Pharm 2: GI GU Flashcards
Nausea & Vomiting
Causes
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
N/V - Stimuli
Drugs
Ketoacidosis
Uremia
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
N/V - Stimuli
Obstruction
Gastroparesis
Visceral pain
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
N/V - Stimuli
Motion sickness
Vestibular inflammation
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
N/V - Stimuli
Higher brain stem:
emotions, sights, smells, tastes
Agents used
Benzodiazepines
Dronabinol
Corticosteroids
Cortical structures
Acts on vomiting center to: Lower diaphragm Contraction of abd muscles Esophageal dilation Reverse direction of peristalsis
N/V - Diagnostic Criteria
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
N/V - Phenothiazines
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
N/V - Antihistamines
Anticholinergics
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
N/V - Benzos
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
N/V - 5-HT3 receptor antagonists
Serotonin Antagonists
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
N/V - Cannabinoids
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
N/V - Prokinetics
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)
N/V - Agent selection
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
N/V -
Lines of treatment
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
GERD
Causes
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
GERD
Diagnosis
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)
Peptic Ulcer Disease
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
Peptic Ulcer Disease
Diagnosis
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)
GERD + PUD
Treatment
Antacids
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
GERD + PUD
Treatment
Histamine 2 receptor Antagonists (H2RAs)
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
GERD + PUD
Treatment
Proton Pump Inhibitors
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
GERD + PUD
Treatment
Antibiotics
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
Treatment
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
GERD + PUD
Treatment
Misoprostol (Cytotec)
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
GERD + PUD
Treatment
Sucralfate (Carafate)
Used for pts w/ duodenal ulcer, stress ulcer prophylaxis
Take on empty stomach
MOA
Viscous, adhesive substance that attaches to and protects ulcers from gastric contents
C/I: hypersensitivity to sucralfate
Adverse events
Constipation
Interactions
Decrease absorption of many meds
Must take 2-6 hrs before or after other meds
GERD + PUD
Treatment
Bismuth Subsalycylate (Pepto Bismol)
MOA
Suppression of acid secretion
Antimicrobial effects, salicylate provides anti-inflammatory action
C/I
Hypersensitivity to salicylates, pregnancy, lactation
Adverse events Black stool Darkened tongue Constipation Tinnitus
Interactions
Increased risk of bleeding w/ anticoagulants or antiplatelets
Effective against H. pylori when used in combo w/ abx
GERD
Special populations
Pediatric Spitting up, fussy around feeding Immaturity of LES Respolves by 12-14 mos Can consider Ranitidine (until pt outgrows GERD)
Women
Heartburn common during pregnancy
OTC antacids safe in moderations
Geriatric
High risk for GERD, slowed gastric motility, decreased saliva
Consider PPI bc 1x daily dosing, efficacy and tolerability
Risk for fractures (PPI)
GERD + PUD
Monitoring
Lifestyle modifications Wt loss Elevate HOB Smaller, frequent meals Less causative foods Avoid tight fitting clothes Smoking cessation ETOH
Monitor w/in 1st few weeks of initiating therapy
Allow sufficient time
6 weeks for H2RA
4 weeks for PPI
PUD
Agent selection
1st line
H.pylori + PUD: PPI + amoxicillin + clarithromycin x 7 days (triple therapy)
NSAID induced: PPI, H2RA, sucralfate (if NSAID can be d/c’d), PPI concomitantly
2nd line
PPI + bismuth subsalycylate + metronidazole + tetracycline (quad therapy)
3rd line: if pt fails 1st and 2nd line
GI for endoscopy and biopsy
PPIs and misoprostol very effective to prevent NSAID induced gastric ulcers
Consider Celecoxib if NSAID must continue - less GI side effects
PUD
Special populations
Pediatric
High rates of H. pylori in children of low socioeconomic status
Must consider triple therapy for eradicating or high risk of recurrence
Women
Misoprostol not to be given during pregnancy
Geriatric
High risk for GI malignancies - endoscopy + biopsy
High rates of tx failure with triple therapy bc of abx resistance
PUD
Monitoring
Expect improvement in 7 days w/ anti ulcer therapy
Once NSAID dc’d - improvement w/in days
Symptoms: 14 days = treatment failure -> refer to GI specialist
* educate pt on full adherence bc of possible tx failure
Constipation
Infrequent or difficult evacuation of stool -> diet, lifestyle, meds
Affects females more than males
More common in > 65 yo
Affects male and female children equally
Diet modification preferred over treatment
Causes
If primary cause present -> constipation is secondary symptom
Lifestyle - inactivity, diet; medication - iron
Chronic idiopathic constipation: slow transit constipation, reduction in propulsive capacity of colon
Opioid drugs
- If fluid absorption in small intestine is reduced, the fluid excess leads to diarrhea
- if there is excess fluid reabsorption, constipation occurs
Constipation
Lifestyle modifications
Diet
Increase soluble and insoluble fiber (fruits, vegetables, whole grains), water intake
Exercise
Bowel habit training: regular pattern for bathroom visits
If lifestyle modifications fail -> Medication
Goal of tx: increase H2o content of feces and increase motility of intestines using lowest dose of laxative for least amount of time
If therapy fails after 3-6 months: colon transit studies
Constipation
Stimulant laxatives
Bisacodyl (Dulcolax)
Senna (Senokot)
MOA
Increase peristalsis through direct effects on smooth muscle of intestines; promote fluid accumulation in colon and small intestine
Onset: PO 6-10 hrs, rectal 15 min - 2hrs
C/I Acute adb, fecal impaction, obstruction, rectal fissures, hemorrhoids severe abd pain fevers committing abd distension guarding on abd exam hypo, absent, hyperactive bowel sounds
Adverse events
n/v, abd cramping, gas
laxative dependence
Interactions
avoid concomitant use of dulcolax w/ antacids/pH lowering agents
For short term use
Long term use -> dependence
Constipation
Saline laxatives
Mag citrate Mag hydroxide (milk of mag) Mag sulfate (epsom salt) Sodium phosphate Sodium biphosphate (fleet enema)
MOA
Draw water into intestines through osmosis -> increase in intraluminal pressure -> increase in intestinal motility
C/I: caution in young children & > 55 yo, renal disease
* phosphates can cause electrolyte imbalance (high phos, low K, low Ca, high Na, metabolic acidosis)
Adverse events
Dehydration
Interactions
Tetracycline and quinolone abx, antifungals
Constipation
Bulk forming agents
Methylcellulose (Citrucel)
Psyllum (Metamucil)
MOA
Work by binding to the fecal contents and pulling water into the stool; stimulate movement of intestines
C/I Opioid induced constipation (not effective) Hx of SBO acute surgical abd decreased PO intake of fluids GI ulceration
Adverse events
Flatulence, bloating
Interactions
Gluten intolerance
Constipation
Lubricant laxatives
Mineral Oil (liquid paraffin)
MOA
Coats and softens stool; prevents reabsorption of H2O from stool by colon
Prevent straining in high risk pts (post op, L&D, CVA, hemorrhoids, hernia, MI)
C/I
DO NOT administer before bed -> aspiration
Adverse events: unpleasant taste
Interactions
Surfactant laxative -> liver toxicity
Warfarin -> decreased vitamin K levels -> increase effects of anticoagulation
Constipation
Surfactant laxatives
Docusate (Colace)
MOA
Reduce surface tension of liquid contents of bowel; promote addition of liquid to stool; softer stool, easier to defacate
C/I
Good for pts on low sodium diets; good for HTN, CHF
Adverse events
Stomach upset
cramping
diarrhea
Interactions
Liver toxicity w/ concomitant use with mineral oil
Constipation
Hyperosmolar laxatives
Lactulose (Cephulac)
Sorbitol
Polyethylene glycol (Miralax)
MOA
Metabolized to solutes in intestinal tract -> osmotic pressure -> stimulates intestinal motility and propulsion of fecal contents
C/I
Caution w/ dehydration
Adverse events
abdominal cramping and nausea
Interactions
Avoid antacids w/ lactulose (interferes w/ MOA)
Lactulose: more rapid action
Miralax: slow action
Constipation
Secretagogues
Chloride channel activators
Lubiprostone (Amitiza)
MOA
Enhance chloride rich intestinal fluid without altering serum sodium and potassium concentrations -> pulls water
C/I Mechanism obstruction severe diarrhea pregnant women children
Adverse events
nausea
No interaction
Prescribed by GI specialist
Constipation
Secretagogues
Guanylate Cyclase C Agonist
Linaclotide (Lizess)
MOA
Stimulates secretion of chloride and bicarb into intestinal lumen -> increases fluid and decreases transit time
C/I
children < 6, mechanical obstruction
Adverse events
diarrhea, abd pain, flatulence, abd distension
Interactions: none
Prescribed by GI specialist