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1
Q

Patient-directed drug therapy for GERD

A

INTERMITTENT, MILD HEARTBURN:
lifestyle mod + patient directed therapy w/ antacids and/or OTC H2RA or PPI no more than 2 weeks
ANTACID
1. Mg hydroxide/aluminum hydroxide w/
simethicone (Maalox)
2. antacid/alginic acid (Gaviscon)
3. calcium carb (tums)

OTC H2RA (no more than 2 weeks, up to BID)
1. Cimetidine 200mg
2. famotidine/Pepcid 10mg-20mg
3. nizatidine/Axid AR 75mg

OTC PPI
1. esomeprazole/Nexium 20mg
2. lansoprazole/Prevacid 15mg
3. omeprazole/Prilosec 20mg
4. omeprazole/sodium bicarb (Zegerid)
20mg/1100mg

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2
Q

What are the underlying causes of GERD (physiologically) & what are some things that can worsen GERD symptoms?

A

DECREASE LES PRESSURE:
1. hiatal hernia (increase pressure, lower LES tone)
2. food: fatty, garlic, onion, coffee/tea, soda, chocolate, ETOH, chili peppers
3. Meds: nicotine, nitrates, progesterone, tetracycline, dopamine, estrogen, barbiturates, anticholinergics

IRRITATE ESOPHAGEAL MUCOSA
1. spicy food
2. tomato or orange juice
3. coffee
4. tobacco
5. ASA or NSAIDs
6. irone
7. KCL
etc.

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3
Q

Patho of GERD

A
  1. retrograde gastric content into esophagus, oral cavity, lungs d/t poor tone lower esophageal sphincter (LES).
  2. Slow esophageal clearance, decreased salivary buffering, impaired mucosal resistance, delayed gastric emptying, & increased intra-abdominal pressure can cause
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4
Q

Most common process causing GERD sx

A

slowed esophageal clearance of gastric contents increasing contact time of refluxate w/ esophageal mucosa NOT increased acid

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5
Q

GERD risk factors

A
  1. obesity
  2. high fat diet
  3. smoking
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6
Q

Main typical, atypical, alarm sx GERD

A

Typical: aggravated by activities/food, heartburn waxing/waning, hypersalvation, regurgitation, bleching

atypical (causality only if typical sx also present): chronic cough, hoarseness, wheezing, asthma, non-cardiac chest pain

alarm (GERD complications Barrett esophagus, esophageal strictures, adenocarcinoma): Odynophagia, dysphagia, weight loss, bleeding

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7
Q

How often sx occur for dx GERD & how dx

A

2+ times/week
endoscopy, biopsy to test for Barrett esophagus
ambulatory esophageal reflux monitoring
esophageal manometry

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8
Q

what’s dyspepsia

A

occurs often w/ PUD
epigastric pain and sometimes other upper GI sx like heartburn
consider dx if pain > 1 month

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9
Q

Options of the most appropriate RX drug therapy for gastroesophageal reflux disease

A

***Moderate-severe PPI should be initial therapy, maintenance if recur

H2RA
1. cimetidine/Tagamet 400mg QID or 800mg
BID
2. famotidine/Pepid 20mg BID
3. Nizatidine/Axid 150mg BID

PPI
1. dexlansoprazole/Dexilant 20mg QD x4 weeks
2. esomeprazole/Nexium 20-40ng QD
3. lansoprazole/Prevacid 15mg QD
4. omeprazole/Prilosec 20mg QD
5. pantoprazole/Protonix 40mg QD
6. rabeprazole/Aciphex 20mg QD

**Doses slightly higher or BID or tx erosive esophagitis **

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10
Q

H2RA side effects

A

mild: HA and nausea
drug interactions
cimetidine specifically: gynecomastia & vit B12 deficiency
renally eliminated so dose adjustment in renal dysfunction

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11
Q

how do H2RAs work

A

decrease acid secretion by blocking histamine 2 receptors in gastric parietal cells

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12
Q

how do PPIs work

A

block gastric acid secretion SIGNIFICANTLY by inhibiting gastric H/K ATP in parietal cells= long-lasting antisecretory effect pH > 4 even during postprandial surges

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13
Q

what PPI can be taken w/o regard to food

A

dexlansoprazole or omeprazole-sodium bicarb

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14
Q

PPI side effects

A

Most common= HA, diarrhea, nausea

long-term: AKI/CKD, bone fx, dementia, electrolyte deficiency (ca, mg, B12), bacterial infections (c.diff, PNA)

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15
Q

First line rx tx for GERD

A

PPI x8 weeks
Can do maintenance or on-demand therapy
Can d/c once sx resolve then reinitiate x2-4 weeks if sx 2+ times in week since d/c

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16
Q

rebound hypersecretion

A

can occur w/ continual PPI use of at least 2 months
should be tapered (individualized) slowly using H2RAs for breakthrough sx.
Rebound hypersecretion can last > 3 months

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17
Q

3 most common causes of PUD

A
  1. H pylori
  2. NSAIDs
  3. stress-related mucosal damage (SRMD)
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18
Q

Plan of care for NSAID induced ulcer

A

Prevention:
PPI or misoprostol (prostaglandin E1 analog- GI SE); H2RAs less effective
PPI more tolerated

Treatment:
*PPI x4 weeks, Sucralfate if NSAID stopped, H2RA effective w/ DU only

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19
Q

First line tx H. pylori

A

? amox allergy, ? h/o macrolide abx, ? alcohol (contraindicated metronidazole)

  1. bismuth quadruple
    bismuth 300mg QID
    metronidazole 250-500 QID
    tetracycline 500mg QID
    PPI BID
  2. concomitant
    clarithromycin 500mg BID
    amoxicillin 1g BID
    nitroimidazole 500mg BID
    PPI BID
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20
Q

Meds that end in “-pitant”

Ex: aprepitant, rolapitant, netupitant

A

neurokinin-1 (NK 1) receptor antagonist
act centrally at NK-1 receptors in vomiting centers within the central nervous system to block their activation by substance P released as an unwanted consequence of chemotherapy.

tx acute/delayed CINV when given WITH 5-HT3 antagonist & corticosteroid

prevent PONV

Numerous drug interactions. NOT renally eliminated

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21
Q

Meds that end in “-setron”

Ex: ondansetron, granisetron, dolasetron, palonoestron

A

5-HT3 antagonists (against serotonin) since 5-HT3 stimulates visceral vagal nerve fibers

tx CINV (chemo releases 5-HT3) & PONV

SE: HA, somnolence, diarrhea, constipation, QT interval changes so ECG if at risk

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22
Q

prevention & tx options CINV

A

dexamethasone OR 5-HT3 antagonist (“setron”) OR combo

Moderate= steroid with “setron”

high risk= NK1 receptor antagonist AND 5HT3 antagonist AND dexamethasone AND olanzapine

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23
Q

olanzapine for CINV

A

antipsychotic effects D2, 5HT3, 5HT2C receptors

give in combo therapy for high emetogenic risk chemo

biggest SE= sedation day 2 of chemo

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24
Q

risk factors CINV

A

poor emetic control prior, female, LOW chronic alcohol use, younger age, motion sickness, NVP

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25
what antiemetics for motion sickness & why
antihistamines & anticholinergic bc vestibular system replete w/ muscarinic cholinergic & histamine receptors
26
chemoreceptor trigger zone (CTZ)
outside blood-brain barrier so stim by uremia, acidosis, toxins Has 5HT3/serotonin, NK1, dopamine2 receptors vagal nerve 5HT3 receptors NAUSEA/VOMIT
27
how do anticholinergics & antihistamines work for n/v
cholinergic & histamine receptors in vestibular system
28
meds that end in "-azine" ex: promethazine, prochlorperazine, chlorpromazine
phenothiazines (dopamine2 antagonists) for n/v SE: sedation, hypoTN, EPS (dystonia, TD, akathesia)
29
meds that end in "-ridol" ex: droperidol, haloperidol
butyrophenone (dopamine2 antagonist) for n/v SE: sedation, agitation, restlessness, ***prolonged QT interval*** *Droperidol black box warning Qt interval & cardiac arrhythmias
30
how do corticosteroids help n/v ex: dexamethasone & methylprednisolone
release of 5HT, reduced permeability blood-brain barrier, decreased inflammation SE: GI upset, anxiety, insomnia, hyperglycemia (long term= DM, decreased bone mineral density, cataracts)
31
meds that end in "ine"
usually antihistamINE for n/v ex: meclizine, hydroxyzine, doxylamine, cyclizine, diphenhydramine
32
transient causes of retrograde gastric contents & why
temp. increase intra-abdominal pressure from straining, exercise, bending, valsalva maneuver
33
why GERD sx common in older people and during sleep
salivation has bicarbonate that buffers acidic gastric content; salivary production decreases in sleep & with age
34
do people with GERD produce too much acid?
NO- most people have slowed esophageal clearance of gastric contents= increase contact time w/ mucosa
35
non-pharm interventions for GERD
lifestyle mod: losing weight, elevate HOB, small meals, no meals 3 hr before HS, avoid foods that exacerbate, smoking cessation, no ETOH
36
best H2 receptor antagonist for GERD/why?
famotidine/Pepcid bc less SE. Cimetidine weak inhibitor w/ many drug interactions. Gynecomastia & b12 deficiency
37
duodenol ulcer tx
H2 receptor antagonist
38
time to admin PPI
am 30-60 min before bkfst NOT with other meds as decrease their efficiency (slow onset/extended release)
39
what Ca replacement w/ low Ca and GERD on PPI and why
Ca citrate NOT carbonate bc better absorption in less acidic environment
40
metoclopramide drug class, mechanism of action, indication, SE, contraindication
central dopamine antagonist accelerates gastric emptying, increases LES pressure can help n/v from chemo, anesthesia, GERD (w/ PPI), diabetic gastroparesis SE: EPS/TD. Can affect mental acuity in young and old! Crosses blood/brain barrier
41
on-demand PPI dosing
stop PPI when sx resolve reinstate therapy x2-4 weeks if sx occur >2 times in a week while off therapy
42
when is rebound hypersecretion a concern
coming off PPI use of at least 2 months, that's why titrate slowly hypersecretion can last > 3 months
43
when is GERD a concern w/ babies
vomiting, apnea, poor weight gain, sleep disturbances, refusing to eat
44
why are reflux episodes common during transient LE relaxations not r/t swallowing in babies
development immaturity of LES or infant diet milk protein allergy can mimic GERD
45
when GERD sx resolve in children usually
12-18 months old
46
receptors in peripheral nervous system (autonomic [sympathetic/parasympathetic]/somatic) that cause n/v
serotonin (5-HT3) and neurokinin
47
corticol (cortex of brain) pathways that cause n/v
dopamine & histamine (from sensory glands/vestibular system)
48
Meds that worsen/cause GERD
nicotine, nitrates, progesterone or estrogen (OCP), tetracycline, dopamine, barbiturates, anticholinergics
49
zollinger-ellison syndrome (ZES)
gastrin-producing tumor (gastrinoma) causing gastric hypersecretion= diarrhea, malabsorption, ulcers Tx with PPI
50
what kind of ulcers do h.pylori cause
more commonly duodenal ulcers
51
what kind of ulcers do NSAIDs cause
gastric
52
what stimulates acid secretion in parietal cells
histamine, acetylcholine, gastrin
53
NSAID & H.pylori effect on acid secretion
NSAIDs dont impact, h.pylori slightly increases acid output
54
how does food effect gastric secretion
increases through vagal nerve stim (sight, smell, taste) & stomach distention
55
how do NSAIDs damage gastric mucosa
direct irritation & blocks COX-2 which=anti-inflammatory & analgesia but ALSO blocks COX-1 which= gastroprotection
56
duodenal ulcer sx
epigastric pain 1-3 hours after meals or night, relieved by food
57
gastric ulcer sx
aggravated by food
58
why is acid suppressive therapy alone contraindicated in h.pylori tx
associated w/ higher incidence of ulcer recurrence and ulcer-related complications
59
when is bismuth quadruple therapy contraindidcated
renal impairment (salicylate toxicity) issue w/ compliance (QID tx) SE: stool & tongue discolor, constipation, n/v
60
clarithromycin triple therapy
clarithromycin 500mg BID amoxicillin 1g BID OR metronidazole 500mg TID PPI BID
61
levofloxacin triple therapy
levofloxacin 500mg daily amoxicillin 1g BID PPI BID
62
Rifabutin triple therapy
*** salvage regimen only rifabutin 300mg daily amoxicillin 1g BID or TID PPI BID
63
common causes constipation
Primary normal-transit slow-transit (ex low caloric intake) defecatory evacuation disorder (ex IBD) Meds (opioids, antihistamine, anticholinergic, andepressant/psychotic, ondansetron, iron, etc) endocrine (DM, hypercalcemia, hypokalemia, hypomag, hypothyroidism, uremia) myopathies neuro (TBI, MS, parkinson) mechanical obstruction (cancer, stricture) laxative abuse immobility
64
lifestyle mod for constipation
scheduled bathroom am/pm elevate feet w/ stool= pelvic relaxation fiber 20-30g/day fluids (men 3.7L/day, women 2.7L/day) exercise pelvic floor exercise
65
what does soluble fiber do & ex of meds and food
dissolved by water, forms gel= slow digestion lentil, apples, nuts, flax, psyllium meds: methylcellulose (Citrucel w/ SmartFiber- less likely to cause gas), calcium polycarbophil (FiberCon), wheat dextrin (BeneFiber), psyllium (Metamucil)
66
insoluble fiber & ex
doesn't dissolve in water, decreases time food/feces traverse intestines whole wheat, corn bran, dark green leafy veggies, skin root veggies
67
What drugs for management of refractory opioid induced constipation? ex? SE and what to avoid
Peripherally acting μ-opioid receptor antagonists (PAMORAs): naldemedine, naloxegol, methylnaltrexone ***all maintenance laxatives d/c before use, resume after 3 days if PAMORA response suboptimal*** stop if opioid stop don't use with other opioid antagonists SE: n/v/d, gas, abd pain, opioid withdrawal sx avoid with ABX, verapamil, amiodorone
68
bulk producer/fiber supplements How do they work? examples? when are they NOT effective
absorb liquid in the intestines and swell to form a soft, bulky stool... swelling in intestinal fluid, forming gel that aids in fecal elimination & promote peristalsis ex: psyllium, polycarbophil, methylcellulose (less gas) NOT effective in delayed transit or obstruct with 240ml/water
69
emollients
soften stool by increasing surface wetting action on stool, reduce friction. Takes up to 72 hrs to work ex: docusate sodium or calcium lactulose (osmotic) mineral oil
70
osmotics and ex
water enter lumen in colon > stim. peristalsis ex: lactulose, sorbitol (may affect blood glucose in DM), glycerin, polythylene glycol/Miralax (BM 1-3 days)
71
lubricants for constipation & SE
mineral oil SE: aspirated into lungs = lipoid PNA in young/old inhibit fat-soluble vitamins
72
stimulant laxatives & ex what meds to avoid if take
selective action on nerve in intestine smooth muscles > peristalsis ex: diphenylmethane (bisacodyl) & anthraquinones (senna) don't given within 1-2 hrs antacids/H2RA/PPI/milk
73
saline agents for constipation
salts of NA, Mg, Ph pull water into lumen increasing enteral pressure concern of electrolyte imbalances esp. w/ renal impairment & HF
74
intestinal secretagogues & ex
Use only after everything else tried lubiprostone (Amitiza)= derived from prostaglandin E1 > intestinal chloride channels increase intestinal fluid secretion > increase motility. SE: nausea, diarrhea, syncope, distention/pain, gas, hypoTN, dyspnea linaclotide (Linzess)= activate GC-C increase GNO which stim chloride & bicarb into intestinal lumen= increased fluid & transit. ***ONLY for IBS-C & CIC in adults. Empty stomach 30 min before foot plecanatide (Trulance)= GC-C agonist ***ONLY for IBS-C & CIC in adults. NOT kids 6-18, concern of dehydration
75
constipation tx pregnant women
balanced meal, water intake bulk producers & stool softeners PROB. safe lactulose & mg products category B (no risk in animals so prob safe but avoid long term) laxatives postpartum if not breastfeeding
76
conditions where laxatives should only be used under physician supervision
colostomy, DM, heart, renal, swallowing difficulty
77
drugs that may cause acute diarrhea
abx, metformin, digitalis, thyroid products, ginseng, st johns warts poison- arsenic, mercury
78
tx chronic diarrhea
calcium polycarbophil (absorbant) loperamide diphenoxylate/atropine bulk-forming products psyllium & methylcellulose may reduce fluid in stool
79
calcium polycarbophil
absorbant to tx diarrhea; binds to water leads to formation of gel that enhances stool ***separate from other meds 2-3 hours
80
meds for acute diarrhea
loperamide diphenoxylate/atropine *bismuth subsalicylate for travel's & nonspecific acute
81
antiperistaltic (antimotility) agents
prolong intestinal transit time in NONINFECTIOUS diarrhea only loperamide (immodium) & diphenoxylatae/atropine (rx only; Lomotil) atropine to deter abuse & has anticholinergic effects loperimide misuse/abuse reported; cardiac arrythmias if OD. Avoid use w/ CYP450 3A4 inhibitors (azole antifungals, clarithromycin, conivaptan, "-mycin") and 2C8 inhibitors (gemfibrozil, clopidogrel) = increase loperimide concentrations > cardiac
82
antisecretory agents for diarrhea
bismuth subsalicylate cannot give if allergic to salicylates/aspirin. Salicylate absorbed in stomach & small intestine ***stool will turn black octreotide for severe diarrhea
83
ssx salicylism
n/v, tinnitus, hypoTN, hyperventilation, agitation, hallucination, fever, bleeding seizures, confusion, renal fail, resp. fail
84
octreotide
antisectory agent for sever diarrhea from chemo, HIV, GM, gastric resection, GI tumor SQ or IV nausea, bloating, gallstones
85
botanicals for abd pain & bloating
peppermint oil relaxes GI smooth muscle german chamomile also antispasmodic (avoid w/ warfarin, BZO, ETOH) primose oil
86
agents for IBS-C
bulk producers (psyllium, methylcellulose) osmotic laxatives (miralax) linaclotide (Linzess) lubiprostone (Amitiza) in women only; men can use but only for CIC or OIC plecanatide (Trulance)- risk diarrhea/dehydration tegaserod maleate (Zelnorm) women < 65 w/o heart/renal/hepatic disease; monitor for depression & SI
87
what's the concern with clopidogrel & PPI? What's the worst PPIs to use w/ this med? Alternative tx?
For Plavix (clopidogrel) to work properly in the body, it requires a special protein, or enzyme, called CYP2C19 to help the body digest and use it. PPIs, on the other hand, can stop this enzyme from working. If this happens, the CYP2C19 protein won’t be available to digest the Plavix, meaning it won’t work as well. Worst PPIs= Omeprazole (Prilosec) and esomeprazole (Nexium) block more CYP2C19 than others Better PPIs= pantoprazole (Protonix), lansoprazole (Prevacid), or Dexilant (dexlansoprazole) Alternative= if for heartburn only then H2RA or switch to diff antiplatelet
88
primary method NSAIDs & H pylori cause ulcers
inhibit mucosal defense system (prostglandins- buffer acid)
89
important contraindications/considerations for H pylori tx with different drugs
QID dosing= issue w/ compliance PCN allergy= no amox. tx tx w/ macrolide= no "-ycin" tx (clarithromycin) alcohol user= no metronidazole renal impairment= risk of salicylate toxicity w/ bismuth SE= usually GI, SUPER/OPPORTUNISTIC infections (yeast); bismuth= tongue/stool discolor pylera & prevac (combo packs) improve adherence but EXPENSIVE resistance to clarithromycin in areas
90
quinolone abx
"floxacin"
91
how to tx h pylori if PCN allergy
bismuth regimen (bismuth, metronidazole, tetracycline, PPI) QID OR clarithromycin (clarithromycin, metronidazole, PPI) BID/TID
92
best 2 meds to prevent NSAID ulcers or alternative NSAID
misoprostol (prostaglandin) or PPI PPI is better tolerated, misoprostol = GI SE OR switch NSAID to COX 2 inhibitor (celecoxib)
93
meds for acute AND delayed chemo induced n/v
palonosetron (the only 5-HT3 antagonists) NK1 agonists (-pitant; *Rolapitant doesn't have as many drug interactions)
94
laxative to avoid in diabetes
sorbitol (osmotic) bc affects blood sugar
95
laxative agents heart/renal disease pts must avoid
saline agents containing Na, Mg, phosphate bc electrolyte imbalances
96
tx chronic idiopathic constipation (CIC), opioid constipation, IBS-C
lubiprostone linaclotide/Linzess (NOT for opioid) plecanatide/Trulance not for children= dehydration
97
meds cause constipation
diuretics, anticholinergics, Ca/aluminum, analgesics, antidepress/psychotic, antihistamines, calcium channel blockers, iron

Pharmacology (12 decks)

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