ANTIDIARRHOEAL AGENT

What is diarrhoea ? Increased frequency or increased fluidity of bowl movements in a given individual is called diarrhoea. What causes diarrhoea? Diarrhoea is mainly caused by bacterial and viral infections and food poisoning. Diarrhoea occurs when the micro-organisms irritate the mucous membrane of the small or large intestine resulting in an abnormally large quantity of water in the motions. The irritated gut becomes very active, contracting excessively and irregularly (colic). This can be accompanied by nausea, vomiting, and cold sweats. In some cases the motions may include some blood.

Mechanism of Diarrhoea ?

Principle of management Rational management of diarrhoea depends on establishing the underlying cause and instituting specific therapy, since most diarrhoeas are self-limiting. Majority of enteropathogens are taken care of by motility and other defence mechanisms of the gut. Therapeutic measures may be grouped into a) treatment of fluid depletion, shock and acidosis. b) maintenance of nutrition. c) drug therapy.

Oral rehydration therapy Oral rehydration therapy (ORT) is a simple treatment for dehydration associated with diarrhea, particularly gastroenteritis or gastroenteropathy, such as that caused by cholera or rotavirus. ORT consists of a solution of salts and sugars which is taken by mouth. It is used around the world, but is most important in the developing world, where it saves millions of children a year from death due to diarrhea - the second leading cause of death in children under five

Rationale of ORS composition Oral rehydration is possible if glucose is added with salt. It capitalizes on the intactness of glucose coupled Na+ absorption, even when other mechanisms have failed or when intestinal secretion is excessive –the secreted fluid lacks glucose and cannot be reabsorbed. The composition of ORS has been debated. The general principle are: a) it should be isotonic or somewhat hypotonic. b) the molar ratio of glucose should be equal to or somewhat higher than Na+. c) enough K+ and bicarbonate/ citrate should be provided to make up the losses in stool.

New formula WHO-ORS NaCl2.6g KCl1.5g Citrate2.9g Glucose13.5g Water1L Total osmolarity 245 mOsm/L

Antidiarrhoeal agent An anti-diarrhoeal drug (or anti-diarrheal drug) is any medication which provides symptomatic relief for diarrhoea.

Classification of anti-diarrhoeal agent A) According to source Diphenooxylate Loperamide Codine B)According to cause a) Bacterial diarrhoea ampicilline Cotrimoxazole b amoebic dysentery metronidazole tinidazole c) Cholera tetracycline Dhaka fluid d) enteric fever chloramphenicol cotrimoxazole e) giardiasis metronidazole tinidazole f) helminthiasis : antihelminthic drug

Tetracycline Tetracycline are broad-spectrum antibiotics obtained from various species of streptomyces. Classification of tetracycline :- 1. Natural :- oxytetracycline chlortetracycline demeclocycline 2. Semi-synthetic :- doxycycline methacycline minocycline Pharmacokinetics of tetracycline :- route of administration :- oral, parenteral and topical absorption :- incomplete, irregular from the gut distribution :- widely distributed – most fluid compartments, can cross the placenta, appears in milk. excretion :- renal routes, non-renal (faeces, bile)

Mechanism of action Tetracycline enters the susceptible bacterial cell by two process : a) partly by passive diffusion through the hydrophilic pores b) partly by energy dependent active transport. schematic representation of the M/A of tetracycline : Tetracycline -- selectively taken up by susceptible organisms by active transport -- compete with bacterial tRNA to bind with 30s ribosome – inhibit bacterial protein synthesis.

Cautions, contraindications, side effects Can stain developing teeth. Can cause permanent teeth discoloration. Inactivated by Ca2+ ion, not to be taken with milk, yogurt, and other dairy products Inactivated by aluminium, iron and zinc, not to be taken at the same time as indigestion remedies Inactivated by common antacids and over-the-counter heartburn medicines Skin photosensitivity; exposure to the sun or intense light is not recommended Tinnitus May interfere with methotrexate by displacing it from the various protein binding sites Can cause breathing complications as well as anaphylactic shock in some individuals Should be avoided during pregnancy as it may affect bone growth of the fetus Passes into breast milk and is harmful to breast-fed infants, and should therefore be avoided during breastfeeding if possible

Streptomycin Pharmacokinetics : Absorption : Peak serum levels are reached within 1 hr following IM injection. Distribution : Appreciable concentrations are found in all organ tissue except the brain. Elimination : Following a single 600 mg dose, 29% to 89% is excreted in the urine within 24 hr.

Streptomycin Mechanism of action: streptomycin enters the bacterial cell by active transport and passive diffusion– combine with 30s sub unit– it blocks the initiation complex of peptide formation- mRNA massage is miss readed– as a result wrong amino acid is inserted into the peptide, resulting in a non functional protein– break up of the polysomes into monosomes and incapable of protein synthesis.

Adverse effect of streptomycin Ototoxicity Nephrotoxicity : renal irritation, crystalluria. Neurotoxicity : curare like effect, peripheral neuropathy. Hypersensitivity reaction : skin rush, drug fever, anaphylactic shock. Nausea Vomiting superinfection

Contraindication of streptomycin Kidney disease Disturbence of hearing