# Pharm block V GI ## anti-emetics * Ondansetron * Antagonizes 5-HT3-R * vagal (-) * central anti-emetic * Adverse * QT prolong => torsades * serotonin syndrome * M1 R * Scopolamine * M1R antagonist * Tx: motion sickness * H1 R * Gq * Diphenhydramine, meclizine * 第一代 H1R blocker * cause sedation, anti-muscarinic * Tx: motion sicknes * Metoclopramide * D2 receptor antagonist * (+) resting tone, contractility, LES tone, motility * Tx: chemotherapy induced vomiting, delayed gastric emptying (upper GI prokinetic) * Contraindic.: small bowel obstruction, Parkinson (D2R already blocked), pre-existing elongated QT interval * Adverse: * diarrhea, * drowsiness & depression (central D2 block), * extrapyramidal (dystonia, akathisia, parkinsonian [central D2 blockade]), * tardive dyskinesia (跟 chronic use 有關, 不自主重複運動), * neuroleptic (-leptic: acting on) malignant syndrome (發燒、僵直、意識改變、自主神經系統不穩定、橫紋肌溶解) * (+) prolactin level => galactorrhea, impotence, gynecomastia (男性女乳), menstrual disorders * torsades * NK1 (neurokinin 1) receptor (activated by substance P) * Aprepritant (Emend) * blocks NK1 receptor * Tx: chemotherapy induced vomiting ## Gastroesophageal refund * H2 R (Gs) => parietal cells on basolateral membrane * M3 R => parietal cells (H+ secretion) * Cimetidine, ranitidine, famotidine, nizatidine * H2 receptor antagonist, (-) H+ secretion by parietal cells * Tx: **nocturnal** secretion of acid, GERD & peptic ulcers (PPI as first line) * Adverse: * inhibitor of CYP450 (multidrug interaction), * 混亂、頭暈、頭痛 (cross BBB), * anti-androgenic * cimentidine, ranitidine => (-) renal creatinine excretion * Ome**prazole**, lansoprazole, esomeprazole, pantoprazole, dexlansoprazole * PPI irreversibly inhibit H/K-ATPase pump (H secretion) * Tx: nocturnal & meal-stimulated scretion of acid, Zollinger-Ellison syndrome (gastrinoma causing hypersecretion) * Adverse: * *C*. *difficile*, pneumonia, * (-) absorption of 二價陽離子 => (+) osteoporosis, hypomagnesemia * Octreotide * long-acting somatostatin analog * Tx: * gastrinoma 當 PPI 沒用時 * Secretary diarrhea (VIPoma & carcinoid syndrome) * *H*. *pylori* * triple therapy: ppi, clarithromycin, amoxicillin/metronidazole ## Relaxatives * laxatives vs. pro-kinetic agents * change consistency of feces vs. direct stimulation of GI (metoclopramide, erythromycin) * Magnesium hydroxide, magnesium citrate * Osmotic laxatives: draw water in GI => distension & peristalsis * Polyethylene glycol (PEG), lactulose, sorbital * 不可吸收的 sugar osmotic laxative * 被腸道菌代謝造成 severe flatulence and cramps * lactulose tx: hepatic encephalopathy ([+] ammonia [NH3] following cirrhosis, metabolized into acidic metabolites, which convert NH3 to NH4+ (trapped in intestinal lumen and excreted), rifaximin [antibiotic] 殺製造ammonia的細菌) * Psyllium * bulk-forming laxative * Stool softeners: surfactant agents * Docusate * Senna * Cathartic agent (stimulant) => enteric nervous system (+) colonic secretion * Opiod agonists * Diphenoxylate, loperamide * (+) μ-opioid receptor * Tx: diarrhea * Loperamide doesn't cross BBB, no analgesia (止痛) nor addiction * Diphenoxylate cross BBB, w/ atropine => 預防 abuse * Adverse: (+) colonic transit time ([+] segmentation contractions [跟會推大便的 peristaltic contraction 不同]) = constipation * Contraindic.: bloody diarrhea & fever * VIPoma => VIP => secretary diarrhea * Carcinoid tumor => serotonin => secretary diarrhea ## GI * Misoprostol: PGE1 analog * (+) gastric mucus, (-) acid production * Tx: * NSAID-induced peptic ulcer * ripens cervix, induction of labor (promotes uterine contraction * Adverse: abortifacient, diarrhea (所以少用) * Sulfasalazine: sulfapyridine (anti-bacterial) & 5-aminosalicylic acid (anti-inflammatory) * 受腸道菌激活 * Tx: ulcerative colitis & Crohn disease * Adverse: oligospermia (寡精), sulfanamide toxicity * Metoclopramide * D2R antagonist * (+) resting tone, contractility, LES tone * Tx: 糖尿病/手術相關 gastroparesis ## Antacids * Adverse: hypokalemia * Aluminum hydroxide * Adverse: constipation, proximal muscle weakness & seizures, hypophosphatemia & osteodystrophy * Magnesium hydroxide * Adverse: diarrhea * Calcium carbonate * Adverse: hypercalcemia => (+) gastrin => acid rebound * Bismuth, sucralfate * physical protection * Tx: travelers diarrhea ## Weight loss * Orlistat * Adverse: steatorrhea, (-) absorption of fat-soluble vitamins * (-) pancreatic lipase => (-) breakdown of fatty acid and (-) absorption * Ursodeoxycholic acid (ursodiol) * non-toxic bile acid, (+) bile, (-) cholesterol secretion => gallstones 分解 (dissolution of gallstones) & 提高 cholesterol saturate bile salts 的 threshold * Tx: primary biliary cirrhosis (bile acid induce hepatocyte apoptosis, ursodiol => EGFR & MAPK => survival signals), biliary stasis in cystic fibrosis * Adverse: increase the risk of cirrhosis ## Cholestatic drugs * Obeticholic acid * semisyntetic bile acid, (+) farnesoid X receptor => (-) cholesterol-7-hydroxylase (bile acid synthesis) * Tx: primary biliary cholangitis * Adverse: itching, serious liver injury (incorrect dosing)