Weekly Recaps: Modules 1-4, Exam 1 Flashcards
The COGENT trial found that addition of ____________ to ______________ reduced gastrointestinal events without increasing cardiovascular events.
Omeprazole (Nexium) and clopidogrel (Plavix)
Patients with known ______________ can remain on PPI therapy.
Osteoporosis
Concern for hip fractures and osteoporosis should not affect the decision to use _______ long-term except in patients with other risk factors to hip fracture.
PPIs
With the exception of non-C.diff enteric infections, after a median of three years of use, ______ (GI drug class) did not increase the risk of chronic kidney disease, dementia, bone fracture, myocardial infarction, pneumonia, micronutrient deficiencies, and gastrointestinal cancer.
PPIs
PPI therapy is safe up to ______ years and that limiting prescription of PPI therapy because of concerns of long-term harm is not warranted.
3
Hallmark symptom of heartburn
Retrosternal chest pain in association with certain foods or in the first hour or two after eating, or constantly.
Treatment goals of PPIs
Relieve associated symptoms, promote esophageal healing, avoid complications, prevent recurrence.
Step 1: Lifestyle modification/non-pharmacological interventions for GERD
Dietary modification, avoid contributing medication, smoking cessation, avoidance of ETOH, weight loss, etc.
The foods that can trigger GERD
chocolate, caffeine, alcohol, acidic food, spicy food.
Drug class of multivalent cations with many precautions, drug interactions and adverse effects.
Antacids
______________ (GI med)
- Caution in renal disease
- Diarrhea
Milk of Magnesia
- Belching
- Constipation
- Caution in renal disease
- Milk Alkali Syndrome
Tums
Maalox regular chewable
- Caution in renal disease
- Constipation
AlternaGel
- Gastric distention/belching
- Caution in renal disease
- Alkalosis
- Fluid retention
Alka-Seltzer
Class of gastric acid-suppressing agents frequently used in various gastric conditions.
H2 Receptor Antagonists (H2RAs)
Cimetidine
Famotidine
Nizatidine
Ranitidine
What drug class?
H2RAs (H2 receptor antagonists)
Esomeprazole
Lansoprazole
Omeprazole
Omeprazole/sodium bicarbonate
What drug class?
PPIs (Proton Pump Inhibitors)
Step 1 Treatment of GERD:
Lifestyle Modifications
Antacids
Patient Directed Therapy
- OTC H2RAs (up to BID)
- OTC PPIs (up to QD)
Step 2 Treatment of GERD:
Lifestyle Modifications
Standard Dose Acid Suppressing Therapy
- H2RAs (BID)
- 6-12 weeks
- PPIs (QD)
- 4-8 weeks
- Increase to BID with inadequate symptom response
Step 3 Treatment of GERD:
Lifestyle Modifications
- PPIs (QD - BID)
- 4-16 weeks
Step 4 Treatment of GERD:
Endoscopic procedures
- RF applied LES
- Formation of plication
- Injection of bulking agent or prosthesis
- Nissen procedure
Typical Clinical Presentation of GERD
“Heartburn” – hallmark symptom
i.e. Retrosternal chest pain in association with certain foods or in the first hour or two after eating, or constantly.
Worsening when recumbent or bending over
Regurgitation
Hypersalivation
Belching
Atypical Clinical Presentation of GERD
Chronic cough
Asthmatic symptoms
Hoarseness
Pharyngitis
Chest pain
Dental erosions
Complicated Clinical Presentation of GERD
Dysphagia
Bleeding
Weight loss
Choking
Chest pain
Non-Pharmacological Treatment of GERD
Individualized lifestyle modifications*
Elevate head of bed 6-8 inches
Dietary changes
Late meals / specific foods
Weight reduction
Avoid contributing medications
ASA, NSAIDs, bisphosphonates
Smoking cessation
Avoid of alcohol
Avoid tight–fitting clothing
Remain upright 30’ p eating
Mechanism of action
Weak bases (increases pH)
Neutralize gastric acid and pepsin
Place in therapy
Used as needed for mild GERD
Immediate relief
Short term, NOT indicated for chronic use
Clinically significant DIs
Binding
Absorption (20 ↑ gastric pH)
Weakly acidic drugs ↓
Renal elimination / reabsorption(20 ↑ urinary pH)
Weakly basic drugs elimination renal tubular reabsorption
Weakly acidic drugs elimination renal tubular reabsorption
Sodium content
HTN, CHF
Antacids
Mechanism of actions
Competitively inhibits histamine on the histamine2 receptor decreasing acid secretion in a dose dependant fashion
Histamine stimulates gastric acid secretion
Place in therapy
Mild1 to moderate2 GERD
Delayed onset of symptom relief
Higher doses may provide greater symptomatic relief and healing of erosive espohagitis3 (50% of patients with GERD)
May be more costly than QD PPIs
Greatest benefit in decreasing acid in fasting state (i.e.. nocturnal acid secretion) vs fed state where acid section is also driven by gastrin and ACh
Adverse effects
Generally well tolerated
Headache, fatigue, dizziness, diarrhea, constipation
Drug Interactions
Cimetidine – cytochrome P450 (3A4, 2D6, 1A2, 2C9)
H2RAs (H2 Receptor Antagonists)
Mechanism of action
Covalently binds to H+/K+ ATPase proton pump of parietal cells
Produces a dose dependent inhibition of gastric acid secretion
PPI’s are prodrugs that need to be exposed to an acidic environment to exert effect
Traditional PPIs should be administered 30-60’ before a meal for max pH control. Newer PPIs have greater flexibility in dosing w/regard to meals
Place in therapy
Superior to H2RAs in moderate to severe disease1
Empirically in patients (up to BID) with troublesome symptoms
Non-response at BID dosing = treatment failure
PPIs are safe in pregnant patients if clinically indicated
Category C
PPIs (Proton Pump Inhibitors)
Antacids < H2RAs < PPIs
-
Onset of Action: < 5 minutes
Duration of Action: 20-30 minutes
Symptomatic Relief: Excellent
Antacids
Onset of Action: 30-45 minutes
Duration of Action: 4-10 hours
Symptomatic Relief: Excellent
H2RAs
Onset of Action: 2-3 hours
Duration of Action: 12-24 hours
Symptomatic Relief: Superior
PPIs
In acid environment it turns into a viscous, sticky polymer that binds selectively to ulcers and erosions creating a protective layer.
Sucralfate
Efficacy comparable to H2RAs
Sucralfate
Foods that may worsen GERD (Decreased LES Pressure)
Fatty/fried foods
Carminatives
Chocolate
Coffee/caffeinated drinks
Garlic
Onions
Chili peppers
Medications that may worsen GERD (Decreased LES Pressure)
Anticholinergics
Barbituates
Benzodiazepines
Caffeine
Dopamine
Estrogen
Ethanol
Isoproterenol
Nicotine
Nitrates
Opioids
Phentolamine
Progesterone
Theophylline
Dihydropyridine Calcium Channel Blockers
Foods that may worsen GERD (Direct Irritants to the Esophageal Mucosa)
Carbonated Beverages
Citrus Fruits
Coffee
Orange Juice
Spicy Foods
Tomatoes
Medications that may worsen GERD (Direct Irritants to the Esophageal Mucosa)
Aspirin
Biphosphonates
Dabigatran
Doxycycline
Iron
NSAIDs
Quinidine
Potassium Chloride
This med, ______________:
- Combination product.
- Forms a viscous solution that floats on surface of gastric contents.
Gaviscon
Patient-directed therapy with antacids (>12 years old):
Maalox - Magnesium hydroxide/aluminum hydroxide with simethicone
Gaviscon - Antacid/alginic acid
Tums - Calcium Carbonate
Patient-directed therapy with nonprescription H2RAs up to twice daily (>12 years old):
Tagamet - cimetidine
Pepcid AC - famotidine
Axid AR - nizatidine
Zantac - ranitidine
Patient-directed therapy (> 18 years old) with nonprescription PPIs (taken once daily):
Nexium 24HR - esomeprazole
Prevacid 24HR - lansoprazole
Prilosec OTC - omeprazole
Zegerid OTC - omeprazole/sodium bicarbonate
There is no significant difference in efficacy among the _____ or _____ when given at equipotent doses.
PPIs, H2RAs.
- Cimetidine is associated with numerous clinically significant DIs
- Dose reduction in renal and hepatic insufficiency and in the elderly
- Duration of suppression ranges from 6-10 hours and varies with dose
Which drug class?
H2RAs
- Food may affect absorption. Given 30-60’ before a meal. More flexibility in term of dosing with newer agents (eg. dexlansoprazole)
- Delayed onset: 3-4 days for full inhibition
- Duration of action up to 24 hours due to covalent, irreversible inhibition of proton pump
PPIs
One thing we always should push BEFORE prescribing medications.
Individualized lifestyle modifications
Lifestyle modification with standard dose (Prescriber directed) acid suppression therapy H2RAs (BID) x 6-12 weeks or PPIs (QD) x 4-8 weeks (↑ to BID with inadequate symptom response )
Which step?
Step 2
PPIs (QD-BID) x 4-16 weeks
Which step?
Step 3
Life style modification / non-pharmacological interventions such as dietary modification, avoid contributing medication, smoking cessation, avoidance of EtOH, weight loss, etc.
Which step?
Step 1
For step ___, PPI therapy should be initiated at once a day dosing, before the first meal of the day.
(PPIs (QD-BID) x4-16 weeks
Step 3 (PPIs (QD-BID) x4-16 weeks
For patients with ________ response to once daily therapy, tailored therapy with adjustment of dose timing and / or twice daily dosing should be considered in patients with night-time symptoms, variable schedules, and / or sleep disturbance.
partial
In patients with partial response to PPI therapy, ____________ the dose to twice daily therapy _________________ may provide additional symptom relief
increasing, or switching to a different PPI
Onset of Action
Antacids:
H2RAs:
PPIs:
2-3 hours. <5 minutes, 30-45 minutes
Antacids: <5 minutes
H2RAs: 30-45 minutes
PPIs: 2-3 hours
Duration of Action
Antacids:
H2RAs:
PPIs:
4-10 hours, 12-24 hours, 20-30 minutes
Antacids: 20-30 minutes
H2RAs: 4-10 hours
PPIs: 12-24 hours
Symptomatic relief
Antacids:
H2RAs:
PPIs:
superior, excellent
Antacids: Excellent
H2RAs: Excellent
PPIs: Superior
Surgical intervention.
Which step?
Step 4
Maintenance PPI therapy should be administered for GERD patients who continue to have symptoms after PPI is discontinued and in patients with complications.
Which step?
For patients with partial response to once daily therapy with a ________ (GI drug class), tailored therapy with adjustment of dose timing and/or twice daily dosing should be considered in patients with night-time symptoms, variable schedules, and/or sleep.
PPI
In patients with partial response to ____ therapy, increasing the dose to twice daily therapy or switching to a different _____ may provide additional symptom relief.
PPI
Maintenance _____ (drug class) therapy should be administered for GERD patients who continue to have symptoms after the PPI is discontinued, and in patients with complications including erosive esophagitis and Barrett’s esophagus
PPI
H_____ (GI drug class) therapy can be used as a maintenance option in patients without erosive disease if patients experience heartburn relief.
Histamine-receptor antagonists (H2RA)
Bedtime H2RA therapy can be added to ____________________ in selected patients with objective evidence of night-time reflux if needed, but may be associated with the development of tachyphylaxis after several weeks of usage
daytime PPI therapy
___________ (gastric and duodenal) are defects in the GI mucosa that extend through the muscularis mucosa
Peptic ulcers
Causal relationships of PUD associate with ___________ infection, NSAIDs and SRMD.
H. Pylori
Therapy for _______ includes non-pharmacological interventions (similar to GERD) and pharmacological with acid suppression (antacids, H2RAs, PPIs) and/or mucosal protection (sucralfate, colloidal bismuth, misoprostol), and if present, H Pylori eradication
PUD
Three treatment options for PUD:
- Acid suppression
- Mucosal protection
- H Pylori eradication
________________ - In acid environment it turns into a viscous, sticky polymer that binds selectively to ulcers and erosions creating a protective layer
- Efficacy comparable to H2RAs
- Chemically, contains Al(OH)3, thus behaves as Aluminum as far as ADRs (eg constipation), DIs (eg chelation)
Sucralfate
___________ - MOA unclear
- coats ulcers and erosions, creating a protective layer against acid and pepsin
- It may stimulate PG and mucus secretion
- It binds bacterial endotoxins and has direct antimicrobial activity against pylori
Bismuth
mis_________ - it stimulates mucus and bicarbonate secretion, replaces PG stores and enhances mucosal blood flow
- Approved for prevention of NSAID-induced ulcers in high-risk patients
Misoprostol
Because of the critical role of __________ in the pathogenesis of peptic ulcer, eradication of this infection is a standard care in patients with gastric or duodenal ulcers
H. pylori
All PUD regimens include ____________ & ______________ therapy (PPI or H2RA)
2 antibiotics & acid suppression
The PUD regimens (which include 2 ABTs and acid suppression therapy, may include __________________
Bismuth preparation
H2RAs not recommended for prophylaxis in treatment of ______________
NSAID induced ulcers
For NSAID induced ulcers:
H2RAs are not recommended for prophylaxis.
NSAID induced ulcers:
Prevention: Misoprostol or PPI.
H2RAs not recommended for prophylaxis.
Treatment of NSAID induced ulcers:
- Discontinue NSAID If possible
- Eradicate H Pylori if (+)
- H2RAs or PPIs
- _________ heal NSAID-related ulcers more effectively as compared with H2RAs and are therefore the antisecretory drug of choice for treating NSAID-related ulcers, especially when NSAIDs are continued
PPIs
- Patients with NSAID-associated ulcers should be treated with a PPI for a minimum of ___ weeks
8
____________ is an option for healing only if NSAID will be stopped
Sucralfate
For stress ulcer prophylaxis there’s no recommendation for PPIs over H2RAs.
-
The American Society of Health-System Pharmacists recommends _______________________________________ in the following scenarios:
- coagulopathy(defined as a platelet count <50,000 cells/mm3, an INR >1.5, or a PT >2 times control)
- mechanical ventilation for longer than 48 hours
- history of GI ulceration/bleed within 1 year before admission
- head/spinal cord injury
- burns on more than 35% of body surface area
- ICU patients with multiple trauma
- transplant patients perioperatively
- and patients with at least two of the following risk factors—sepsis, ICU stay longer than 1 week, occult bleeding for at least 6 days, and use of high-dose corticosteroids (>250 mg daily of hydrocortisone or its equivalent).
stress ulcer prophylaxis
In rare cases where PPIs or H2 blockers cannot be administered for stress ulcer prophylaxis, ______________ is a suitable oral alternative.
sucralfate
Approach to treatment of constipation should begin with determination of cause, including these options:
- Opiates
- Anticholinergics (eg. tricyclic antidepressant (amitryptiline), diphenhydramine, benztropine, etc.)
- NDHP-CCB (eg verapamil)
- Oral iron preparations
- Calcium or aluminum antacids
- NSAIDs
- Clonidine
- Diuretics
Non-pharmacological interventions for constipation: _____, _____, _____
- Probiotics: limited data
(diet (fiber), exercise, fluids)
Three medications for constipation that are safe in pregnancy:
- Bulk formin agents (methylcellulose - Citrucel)
- Emolients [softeners] (docusate - Colace)
- Hyperosmotics (polyethylene glycol - Miralax)
- Administer 240 mL of water with each dose to prevent esophageal / GI obstruction and worsening symptom
- Physical binding of other substances including medications
- Safe in pregnancy
Bulk-forming agents
- Facilitate mixing of aqueous and fatty materials in the intestinal tract
- Used for prevention, NOT treatment. Commonly prescribed with medications that may cause constipation (chronic opiate use, iron supplementation)
- Safe in pregnancy
Emolients
- Osmotic effects to retain fluid in GI tract
- Safe in pregnancy
Hyperosmotics
DO NOT use this constipation med in pregnancy
Lubricant laxative - (mineral oil, castor oil)
Goals of treatment for diarrhea:
- Identify and treat primary cause
- Manage secondary causes
- Prevent electrolyte & acid/base disturbances & dehydration
- Provide symptomatic relief
Note the __________ goal is NOT ALWAYS to stop diarrhea!
primary
Secondary causes of diarrhea can include __________________. An evaluation of ______________ and possible substitution of offending ________________ should be considered (if possible).
medications
Medications that can cause diarrhea:
- Magnesium containing antacids
- Metformin (1/3 of patients)
- Antibiotics (25% incidence)
- Anti-inflammatory / anti-gout agents (eg. colchicine)
We do not routinely use _________ antibiotics in patients with acute diarrhea.
empiric
This classic diarrhea is due to enterotoxigenic Escherichia coli (ETEC), and generally produces malaise, anorexia, and abdominal cramps followed by the sudden onset of watery diarrhea. The illness is generally self-limited with symptoms lasting for approximately one to five days.
Traveler’s diarrhea
Antibiotics are warranted to treat diarrhea in those who develop ______ diarrhea, characterized by more than ______ unformed stools daily, fever, or blood, pus, or mucus in the stool. In addition, some travelers desire antibiotic treatment for milder disease if the illness is a large burden on a business trip or vacation.
severe
four
For mild to moderate diarrhea, ____________ drugs (eg. loperamide) may be used as monotherapy.
anti-motility
For severe diarrhea, anti-motility drugs [eg. _____________ (med)] may be used cautiously as adjunctive therapy.
loperamide
Severe diarrhea is characterized by:
more than four unformed stools daily, fever, or blood, pus, or mucus in the stool.
The initial step in the treatment of Clostridium difficile infection (CDI) caused by an ABT is ______________ of the inciting antibiotic as soon as possible
cessation
Therapy for ___________ difficile infection (CDI) consists of oral metronidazole »_space; oral vancomycin
non-severe
“general purpose antiemetic”
Promethazine
Promethazine is an example of a:
“general purpose antiemetic”
P_________________ (med) is not very effective in treatment of severe N/V.
Promethazine
Lorazepam is a:
Benzodiazepine
________________ are sedatives, not antiemetic agents.
benzodiazepines
B_____________________ (psych drug class) bind to GABA-A receptors. GABA is the major inhibitory NT in the CNS
Benzodiazepines
Sedative and anti-anxiety effects → reduce anticipatory N/V associated with chemotherapy
b___________ (psych drug class)
Benzodiazepine
ADRs - CNS - sedation, hallucinations, euphoria; CV - hypotension
b______________ (psych drug class)
Benzodiazepines
Why is self-directed therapy (OTC) limited to 2 weeks?
- prevent serious conditions from going undiagnosed
- re-evaluate for efficacy
- prevent adverse effects of PPIs.
3 most common causes of peptic ulcer disease:
H. pylori, NSAIDs, and stress-related mucosal damage.
Regarding NSAID-induced ulcer therapy, if on an NSAID…
…get off of it.
Bloody stools are usually, not always, in __________________.
infectious diarrhea
For treating C. Diff, take m______________ for mild to moderate diarrhea, and v_________________ for severe diarrhea.
Metronidazole, vancomycin.
NSAID ulcer prevention:
Reduce NSAID dose, or use prophylactically with misoprostol or a PPI.
Traveler’s diarrhea subsides in ______ days.
2-3
Mineral oil can cause an increased risk of _________________
aspiration pneumonia.
________________ the diarrhea is NOT a goal of treating diarrhea.
Stopping
What are the underlying causes of GERD (physiologically) and what are some things that can worsen GERD symptoms?
Anything that puts pressure on the stomach/gastric area. This includes hiatal hernias, gastric band, gastric sleeve, pregnancy, tight pants/belt.
What non-pharmacological interventions should be instituted for all GI conditions discussed?
- Losing weight
- Elevate HOB with foam wedge 4-8”
- Dietary guidance
- Avoid tight clothes and waist bending
- Smaller meals
- No eating within 3’ of sleep
- No ETOH or smoking
- Evaluate current meds
All PPIs and H2RAs are equally effective at standard doses,
-
If the pt doesn’t like a PPI, take them off it.
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