PHARM Lecture 1 Flashcards
Pathophysiology of GERD
- decreased LES pressure
- Anatomic factors
- esophageal clearance
- mucosal resistance
- gastric emptying
- composition of refluxae
The treatment goal for GERD
- alleviate/eliminate symptoms
- decrease frequency, duration and recurrence
-promote healing and injured mucosa - prevent complications
Non-pharmacologic therapy
- elevated head of bed 6”-8” while sleeping
-weight reduction
-avoid high-risk foods
-protein-rich diet to increase LES pressures
-small meals
-avoid eating junk food before bed
-avoid smoking/alcohol
-avoid tight-fitting clothing
Pharmacologic therapy
Antacid, H2 antagonist, and PPI
Antacid MOA
neutralize acid and raise intragastric PH, increase LES pressure
Efficacy of antacid
short duration, can take used PRN in adjunctive to H2RA and PPI
Onset and duration of antacids
Onse: 5 minutes
Duration: 30 minutes
Dosing for antacid
generally 2 tablets after meals
When to use antacid
minor GERD symptoms , <2 times/week
Adverse effects of magnesium
diarrhea
Contraindication for magnesium
impaired renal excretion or on dialysis
Adverse effects of aluminum
constipation
rare - bone demineralization, intestinal obstruction
relationship of aluminum with phosphate
decrease phosphorus concentration which leads to bone demineralization
contraindication for sodium
CKD,CHF, HTN
adverse effects of calcium
constipation
Drug interactions of antacids
tetracycline, fluoroquinolones, z pac, ferrous sulfate, ketoconazole, itraconazole, levothyroxine
Which medication relays on acidic environment for absorption
ketoconazole, itraconazole, levothyroxine
H2 receptor antagonists meds
-ends in dine
*cimetadine
* famotidine
*rantidine - associated with carcinogen
MOA of H2RA
competitive inhibition of histamine at H2 receptors of gastric parietal cells –> inhibits gastric acid secretion and increase pH
Onset and duration of H2RA
Onset: 30 minutes
Duration: 4-10 hours
Dosing of H2RA
generally BID
- reduce dosing if CrCl < 50mL/min
Adverse effects of H2RA
headache, fatigue, dizziness, constipation/diarrhea
* thrombocytopenia
Drug interaction with H2RA
Cimetidine is a moderate inhibitor of CYP1A2, CYP2C19 and CYP3A4
PPI
ends in -prazole
MOA of PPI
block gastric acid secretion by inhibiting gastric H+/K+ in gastric parietal cells
Onset and duration of PPI
Onset: 2-3 hours, up to 4 days
Duration: 24 hours
Dosing for PPI
Standard: once daily with food
BID dosing: severe or complicated GERD
- no renal accumulation or dose adjustment
Can you use PPI PRN
No, need to combine with H2RA and antacid due to slow onset
adverse effects of PPI
headache, dizziness, n/v/d
Drug interactions of PPI
-methotrexate: increase MTX toxicity
- clopidogrel (omeprazole, esomeprazole, rabeprazole)
-HIV meds need acidic environment
PPI-Clopidogrel drug interactions
Clopidogrel is metabolized to its active metabolite by CYP2C19 but some of the PPI can inhibit CYP2C19
Treatment for mild GERD (<2 times/week and NOT troublesome)
- antacid and/or H2RA BID or PPI once daily
Symptomatic relief of GERD (>2 times week or troublesome)
PPI daily (4-8 weeks) or H2RA BID (6-12 weeks)
Alarm symptoms
weightloss more than 10%, family history of cancer, anemia, persistent vomiting
Treatment for Alarm symptoms
EGD or further diagnostic testing needed
Treatment for chest pain reflux
- cardiac workup
- PPI BID for 4 weeks
if symptoms persists consider diagnostic testing
Moderate-sever symptoms treatment/ esophageal injury
PPI daily or BID for 8-16 weeks or H2RA QID (except famotidine BID) or interventional therapy
Patients with atypical GERD treatment
PPI BID for 3-4 months
Elderly patient with GERD treatment
older than 60 years old
- PPI once daily
Atypical symptoms of GERD
- chest pain
-asthma
-poor dentition
-jaw pain
Refractory Gerd treatment
- ensure compliance, further testing, test H.pylori status
treatment - increase dose
-switch to another PPI
-add H2RA at bedtime
-antireflux surgery
Concerns with discontinuing therapy
can cause rebound
Common cause of PUD
NSAIDs and H.pylori
Nonpharmacologic therapy for PUD
reduce stress, smoking cessation
Pathophysiology of H.pylori infection
gram negative rod
- produce cytotoxins that damage mucosal cells
diagnostic h.pylori
Biopsy urease and urea breath test
what causes a false negative for H.pylori testing
If the patient is on PPI, bismuth, antibiotics
How long to withhold meds for H.pylori testing
1-2 weeks before test
4 weeks for bismuth or antibiotics
What medication cause QTc prolongation
Clarithromycin
Which medication cause discolored urine and bodily fluids
metronidazole
Which medication is a strong CYP3A4 inhibitor
Clarithromycin
SE of Bismuth
discoloring of tongue and stools, GI upset, tinnitus
Which medication is a contraindication for <8 y/o and pregnancy
tetracycline
- PCN allergy: none
- MCL exposure: none
Bismuth quadruple, nonbismuth quadruple, triple therapy with amoxicillin
- PCN allergy: no
- MCL exposure: no
Bismuth quadruple, PPI triple with metronidazole
PCN allergy: N
MCL exposure: Y
Bismuth quadruple
levofloxacine or triple sequential
PCN: Y
MCL exposure: Y
Bismuth quadruple
1st line treatment for H.pylori
Bismuth- based quadruple therapy and concomitant PPI triple therapy (non bismuth quadruple)
Alternative 1st line for H.pylori
PPI triple therapy
Which treatment are you concerned about compliance issue for H.pylori
Bismuth-based quadruple therapy
- pt needs to take it QID
Meds included in the Bismuth-based quadruple therapy
PPI BID
Bismuth QID
Metronidazole QID
Tetracyclein QID
Meds in non-bismuth quadruple therapy
PPI BID
Clarithromycin BID
Amoxicillin BID
Metronidazole BID
Meds in PPI triple therapy
PPi BID
Clarithromycin BID
Amoxicillin BID or Metronidazole BID
When to test for eradication of H.pylori
4 weeks after therapy completion
Treatment failure for H.pylori
Patient adherence, resistant organisms, low intragastric pH, high bacterial load
How long to use PPI for H.pylori infection
additional 4 weeks after the completing therapy
Which NSAIDs is COX 1 selective
ketorolac
Which NSAIDs is COX 2 selective
Celecoxib
Why do NSAIDs increase the risk of ulcers
COX 1 inhibits prostaglandins which is important GI protective barriers
NSAIDs Boxed Warning
GI risk for general NSAIDs, the cardiovascular risk associated with celecoxib
Explain the GI risk and CV risk associated with Aspirin
GI risk moderate, CV risk is low/protective
Explain the GI risk and CV risk associated with Celecoxib
GI risk: low, CV risk: moderate - high
Patient factors for increased NSAID toxicity
> 65 y/o, concomitant anticoagulant use, previous PUD or PUD complications, multiple NSAID use, cigarette smokers
NSAID induced treatment
Discontinue or lower dose of NSAID, use alternative pain meds and
- PPI once daily for 4 weeks
- H2RA for 6-8 weeks
-Sucralfate for 6-8 weeks
Adverse effects of Sucralfate
constipation
Purpose of Sucralfate
mucosal coating agent
D-D interactions for sucralfate
inhibits drug absorption
- space out from other meds by 2 hours
- take antacids at least 30 minutes before or after sucralfate (has aluminum in it)
NSAID induced prevention
PPI, misoprostol
Adverse effects of misoprostol
diarrhea, abdominal cramping
Contraindication for misprostol
pregnancy
What is misoprostol
synthetic prostaglandin E (protective) which reduces GI side effects
Are H2RA and antacids recommended for NSAID ulcer prophylaxis?
No
low CV risk (not on aspirin)
low GI risk (0 risk factors)
NSAID alone
Low GI risk (0 risk factors)
High GI risk (on ASA)
Naproxen + PPI or misoprostol
Moderate (1-2 RF)
Low CV risk
NSAID + PPI or Misoprostol
High CV risk (on ASA)
Moderate GI risk
Naproxen + PPI or misoprostol
High GI risk ( > 2 RF or history of complicated ulcer)
Low CV risk (not on ASA)
Alternative therapy is possible or COX 2 inhibitor + PPI or misoprostol
High CV risk
High GI risk
Avoid NSAID and COX 2 inhibitors
Pathophysiology of stress-related mucosal damages
Decreased blood flow leads to ischemia and bleeding
- 75% of critically ill patient develop SMRD
Prophylaxis for stress related mucosal damage
H2RA is preferred, and PPI are potential alternative
**Prophylaxis are not needed if the patient is discharged from ICU and/or risk factors no longer present*
Concerns with chronic PPI use
Risk of fractures, infections, and interfere with vitamin/mineral absorption
How long can you use PPI without concerns
up to 3 years