n/v, constipation, diarrhea, IBS, GERD, PUD, upper GI bleed, IBD Flashcards
causes of N/V (7)
- general (gastroenteritis, pancreatitis)
- disorders of balance
- N/V pregnancy
- gastroparesis
- post-op N/V
- chemo and radiation induced N/V
- N/V in children
what is gastroparesis?
impaired neuronal transmission –> slow stomach motility –> delayed gastric emptying
aka: food staying in the stomach for too long!
cause of gastroparesis
DM!
which causes of N/V do we start with self care?
GENERAL (gastroenteritis) – YES
DISORDER OF BALANCE – YES
N/V PREGNANCY – YES
gastroparesis – no
post-op N/V – no
chemo/radiation induced – no
N/V IN CHILDREN – YES
1 cause of gastroenteritis?
viruses – norovirus
(other causes are bacterial – food borne)
N/V self-care exclusions
- DM
- suspected food poisioning > 24 hours
- severe abdominal pain
- prolonged N/V + fever +/- diarrhea
- blood in vomit
- yellow skin/eyes + dark urine
- stiff neck +/- HA +/- light sensitivity (meningitis!!)
- head injury + N/V, blur vision, numb, tingle
- significant comorbidities
- age < 6 months
- children: lack of urination for 8-12 hours
N/V pharm treatment options
- antihistamines
- phenothiazines
- serotonin antagonists (5-HT3)
- prokinetics
- corticosteriods
antihistamine MoA
block H1
antihistamine potency
not super potent
antihistamine dosage form
all PO except scopolamine
meclizine indication
ELDERLY!!! –> if > 65 years, recommend meclizine (bc of the pearls…)
meclizine pearls
- less sedating
- least CNS/BBB penetration
doxylamine formulation
coformulated with vitamin B6
scopolamine dosage form
PATCH – transdermal, behind ear
* leave on for 3 days
scopolamine potency
very potent –> hence why use for post-op n/v
scopolamine CI
elderly!!
antihistamine AE
- drowsiness, dry mouth, constipation
- fall risk in patients > 65 years because impairs cognition/cause confusion!
antihistamine options
- meclizine
- dimenhydrinate (Dramamine)
- scopolamine
- doxylamine
- hydroxyzine
phenothiazine options
- promethazine
- prochlorperazine
- chlorpromazine
phenothiazine MoA
inhibit dopaminergic , histamine (H1), muscarinic receptors
phenothiazine dosage forms
PO, IV, DEEP IM
which phenothiazine comes as a rectal suppository
prochlorperazine
which phenothiazine has least QT prolongation?
prochlorperazine
phenothiazine AEs
- tissue damage –> hence DEEP IM injection
- hypotension –> hence give IV as slow IV push, patient lying down
- QTc prolongation
- dystonia: locked/rigid/frozen, like parkinson’s
- extrapyramidal symptoms (EPS): tardine dyskinesia, purposeless movements they can’t control (tongue, hand)
5-HT3 antagonists (serotonin antagonist) options
- ondansetron (Zofran)
- dolasetron
- granisetron
- palosetron
what is the most common/workhorse class of N/V?
5-HT3 antagonists –> ondansetron
serotonin antagonist dosage form
PO, IV, ODT
N/V pregnancy first line
doxylamine + vit B6
*NOT ONDANSETRON
serotonin antagonist AEs
- HA
- constipation
- QT prolongation (as doses inc, IV)
- well tolerated
prokinetic options
- metoclopramide (Reglan)
- erythromycin
metoclopramide MoA
- block dopamine, serotonin
- enhance Ach response –> inc gastric emptying and inc lower esophageal sphincter tone –> keeps material in stomach and moving through stomach
prokinetic dosage form
PO, IV
metoclopramide AE
- EPS, dystonia (IV and higher doses inc risk)
- QTc prolongation
- diarrhea
erythromycin MoA
agonize motilin receptors –> inc peristalsis (GI tract movement) in stomach and duodenum
erythromycin AEs
- N/V
- QTc prolongation
- diarrhea
corticosteroid MoA
dec prostaglandin formulation –> dec 5-HT release from gut
corticosteroid options
dexamethasone
corticosteriod AEs
- weight gain
- hyperglycemia
- insomnia
- stomach upset/irritation (inc risk (ulcer) when given with NSAIDs)
- inc BP
- agitations (hyper/manic feelings)
which N/V drug classes have QTc prolongation?
phenothiazines
serotonin antagonists
prokinetics
bismuth subsalicylate MoA
- antisecretory and antimicrobial action –> directly against bacterial and viral pathogen
bismuth subsalicylate limitations
- > 12 years old
- 2 day use
bismuth subsalicylate AEs
- fecal discoloration (black)
- tongue discoloration
- chelate with fluoroquinolone antibiotics
phosphorated carbohydrate solution (emetrol) limitations
- > 2 years old
- 1 hour max
constipation definition
less than or equal to 3 bowel movements per week
constipation causes
- drugs: opioids, anti-cholinergics (antihistamine, TCAs, CCBs), iron
- comorbidities: DM, pregnancy, IBS, hypothyroidism
- low fiber
- not enough water
constipation self care exclusions
- age < 2 years
- sudden change in bowel habits lasting > 2 weeks
- laxative use for > 7 days
- laxative use but no bowel movement
- severe abdominal pain
- N/V
- rectal bleeding
types of constipation and which we treat with OTC
- general constipation – OTC
- CIC (chronic idiopathic constipation) – OTC failed
- IBS-C – OTC failed
- opioid-induced constipation – OTC
constipation options
- bulk forming lax
- emollient lax
- hyperosmotic lax
- stimulant lax
- saline lax
- lubricant lax
- other Rx treatment
- opioid-induced treatment
soluble fiber products (bulk-forming lax) MoA
inc absorption of water in small and large intestine –> viscous gel
*NEED fluid!!!
soluble fiber products CI
CHF
soluble fiber products AE
cramping
docusate (emollient lax) MoA
surfactant/emulsifier: incorporates water –> softens stool
polyethylene glycol 3350 and glycerin (hyperosmotic laxative) MoA
large, poorly absorbed molecules –> draws water into colon
glycerin suppository AE
rectal irritation
sennosides, senna, and bisacodyl (stimulant lax) MoA
- directly stimulate colonic mucosa
- stimulate myenteric plexus
- inc water secretion into intestines
sennosides, senns, bisacodyl AE
cramping and abdominal pain
magnesium citrate, milk of magnesium, sodium phosphate (fleet enema) (saline lax) MoA
pulls fluid into intestines –> inc intraluminal pressure
mag citrate, milk of mag, sodium phosphate AEs
- abdominal cramping
- dehydration
- electrolyte imbalances
mineral oil (lubricant lax) MoA
- ease passage of stool by dec water absorption and lubricate intestine
- stops colon water absorption
**similar to docusate, docusate preferred
which OTC options do not cause cramping
- Miralax
- glycerin suppository
which OTC options are stool softeners
- docusate
- mineral oil enema
therefore also no cramping
Miralax age range
labeled indication: greater than or equal to 17 years old
could use off-label: 6 years and above
PEG 3350 MoA
inert substance –> pulls water into colon –> expands stool –> trigger expulsion and softenstool
**no direct stimulation –> no cramping
lactulose MoA
non-absorptive sugar –> causes water to be pulled into colon –> contraction
*similar to PEG
lactulose AE
- diarrhea
lactulose dosage form
syrup –> super sweet
osmotic agent uses
colonoscopy: PEG
hepatic encephalopathy: lactulose
lubiprostone MoA
works on Cl channels to inc Cl and water in colon –> improve fecal transit
lubiprostone AE
- diarrhea
- nausea
linaclotide and plecanatide MoA
- guanalyate cyclase receptor agonist (cGMP) –> inc bicarb and Cl secretion into stool –> inc fluid –> dec fecal transit time
- secretogogues
**same class –> same MoA
linaclotide and plecanatide AE
diarrhea
opioid induced constipation Rx class/MoA
mu peripheral antagonists
**opioids act on the mu receptor –> THEREFORE, the opioid will still have analgesic effects bc works in the CNS, but the GI effects will be inhibited bc they are peripheral effects
mu peripheral antagonist options
- methylnaltrexone
- naloxegol
- naldemedine
mu peripheral antagonist AEs
BBW: caution in GI wall issues (diverticulitis, IBD, colon cancer) –> can cause bowl preforations
diarrhea definition
greater than or equal to 3-4 stools in a 24 hour period
diarrhea causes
- virus (gastroenteritis –> *norovirus)
- IBD, IBS-D, celiac
- drugs –> antibiotics, metformin, chemotherpay
- food –> lactose
when are probiotics indicated?
pediatric, shorten duration of gastroenteritis and symptoms
*NOT adult c. diff prevention!
diarrhea self care exclusions
- pregnancy
- age < 6 months
- severe abdominal pain
- recent antibiotic use
- diarrhea > 14 days
- severe dehydration
- protracted vomiting
- blood, mucus, pus in stool
- DM, CHF
- immunosuppression
- high fever (>102.2 F)
diarrhea oral rehydration indication
ESSNETIAL in children (N/V and diarrhea) –> higher doses for diarrhea
bismuth subsalicylate MoA
bismuth: antimicrobial effects
salicylate: antisecretory effects
**both work on pathogen!!
bismuth subsalicylate age
> 12 years
what is child’s pepto bismol?
calcium carbonate –> antacid
NOT TREAT DIARRHEA!!
adult pepto AEs
black staining of tongue and stool
chelate with fluoroquinolones
probiotic MoA
dec symptoms and duration of infectious diarrhea IN CHILDREN ONLY
- mixed data on if prevent antibiotic associated c. diff!
digestive enzyme MoA
lactaid: lactase enzyme replacement
loperamide MoA
opioid derivative without central activity (only peripheral activity) –> therefore, slows transit time and dec chloride secretion –> locks you up
this makes sense –> opioids cause constipation –> therefore this is the peripheral opioid effect!
loperamide age limit
6 years or older
loperamide pearl
opioid derivative/mu peripheral agonist –> can make you high if take enough!
loperamide CI
bacterial cause of diarrhea –> do not want to lock in the bacteria –> bad!
mu peripheral agonist MoA
works in gut –> cause constipation essentially
diphenoxylate + atropine MoA
diphenoxylate: similar to meperidine (opioid) –> inhibit excessive GI motility and propulsion
atropine: strong anticholinergic –> AE: hot, dry, blind –> DISCOURAGES ABUSE!
octreotide
inhibit serotonin, gastrin secretion, secretin, motilin, insulin, glucagon —-> overall dec intestinal motility and secretion
- a somatostatin (hormone) analog
octreotide dosing
SQ daily –> IM depot q 4 weeks
octreotide indications
- intestinal carcinoid tumors
- chemo-induced diarrhea
diphenoxylate + atropine indication
- IBD-UC
- adjunctive therapy (add on when so much stool even after treatment)
digestive enzymes age
greater than or equal to 4 years old
IBS definition
chronic abdominal pain with altered bowel habits
IBS Dx
- chronic abdominal pain for 1 day/week for 3 months
AND - atleast 2 of following: associated with – defecation, change in stool frequency, change in stool consistency
IBS patho
no functional changes but still symptoms –> Dx of exclusion
gut hypersensitivity: mismatch between what is happening in gut, and what is signaled to brain
IBS symptoms
- change in bowel habits
- global symptoms: pain, bloating
**today we treat both
what is IBS associated with?
- inc bacteria in colon (SIBO)
- gastroenteritis
- physchological stress
treatment goals for IBS
- improve global symptoms
- improve QoL
- improve stools
- improve bloating
how do we classify IBS?
type of stool
types of IBS
IBS-C: hard stool > 25% of time
IBS-D: liquid stool > 25% of time
IBS-M: mixed stool, C > 25% time and D > 25% time
lubiprostone IBS indication
ONLY WOMEN with IBS
lubiprostone AE
diarrhea, N –> reduce by taking with food
lineclitide and plecanatide additional effects
some pain receptor effects in colon
lineclitide and plecanatide AEs
diarrhea
tegaserod MoA
- inc GI secretion and motility
- dec visceral pain (gut pain)
- 5-HT4 agonist (NOT 5-HT3 SEROTONIN!)
tegaserod indication
women, < 65 years, no history of CV ischemic event (stroke, TIA, angina, heart attack/MI)
**REMS –> bc cardiac event causes
when to D/C tegaserod?
if no effect in 4 weeks –> bc and increased cardiac event risk so want to stop if not working
tegaserod AE
- HA
- diarrhea
- cardiac events
- well tolerated
tenapanor MoA
- GI Na/H exchanger isoform III –> dec sodium and phosphate absorption into body –> inc water secretion into stool
- GI pain receptor effect
tenapanor AE
diarrhea
IBS-C options
- lubipristone (women)
- lineclitide
- plecanantide
- tegaserod (women, <65, no ischemic Hx)
- tenapanor
IBS-D options
- rifaximin
- eluxadoline (Vibrezi)
- alosteron
rifaximin MoA
poorly absorbed antibiotic –> therefore stays in gut
INDICATION: SUSPECT BACTERIAL OVERGROWTH!
rifaximin dosage
550mg TID PO x 14 days
- can repeat twice prn
does rifaximin have systemic AE?
not really bc it stays in the gut –> no systemic absorption
eluxadoline MoA
mu, delta, kappa agonist –> inhibit bowel contraction
*makes sense bc acts like an opioid
eluxadoline main AE
**sphiner of oddi dysfuntion (the muscle valve that connects the bile duct/pancreatic duct to the small intestine
- can cause sphincter spasm –> back up of bile and stuff –> pancreatitis
eluxadoline CI
- Hx pancreatitis
- Hx alcoholism
- drink 3 drinks/day
eluxadoline AE
- N
- andominal pain
- constipation
alosetron MoA
serotonin antagonist (like ondansetron) –> dec transit time, inc water absorption –> dec stool liquidity
alosetron AE
- SEVERE CONSTIPATION
- ischemic colitis
therefore –> REMS!
alosetron indication
women with severe IBS-D
which 3 IBS agents are only for women?
- lubipristone -> IBS-C
- tegaserod -> IBS-C
- alosetron -> IBS-D
which IBS agents are on REMS?
- tegaserod -> IBS-C
- alosetron -> IBS-D
other IBS options
- TCA antidepressants
- soluble fiber
TCA MoA for IBS
- help with brain-gut miscommunication
- TCAs»>SSRIs for IBS –> but due to AEs, providers often do SSRIs
effect:
- improve pain
- global IBS of bloating and pain s/s
TCA options
- amitriptyline
- nortriptyline
TCA AEs
**anticholinergic –> dry, sedation, CONSTIPATION!!
- therefore take at night
which TCA is for IBS-D? why?
amitriptyline
- older, more AE –> constipation is an AE –> therefore use with diarrhea
which TCA is for IBS-C? why?
nortriptyline
- newer, fewer AE –> constipation is an AE –> therefore since already have constipation, want to dec that effect!
soluble fiber options
- psyllium (metamucil)
- barley
- oatbran
- beans
soluble fiber MoA
soluble: pull water into gut and make a gel
vs
insoluble: not digested, fermented in colon -> gasey
GERD disease differences
heartburn: burning in substernal chest, moves up, taste acid
GERD: heartburn that occurs 1-2 times/wk, 3 or more months, not respond to OTC therapy
VS
dyspepsia: discomfort, pain, burning, gnawing, early satiety in epigastrium
gastritis/duodenitis: superficial inflammation of stomach mucosa lining
PUD: inflammation to submucosa
GERD complications
barrett’s esophagus
esophageal adenocarcinoma
self-care exclusions for GERD
- symptoms > 3 months
- age < 2 years
- symptoms despite PPI or H2RA OTC for 2 weeks
- difficulty/pain when swallowing
- vomiting blood, black/tarry stools
- chronic hoarseness, choking
- unexplained weight loss
- continuous N/V/D
- chest pain + sweating, radiating to shoulder/arm
- SOB
- pregnant/nursing
alarm symptoms –> need a GI or other workup FIRST
- substernal pain: cardiac
- suspected GI bleed –> coughing up blood
- unexplained weight loss
- dysphagia –> hurts to swallow
- anorexia: not want to eat
antacid MoA
neutralize stomach acid (buffer)
- Mg –> diarrhea
- Al and Ca –> constipation
H2RA MoA
inhibit histamine receptor on parietal cell –> dec acid produciton i think
PPI MoA
inhibit parietal cell H/K ATP pump –> prevent stomach acid secretion i think
which do you take on an empty stomach?
PPIs
30min before first meal –> if forget, do 30 min before second meal
H2RA age limit
12 years old
PPI age limit
18 years old
how long is heartburn/GERB/dyspepsia OTC treatment??
14 days ONLY
most potent OTC for gerd?
PPI
why does barrett’s need lifelong PPI?
dec risk esophageal adenocarcinoma!
which indications for long term PPI?
- barrett’s
- GERD complications: severe erosive esophagitis, narrowing/strictures
long term PPI AEs
- bone fracture, hip fracture
- B12 deficiency
- dementia
- CKD from AIN
- c. diff, gastroenteritis
why do we limit PPI use?
stomach acid helps with absorption and killing so don’t want to suppress it forever!!
PPI long term monitoring
- kidney as usual
- daily recommendations of B12, D, and Ca
gastritis/duodenitis
inflammation of top layer - muscosa only
ulcer
inflammation down to submucosa
* >5mm in size
**more blood vessels therefore more GI bleed risk, life-threatening
major complication of PUD
GI bleeding
causes of PUD
1 cause: H. pylori
#2 cause: NSAIDs
h pylori pud duration of treatment
14 days
h pylori pud 1st line
quad therapy –> QID
ppi bid
+
bismuth subsalicylate
+
tetracycline
+
metronidazole
h pylori pud 2nd line
triple therapy –> bid
ppi bid
+
azithromycin
+
amoxicillin or metronidazole
which h pylori pud treatment needs eradication confirmation?
triple therapy
*wait 4 weeks AFTER TREATMENT ENDS to confirm testing
NSAID PUD risk factors
- age > 65 years
- using steriods concurrently
- non-COX selective use
- anticoagulants
- antiplatelets
- previuos Hx PUD
- high dose NSAID
- multiple NSAIDs
if you have a NSAID ulcer and can stop the NSAID, how long PPI?
4-8 weeks
why are COX-2 NSAIDs prefered?
less impact on GI prostaglandins –> less PUD risk
COX-2 selective nsaids
- celecoxib
- nabumetone, meloxicam, etodolac
PUD NSAID patho
NSAID –> COX inhibition –> dec PG (to dec pain) –> ALSO inc acid secretion, dec proliferation of cells, dec bicarb –> epithelial cell damage –> ulcer
upper GI bleed s/s
- melena (black stool)
- hematemesis (throwing up blood)
- lightheaded
- HA
- inc HR
- dec BP, Hgb, Hct
why do we treat upper GI bleed with PPI asap?
stomach acid will reduce activity of platelets and clotting factors –> we need those to be working in order to clot the bleeding spot
upper GI bleed PPI treatment breakdown
step 1: 80mg IV bolus
step 2: 40mg IV bolus BID OR 8mg/hr continous IV
step 1 + 2 = 72 hours (3 days)***
step 3: oral PPI x 2 weeks
step 4:
- h pylori: add the antibiotics for 2 weeks oral ppi totoal
- NSAID: continue so total oral ppi either 4-8 weeks or conituous
what two categories of patho does IBD impact?
- GI mucosa
- GI pathogen recognition
unique s/s of IBD
- blood in stool
- weight loss
- abdominal pain
- cramping
IBD Dx
- stool studies: leukocytes, LACTOFERRIN, CALPROTECTIN (non-invasive) (both bowel inflammatory markers)
- colonoscopy with small-bowel follow thru
- inc ESR, inc CRP –> non-specific markers of inflammation
- CT scan, MRI –> penetration into other tissues
main mode of IBD Dx
colonoscopy!
UC complications
- toxic megalocolon
- colon cancer
- colectomy
CD complications
- malnutrition, vit deficiency
- strictures
- fistulas
which IBD do we have a cure for?
UC –> colectomy
what OTC do we avoid in IBD?
NSAIDs –> induce flares!
5-ASA MoA
locally inhibit COX enzymes –> reduce prostaglandins –> reduce inflammation and pain
5-ASA absorption
rapidly absorbed into the SI but want it to stay in GI –> THEREFORE need a carrier to keep it in GI (targetted drug delivery)
sulfasalazine AE
rash/allergy
sulfasalazine carrier
sulfa
balsalazide carrier
inert
mesalamine carrier
many product that bring to diff part of GI!! ohhhhh
mesalamine suppository (Canasa)
rectum
mesalamine enema (Rowasa)
rectum + distal colon
mesalamine oral DR (Asacol)
terminal ileum –> CD
mesalamine oral (Pentasa)
jejunum –> CD
immunomodulator MoA
immunosuppressant properties
which immomodulators are related?
azathioprine (prodrug) –> 6-mercaptopurine
why do we use azathioprine with biologics or steriods?
aza…
- takes 3 months to work
- inc efficacy, dec ADA formation
- steriod sparing
azathioprine monitoring
- CBC q3months –> bone suppression
- LFTs
- pancreatic enzymes
azathioprine BBW
lymphoma risk inc when use with biologic!!!
methotrexate dosage form
IM/SQ —> PO when stable
corticosteroid MoA
dec immune response, dec inflammation
why is budesonide good for IBD?
high first-pass effect –> therefore, more stays in GI –> less systemic effect, very effective in GI
*poor systemic absorption
15x more potent than prednisone bc local effect
which budesonide oral is for UC?
Uceris –> colon
which budesonide oral for CD?
Entocort –> terminal ileum
duration for budesonide treatment?
8 weeks
antibiotic indication
CD –> perianal disease (fissures, fistulas)
antibiotic options
**enteric gram (-) (e coli, protese)
**anaerobes
these are what is most present in GI tract!
metronidazole
ciprofloxacin
3rd gen cephal
which biologic has best evidence?
infliximab
anti-TNF BBWs
1) infection –> TB, invasive fungal, bacterial, viral, opportunistic
- therefore: PPD, chest x-ray, HBV, HCV, HIV baseline
- HOLD when sick
2) malignancy –> lymphoma
- when + azathioprine
- but inc efficacy with azathioprine
natalizumab MoA
inhibit leukocyte trafficking and T cells (everywhere)
natalizumab BBW
PML –> CNS infection
**REMS
THEREFORE WE PREFER VEDOLIZUMAB
vedolizumab MoA
inhibit T-cells tagged/going to GI tract
JAKi BBWs
- cancer
- cardiac events
- thrombosis
- death
- infection
JAKi indication
bc so many BBW…
failed 1 or more TNF inhibitors
how to give mesalamine enema
at night in bed as retention enema
- wear adult diaper
