Gastrointestinal Drugs Food Group Carbohydrates Protein Fat Mouth Salivary amylases Ptyalin starts to break down complex carbohydrates No effect Stomach Little effect No effect Pepsin acid activated breaks proteins into peptones Little effect food transformed into chyme Small Intestine Complex Carbs broken down into simple sugars by amylases from pancreas Peptones broken into peptides and free amino acids by proteases from the pancreas Emulsified by bile from the liver Fatty acids released by lipases from pancreas Nutrients absorbed by small I water by large I Acid requirement for Pepsin activity o Pepsin is unusual most proteins are denatured in acid o Try mixing milk with lemon juice or vinegar Protection from stomach acid pepsin Treatment of stomach or duodenal ulcers o Ulcers o Mucus layer blocks acid and pepsin attack on tissue and bicarbonate neutralizes acid diffusion Occur when protective mechanisms in stomach are overwhelmed by acid secretion Caused by a bacterial infection by Helicobacter pylori Can be induced by NSAIDs such as aspirin that block prostaglandin production Antacids o Antacids salts for neutralizing acids Sodium based systemic causes easily taken up in the GI alkalosis of the blood over long time Aluminum based induces constipation in lower GI Caniculus Acid secretion from parietal cells after meal 4 times a day not very complaint Calcium based can cause hypercalcemia Magnesium based induces diarrhea o Treat symptoms but not cause o Our prototype is Aluminum Hydroxide mixed with Magnesium Hydroxide Maalox Agents to Protect the Stomach lining Take on empty stomach or proton acid pump o Sucralfate avoid antacids inhibitors Needs stomach acid to work Coats ulcer but compliance is major problem Hard because needs 1 hr before 1 hr o Misoprostol Prostaglandin analog that increases mucous secretion in stomach in pregnant women causes spontaneous aborption Indicated for NSAID induced ulcers Contraindicated Causes cramping in GI tract Inhibitors of Stomach acid secretion o Omeprazole Prilosec prototype Blocks acid pump in stomach can block cytochrome P450 and cause drug interactions Chemical variant Esomeprazole Nexium also used to treat Gastro Esophageal Reflux Disease GERD Also used to treat Zollinger Ellison syndrome caused by gastrin secreting tumors of pancreas Long lasting effect that requires 3 5 days to recover acid secretion Can cause lower GI upset headaches H2 Receptor Antagonists o Block histamine induced stomach acid secretion by blocking H2 histamine receptors o Approved H2 blockers Ranitidine prototype Other blockers Famotidine Nizatidine Cimetidine has most side effects and drug interactions o Drug interactions by blocking cytochrome P450 o Blocks androgenic receptors Can cause loss of libido and gynecomastasia All available OTC problems of self medication o Used to kill Helicobacter pylori o Tritec is a pill combination of bismuth and ranitidine to be taken with an antibiotic such as clarithromycin prevention of relapse has been reported with this combination after allowing the stomach to heal o Another combination pill is omeprazole clarithromycin Prilosec Biaxin Antibiotics to Tx ulcers Tx of emesis vomiting o Vomiting reflex Activated by signals coming to chemoreceptor trigger zone CTZ Action coordinated by emetic center in medulla oblongota in brain stem Chemotherapy induced Emesis o Inputs to emetic center include Emotional responses from higher CNS Irritation of GI tract Increased intracranial pressure Sensory inputs Vestibular stimulation Stimulation of the CTZ o Chemotherapy for cancer is particularly prone to inducing vomiting Neutral Control of Vomiting o Neurotransmitters involved Dopamine D2 receptor in GI tract and CTZ Acetylcholine in emetic center Histamine H2 receptor may be anticholinergic effects Serotonin 5HT3 receptors in GI tract CTZ and emetic center Drugs to Block emesis vomiting o Ondansetron Serotonin 5HT3 antagonist prototype Indicated to block vomiting associated with chemotherapy radiation or some operations Contraindicated by hepatic impairment may cause tachycardia or angina or Parkinson s like symptoms Administer 30 minutes before treatment o Other agents include Metoclopramide see below Scopolamine muscarinic antagonist Marijuana derived drugs dronabinol Corticosteroids Antihistamines Droperidol Benzodiazepines o Anti emetics are more effective if given before nausea occur Drug Combinations Emetic Agents o More effective than single drug o Various combinations are better for different Chemotherapy treatments o Cause vomiting used to clear stomach from poisoning or drug overdoses o Ipecac syrup has emetine is our prototype but is no longer recommended since 2003 o Caution Do not induce vomiting in unconscious patients patients who have swallowed corrosive substances patients with depressed gag or cough reflexes o Ipecac may be abused by patients with eating disorders overuse can cause cardiomyopathy ventricular fibrillation and death GI stimulants o Metoclopramide Reglan is prototype o Indicated for diabetic gastroparesis GERD used for nausea vomiting off label o Blocks dopamine 5HT receptors in CTZ enhances cholinergic effects on GI o Side effects Extrapyramidal movement disorders Parkinson like symptoms mental depression tardive dyskinesia o Drug interactions Counteracts L DOPA in Parkinson s anti cholinergics muscarinic antagonists or narcotics block o Contraindications If GI stimulation is dangerous e g GI hemorrhage blockage pheochromocytoma seizures effects Parkinson s or similar diseases Digestive Enzymes o Pancrelipase Pancrease others o Indicated for cystic fibrosis pancreatectomy pancreatic cancer etc o Contains replacement amylases lipases and proteases o Made from pork religious issues Lipase Inhibitors o Orlistat Xenical Alli OTC is used to manage obesity o Blocks lipase metabolism of fat neither absorbed o Contraindicated by malabsorption syndrome organic causes of obesity hypothyroidism cholestasis use caution with diabetes thyroid disease or anti coagulants o Decreases absorption of fat soluble vitamins A D K E may require supplements o Patients should decrease intake of fat 30 or risk diarrhea or fecal incontinence o Omit dose for meals that contain no fat Diarrhea and Constipation o If the intestines remove too much water the patient experiences constipation o If the intestines remove too little water diarrhea occurs o Diarrhea can be fatal if not treated o Rehydration therapy is effective and