Blooded vomiting or blooded stool 	Prolong time Vomiting (> 48 hours) 	High grade Fever (> 101°F) 	Swelling of abdomen or pain arisein right to lower side of the abdomen. 	Dehydration – which represented by low or no urination, dry mouth, very high thirst, and lack of tears. [18] 2.4.Prevalence Prospective population-based studies were performed in United States to calculate the occurrence of gastroenteritis and the related pathogens in the general communities’ population. Two consecutive cohorts were conductedon the basis of weekly reporting record from December 2009 to November 2010.Stool samples supplied data on a questionnaire form.The actual gastroenteritis occurrences were 284 /1,000 person-years. 6% of cases accountedby Bacterial pathogens, while parasites andviral pathogensfor 6%, and for 21%,respectively reported Among the viral pathogens Norwalk-like virus (NLV) as the main pathogen in 11% of cases. The ratios of gastroenteritis occurrence were higher in England, butvery low form the United States. In the community the viral pathogens were the main cause of gastroenteritis. In large number of countries, safety measures are taken to slow down bacterial infections. [21] A health maintenance organization consists of 270,000 members in Georgia, USA, who almost exclusively seeks care for gastroenteritis in members. Some of the microbiology laboratories serve the whole population of Georgia members and they collect 140 stoolsamples every month from outpatients medical care units.[20]. Total 573 samples were collected for study. On all samplebacterial culture and viral PCR were conducted, and among them 374 (66.6%) are performed for parasitesand ova, 162 (28.1%) for D.mifficile, and 29 (4.9%) for rotavirus. Patients from 25–64 years old presented 324 (56.8%) of the sample tested and 317 (55.9%) was from female.Test result of the laboratory shows a pathogen in 43 (7.7%) samples. While the subsequent PCR testing at CDC shows >2 virus in 54 (9.8%) samples, in 89 sample, viruses were reported in 54 (60.2%), while bacteria was in 34 (37.1%), and parasites in 7 (8.0%), while in 4 samples multiple pathogens were reported only. Detection of any type of pathogen in stool were mostly found in children <6 years (33.2%) and slow down quickly with age to 4.7% in patients of>65 years of age.[17]

2.5. Epidemiology 2.5.1. Mortality and Morbidity Rate in world According to WHO and UNICEF, in developing countries there are about 02 billion cases of diarrhea and its related diseases worldwide per year, and about 02 million children below5 years death occurs due to diarrhea per year. This data concludes that 18% deaths ofchildren below five yearsor more than 5000 children are dying per day due to diarrhea and its related diseases. Most of child deaths from diarrhea, 78% occur in the African countries and South-East Asian regions.[9] The average of this data shows that each child below 5 years experiences three episodes of acute diarrhea per year. Worldwide the second death cause of children under 05 years is acute diarrhea while the second is pneumonia. Diarrhea and pneumonia both are the risk of mortalityin children below 5 years, particularly during infancy. [9] 2.5.2. Mortality and Morbidity Rate in Pakistan							Thecollective study were performed in the village Budhni of district Peshawar. This data were analyzed in PMRC (Pakistan Medical Research Council)& PGMI (Postgraduates Medical institute)Peshawar. Two hundred & eighty-four children presented to PMRC of the age of five year to the Health Centre of the village of Budhni during the study time; out of these 186 (66%) was males and 97 (33%) females while with the ratio of 1.9:1 of male to female. Gastroenteritis were reported in 41cases (14%), totally Nine deaths reported out of these 6 cases (66.7%) were male babies and 3 cases (33.3%)were females babies.[9] 2.6. Diagnostic tests

2.6.1 Serum Electrolytes, Urea, Creatinine

Measurements of, urea, creatinine and serum electrolytes are not necessary to assess children while suffering from acute gastroenteritis, as the results do not change the therapeutic strategy. These tests are recommended in a subset of patients having severe dehydration and receiving IV therapy. Result usually normal; abnormal if severe dehydration is present 2.6.2 Full Blood Count

These tests are rarely required. It is recommended if another cause of infection or sepsis is suspected. WBC and granulocyte counts are not sufficiently informative for the early differential diagnosis of viral and bacterial gastroenteritis Result: usually normal; elevated WBC count and granulocytes if sepsis is present 2.6.3 Stool Microscopy These tests should be necessary in children having bloody diarrhea. Result: presence of WBCs suggests that infection with an invasive cytotoxin-producing organism include such as Salmonella, Shigella, or Yersinia enterocolitica 2.6.4 Stool Culture These tests are often performed. Stoolculture isconsidered in children while suffering from bloody diarrhea to know about the causes. 2.6.5 Enzyme Immunoassay For Detection of Viral Antigen

Rarely required and recommended only for epidemiological purposes when there is a public health imperative to know about the pathogen and about its source. This method is highly sensitive and specific and is the diagnostic methods of choice. Result: may show the causative viral pathogen (rotaviruses, noroviruses, astroviruses, adenoviruses) that cause the diarrhea [3].[15] 2.7. Treatment The human body has the ability to fight against such infectious disease and recovers by its own.Restoration of fluids and electrolytes that were lost because of the diarrhea and vomiting is most important. Foods nutrients that are rich in  complex carbohydrates, such as lean meats,potatoes, electrolytesand whole grains are very helpful to replace nutrients. Some timestay in hospital isnecessary, that nutrients can be supplied by intravenous route.[3] Some general methods which are helpful in treatment of gastroenteritis are following. 2.7.1. Fluids - have lots to drink These will help to stop dehydration, when it has occurred. 	It is recommended especially after each watery stool to take electrolytes (ORS) minimum 200 ml after each trip of diarrhea. 	The 200ml are in addition to usually drink. Suppose an adult will generally drink about two liters per day are advice of 200 ml after each trip of diarrhea is in addition to this usual amount that you would drink. 	If there is vomiting stop taking electrolytes for 5-10 minutes and again start taking electrolytes, slowly at regular interval. 	In case of dehydration drink as much possible.

Water is most suitable fluid to drink during dehydration some time soup can also be used.Forpeople who are frail, or over the age of 60year, or who have some other health problems rehydration drinks are highly recommended.Good balance of water, salts, and sugar in body can be replaced by ORS. [3]

2.7.2. Eat as normally as possible If it is possible start eating in smallamount, of light meals. Some time people are not feel to eat food but start as soon as you are ablekeep away from fatty,heavy or spicy food at beginning[14] 2.7.3Medication Because most infectious diarrhea is self-limited, medical care is primarily supportive and may include the following: 	Oral rehydration: Live Lactobacillus GG and heat-killed Lactobacillus LB reduce the duration of diarrhea in children when added to oral rehydration solution 	When oral rehydration is unsuccessful, intravenous (IV) rehydration 	Close monitoring for secondary complications 	For some bacterial gastroenteritis infections, antimicrobial therapy 	For refractory cases of Cryptosporidium infection, ant motility agents.[7] 2.7.3.1.Selected Oral Antibiotics for Infectious Gastroenteritis Organism 	Antibiotic 	Adult Dosage 	Pediatric Dosage Vibrio cholerae	Ciprofloxacin

1 g once	NA Doxycycline

†	300 mg single dose	 6 mg/kg single dose TMP/SMX	1 DS tablet bid for 3 days	4–6 mg‡/kg bid for 5 days Clostridium difficile	Metronidazole

250 mg qid or 500 mg tid for 10 days	7.5 mg/kg qid for 10 days Vancomycin

125–250 mg qid for 10 days	10 mg/kg qid for 10 days Fidaxomicin	200 mg bid for 10 days	NA Shigella	Ciprofloxacin

500 mg bid for 5 days	NA TMP/SMX	1 DS tablet bid	4–6 mg‡/kg bid for 5 days Giardia intestinalis (lamblia) 	Metronidazole

250 mg tid for 5 days	5 mg/kg tid for 5 days (maximum 750 mg/day) Nitazoxanide

500 mg bid for 3 days	1–3 yr: 100 mg bid for 3 days 4–11 yr: 200 mg bid for 3 days ≥ 12 yr: 500 mg bid for 3 days Entamoebahistolytica	Metronidazole

750 mg tid for 5–10 days	12–16 mg/kg tid for 10 days (maximum 750 mg/day) Campylobacter jejuni	Azithromycin

500 mg once/day for 3 days	10 mg/kg once/day for 3 days Ciprofloxacin

500 mg once/day for 5 days	NA Dietary measures include the following: 	Begin with the BRAT diet (ie, bananas, rice, applesauce, toast) 	Introduce lean meats and clear fluids as soon as possible 	When giving lactose-containing dairy products, be alert for signs of malabsorption 	For infants, continue breastfeeding throughout the illness.[7]