Pharm 2: GI GU

Ingestion/Admin of substance/drug * chemo, opiates, abx, NSAIDs, hormonal therapy GI disorders Mechanical gastric outlet obstruction, inta-abd emergencies (appendicitis), gastroenteritis Neuro Cerebellar hemorrhage, tumor, hydrocephalus Metabolic Addisons, volume depletion, DKA, hypercalcemia Presence of noxious stimuli Pt specific factors that increase risk Age (younger), previous n/v (post-op, queezy when others vomit), gender (women), obesity, anxiety Post-op n/v: prophylactic tx Other Pregnancy, noxious odor, ingestion of irritant, operative procedure, septicemia, nicotine

Agents used Phenothiazines Metoclopramide Chemoreceptor trigger zone - dopamine, opiate receptors Acts on vomiting center to: Lower diaphragm Contraction of abd muscles Esophageal dilation Reverse direction of peristalsis

Agents used Metoclopramide Visceral pain: analgesics Afferent impulses from periphery - dopamine, opiate receptors Acts on vomiting center to: Lower diaphragm Contraction of abd muscles Esophageal dilation Reverse direction of peristalsis

Agents used Antihistamines Anticholinergics Vestibular apparatus - acetylcholine, norepi receptors Acts on vomiting center to: Lower diaphragm Contraction of abd muscles Esophageal dilation Reverse direction of peristalsis

Agents used Benzodiazepines Dronabinol Corticosteroids Cortical structures Acts on vomiting center to: Lower diaphragm Contraction of abd muscles Esophageal dilation Reverse direction of peristalsis

3 phases of emesis Nausea: w/wo emesis: flushing, pallor, hyper-salivation Retching: involuntary, synchronized labored movement of abdominal and thoracic muscles before vomiting Vomiting: coordinated contractions of abd and thoracic muscles to expel gastric contents Causes: Recent travel Hypoactive bowel sounds Fever Work with sick population

Prochlorperazine (Compazine) Promethazine (Phenergan) Mild to moderate n/v, in combo for severe MOA Dopamine receptor blockade in CTZ Bind to and block cholinergic, alpha 1 adrenergic & histamine 1 receptors C/I Concomitant use of drugs that cause CNS depression (sedatives, hypnotics, opiates) Exacerbation of Parkinsons s/s Decrease sx threshold Preg Cat C Adverse events Drowsiness, sedation EPS: block central dopaminergic receptors - drooling, tremor, inability to initiate voluntary movement, rigidity, dry mouth, urinary retention, hypotension, sedation Interactions ETOH and other CNS depressants Propranolol - increased drug Anticonvulsants - lower sz threshold Caution in elderly

Hydroxyzine (Vistaril) Meclizine (Antivert) Dimenhydrinate (Dramamine) Scopalamine (Transderm Scop) Mild nausea, motion sickness MOA Interruption of visceral afferent pathways that stimulate n/v C/I Breastfeeding Asthma Glaucoma GI/urinary obstruction Prostatic Hypertrophy (BPH) Adverse Events Sedation, drowsiness, confusion Blurry vision, dry mouth, urinary retention, tachycardia S/s of OD: dilated pupils, tachycardia, HTN, CNS depression, flushed skin, Respiratory failure, circulatory collapse Interactions ETOH Tranquilizers Sedative hypnotics

Lorazepam (Ativan) Tx and prevent emesis, anxiolytics, amnesia (good for anticipatory n/v - chemo) MOA Hepatic or renal failure Preg Cat D Adverse Events CNS depression: drowsiness, fatigue, memory impairment, impaired coordination, confusion Paradoxical CNS stimulation Constipation, HA, inc/dec appetite Hypotension, bradycardia, apnea (parenteral) Monitoring: CV, resp status, LFTs Interactions CNS depressants, ETOH

Ondansetron (Zofran) Tx of chemo - induced n/v MOA Antagonize type 3 serotonin receptors centrally in CTZ and peripherally at afferent fibers upper GI tract C/I May harm fetus, may pass into breastmilk Preg Cat B (may cause cleft palate later in pregnancy) Adverse Events HA Diarrhea Abd/epigastric pain Elevated LFTs HTN Fatigue Constipation Pruritis Fever Arrhythmia/heart block (prolong PR, QT, wide QRS) Interactions Diuretics Drugs that prolong cardiac conduction

Dronabinol (Marinol) Only for chemo-induced n/v MOA: unknown Therapeutic level of THC must be in blood before admin of chemo to prevent emesis (6-12 hrs) Pt w/ previous recreational use -> better antiemetic effect C/I Preg Cat D Adverse Events CNS effects (no driving or operating machinery) Sedation, ataxia, dysphoria, confusion, hallucinations, anxiety, fear, orthostatic hypostatic, blurry vision, tachycardia Indications ETOH CNS depressants

Metoclopramide (Reglan) Diabetic gastric stasis, post surgical gastric stasis, gastroesophageal reflux MOA Unknown C/I Gi toxicity (take w/ PO), high blood glucose levels, mood swings, depression, anxiety, aggression, psychosis, HA, restlessness, insomnia Long term: muscle wasting, fluid/electrolyte imbalance, cataracts, osteoporosis, pathological fractures Interactions Decrease effect of barbiturates, hydantoins, rifampin, ephedrine Monitor: K levels when taken w/ K (depletes w/ diuretics)

Determine cause: Drug induced: d/c or reverse drug Diabetic ketoacidosis: tx with insulin, alkalosis Hypercalcemia: IV hydration, diuretics, pamidronate Increased ICP: surgery, steroids EPS: tx w/ diphenhydramine or benztropine

1st line Phenothiazine: mild or moderate n/v (promethazine, prochlorperazine) 2nd Antihistamine or anticholinergic: good for mild nausea when 1st isn’t effective 3rd line Re-eval physiological cause Education take meds 1-2 hrs prior long term use required monitoring: CBC, BMP, EKG

Relaxation of lower esophageal sphincter Increased intra-abd pressure (obesity, pregnancy) Delayed gastric emptying Hiatal hernia fatty foods chocolate, peppermint/spearmint garlic, onions, chili peppers ETOH, coffee/caffeine spicy foods, citrus foods/tomato tobacco aspirin, iron, NSAIDs

Symptoms occur after meals Symptoms worse when reclining or lying down Pt responds to empiric trial of acid suppression therapy Treatment: Relieves symptoms Decrease frequency/duration of reflux Heal esophageal mucosa Prevent complications (esophagitis, esophageal ca, peptic stricture, barretts's esophagus) Symptoms: Heartburn Dyspepsia Nausea, bloating, belching, epigastric fullness/pressure/pain Chronic cough/throat clearing Asthma, wheezing, hoarseness, sore throat Diagnose w/ endoscopy (with biopsy)

Tissue injury from acid and digestive functions of GI tract Common forms: Helicobacter pylori-positive ulcers (chronic) NSAID-induced ulcers (chronic) Stress ulcers (critically ill, following major trauma/illness) Cause: Breakdown of gastric tissue and tissue injury from acid and digestive functions

Symptoms Epigastric abd pain Heartburn, belching, bloating H. Pylori affects duodenum: pain 1-3 hrs after meal, food makes pain better NSAIDs affect stomach: n/v, anorexia, food precipitates ulcer pain Diagnose w/ endoscopy (with biopsy) Cultures for H. pylori detection Complications GI bleeding (melena, hematemesis) Perforation (sharp, sudden pain) Gastric Outlet obstruction (bloating, anorexia, n/v, wt loss)

H. Pylori induced ulcers: combo of abx and acid suppression Calcium Carbonate. (Tums), Mag Salts, Aluminum Salts MOA Neutralize HCl acid in stomach -> increase pH C/I: none Adverse: Rebound acidity (mag containing antacids) Constipation (aluminum containing antacids) Interactions Alter rate of absorption of iron, sulfonylureas, tetracycline, quinolone abx Take 1-4hrs AFTER meds that alter absorption Used for mild intermittent symptoms (less than 2x per week) Short duration of action Do not heal ulcers, only mask signs

Cimetidine (Tagamet) Famotidine (Pepcid) Ranitidine (Zantac) MOA Inhibit histamine 2 on gastric parietal cells -> decrease acid secretion & pepsin activation C/I: hypersensitivity to H2RAs Adverse events HA, dizziness, confusion Caution in elderly and renal disease Interactions Tagamet inhibits CYP450 (warfarin, phenytoin, theophylline) Take antacids 1-2 hrs after H2RA Effective in: Mild GERD Healing ulcer H. pylori eradication Prevention of NSAID related ulcer Only use 1-2x daily Onset of action 1-2 hrs after admin

Omezaprole (Prilosec) Lansoprazole (Prevacid) Pantoprazole (Protonix) Esomeprazole (Nexium) MOA Inhibit gastric proton pumps located in parietal cells -> long lasting suppression of acid secretion C/I: hypersensitivity to PPis Adverse events HA, diarrhea, constipation, abd pain Long term use: hypergastrinemia, fracture, GI infection (C. diff, gastrointeritis), Vit B12 deficiency, hypomagnesemia Interactions Omeprazole and Lansoprazole: May affect clopidogrel (plavix) Caution in pts taking plavix Most potent acid suppressing agent Onset is 5 days, most effective when taken in the morning 30-60 min BEFORE food

Amoxicillin (Amoxil) Clarithromycin (Biaxin) Metronidazole (Flagyl) MOA Used in combo w/ acid suppressing meds to eradicate H. pylori, PUD Kills bacteria and inhibit bacteria protein synthesis C/I: Allergy; concomitant use w/ meds that prolong QT Adverse events N/v/d metallic taste Interactions Amoxicillin - increase effects of warfarin (increase INR) Clarithromycin - CYP3A4 inhibitor Metronidazole - avoid w/ ETOH and warfarin

GERD First line: Mild s/s: lifestyle changes -> OTC antacids -> H2RA, PPIs Moderate-severe: prescription acid suppression (PPIs favored) Step up tx: lifestyle w/ gradual increase of pharm intervention; H2RA -> PPI -> surgery Step down tx: start w/ high dose PPI -> titrate to lowest dose Second line: for pt w/ incomplete response to acid suppression Add H2RA at bedtime (2nd line after PPI) Third line Anti-reflux disease

For pts taking high dose NSAIDs MOA Synthetic prostaglandin E1 analog -> inhibits acid secretion, increased mucosal defenses C/I Pregnancy -> uterine contractions -> AVOID Adverse events Diarrhea, abd pain, cramping, nausea Interactions Antacids may increase side effects Used for prophylaxis against NSAID induced ulcers