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
Constipation
Secretagogues
Peripherally acting Mu-opioid receptor antagonist (PAMORA)
Naloxegaol (Movantik)
MOA
Antagonist of opioid binding at mu-opioid receptor -> decreased constipating effects of opioid
C/I
Known or suspected GI obstruction; potential for GI performation
Can cause opioid withdrawal in pts on methadone
Preg cat C
Adverse events Abd pain N/v/d flatulence HA, hyperhidrosis AVOID in surgical adb
Interactions
CYP34A inhibitors: Diltiazem, erythromycin, verapamil,
risk for withdrawal withdrawal in other opioid antagonists
Constipation
Agent selection
1st line
Bulk forming laxative for all types of constipation (take with plenty of water)
Docusate - most effective to prevent straining
2nd line
Mag hydroxide, saline laxative, lactulose, sorbitol
More rapid onset of action
3rd line
Stimulant laxative
- Goal is not to increase frequency of defamation -> dehydration
- Goal is to increase comfort during defecation
Increase PO fluid -> improves efficacy
Safe when used in moderation
Chronic constipation - bulk forming are safer - take at least 3 days to work
Constipation
Special population
Children
Not usually pathologic - potty training stress, painful stool
Can cause urinary incontinence and UTI
Increase fluids, bowel routine
Pharm tx not usually recommended - PEG prep, mineral oil
* NO ENEMAS < 2
Women
Docusate for pregnant women
Castor oil can stimulate contractions - AVOID
Geriatric
Bowel obsessed
Eliminate causative agents (antipsych, TCA, calcium)
High risk of electrolyte imbalance w/ laxatives
High risk for dehydration - caution
Diarrhea
Increased frequency of loose, watery stool (>3x daily) over 24-48 hrs
Causative organism transferred from person to person via food and water
Can cause serious dehydration
Causes: Meds Mag containing antacids Abx SSRI antidepressants Cholinergic agents Digoxin GI stimulants Laxatives Metformin Prostaglandins Quinidine
Disorders AIDS Bowel rsxn Colon ca Diverticulitis Enteral feeding Gastroenteritis Hyperthyroid IBD IBS Lactose intolerance Malabsorption Pheochromocytoma
Acute: lasts 1-14 days
Persistent: 14-30 days
Chronic: > 30 days
Diarrhea
Diagnosis
Fecal leukocyte, lactoferrin and hem occult blood test, stool cx
Ova and parasites:
person not previously treated w/ empiric anti parasitic therapy
persistent diarrhea > 7 days
recent travel to mountainous regions, Russia or Nepal
exposure to infants at daycare centers
blood diarrhea w/ few or no fecal leukocytes
rectal sex; AIDS
Initiate therapy & evaluate inflammatory pathogen:
profuse, watery diarrhea w/ dehydration
passage of blood and mucus
fever > 101.3F
- Prophylaxis for those that cannot comply w/ dietary restrictions
- travelers to places w/ contaminated drinking water
Diarrhea
Antimotility Agents
Diphenolxylate w/ atropine (Lomotil)
MOA: decrease GI motility
C/I:
Exacerbate infectious diarrhea-won’t excrete infectious organism
Don’t use when assoc w/ fever, bloody diarrhea, fecal leukocytosis
Caution w/ hepatic dysfunction
Adverse events:
abd discomfort, constipation, dry mouth, dry eyes, urinary retention
-drowsiness, blurry vision, dizziness
-Caution: pts w/ liver disease, fever, bloody stools, fecal leukocytosis
AVOID in children < 4yo
Interactions:
Antidepressants, ETOH, barbiturates, benzos (react w/ diphenoxylate)
HTN crisis w/ MAOIs
TCA, antipsych, antihistamines (react w/ atropine)
Loperamide (Imodium)
MOA:
Opioid receptor agonist - acts on mesenteric plexus of large intestine
C/I:
Fever, bloody, stools, fecal leukocytosis
Adverse events
Abd discomfort, constipation, drowsiness, dry mouth
Interactions
Does not cross BBB, can cause drowsiness -> warn if driving or performing activities requiring alertness
- causes stools to be more formed, less watery
Avoid in infectious diarrhea, traps infection in gut, makes course of infection longer
Diarrhea
Atypical antidiarrheals
Antisecretory agents
Subsalicylate (Pepto Bismol), (Kaopectate)
MOA
anti-inflammatory action, antacid, antibiotic and antiviral properties
C/I
hypersensitivity to ASA
AVOID in kids w/ flu or chicken pox -> Reyes syndrome
Adverse events
black stool, dark tongue, tinnitus
Interactions: meds that interact w/ ASA
Aspirin
Warfarin
Diarrhea
Adsorbents & Absorbents
Adsorbent: Kaolinite (Kaopectate)
Absorbent: Polycarbophil (Fibercon)
MOA
Adsorbent: bind to bacteria -> solidification of of loose stools (add dose after each BM)
Abdorbent: water is absorbed in GI tract -> less watery stools
C/I: none
Adverse events:
Constipation and feeling of fullness
Stomach upset, bloating and gas
Interactions
Not selective: may absorb other meds & nutrients -> take separately from other meds and food
Diarrhea
Semisynthetic Abx
Rifaximin (Xifaxin)
- for non-invasive strains of E. coli
- best for travelers diarrhea
MOA
Blocks transcription of bacteria -> inhibits bacterial synthesis and growth
C/I
hypersensitivity to Rifaximin
Adverse events
Peripheral edema, nausea, dizziness, fatigue, muscle spasms, HA
Interactions
Poorly absorbed into bloodstream -> low risk for interactions
Diarrhea
Agent Selection
1st line
Loperamide - more effective than adsorbents (drowsiness - may not be tolerated as first line)
Travelers diarrhea: Ciprofloxacin, Levofloxacin, Rifaximin
2nd line
Adsorbent or antisecretory agent
3rd line
Lomotil (schedule 5; causes anticholinergic effects + CNS effects)
Zithromycin
Diarrhea
Special Populations
Children
Oral hydration is priority
Antidiarrheal agents not recommended
Women
Loperamide NOT given bc not studied
Absorbents = 1st line
Geriatric
Rehydration is priority
Diphenoxylate/loperamide -> sedation when combined w/ benzos, antidepressants, anticholinergics, antipsych
Diarrhea
Monitoring
All patients at risk for: dehydration hypotension tachycardia orthostatic hypotension poor skin turgor
Monitor serum electrolytes
Irritable Bowel Syndrome
Functional bowel disorder w/ abd discomfort and alteration in bowel pattern
Classic symptoms: abd pain bloating constipation diarrhea
Causes
Dysregulation btw brain and gut
increased and abnormal contractions on intestinal tract -> either diarrhea OR constipation
onset over weeks to months
worse during physical and emotional stress -> sexual/physical abuse
Food can be trigger
Meds may be required only intermittently
Irritable Bowel Syndrome
Diagnosis
Abd pain Change in consistency of stools -> relieved w/ defecation Young adulthood onset Wt loss rectal bleeding fever acute onset onset > 50 yo unusual
ROME III criteria for IBS
Recurrent abd pain 3 days/mo in the last 3 months with 2 of the following:
-Improvement w/ defecation
-Onset assoc w/ change in frequency of stool: more or less frequent
-Onset assoc w/ change in appearance of stool: formed vs liquid
Irritable Bowel Syndrome
Treatment
Mild symptoms:
Responsive to dietary and lifestyle changes
- Avoid cereals, spicy food, lactose, caffeine, beans, cabbage, fatty foods, ETOH)
- Maintain daily diary of food intake
-Biofeedback: relaxation; good for stress induced IBS
-Incorporate exercise into daily activities
Irritable Bowel Syndrome
Medication tx
Bulk-forming Laxatives Hyperosmotic Laxatives Stimulant Laxatives Surfactant Laxatives Antidiarrheal Agents (Lomodil, Immodium) Semi-synthetic Antibiotic
Irritable Bowel Syndrome
Antispasmodics (Anticholinergics)
Dicyclomine (Bentyl)
Mechanism of action
Direct relaxation of the smooth muscle of the GI tract
Contraindications
Glaucoma, unstable CAD, GI/GU obstruction, paralytic ileus, severe ulcerative colitis
Adverse Events
Drowsiness, anticholinergic effects, paradoxical excitement
Interactions
Antacids inhibit absorption
Additive anticholinergic effects with anticholinergics, antihistamines, narcotics, tricyclic antidepressants, narcotics
Irritable Bowel Syndrome
Agent Selection
1st line
IBS-Constipation:
linaclotide or lubiprostone
osmotic laxative to avoid incidence of diarrhea
IBS-Diarrhea:
Loperamide- fewest CNS complications
Dicyclomine for pain, gas, bloating
2nd line IBS-C Osmotic laxatives IBS-D diphenoxylate HCl for short term use Rifaximin for long term
3rd line
IBS-C
stimulant laxatives for resistant cases- short term only
Irritable Bowel Syndrome
Special Populations
Pediatric
No tx criteria established
Antidiarrheals, antispasmodics and fiber
Women
More likely to have IBS
Hx of verbal and sexual abuse has been linked to IBS
Geriatric
Presence > 50 yo rare
Consider abd pain as more concerning clinical symptom
Irritable Bowel Syndrome
Monitoring
Re-eval within 3-6 weeks of initial evaluation
Psychological counseling may also be helpful
Mild to intermittent s/s can be managed by PCP
Exacerbations and remissions:
Can achieve recovery within 12-18 mo (70% of the time)
May consider GI referral
Irritable Bowel Disease
Crohn’s and Ulcerative Colitis
IBD: describes two main chronic inflammatory conditions of GI tract:
Crohn’s Disease:
Chronic inflammatory disease characterized by transmural lesions located at any point in the GI tract
Ulcerative Colitis:
Chronic disease of mucosal inflammation limited to the colon and rectum
Irritable Bowel Disease
Causes
Dysregulation of immunologic mechanisms- thought to be autoimmune
Genetic predisposition
Defect in mucosal barrier > enhanced permeability > increased uptake of proinflammatory molecules/infectious agents
Differentiate by endoscopic findings only
Irritable Bowel Disease
Diagnosis
Diagnosed with endoscopy
Physical exam, abdominal exam, recent use of abx, international travel, diet hx, use of laxatives vs antidiarrheals, family history
Many concomitant symptoms:
Arthritis, fever, diarrhea, weight loss, rectal bleeding, abdominal pain
Irritable Bowel Disease
Aminosalicylates
Sulfasalazine (Azulfidine)
mesalamine (Asacol, Rowasa, Pentasa)
Mechanism of Action
Decrease inflammation in the GI tract by inhibiting prostaglandin synthesis (quick onset- 1 week)
Contraindications
ASA allergy, sulfa allergy, G6PD Deficiency
Adverse Events
Nausea, HA, abd pain, diarrhea
Interactions
Sulfasalazine decreases effect of warfarin
- Gold standard for mild-moderate Crohn’s and Ulcerative Colitis
Irritable Bowel Disease
Corticosteroids
Prednisone methylprednisolone hydrocortisone dexamethasone budesonide
Mechanism of Action
Immunosuppression and prostaglandin inhibition when disease fails to respond to aminosalicylates
Contraindications
Active GI bleeding
Adverse Events
Hyperglycemia, increased appetite, insomnia, anxiety, tremors, HTN, fluid retention, electrolyte imbalances, decreased bone density
Interactions
Many are P450 34A substrates and should be used cautiously
Decrease efficacy of antidiabetic and anti-HTN medications
- Intermittently used to treat IBD exacerbations only
- Can be used in combo w/ all other IBD meds
- Cyclosporine is for severe, acute exacerbations of UC
Irritable Bowel Disease
Immunosuppressive agents
Azathioprine (Imuran)
cyclosporine
6-mercaptopurine (Purinethol)
methotrexate (rheumatrex)
Mechanism of Action
Decrease production of various inflammatory mediators
Contraindications
Pregnancy, liver disease, bone marrow suppression
Adverse Events
Pancreatitis, fever, arthralgias, rash, hepatotoxicity, cirrhosis, neutropenia, nausea, diarrhea, HTN
Interactions
Cyclosporine P450 34A cytochrome. Grapefruit juice increases blood levels and risk of side effects
Irritable Bowel Disease
Antibiotics
Metronidazole (Flagyl)
ciprofloxacin (Cipro)
Mechanism of Action
Link between IBD and infectious cause
Abx that act against gram (-) and Mycobacterium organisms with low side effect profile
Contraindications
Liver failure, renal failure, pregnancy, seizure disorder, no Cipro to children < 12 (also, risk of tendon rupture)
Adverse Events
Nausea, diarrhea, dizziness, photosensitivity
Interactions
No Flagyl + ETOH
Cipro inhibits theophylline metabolism
Irritable Bowel Disease
Biological Agents - Tumor Necrosis Factor Inhibitors
(TNF-a inhibitors)
Infliximab (Remicade)
adalilimumab (Humira)
certolizumab pegol (Cimzia)
Mechanism of Action
Overexpression of immunologic cytokines including TNF seen in Crohn’s
TNF inhibitors neutralize soluble forms of TNF and inhibit its binding to TNF receptors
Contraindications
Active TB , heart failure, hep B,
Adverse Events Opportunistic infections (TB, fungal, bacterial, viral), lymphoma, lupus-like syndrome, injection site reactions
Interactions
not to be given with live vaccines
- For severe, refractory Crohn’s disease
- Maintain remission of Crohn’s disease;
- Treat Ulcerative Disease and Crohn’s disease
Irritable Bowel Disease
Biological agents-
Selective adhesion molecule inhibitors
Natalizumab (Tysabri)
vedolizumab (Entyvio)
Mechanism of Action
Prevent migration of inflammatory lymphocytes into the gut mucosa
Contraindications
Active TB, Hep B, active progressive multifocal leukoencephalopathy (PML)
Adverse Events Opportunistic infections (TB, fungal, bacterial, viral), lymphoma, lupus-like syndrome, injection site reactions, PML
Interactions
not to be given with live vaccines
- Reserved for pts who have inadequate response or are unable to tolerate conventional Crohn’s therapies and TNF inhibitors
Irritable Bowel Disease
Agent selection
Crohn’s
Mild: oral/rectal aminosalicylate OR rectal corticosteroid
Moderate: oral AND rectal aminosalicylate AND short term steroids
Severe: IV corticosteroid AND/OR IV Cyclosporine
Fulminant: IV corticosteroid, AND/OR IV cyclosporine, IV infliximab or SC adalimumab
Also, supportive care including IV fluids, bowel rest, parenteral nutrition
For UC anf Crohn’s there is no 1st, 2nd, 3rd line tx
Tx based on location and inflammation, severity, and extent of disease
Consider pt tolerance to therapy, compliance, and cost
Irritable Bowel Disease
Agent selection
Ulcerative Colitis
Mild: combination oral AND rectal aminosalicylates
Moderate: aminosalicylates + corticosteroids
Severe: require hospitalization, DC oral/topical agents, add corticosteroids
If no resolution of symptoms in 7-10 days consider IV cyclosporine, IV infliximab, SC adalimumab, IV vendolizumab
- Surgery for pts who fail to respond to drug therapy
Irritable Bowel Disease
Special Populations
Pediatrics
IBD diagnosed early in life
Must limit nutritional deficiencies > stunted growth, malnutrition, anemia
No long term steroids
Infliximab (CD, UC) and Adalimumab (UC) > 6yo for inducing and maintaining remission
Women
Increased rates of abortions
stillbirths
developmental defects seen with active disease
Treat aggressively to prevent dehydration, anemia, nutritional deficiencies
Irritable Bowel Disease
Monitoring
Monitor nutritional parameters: weight, albumin, vitamin B12, iron levels & transferrin
Mental health and quality of life: social interactions, attendance at work, completion of ADLs
Monitoring drug toxicities: CBC, LFTs, renal function
Biologics: monitor for heart failure, TB, infection, hepatotoxicity, lupus-like syndrome
UTI
Causes
Broad term used to describe inflammation of the urethra, bladder and kidney
Bacteria, yeast or chemical irritants can cause inflammation of urinary tract
Women:men 30:1, after age 65 1:1
Peak incidence 18-24 yo
Shorter urethra, closer to rectum, sexual intercourse is contributing factor
Men cannot have uncomplicated infections
Distance between end of urethra and bladder
Incomplete bladder emptying- stagnant urine
Other causes:
Pregnancy, DM, constipation, sickle cell disease, structural defects of the urinary system
UTI
Pre-disposing factors
Female sex Pregnancy Diabetes Chronic degenerative neurological conditions Paralysis Recurrent UTI Ineffective bladder emptying Estrogen deficiency Constipation Delayed post coital micturition Sickle cell disease Renal transplant
UTI
Diagnosis
Most pathogens enter the urinary tract > ascend the urethra > in the bladder bacteria multiply
Triad of symptoms:
Urgency, frequency, dysuria
Uncomplicated: premenopausal, sexually active, non pregnant woman without recent UTI
Complicated: man, postmenopausal, pregnant, urinary structural defects, neurologic lesions, catheter, symptoms > 7 days
History, physical exam, lab studies including urinalysis and culture
Tx: abx
- 25-42% uncomplicated acute cystitis resolve without intervention
- All symptomatic UTIs treated
UTI
Treatment
Trimethoprim-sulfamethoxazole (Bactrim)
Adverse events: N/V, anorexia, megaloblastic anemia, hallucinations, depression, seizures
Contraindications: megaloblastic anemia, pregnancy (Cat C), breastfeeding
Nitrofurantoin (Macrobid)
Adverse Events: Nausea, pulmonary allergic reaction, dizziness, hemolytic anemia, diarrhea, vaginitis, rhinitis, HA
Contraindications: anuria, oliguria, pregnancy at term, breastfeeding mother
Take with food to increase absorption
Ciprofloxacin (Cipro)
Adverse events: nausea, diarrhea, altered taste, dizziness, drowsiness, HA, insomnia, agitation, confusion
SERIOUS: pseudomembranous colitis, SJS
Contraindications: Allergy to fluoroquinolones, <18 yo, pregnancy, renal disease, breast feeding mothers
Interactions: increases serum levels of theophylline, food slows absorption
UTI
Urinary analgesics
Methenmamine (Urised)
phenazopyridine (Pyridium)
Mechanism of Action
Topical analgesic on the mucosa of the urinary tract
Adverse Events
Rash, GI upset, headache, difficulty urinating, urine discoloration
Contraindications
Glaucoma, patients < 6 yo, renal insufficiencies, pregnancy/lactation
- Not to be used for more than 2 days for pain relief in setting of UTI
UTI
Agent selection
Uncomplicated Cystitis
1st line
Bactrim (3 days vs 7 days) OR nitrofurantoin (7 days)
2nd line
Bactrim 7 days, 7 days: cipro-, levo-, o-, norfloxacin
3rd line
Culture and sensitivity testing
Treat based on results
Tx when pt has dysuria, urinary urgency, frequency
If flank pain, n/v, CVA tenderness, fever >38C ->cx for pyelonephritis
UTI
Special populations
Children
Treat quickly- high risk for renal scarring
< 3 yo need renal US
1st line: Augmentin, Bactrim, cefpodoxime
Geriatric
Usually asymptomatic, consider UTI if change in mental status
Usually r/t incontinence, malnutrition, incomplete bladder emptying
No nitrofurantoin in elderly
Pregnancy
UTI > prematurity and still birth
Amoxicillin, cephalexin, nitrofurantoin (through 2nd trimester)
Overactive Bladder
Symptoms
Urinary urgency accompanied by frequency (voiding > 8x/24 hrs)
Nocturia (>2 night wakings to void) with or without urge urinary incontinence (UUI)
Multifactorial: anatomic, physiologic, comorbidity-related
Bladder fills with urine > urge to void at ~ 75% capacity > neural control defers urination
Overactive Bladder
Diagnosis
Assess degree of impairment/annoyance
Behavioral interventions: bladder training, pelvic floor muscle exercises, weight loss
Anticholinergic: 1st line
Goals of therapy: resolution of symptoms, cessation of incontinence episodes, return to previous level of social functioning
Dx is difficult
Grossly under-reported due to embarrassment
Reduce fluid consumption Reduce alcohol consumption Reduce caffeine consumption Bladder training Pelvic floor exercises
Overactive Bladder
Treatment
Oxybutynin (Detrol)
trospium (Sanctura)
solifenacin (VESIcare)
Mechanism of Action
Increase bladder capacity, decrease intensity and frequency of bladder contractions, delay initial urge to void
Adverse Events
Anticholinergic response- dry mouth, constipation, urinary retention
Contraindications
Glaucoma, renal impairment
Interactions
Prolonged QTc, CYP34A inhibitors/inducers
Overactive Bladder
Beta-Adrenoreceptor Agonists
Mirabigron (Myribetriq)
Mechanism of Action
Promotes relaxation during filling phase, Increases bladder capacity and decreases frequency of micturition
Adverse Events
Less cases of dry mouth, constipation, urinary retention
Contraindications
Can elevate BP in some cases, otherwise less anticholinergic response than other meds
Interactions
Low potential for drug interactions
Overactive Bladder
Agent Selection
1st line
Behavioral therapy
Anticholinergics
2nd line
Add second anticholinergic medication
Overactive Bladder
Special Populations
Pediatric
Usually secondary to deficits in learned neural control, fecal impaction or underlying structural abnormalities
Oxybutynin IR & ER have been approved
Women
Postmenopausal symptomatology- vaginal atrophy, urogenital changes
Antimuscarinic 1st line
Geriatric
Usually anatomic, physiologic, age-related
Many side effects including impaired cognition
Antimuscarinic 1st line
Prostatitis
Causes
Most common urological infection in adult men:
Category I: Acute bacterial
Category II: chronic bacterial
category III: chronic nonbacterial
category IV: asymptomatic inflammatory
Chief organisms are E. coli & Pseudomonas
Acute bacterial:
Ascending infection up the urinary tract (can affect younger men)
Chronic, non-bacterial:
Inflammatory response: eosinophil infiltration; granulomatous inflammation by macrophages
Diagnostic criteria:
Abd pain, urinary retention, fever, painful ejaculation, rectal/perineal pain,
Need prostatic urine culture to dx: urine collected after prostate massage and after full bladder void
Prostatitis
Diagnosis
Agent Selection
Non-bacterial forms are treated without use of antibiotics
Antibiotics are treatment of choice:
Course is 4-6 weeks, up to 12 weeks, in duration
1st line: fluoroquinolones- (Cipro) best tissue concentration followed by Bactrim (more resistance in US)
2nd line: Doxycycline, azithromycin, clarithromycin
Sitz baths, analgesics, stool softeners, antipyretics, rest
Goals of therapy: eradicate causative organism and restore prostate health
Monitor creatinine clearance in older men taking fluroquinolones
Should begin to elicit results after 1st week of therapy (sometimes 2 weeks)
Prostatitis
Trimethorpim-Sulfamethoxazole (Bactrim)
Mechanism of action
Affects the production of proteins and nucleic acids of bacteria at prostate; inhibits growth of bacteria
Adverse events
GI distress, rash
Contraindications
Allergy to sulfa
Interactions
Dilantin, hypoglycemic, Coumadin levels- monitor for seizures, BG and PTT
Prostatitis
Fluoroquines
Mechanism of action
Decrease the growth and replication of bacteria by inhibiting bacterial DNA during synthesis
1st choice when allergic to sulfa
Adverse events
Headache, diarrhea, nausea, drowsiness, altered taste, insomnia, agitation, confusion, pseudomembranous colitis, Stevens-Johnson syndrome
Contraindications
Pregnancy/lactation, allergy to macrolides, caution in liver and kidney disease
Interactions
Absorption is reduced by milk, antacids, iron and sucralfate
Can increase levels of systemic theophylline and warfarin (may need to lower the dosages of these medications)
Prostatitis
Doxycycline
Mechanism of action
Inhibits protein synthesis
Adverse events
GI distress, potential acute hepatotoxicity and nephrotoxicity
Contraindications
Pregnancy/lactation, hypersensitivity to tetracyclines
Interactions
Interact with metal ions: aluminum, calcium, iron, magnesium and zinc- must separate meds by 2 hours
BPH
Most common prostate problem in men older than age 50
Cause is not well understood
Overgrowth of normal cells in the stromal and epithelial tissues of the prostate gland
Blood levels of testosterone < and estrogen > as men age, lower levels of testosterone and higher levels of estrogen thought to contribute to hyperplasia of prostate cells
BPH
Diagnosis
Digital rectal exam and PSA
AUA symptom scale > 7
Eval for post-void residual- > 100mL is considered significant
Symptoms of BPH stem from obstruction:
Problems with urination (hesitancy, weak stream, urgency, retention, frequency, dysuria, incontinence)
Goal of tx:
Reduce bladder outlet obstruction
improved quality of life
fewer symptoms and decreased residual urine volume
BPH
Alpha-Adrenergic Blocker
Terazosin (Hytrin) doxazosin (Cardura) tamsulosin HCl (Flomax)
Mechanism of action
Better for men with smaller (still enlarged) prostate or who need a fast result
Relax smooth muscle in prostate and bladder neck and decrease bladder resistance to urinary outflow
Adverse events
Orthostatic hypotension, somnolence, dizziness
Contraindications
tachyarrhythmias, HTN, pregnancy/lactation, cardiac, renal, hepatic insufficiency, orthostasis, priapism, impotence
Interactions
Take at bedtime to avoid hypotension
BPH
5-a-Reductase Inhibitor
Finasteride (Proscar)
dutasteride (Avodart)
Mechanism of action
Reduce prostate size by 20-40% after 6 mo use
Block 5-a-reductase- enzyme that activates testosterone in the prostate
Adverse events
Impotence, decreased libido, hypotension, priapism, increased risk for prostate CA
Contraindications
Not to be handled by pregnant women, sensitivities to sulfonamides
Interactions
May take up to 6 mo to work
BPH
Phosphodiesterase 5 Inhibitor
Tadalafil (Cialis) used for erectile dysfunction, also approved for BPH
BPH
Agent selection
1st line- no medical treatment is recommended if AUA score < 7
2nd line > 3rd line- initiate when AUA score > 7; a-adrenergic blocker > + 5-a-reductase inhibitor when symptoms are moderate to severe
4th line- referral to urology to discuss surgical options
BPH
Monitoring
AUA score
Monitor patients BP within first 2 weeks of initiating treatment
Lifestyle changes:
Decrease fluid intake several hours before bed, avoid diuretics and ETOH, anticholinergics, antihistamines and antidepressants
Erectile Dysfunction
Most common sexual problem in men – repeated inability to achieve or maintain and erection that is firm enough for sexual intercourse (total inability, inconsistent ability or brief erection)
Causes: usually secondary to a decline in testosterone levels, psychological/ psychiatric problems, damage to nerves/arteries/smooth muscles/fibrous tissue
Risk factors: age, CVD, smoking, DM, HTN, high cholesterol, obesity, sedentary lifestyle
Erectile Dysfunction
Diagnosis
Medical conditions, medications, sexual function, cardiac history
Fasting glucose levels, lipid panel, TSH, morning total testosterone level
Goal: achieve sexual satisfaction and achieve/maintain an erection
Erectile Dysfunction
Phosphodiesterase 5 inhibitor (PDE5)
Tadalafil (Cialis)
vardenafil (Levitra)
sildenafil (Viagra)
Mechanism of action
Inhibit the breakdown of one of the messengers involved in the erectile response > facilitate and maintenance of an erection
Adverse events
Headache, flushing, GI disturbance, nasal congestion, rash, priapism- vasodilatory
Contraindications
Nitrates, a-blockers within 4 hours of use
Interactions
Potent CYP3A4 inhibitor
Erectile Dysfunction
1st line
Lifestyle changes, modify meds that are contributory
PDE5 inhibitor
2nd line
Urology consult
Pt w/ BP <170/110
- lifestyle changes + PDE5 inhibitor
- if successful, continue
- if unsuccessful, refer to urologist
BP > 170/110
Stabilize pt, then start PDE5 inhibitor
