Module 1 - GI Disorders Flashcards
Symptoms associated with N/V
pallor, tachycardia, diaphoresis
CTZ
Chemoreceptor Trigger Zone
NTS
Nucleus of the Tractus Solitarius (vomiting center)
Which medication should not be used in children and why?
promethazine; respiratory depression
Serotonin Antagonists at CTZ, NTS, and GI tract
- ondansetron
- granisetron
- palonosetron
Aloxi (brand)
palonosetron (generic)
Butyrophenones MOA
Dopamine inhibition at CTZ
Compazine (brand)
prochlorperazine (generic)
Maalox, Mylanta
Aluminum Hydroxide, Magnesium Hydroxide, Simethicone
antacid
Zantac (brand)
ranitidine (generic)
Phenothiazines MOA
Dopamine inhibition at CTZ
Drugs with SE of EPS
- Phenothiazines (promethazine, eg)
- Butyrophenones (droperidol, eg)
- Benzamides (metoclopramide, eg)
hyperemesis gravidarum
complication of pregnancy characterized by severe n/v such that weight loss and dehydration occur
Assessment of NV
- # of episodes
- Onset
- Duration of sx
- Severity of nausea (0-10)
Which drug used to tx NV has a BB Warning for the risk of EKG abnormalities (QT prolongation)?
droperidol (Inapsine)
Which drug is excellent for breakthrough NV?
olanzapine
List 3 Neurokinin-1 Antagonists
- aprepitant (PO)
- fosaprepitant (IV)
- rolapitant (PO)
Marinol (brand)
dronabinol (generic)
Emend (brand)
aprepitant (generic)
Cesamet (brand)
nabilone (generic)
Cannabinoids
dronabinol (CIII)
nabilone (CII)
Which drug class is especially useful for anticipatory NV?
Benzodiazepines (lorazepam, alprazolam, eg)
Reglan (brand)
metoclopramide (generic)
metoclopramide dose for NV
(pre-tx with Benadryl to prevent EPS), then:
20-50 mg
About how long is the onset for an IM dosage form in tx of NV?
~30 minutes
ODT, IV, PR faster
When to apply scopolamine patch? Duration of action?
Appy 6-8 hrs before needed;
Duration 72 hrs
When to take dimenhydrinate or meclizine to tx motion sickness?
30-60 min before needed (PO)
Dramamine (brand)
dimenhydrinate (generic)
Bonine (brand)
meclizine (generic)
PONV treatment of highest risk pts
Always use 2 agents:
- 5-HT3 antagonist
- dexamethasone, droperidol, aprepitant, or metoclopramide
CINV Acute Emesis (onset, max, resolution)
After chemo administration–
Onset: 1-2 hrs
Max: 5-6 hrs
Resolve: 12-24 hrs
CINV Delayed Emesis (onset, max, resolution)
After chemo administration–
Onset: post 24 hrs
Peak: 48-72 hrs
Resolve: gradual over 1-3 days
Most difficult type of CINV to tx
Delayed Emesis
Highly emetogenic drugs
#1. cisplatin 2. cyclophosphamide + doxorubicin
Prevention of Acute CINV (high emetic risk)
3 drug approach over 2-4 days:
- 5-HT3 antagonist
- dexamethasone
- aprepitant or olanzapine
- (+/-) lorazepam
Prevention of Acute CINV (moderate emetic risk)
- 5-HT3 antagonist (palonosetron preferred)
2. dexamethasone
Prevention of Acute CINV (low emetic risk)
*dexamethasone,
metoclopramide, prochlorperazine, ondansetron, granisetron
ROA for Acute vs Breakthrough CINV
Acute: PO whenever possible
Breakthrough: IV/PR often required
Tx of Acute Breakthrough CINV
Agent from different drug class
- prochlorperazine
- nabilone
- metoclopramide (+ benadryl)
- haloperidol
- olanzapine
Acute constipation
Less than 3 BM/week
Chronic constipation
Sx > 6 weeks
Disease states that slow down GI motility
- Diabetes
- Parkinson’s
- CNS/spinal cord injury
Constipation referral
Sx > 2 weeks w/o significant relief
How much fiber recommended per day?
20-30 g fiber/day
Metamucil (brand)
psyllium (generic)
Citrucel (brand)
methylcellulose (generic)
Fibercon (brand)
calcium polycarbophil (generic)
Which bulk laxative produces less gas?
methylcellulose (Citrucel)
-mix with cold water
Which bulk laxative produces less gas?
methylcellulose (Citrucel)
-mix with cold water
Surfactant (stool softner)
docusate (Colace)
Saline Laxatives
- MOM
- Mg Citrate
- Fleet’s Saline Enema
Hyperosmotic Agents
- Sorbitol
- Lactulose
- PEG
- Glycerin supp.
- Karo Corn Syrup
Stimulant Laxatives
- Senna
- Bisacodyl
- Castor Oil
Stimulant Laxative MOA
Locally irritates nerves which stimulates motility
Cl- Channel Activator for idiopathic constipation or IBS-C
lubiprostone (Amitiza)
Amitiza (brand)
lubiprostone (generic)
lubiprostone (Amitiza) dosing
Take with food and water:
24 mcg BID (constipation)
8 mcg BID (IBS-C)
*avoid in pregnancy
Guanylate Cyclase Activator for idiopathic constipation or IBS-C
linaclotide (Linzess)
Linzess (brand)
linaclotide (generic)
linaclotide (Linzess) dosing
Empty stomach, 30 min before breakfast:
145 mcg daily (constipation)
290 mcg daily (IBS-C)
Mu opioid receptor antagonists for constipation tx
- methylnaltrexone (Relistor): 8-12 mg SC QOD
2. naloxegol (Movantik): 25 mg PO daily on empty stomach
Relistor (brand)
methylnaltrexone (generic)
Movantik (brand)
naloxegol (generic)
alvimopan (Entereg) indication
tx of post-op ileus (leads to constipation)
-restricted-access program; high risk pts only
GI Prep: tx classes
Hyperosmotics or Saline Laxatives
Classifications of diarrhea (acute, persistent, chronic)
Acute: less than 2 weeks
Chronic: greater than 1 month
Most common infectious cause of diarrhea in adults?
Rotavirus
4 types of diarrhea pathophysiologies?
- Secretory: ion transport
- Osmotic: poorly absorbed substances
- Exudative: IBD
- Altered Intestinal Transit: decreased exposure time (bowel resection, promotility meds, etc); anything that speeds up intestine
Which diarrhea pathophysiologies are characterized by large stool volumes (> 1 L/day)?
Secretory and Exudative
Which diarrhea pathophysiology resolves if patient stops eating?
Osmotic
Prevention of Traveler’s Diarrhea?
Pepto-Bismol 1-4 x daily, prophylactically
Antimotility drugs MOA
Activate Mu opioid receptors on bowel smooth muscle to: reduce peristalsis and increase segmentation (mixing)
List 4 antimotility agents
- Loperamide
- Diphenoxylate
- Difenoxin
- Codeine
Imodium (brand)
loperamide (generic); OTC
Lomotil (brand)
diphenoxylate/atropine (generic); Rx-only
Motofen (brand)
difenoxin/atropine (generic); Rx-only
loperamide dosing
4mg (2 tabs) initially, then 2mg (1 tab) after each loose stool
Max: 16 mg/day (8 tablets)
diphenoxylate/atropine dosing
5 mg (2 tabs) 4 x daily Max: 20 mg/day (8 tablets)
Absorbents MOA
Use in chronic diarrhea; oral non-absorbed agents absorb excess fluid to help form solid stools
List 2 Absorbents used to treat diarrhea
- polycarbophil (Fibercon)
2. psyllium (Metamucil) – powder formulation absorbs more water than tablet
Which antisecretory treatment of diarrhea also has antimicrobial and anti-inflammatory effects?
Bismuth subsalicylate (Pepto-Bismol)
Pepto-Bismol dosing
2 tabs or 30 mL every 30-60 min PRN
(up to 8 doses/day)
AVOID in pts who shouldn’t take salicylates
4 subtypes of IBS
IBS-C, IBS-D, IBS-M, IBS-U
Lotronex (brand)
alosetron (generic)
5HT-3 antagonist for IBS-D
alosetron (Lotronex) classification and dosing
5HT-3 antagonist for IBS-D
Initial: 0.5 mg BID x 4 weeks
*REMS d/t severe constipation in overdose (ischemic colitis)
tegaserod (Zelnorm) classification and indication
5HT-4 agonist for IBS-C
*restricted use only d/t risk of CV disorders
Bentyl (brand)
dicyclomine (generic)
Antispasmotic and anticholinergic for IBS
dicyclomine (Bentyl) classification and indication
Antispasmotic and anticholinergic for IBS
take 30-60 minutes before meals
hyoscyamine (Levsin) classificaiton and indication
Anticholinergic for IBS
rifaximin (Xifaxan) indication and dosing
IBS with diarrhea
550 mg TID x 14 days
eluxadoline (Viberzi) classification and indication
Mu-opioid agonist, Delta-opioid antagonist (C-IV)
MOA: slows motility and relieves pain
IBS with diarrhea
Pathophysiology of GERD (6 factors)
- Defective LES pressure
- Anatomic factors (hiatal hernia, eg)
- Delayed gastric emptying
- Esophageal clearance
- Mucosal resistance
- Refluxate composition (pH, volume)
Causes of defective LES pressure (6 factors)
- spontaneous LES relaxations
- increased abdominal pressure
- atonic LES
- pregnancy
- foods
- medications
3 causes of delayed gastric emptying
- high-fat meals
- smoking
- diabetic gastroparesis
Atypical GERD sx
(aka extraesophageal sx)
- chronic cough
- hoarseness
- non-allergic asthma
- dental enamel erosions
Alarm GERD sx
- dysphagia
- odynophagia
- bleeding
- unexplained weight loss
- continual pain
Best diagnostic tool for GERD
PPI trial of 8 weeks
Type of cell that produces acid in the stomach?
Parietal cell
Indication for antacids as first line tx?
PRN for intermittent GERD sx
sx LESS THAN twice weekly
Only acid suppressing therapy appropriate for erosive GERD?
PPI
NOT antacids or H2RAs
Antacid adverse effects: Mg vs. Al vs. Ca
Magnesium: diarrhea
Aluminum: neurotoxicity, anemia, constipation
Calcium: Milk-Alkali syndrome (HA, nausea, irritability)
Antacid DDI causes
- reduced absorption of other drugs d/t higher pH (digoxin, iron, ketoconazole)
- chelation and adsorption to some antibiotics
**separate antacids 2 hours before/4 hours after other drugs
PPIs with IV formulations
pantoprazole
esomeprazole
PPI capsules you can open and sprinkle in applesauce or down NG tube (4)
- omeprazole
- esomeprazole
- lansoprazole
- dexlansoprazole
PPI with ODT formulation
lansoprazole
PPI with instructions NOT to crush
pantoprazole
rabeprazole
In what type of pts would you consider using a H2RA over a PPI?
- pt with recent antibiotic use d/t increased risk of C diff with PPI
- pt on HIGH DOSE, IV methotrexate d/t increased risk of toxicity
Which PPIs should be avoided d/t inhibition of CYP 2C19?
Omeprazole and Esomeprazole
Promotility agent most commonly used in diabetic gastroparesis
metoclopramide (Reglan); increases gastric emptying and LES tone
Nexium (brand)
esomeprazole (generic)
Dexilant (brand)
dexlansoprazole (generic)
Pepcid (brand)
famotidine (generic)
Prilosec (brand)
omeprazole (generic)
Protonix (brand)
pantoprazole (generic)
Prevacid (brand)
lansoprazole (generic)
Tagamet (brand)
cimetdine (generic)
Axid (brand)
nizatidine (generic)
Zantac (brand)
ranitidine (generic)
famotidine dosing- GERD and active PUD
OTC: 10 mg BID
GERD: 20 mg BID
PUD: 20 mg BID, or 40 mg at bedtime
ranitidine dosing- GERD and active PUD
OTC: 75 mg BID
GERD: 150 mg BID
PUD: 150 mg BID, or 300 mg at bedtime
cimetidine dosing- GERD and active PUD
OTC: 200 mg BID
GERD: 400 mg BID
PUD: 400 mg BID, 300 mg QID, or 800 mg HS
omeprazole dosing- GERD and active PUD
OTC: 20 mg daily x 14 days Q 4 months
Nonerosive GERD: 20 mg daily
Erosive GERD: 20 mg BID
PUD: 20-40 mg daily/BID
pantoprazole dosing- GERD and active PUD
Nonerosive GERD: 40 mg daily
Erosive GERD: 40 mg BID
PUD: 40 mg daily/BID
lansoprazole dosing- GERD and active PUD
OTC: 15 mg daily x 14 days Q 4 months
Nonerosive GERD: 15-30 mg daily
Erosive GERD: 30 mg BID
PUD: 15-30 mg daily/BID
esomeprazole dosing- GERD and active PUD
OTC: 20 mg daily x 14 days Q 4 months
Nonerosive GERD: 20 mg daily
Erosive GERD: 40 mg daily
PUD: 20-40 mg daily/BID
Sucralfate MOA
Mucosal protectant for duodenal ulcer
MOA: breaks down to insoluble aluminum/sucrose paste and adheres to ulcer to allow protection and healing
sucralfate dosing
1 g QID, or 2 g BID
*administer on empty stomach; separate from other meds 2 hours before or 4 hours after
misoprostol MOA
synthetic prostaglandin E1 (replaces PGs inhibited by NSAIDs); mucosal protectant
misoprostol adverse effects
TERATOGENIC
significant GI effects (diarrhea, abdominal pain); use-limiting
Treatment of Non-NSAID/H. pylori PUD
H2RA or sucralfate x 6-8 weeks
PPI x 4 weeks
PPI based regimen for H. pylori PUD
- Clarithromycin 500 mg BID
- Amoxicillin 1 g BID, or Metronidazole 500 mg BID
- PPI, BID: Omeprazole 20 mg, Lansoprazole 30 mg, Pantoprazole 40 mg, Esomeprazole 20 mg (or 40 mg daily), or Rabeprazole 20 mg
Bismuth based regimen for H. pylori PUD
- Bismuth
- Metronidazole
- Clarithromycin, Amoxicillin, or Tetracycline
- PPI or H2RA: Omeprazole, Lansoprazole, Pantoprazole, Esomeprazole, Rabeprazole, Cimetidine, Ranitidine, Famotidine, Nizatidine
Treatment of NSAID induced PUD
- if NSAID discontinued: PPI, H2RA, or sucralfate x 6-8 weeks
- if NSAID continued: PPI x 8-12 week, (or as long as NSAID is required)
Antiplatelet induced PUD prophylaxis
- PPI preferred but if taking clopidogrel, then choose Pantoprazole d/t DDI with esomeprazole and omeprazole
- Famotidine 20 mg BID
pH goal in management of PUD in ED/ICU
Maintain pH > 6
4 complications that designate “clinically important bleeding” in SRMB
- hemodynamic instability
- decreased Hgb
- necessity of RBC transfusions*
- increased ICU length of stay
How does SRMD differ from PUD?
- SRMD: multiple, superficial lesions primarily in the stomach with more congestion and bleeding.
- PUD: few, deeper lesions primarily in the duodenum with perforations being more common.
4 factors that lead to development of an acute stress ulcer
- reduced HCO3 secretion
- reduced mucosal blood flow
- decreased GI motility
- acid back diffusion
2 major risk factors for development of a stress ulcer
- Respiratory failure: mechanical ventilation for ≥ 48 hours
- Coagulopathy: plt count 1.5, or PTT > 2x control value
Indication for SRMD prophylaxis (ICU only)
- Mechanical ventilation ≥ 48 hours
- Coagulopathy
- Hx of GI ulcer/bleeding within 1 year of admission and at least 2 of the following 4 factors:
- sepsis, ICU > 1 week, occult bleeding ≥ 6 days, or high-dose corticosteroids
Notable ADE of H2RA vs. PPI
H2RA: tachyphylaxis (tolerance)
PPI: risk of Clostridium difficile colitis
Neonate
0-28 days
Term + 28 days (if born premature)
Infant
1-12 months
Child
1-12 years
Adolescent
13-18 years
1 oz to mL
1 oz = 30 mL
1 tablespoon to mL
1 T. = 15 mL
Bedside Schwartz equation
eGFR (mL/min per 1.73 m2) = 0.413 x (ht in cm/SCr)
Peds: ranitidine dosing
IV: 1-2 mg/kg Q 8-12 hrs
PO: 2-4 mg/kg BID
Peds: famotidine dosing
IV: 0.5 mg/kg 1-2 times daily
PO: 0.5 mg/kg BID
Peds: lansoprazole dosing
PO: 1 mg/kg/day
Peds: omeprazole dosing
PO: 1 mg/kg/day
Encopresis definition
(fecal incontinence)
repeated passage of feces into inappropriate places
-often secondary to soft stool leaking around large mass of stool in rectum
What age is bowel continence expected by?
Age 4; otherwise termed delayed bowel training
Circular smooth muscles (2) that are part of the physiology for a bowel movement
- internal anal sphincter
2. rectum
Skeletal muscles (2) that are part of the physiology for a bowel movement
- external anal sphincter
2. puborectalis muscle
Diarrhea definition (#/day)
3 or more loose or liquid stools per day
Chronic diarrhea
Lasting 14 or more consecutive days
Peds: calculating fluid requirements (per 24 hours)
Up to 10 kg: 100 mL/kg
10-20 kg: 1000 mL + (50 mL/kg x kg over 10)
>20 kg: 1500 mL + (20 mL/kg x kg over 20)
Common complication of TPN long term in SBS
Cholestasis: reduction or stoppage of bile flow from the liver to the duodenum
-can lead to liver failure (PNALD)
Medication used to prevent or treat PNALD
Ursodiol
MOA: minor component of bile acid; helps to solubilize cholesterol. PO administration.
Cytokines increased in CD vs UC
CD: increased Th1 cytokine activity
UC: increased Th2 cytokine activity
both: TNF-alpha plays key role
Two types of IBD
Ulcerative colitis (UC) Crohn's disease (CD)
Smoking effects in UC vs CD
UC: protective; fewer flare-ups
CD: increased frequency and severity
local complications of UC
hemorrhoids, anal fissures, perirectal abcesses
common during flares
severe, life-threatening complication of UC
Toxic megacolon
-colonic dilation/distention, increased depth of ulceration; s/sx of systemic toxicity
difference in complications btwn UC and CD
UC: increased bleeding, carcinoma risk, and rectal involvement
CD: fistulas, strictures, and perianal disease common
What markers distinguish IBD from IBS?
fecal calprotectin
fecal lactoferrin
(specific to inflammation in GI tract)
What antibodies distinguish UC vs CD?
UC: (+) perinuclear antineutrophil cytoplasmic antibodies (pANCA)
CD: (+) anti-Saccharomyces cervisiae antibodies (ASCA)
UC: proctitis
involving the rectal area
UC: proctosigmoiditis
involving rectum and sigmoid colon
UC: pancolitis
involving majority of colon
UC: distal
(left-sided); distal to splenic flexure
descending colon, sigmoid colon, rectum
UC: extensive
extending proximal to splenic flexure
UC: mild disease
- less than 4 stools/day (+/- blood)
- no systemic disturbance
- normal ESR
UC: moderate disease
- greater than 4 stools/day
- minimal systemic disturbance
UC: severe disease
- greater than 6 stools/day with blood
- systemic disturbance (fever, tachycardia, anemia, or ESR > 30 mm/h)
UC: fulminant disease
- greater than 10 stools/day with continuous bleeding
- toxicity (severe systemic disturbance)
- abdominal tenderness
- need for transfusion
- colonic dilation
splenic flexure
curvature on the left side of the colon between the transverse colon and descending colon
fulminant definition
severe and sudden in onset
What is the difference between hematochezia and melena?
hematochezia: gross blood per rectum; indicates lower GI bleeding (sign of CD)
melena: black tarry stools; indicates upper GI bleeding
sulfasalazine chemistry and indication
- sulfapyridine (inactive, associated with ADRs, but prevents systemic absorption in small intestine)
- mesalamine (5-ASA, active, anti-inflammatory effects)
Indication: mild IBD
- mesalamine (5-ASA, active, anti-inflammatory effects)
Advantages/disadvantages of budesonide
Pros: extensive first pass metabolism so minimal systemic absorption (can take PO for 8 weeks); well tolerated
Cons: CYP3A substrate so DDI with inhibitors increase systemic exposure
Mercaptopurine (6-MP) metabolism
AZA (prodrug) > 6-MP > inactive metabolite or active toxic metabolite (TGN)
TMPT: metabolizes 6-MP to inactive metabolite
TGN: accumulation results in bone marrow suppression
Azathioprine (AZA) and Mercaptopurine (6-MP) indication
induction and maintenance of remission in UC and CD
- after failure of 5-ASA tx
- slow onset (3-6 months)
- long term tx
Cyclosporine indication
induction of remission in refractory IBD
- bridge therapy; not for long term use
- better data in UC
Methotrexate indication
induction and maintenance of remission in CD
- add folic acid 1 mg daily to prevent bone marrow suppression
- teratogenic (pregnancy CI)
Remicade (brand)
infliximab (generic)
Humira (brand)
adalimumab (generic)
Simponi (brand)
golimumab (generic)
Cimzia (brand)
cerolizumab pegol (generic)
TNF-alpha antagonists
induction and maintenance therapy
- infliximab (Remicade)
- adalimumab (Humira)
- golimumab (Simponi)
- certolizumab pegol (Cimzia)
Anti-Adhesion biologics
- natalizumab (Tysabri)
2. vedolizumab (Entyvio)
Biologic(s) only used for CD
- certolizumab pegol
2. natalizumab
Biologic(s) only used for UC
golimumab (Simponi)
Biologics used for CD and UC
- infliximab (Remicade)
- adalimumab (Humira)
- vedolizumab (Entyvio)
TNF-alpha antagonists: Class ADRs
- increase risk of serious infections
- injection site reactions
- risk of malignancy/demyelinating disease
- hepatosplenic T-cell lymphoma (HSTCL) risk
- may exacerbate CHF
Baseline monitoring for TNF antagonists
PPD, CXR, Hep B/C
-ensure no latent infection that could be reactivated
(live vaccines CI during and 3 months after tx)
Biologics administered via IV infusion
- infliximab (2 hour infusion)
- natalizumab (1 hour infusion)
- vedolizumab (30 min infusion)
Which biologic is associated with PML?
natalizumab (Tysabri)
-must test for JC antibody prior to initiation
First-line treatment in mild-moderate active UC
if extensive disease: need systemic tx (PO)
-oral sulfasalazine or mesalamine
if distal disease: within reach (topical)
-mesalamine enema or suppository
Alternatives for mild-moderate active UC
- Budesonide CR
- Prednisone 40-60 mg/day if refractory to ASAs
- topical corticosteroids for distal disease
- AZA or 6-MP if refractory to ASAs
Moderate-Severe active UC
- systemic corticosteroids (PO prednisone 40-60 mg daily)
2. TNF-alpha inhibitors if unresponsive
Severe-Fulminant active UC
- parenteral corticosteroids (IV: methylprednisolone or hydrocortisone)
2-3. TNF-inhibitor or cyclosporine (similar efficacy)
*transition cyclosporine to 6-MP or AZA for maintenance to
Agents that can be used in UC maintenance
- ASA (mesalamine > sulfasalazine)
- AZA or 6-MP
- TNF-alpha antagonist
NOT corticosteroids or cyclosporine
Mild-Moderate active CD
- 5-ASA (minimal efficacy in CD)
- Budesonide CR (distal/right-sided disease)
- Antibiotics (perianal disease)
Moderate-Severe active CD
- systemic CS (PO prednisone 40-60 mg/day)
- MTX
- TNF-antagonist
*AZA/6-MP not rec for induction tx d/t slow onset (can maintain remission after induction with steroids)
Severe-Fulminant active CD
- parenteral corticosteroids x 3-7 days then PO (methylprednisolone or hydrocortisone)
- Biologic (infliximab, eg)
- Cyclosporine (limited data, last resort)
Agents used in CD maintenance of remission
- AZA or 6-MP (first-line)
- MTX
- TNF-antagonist or other biologic
(or infliximab + AZA or 6-MP)
Pro/Con of combination therapy: TNF antagonist + AZA
Pro: more effective in preventing development of anti-drug antibodies (ADAs)
Con: increase risk of HSTCL
What vessels comprise the Hepatic Portal Triad that supplies blood to the liver?
- Bile duct
- Hepatic artery
- Portal vein
AST and ALT normal values
Aspartate Aminotransferase (AST): 0-50 IU/L Alanine Aminotransferase (ALT): 5-60 IU/L
ALP normal value
Alkaline Phosphatase (Alk Phos): 35-130 IU/L
GGT normal value
Gamma Glutamyl Transferase (GGT):
0-85 IU/L
Bilirubin normal value
Bilirubin: 0-1.4 mg/dl
Direct/Conjugated Bilirubin: 0-0.3 mg/dl
Albumin normal level
Serum albumin: 3.6-5 g/dl
(LOW in liver disease) - b/c created by liver
BUN normal values
Blood Urea Nitrogen (BUN): 10-20 mg/dl
(LOW in liver disease) - b/c created by liver
Components of LFTs
- albumin
- bilirubin
- cholesterol
- BUN
- INR
Components of LITs
- AST
- ALT
- Alk Phos
- GGT
Modes of transmission for Hep A, B, and C
HepA: fecal-oral
HepB: sexual, parenteral, perinatal
HepC: parenteral
Centrilobular Necrosis- definition and drug cause(s)
direct/metabolite-related hepatotoxicity; damage spreads outward from middle of a lobe
-Acetaminophen
Nonalcoholic Steatohepatitis (NASH)- definition and drug cause(s)
accumulation of fatty acids in hepatocytes
- Tetracycline
- Valproate
Phospholipidosis- definition and drug cause(s)
accumulation of phospholipids in hepatocytes
-Amiodarone
(long half-life)
Generalized Hepatocellular Necrosis- definition and drug cause(s)
drug induction of innate immune response (auto-immune type)
-Isoniazid
Toxic Cirrhosis- definition and drug cause(s)
scarring effect of hepatitis (mild, undetected) leads to cirrhosis
- Methotrexate
- Vitamin A
Cholestatic Injury- definition and drug cause(s)
accumulation of toxic bile acids in liver
- Chlorpromazine
- Amoxicillin-Clavulanic Acid
- Carbamazepine
Liver Vascular Disorder- definition and drug cause(s)
development of large, blood-filled lacunae
- Androgens, Estrogens
- Tamoxifen
- Azathioprine
Hepatocellular Injury examples (4)
- damage directly to hepatocytes
1. Centrilobular Necrosis
2. Steatohepatitis
3. Phospholipidosis
4. Generalized Hepatocellular Necrosis
Three main histological phases of Alcoholic Liver Disease?
- Steatosis/fatty liver
- Acute alcoholic hepatitis
- Cirrhosis
Most common cause of cirrhosis?
Alcoholic Liver Disease
Interpreting Maddrey’s Score
Acute Alcoholic Hepatitis (AAH) assessment
Score > 32
-poor prognosis
-threshold for starting corticosteroids or pentoxifylline
Pentoxifylline indication and MOA
Anti-inflammatory and vasodilator used to treat alcoholic hepatitis
MOA: PDE inhibitor and TNF-alpha modulator
Dose: 400 mg PO TID
ETOH Withdrawal treatment
- fluid resuscitation
- thiamine 100 mg daily
- folic acid 1 mg daily
- multivitamins daily
- benzodiazepines
Complications of Cirrhosis (7)
- portal HTN
- varices
- ascites
- hepatic encephalopathy (HE)
- coagulation defects
- spontaneous bacterial peritonitis (SBP)
- hepatorenal syndrome (HRS)
Immediately life-threatening complications of cirrhosis
- acute variceal bleeding
2. spontaneous bacterial peritonitis (SBP)
Risk factors for variceal bleeding
- poor liver function
- large varices
- alcoholic etiology of cirrhosis
- red wale markings
Complications of cirrhosis mainly d/t Portal Hypertension
- varices/variceal bleeding
- ascites
- encephalopathy
Complications of cirrhosis mainly d/t Liver Insufficiency
(lack of hepatic enzymes/function)
- encephalopathy
- coagulopathies
Octreotide MOA and dosing
MOA: selectively vasoconstricts splanchnic vasculature thereby decreasing portal BP
Dosing: 50-100mcg IV load, then 25-50mcg/hr continuous IV infusion x ~5 days
splanchnic vasculature defintion
vasculature that flows into hepatic portal vein
-mesenteric, gastric, splenic, pancreatic veins
PPI treatment in variceal bleeding
Esomeprazole or Pantoprazole
dose: 80 mg IV load, then 8 mg/hr continuous infusion
* high dose oral PPI x 4 weeks post-bleed
prophylactic antibiotics during acute variceal bleed
-to prevent SBP (serious infection)
Short course (max 7 days):
1. Cephalosporin- ceftriaxone 1g IV q 24 hours
2. Fluoroquinolone- ciprofloxacin 400mg IV BID
Comprehensive Treatment for Variceal Bleed
- volume resuscitation
- PPI
- Octreotide IV (~5 days)
- EVL (banding procedure)
- 3rd gen. cephalosporin (~7 days)
* secondary prophylaxis: nonselective BB
Prevention of variceal bleeding- drug(s) and dosing
Non-selective beta blocker
- Propanolol 10mg BID or TID
- Nadolol 20mg daily
- titrate to HR goal: 55-60 bpm
most common complication of cirrhosis
ascites
-fluid accumulation in peritoneal space
Serum Ascites Albumin Gradient (SAAG)
-determines cause of ascites
Albumin (serum) - Albumin (ascites) = SAAG
SAAG > 1.1 g/dl = d/t portal HTN
Ascites Treatment
- Spironolactone** 25-50 mg daily
- Furosemide 20-40mg daily
* *most effective b/c aldosterone antagonist that counteracts RAAS activation that causes ascites
Spironolactone : Furosemide ratio
100: 40
- maintain at all times to ensure K+ balance
- max: 400mg/160mg
Volume expander needed along with Paracentesis for large volume/refractory Ascites
Albumin infusion: 8g per L of ascitic fluid removed
if tap >5L
SBP mechanism
bacterial translocation through intestines to peritoneal fluid; “spontaneous” infection of ascitic fluid
Diagnosis of SBP
PMN > 250 cells/mm3
PMN = WBC x %neutrophils
Treatment of SBP
Choose one for empiric coverage (x 5 days):
1. Ceftriaxone 2g IV q 24 hours
2. Zosyn 3.375g IV q 6 hours
3. Ciprofloxacin
*If SCr >1, BUN >30, or bilirubin >4:
Albumin infusion: 1-1.5 g/kg to prevent HRS
Primary/Secondary Prophylaxis of SBP
Choose one for life (if secondary):
- Cipro 500-750mg PO daily
- TMP/SMX 1 DS tab PO daily
- Norfloxacin 400mg PO BID
Asterixis
Hand flapping tremor (“waving goodbye”); symptom of HE
Normal ammonia level
normal: less than 35 umol/L
-NOT diagnostic of HE if elevated
AMS + cirrhosis = HE
Treatment of HE
- Lactulose 45 mL/hr until catharsis, then maintenance titrated to 3-4 soft BMs daily
- Metronidazole 250mg q 6-12 hrs
- Rifaximin 400mg TID x 5-10 days, then 550mg BID for prevention
- Flumazenil (no long term benefit)
Treatment of HRS
(Discontinue diuretics)
- albumin + octreotide + midodrine
- liver transplant
albumin 1g/kg x 1 day, then 20-40g daily
octreotide 100mcg SQ TID
midodrine 5-7.5mg PO TID
Pain management in Cirrhosis
- Acetaminophen
- Tramadol
- Fentanyl
- Hydromorphone
* Avoid NSAIDs
