Drugs acting on GI tract

Overview of vomiting Vomiting is a reflex that help get rid of harmful substances from Upper GI Tract It is Stimulates by Chemoreceptor trigger zone (CTZ) Vestibular system Peripheral afferents from the pharynx and GI tract Psychic input from CNS

Antiemetics Cholinergic antagonists: (hyosine) H1 blockers: ( cyclizine, promethazine) Dopamine antagonists Metoclopramide ( inhibits the CTZ) Phenothiazine (ChropromoZINE, ProchlorperaZINE) Butyrophenone (HaloperiDOL, CloperiDOL) Serotonin antagonists (OndanSETRON, GranSETRON) Cannabinoids (dronabinol, nabilone) Glucocorticoids (dexomethasone) Benzodiazepine ( Diazepam, Lorazepam)

Emetics Drugs used to induce emesis. This is indicated in poisoning Ipecac ( Stimulate the CTZ) Apamorphine ( Dopamine agonist that stimulate the CTZ)

Treatment of Upper GI disorders The main aims of treatment are 1. Neutralizing the acidity 2. Inhibiting acid secretion 3. Protection of the gastric mucosa

1. Drugs used to neutralize acidity Antacids: which are weak bases that bind with acid and produce water and salt Examples Sodium Bicarbonate Aluminum Hydroxide Magnesium Hydroxide

2. Inhibition of acid production H2-Receptor blocker Cimetidine, Famotidine, Ranitidine Anticholinergics Isopropamide & scopolamine M1- Receptor blocker Pirezapine Proton Pump Inhibitors Omeprazol, Lansoprazole

3. Protective agents Sucralfat ( increase mucus production and prevent further damaged mucosa) Mesoprestol ( which is a Prostaglandin E that is important is cytoprotection in maintaining the integrity between the epithelium cells and inducing bicarbonate production)

Treatment of H.Pylori induced Peptic ulcers The aim of treatment is irradiation of H.Pylori. Because that causes rapid healing of the damaged mucosa. 1 st line therapy: Clarithromycin, Amoxicillin & Omeprazole 2 nd line therapy: Bismuth subsalicylate, metronidazole, tetracyclin, Omeprazole

Treatment of NSAID Induced peptic ulcer – Neutralizing the acidity (Antacids) – Inhibiting acid secretion (PPI, H2- Blockers) – Protection of the gastric mucosa (sucralfat) – Safer NSAIDS (-COXIB, such as Celecoxib & refecoxib)

Non specific anti-diarrheals Opiates and opiod containing preparations ( they bind to μ receptors and decrease the transit time and increase absorption). Example: opium tincture and codiene, Diphenoxylate. Anticholinergics: example; atropin, scopolamine and propamtheline Adsorbents: Kaolin and pectin Oral rehydration therapy : which contain suffecient amount of electrolytes and glucose

Anti-diarrheals for specific causes Traveler s Diarrhea: Loporamide Bismuth subsalicylate ( Bind to toxins produced by E.Coli and V. Cholera) Inflammatory bowel disease Sulphasalazine and olsalazine

Drugs used to dissolve Gallstones The criteria of using this method are: Small stones (5-10mm) Cholesterol stones In cases where surgery is not possible Asymptomatic cases

Drugs used to dissolve Gallstones Chenodiol (Chenodeoxycholic acid): inhibits HMG-COA reductase and therefore inhibits cholesterol synthesis & induce bile acid synthesis. Ursodiol (Ursodeoxycholic acid): inhibits cholesterol secretion in bile but little affect on bile acids. Methyl-ter-butyl-ether (MTBE): Directly dissolves cholesterol stones

Laxatives Bulk forming agents are hydrophelic agents that are poorly absorbed and increase luminal mass therefore induce peristalsis: ex. Methyl-cellulose. Osmotic agents Salt osmotic agents (Magnesium sulfate) Salt-free osmotic agents (lactulose) Irritants are agents that irritates the mucosa and induced secretion (ex. castor oil and senna) Stool softeners (ex. Sodium docusate)

Treatment of amebiasis Ingested cysts Trophozoites Systemic amebiasis Metroniadizole Luminal amebiasis Didoxanide

Anthelmintics Mebendazole/ Albendazole* ( Inhibits glucose uptake by parasite decrease ATP production immobilization Thiabendazole* (Inhibits microtubules assembly and parasitic metabolism) Ivermectin* (paralysis of the parasitic muscles by opening Cl- gated channels) Prazequantel ** ( paralysis of the warm and activate the immune system) * Are used for nematodes ** Are used fro cestodes

Chemotherapy for GI tumors Colorectal cancer: 5-Flurouracil (5-FU): which inhibits DNA synthesis by inhibiting thyamidine synthesis & levamisole: anthelmintic that activate cell mediated immunity OR 5-FU & Leucovarin (inhibits folate co- enzymes which are required for thyamidine synthesis)

Chemotherapy for GI tumors Pancreatic cancer 5-FU &/or Gemcitabine Gastric cancer 5-FU & Methyl-CCNU 5-FU & mitomycin C ( which inhibits DNS synthesis by alkalating double stranded DNA and forming cross links.