Term
| What is cirrhosis (how is it characterized?) |
|
Definition
Characterized by replacement of normal liver tissue with abnormal nodules and FIBROSIS
Blood flow through the liver is disturbed
Unable to perform normal functions |
|
|
Term
| Normal functions of the liver? |
|
Definition
1. Produces clotting factors, albumin, bile, numerous other products
2. Stores energy (glycogen)
3. Metabolizes cholesterol
4. Detoxifies toxins, alcohol |
|
|
Term
|
Definition
Drugs! and Alcohol (60-70% of cases)
Infection: Hep B and C
Metabolic: Hemochromatosis, Wilson's Disease, porphyria (hemoglobin not made properly)
Biliary Obstruction
CV: CHF
Autoimmune disorders
Nonalcoholic steatohepatitis (NASH) |
|
|
Term
| Drug Causes of Cirrhosis? |
|
Definition
Amiodarone
Estrogen
Isoniazid
MTX
Methyldopa
Nitrofurantoin
Phenothiazines (chlorpromazine, promethazine)
Anabolic Steroids |
|
|
Term
| What does the portal vein connect? |
|
Definition
Stomach to liver
Supplements first pass metabolism |
|
|
Term
| What are other organs (in addition to stomach and liver) that the portal vein is near, and thus might effect the blood supply/pressure of? |
|
Definition
|
|
Term
| Thrombocytopenia is bad because _____? |
|
Definition
| Low platelets = increased risk of bleeding |
|
|
Term
| Physiologically, cirrhosis (liver cells being replaced by fibrosis) can cause what to occur? |
|
Definition
1. Splenic congestion (throbocytopenia)
2. Pressure increases in portal circulation (varices)
3. Fluid accumulation (ascites)
4. Increased bilirubin (jaundice, dark urine) |
|
|
Term
| T or F: all thrombocytopenia is equal |
|
Definition
| F - patients with cirrhosis will have normal platelet function down to ~60,000 (there is some compensatory activity) under this value, tend to see negative consequences |
|
|
Term
| Expected aminotransaminase values in patients with cirrhosis? |
|
Definition
ALT and AST are elevated in acute liver damage
They can be either elevated or normal in chronic liver damage |
|
|
Term
| Expected albumin and coagulation factor levels (lab values) in patients with cirrhosis |
|
Definition
| Decreased because of damaged hepatocytes |
|
|
Term
| Expected platelet counts in people with cirrohsis |
|
Definition
decreased (aka thrombocytopenic) in 30-64% of cirrhotic patients
Thrombocytopenia: <150,000 |
|
|
Term
| How does thrombocytopenia develop in cirrhosis? |
|
Definition
1. Splenomegaly is caused by portal HTN, this causes platelets to pool in the spleen
2. Decreased thrombopoeitin (b/c liver dysfunction) |
|
|
Term
| Does bilirubin increase or decrease in cirrhosis? |
|
Definition
| Increases - breakdown product of hemoglobin from RBC |
|
|
Term
| Expected lab values of Alkaline phosphatase & gamma-glutamyl transpeptidase (GGT) in cirrhosis |
|
Definition
Increases
But neither is produced in the liver
When both increased - sensitive and specific marker of cholestatic liver disease
-so good to look at if cirrhosis expected |
|
|
Term
| How will excessive fluid in cirrhosis present on a lab panel? |
|
Definition
| Hyponatremia and hypokalemia |
|
|
Term
| In cirrhosis would you expect ammonia to increase or decrease? |
|
Definition
| Increase (less ability to detoxify via liver) |
|
|
Term
| OVERALL: expected (possible) lab value changes in cirrhosis |
|
Definition
| 1. Increased: ALT/AST (or normal levels) 2. Decreased: Alb, coagulation factors 3. Decreased platelets 4. Increased bilirubin 5. Increased alkaline phosphatase and GGT 6. Hyponatremia/Hypokalemia 7. Elevated ammonia **Can have any or all of these |
|
|
Term
|
Definition
Fatigue, anorexia, weight loss
-Pruritis, Jaundice (increased bilirubin)
-Bleeding/bruisng (decreased clotting factors)
-palmar erythema, spider angiomata, gynecomastia (decreased estrogen degradation)
-edema, ascites, pleural effusion, respiratory difficulty (decreased albumin)
-confusion-hepatic encephalopathy (increased ammonia) |
|
|
Term
| Two ways to classify severity of cirrhosis |
|
Definition
1. Child-Pugh Grading of Chronic Liver Disease (older, more subjective)
2. Model for End-Stage Liver Disease (MELD) Score (newer, only objective) |
|
|
Term
| Child-Pugh Grading of Chronic Liver Disease - what does it measure? |
|
Definition
1. Bilirubin
2. Albumin
3. Ascities
4. Encephalopathy
5. Prothrombin time
Can Score 1-3 |
|
|
Term
| Model of End-Stage Liver Disease (MELD) Score |
|
Definition
Newer than the Child-Pugh Grading System
Accepted by the liver transplant organization (UNOS)
Takes into account SCr, Bilirubin, INR, etiology of liver disease
(has an equation) |
|
|
Term
| Treatment strategies of cirrhosis |
|
Definition
Identify and eliminate the cause (ex: alcohol)
Minimize complications: prevent and treat (drugs, diet, surgery)
Liver transplant (last line) |
|
|
Term
| Complications of Cirrhosis |
|
Definition
Portal HTN
Varices
Hepatic Encephalopathy (HE)
Ascites
Spontaneous bacterial peritonitis (SBP)
Hepatorenal Syndrome (HRS)
Coagulopathy |
|
|
Term
| How does portal HTN develop with cirrhosis? |
|
Definition
Because of the fibrosis of the liver it causes a resistance to blood flow
Pressure in the portal vein becomes greater than systemic pressure |
|
|
Term
| What occurs with portal HTN - how does the body adjust for this pressure increase? |
|
Definition
Alternate blood flow routes develop in order to bypass the liver = VARICES
this can occur with gastric and esophageal venous systems as well |
|
|
Term
| What is the most lethal cause of death from cirrhosis? |
|
Definition
|
|
Term
|
Definition
| alternative routes of blood flow due to increased portal pressure from cirrhosis |
|
|
Term
| Treatment goal of portal HTN/varices |
|
Definition
Goal: prevent variceal bleed
If rupture: GI bleed, hematemesis |
|
|
Term
| What pressure difference (between portal vein and vena cava) is usually seen that puts patients at risk for variceal bleeding? |
|
Definition
~12 mmHg
portal venous pressure > vena cava pressure |
|
|
Term
| Treatment of portal HTN and varices depends on what? |
|
Definition
stage of disease:
1. Primary prophylaxis - prevent first bleed
2. Treatment of variceal hemorrhage (acute tx)
3. Secondary prophylaxis: prevent rebleeding in patients who have already had a bleed |
|
|
Term
| Possible treatment options for primary prophylaxis of variceal bleeding |
|
Definition
Nonselective beta-blocker (Propranolol, Nadolol) Endoscopic Band Litigation (EBL) Endoscopic Injection Sclerotherapy (EIS) Selective beta-blockers - carvedilol: larger decrease in BP, which patient might not be able to tolerate as well
varical bleeding is often caused by portal HTN - so address cause |
|
|
Term
| Name 3 things that can put someone at high risk for variceal bleeds |
|
Definition
|
|
Term
| What is the controversial treatment of variceal bleeds in cirrhotic patients? |
|
Definition
| Nitrates - no longer recommended as an alternative or adjunctive therapy to beta blockers |
|
|
Term
| What is generally the first line treatment for prophylaxis of variceal bleeds? |
|
Definition
non-selective beta-blockers
(propranolol, nadolol)
MOA: decrease CO, portal vein pressure; splanchnic nerve vasoconstriction via beta-2 (good because forces blood to flow where it is supposed to)
Prevents bleeding by 25-50% (DOES NOT PREVENT VARICES)
Associated with reduced mortality |
|
|
Term
| T or F: non-selectve beta-blockers prevent varices the best |
|
Definition
| F - the do NOT prevent varices - they only decrease risk of bleeding |
|
|
Term
| Which is better for compliance: nadolol or propranolol? |
|
Definition
| nadolol - QD vs propranolol (BID-TID) |
|
|
Term
| How are beta-blockers dosed for cirrhosis? |
|
Definition
Titrate to heart rate (as tolerated)
Reduce resting HR by 20-25%
Absolute HR of 55-60 bpm
Will be on beta-blocker for life as long as it is tolerated |
|
|
Term
| What is endoscopic band litigation (EBL) |
|
Definition
The placement of rubber bands around varices (found with cirrhosis)
-For bleeding prophylaxis and to control bleeding
-varix will slough off after 72 hours
Should do in conjunction with med therapy |
|
|
Term
| What are two non-drug therapy options for the prophylactic treatment of varices in cirrhosis? |
|
Definition
1. Endoscopic Band Litigation (EBL)
2. Endoscopic Injection Sclerotherapy (EIS) |
|
|
Term
| What is the difference between primary and secondary prophylaxis for variceal hemorrhage |
|
Definition
Primary - prevent the first bleed
Secondary - prevent a re-bleed |
|
|
Term
| For acute variceal hemorrhage, what are the goals of thereapy? |
|
Definition
Maintain Hgb of ~8
Correct coagulopathy and thrombocytopenia (this is a hemodynamic issue)
Control bleeding |
|
|
Term
| In addition to drugs, what else is given to patients with acute variceal hemorrhage? |
|
Definition
| Colloids and blood products (helps maintain blood volume and a Hgb ~8 |
|
|
Term
| What are some ways that we can control bleeding in acute variceal hemorrhage? |
|
Definition
Endoscopic band litigation
Endoscopic injection sclerotherapy
Vasoactive drugs: OCTREOTIDE, somatostatin, terlipressin, vasopressin |
|
|
Term
| What endoscopic injection sclerotherapy (EIS)? |
|
Definition
| Injection of sclerosing agent into varices (can be done in combination with Endoscopic Band Litigation for variceal bleeding prophylaxis and control |
|
|
Term
| MOA of vasoactive drugs for variceal bleeding |
|
Definition
Splanchinic vasoconstrictors
-decrease portal blood flow and thus reduce pressure |
|
|
Term
| What type of patients are esophageal varices usually seen in? |
|
Definition
|
|
Term
| Recurrence rate is ____ (high/low) for esophageal varices. |
|
Definition
| HIGH - most people will die within 5 years of initial bleed |
|
|
Term
| T or F: a patient with alcoholic liver disease who is at risk for esophageal varices will greatly decrease their risk of a variceal bleed if they stop drinking. |
|
Definition
| F - it might improve their condition, but for the most part the damage is already done. |
|
|
Term
| What is the first line drug therapy for esophageal bleed? |
|
Definition
Octreotide
Available alternatives: Vasopressin
(Terlipressin not in US yet) |
|
|
Term
Octreotide is an analog of what?
Terlipressin is an analog of what? |
|
Definition
Somatostatin Analog (O)
Selective-Vasopressin Analog (T) |
|
|
Term
| When should octreotide be given for variceal bleeding? |
|
Definition
As soon as a bleed is suspected
-It should be continued 3-5 days after diagnosis is confirmed |
|
|
Term
| Why isnt somatostatin used (versus octreotide) for variceal hemorrhage? |
|
Definition
Somatostatin isnt available in the US
Octreotide has a much longer half-life (somatostatin ~2-3 min, O: ~90 min) |
|
|
Term
| What is the best approach when a variceal bleed is suspected? |
|
Definition
| Do endoscopy and drug therapy (octreotide) |
|
|
Term
| Vasopressin is an alternative agent for variceal bleeding. Why isn't it commonly used? |
|
Definition
Hemodynamic side effects
It is a potent nonselective vasoconstrictor
ADR: HTN, HA, coronary ischemia
-DO NOT use for >24 hours (to minimize ADRs)
Must always be given with IV NTG to control BP
(Dose: CI 0.2-0.8 U/min) |
|
|
Term
| How is octreotide given in variceal bleeding? |
|
Definition
IV 50-100 mcg bolus then 25-50 mcg/hr CI
SQ intermittent
First line, but unlabeled use |
|
|
Term
| What is the only drug for variceal hemorrhage control to have shown a decrease in mortality? |
|
Definition
| Terlipressin - why people are so anxious to get it in US |
|
|
Term
| Is their an advantage to combination therapy with octreotide and a PPI when variceal bleeding is confirmed? |
|
Definition
| NO - discontinue the PPI unless otherwise indicted |
|
|
Term
| T or F: All patients with active variceal bleeding should receive prophylactic antibiotics? |
|
Definition
|
|
Term
| What type of bacteria should be targeted when prophylactically treating a variceal bleed with ABX? |
|
Definition
| Gram negative bacteria common to the gut (close proximity) |
|
|
Term
| What are the usual antibiotic agents used for infection prophylaxis in variceal bleeding? |
|
Definition
Norfloxacin, Cipro, (Levo) - FQ
-BID x 7 days (IV or PO)
-Norfloxacin is the most studied)
If advanced cirrhosis can use Ceftriaxone 1 gm/day IV
-may be more effective (FQ resistance) |
|
|
Term
| Which type of infection are people with variceal bleeds most likely to get? |
|
Definition
Spontaneous Bacterial Peritonitis (SBP)
-Infection is associated with early recurrence of variceal hemorrhage and greater mortality. |
|
|
Term
| What is the general treatment for secondary prophylaxis of variceal bleeding? |
|
Definition
Beta blockers (Propranolol or Nadolol) + EBL/EIS (endoscopy prodecures)
IF THIS FAILS: TIPS or shunting are alternatives |
|
|
Term
| What does TIPS stand for and what is it? |
|
Definition
Transjugular Intrahepatic Portosystemic Shunting
Stent(s) between portal vein and hepatic vein -- reduces pressure |
|
|
Term
| What are some complications that are common with TIPS procedures? |
|
Definition
Encephalopathy (30%)
Shunt malfunction (50%) |
|
|
Term
| Who is TIPS indicated for? |
|
Definition
When hemorrhage from esophageal varices cannot be controlled
When bleeding recurs despite combination of drug and endoscopic therapy |
|
|
Term
| What is balloon tamponade? |
|
Definition
| used as a temporizing measure (max 24hr) in patients with uncontrollable bleeding for whom a more definitive therapy (ex: TIPS or endoscopy) is planned |
|
|
Term
| What is EGD (Esophagogastroduodenoscopy) |
|
Definition
| performed within 12 hours, used to make diagnosis and treat variceal hemorrhage, either by EVL or sclerotherapy (or both) |
|
|
Term
| What are two types of Endoscopic treatments for variceal bleeding? |
|
Definition
EVL (endoscopic variceal ligation) mechanical ligation and strangulation by application of small, elastic O rings
Sclerosing agents (different chemicals) used to vasoconstrict vessels and stop blood flow
Can do both by sclerosing then EVL |
|
|
Term
| What is hepatic encephalopathy and how does it develop? |
|
Definition
It is a CNS disturbance
Shunting of blood bypasses the liver (so it doesnt get filtered/material doesnt get metabolized) -->accumulation of gut-derived nitrogenous substances in systemic circulation (ammonia, glutamate, benzo receptor agonists, manganese) --> nitrogenous substances enter the CNS (affects consiousness and behavior and asterixis [flapping tremor]) |
|
|
Term
| T or F: serum NH3 levels are poorly correlated with severity of hepatic encephalopathy (HE). |
|
Definition
|
|
Term
| Name 3 general treatment options for hepatic encephalopathy. |
|
Definition
1. Lactulose (first line)
2. Antibiotics - add on therapy; if cant tolerate lactulose, this might be the only thing left
3. Limit excess protein in diet (<10-20 gm/day) **dont want to trade of nutrition for this, because these patients are usually so sick, dont usually do this. |
|
|
Term
| Lactulose MOA and dosing for HE |
|
Definition
MOA: [1] cathartic and [2] acidifies gut - lowers blood NH3 by altering bacterial metabolism (less protein degradation)
Dosing: Titrate to 4 BM (3-5 ok) per day
-start at 45 mL q1h, then titrate |
|
|
Term
| What antibiotics can be used to treat HE and what is their MOA (general)? |
|
Definition
Rifaximin 400 mg PO TID (550 BID) - to reduce recurrence * MOST USED NOW (b/c few ADR)
Metronidazole 500 mg PO TID
Neomycin 3-6 gm QD x1-2weeks during acute HE
Inhibit activity of urease producing bacteria |
|
|
Term
| Major ADR with Metronidazole? |
|
Definition
| Neurotoxicity b/c impaired hepatic clearance |
|
|
Term
| Most used antibiotic used in hepatic encephalopathy |
|
Definition
Rifaximin
b/c few ADRs and drug interactions |
|
|
Term
| What are the ADRs/drawbacks of using neomycin for HE treatment? |
|
Definition
ototoxicity, nephrotoxicity, staph superinfections
Especially with chronic use |
|
|
Term
|
Definition
accumulation of lymph fluid in the peritoneal cavity
-Distended abdomen
-Clinically detected when 1.5 L+ is present (detected by ultrasound)
-One of the most common presentations of cirrhosis |
|
|
Term
| T or F: Ascites is a low mortality complication of cirrhosis |
|
Definition
F - poor prognosis
Cirrhosis: 50% will develop acsities in 10 yrs
Ascites: 50% will die in next 2 years
**Consider transplant once develop ascities with cirrhosis |
|
|
Term
| Pathophysiology of ascites - how does it develop? |
|
Definition
Portal HTN -->Vasodilation/NO (to compensate) --> Hypotension/RAAS activation (Na saving) --> Water retention (fewer ions in blood so fluid goes to tissues/spaces)
Other contributing factors: increased lymph productions/leakage; decreased albumin; decreased plasma oncotic pressure |
|
|
Term
| What is done to correct ascites? |
|
Definition
1. NO alcohol
2. Sodium restriction (2 gm/day) - no fluid restriction unless hyponatremic (<120-125)
3. Diuretics
4. Large Volume Paracentesis (LVP) |
|
|
Term
|
Definition
Serum Ascites Albumin Gradient
-Serum albumin - ascitic fluid albumin
-If SAAG> 1.1 ->portal HTN (97% accurate)
Important because other things besides liver issues can lead to ascites |
|
|
Term
| What two diuretics are commonly used to treat ascites and what are the doses? |
|
Definition
Spironolactone 100 mg QD
Furosemide 40 mg QD
-combo used to target natiuresis and prevent hypokalemia
*Can increase both, but MAINTAIN RATIO OF 100:40 (Max: 400:160)
NOTE: if only use one, use spironolactone |
|
|
Term
| What is the target goal when using diuretics to treat ascites? |
|
Definition
Goal = maximum daily weight loss of 0.5 kg
-Initially can be greater |
|
|
Term
| What might indicate overdiuresis in ascites - would need to HOLD DIURETICS |
|
Definition
SCr>2 or [Na] <120 mEq/L
can cause prerenal kidney impairment |
|
|
Term
| What should be give post-paracentesis to decrease reacumulation of fluid in the abdomen in ascites? |
|
Definition
|
|
Term
| If you remove more than _____ (amount) of fluid in paracentesis, albumin should be given. |
|
Definition
Over 5 L of fluid - give albumin
(Otherwise it would be like a big decrease in BP and lead to low perfusion, especially to kidneys) |
|
|
Term
| If albumin is required in patients undergoing paracentesis, what is the dose? |
|
Definition
| 6-8 gm/L of fluid removed |
|
|
Term
| How does someone with cirrhosis develop peritonitis (SBP)? |
|
Definition
They have altered gut permeability which makes it easier for organisms to pass thru
Ascitic fluid = greater bacterial growth medium |
|
|
Term
| What are the most common organisms for spontaneous bacterial peritonitis due to cirrhosis? |
|
Definition
E coli (most common)
Klebsiella pneumo
Strep pneumo |
|
|
Term
| How is peritonitis diagnosed? |
|
Definition
Paracentesis
Bacteria present, PMN >250 cell/mm3
-Culture and WBC |
|
|
Term
| Symptoms of bacterial peritonitis |
|
Definition
fever
leukocytosis
abdominal pain
hypoactive/absent bowel sounds
rebound tenderness
CAN BE ASYMPTOMATIC |
|
|
Term
| Who should be treated for peritonitis? |
|
Definition
All patients with ascitic PMN >250 cells/mm3 (regardless of signs and symptoms
All patients with signs and symptoms of infection even if PMN < 250 |
|
|
Term
| Treatments for spontaneous bacterial peritonitis |
|
Definition
Broad spectrum antibiotics
(E.coli, Kleb.pneumo, Strep.pneumo)
IV 3rd gen cephalosporin or FQ -preferrably ceftaxime 2gm Q8H
-Alt: Ofloxacin 400 mg BID (cipro too)
albumin (improves mortality in patients with:
(Scr >1 mg/dl; BUN>30; or total bili >4) |
|
|
Term
| Treatment of SBP (peritonitis) with albumin |
|
Definition
1.5g/kg within 6 hours of admission and 1g/kg on Day 3
*Max dose = 100 gm
Give to patients with atleast one of the following:
-SCr>1mg/dl
-BUN>30mgdl
-Total Bilirubin >4 |
|
|
Term
| Who should receive prophylaxis for SBP? |
|
Definition
All patients who have had an episode SBP
(70% recurrence in 1 yr)
High risk patients |
|
|
Term
| What drugs are usually used for prophylaxis for SBP? |
|
Definition
Long term FQ or Bactrim
-FQ most studied
-most of these patients are prone to renal dysfunction and drs may be hesitant to use bactrim
Daily dosing (vs. intermittent) to prevent resistance |
|
|
Term
| Who are high risk patients for SBP? |
|
Definition
1. Prior variceal bleed + low protein ascites (<1gm/dL)
2. If cirrhosis and ascites:
If ascitic protein <1.5 g/dL and at least 1 of the following:
-SCr of 1.2+mg/dl
-BUN of 25+ mg/dl
-Na of 130 or less
-Child-Pugh of 9+ with bili of 3+ |
|
|
Term
| What is hepatorenal syndrome and how does it develop? |
|
Definition
Renal failure do to cirrhosis (2 types)
Caused by vasoconstriction to kidneys --> decreased renal perfusion
Risk Factors: refractory ascites, SBP, large volume paracentesis without albumin replacement
affects 40% of people with cirrhosis and ascites in 5 years |
|
|
Term
| What are three indications of albumin in cirrhosis related conditions? |
|
Definition
1. Increase oncotic pressure in ascites (6-8g/L removed)
2. SBP (1.5g/kg upon admission, then 1g/kg on day 3)
3. Hepatorenal Syndrome (1m/kg/day initially, then ~20-60g/day thereafter)
-max =100gm |
|
|
Term
| What are some things that can be done to help lessen hepatorenal syndrome in cirrhosis (besides adding drug therapy) |
|
Definition
1. WILL need a transplant - hemodialysis can bridge to transplant (however probably wont last as long as ESRD patients on dialysis)
2. Eliminated concurrent nephrotoxins: NSAIDs, AGs
3. Decrease/discontinue diuretics |
|
|
Term
| What is albumin used for in hepatorenal syndrome (in cirrhotic patients) and what is the dose? |
|
Definition
initial volume expansion
1g/kg/day initially (max = 100gm)
-Maybe 20-60g/day thereafter
-Do NOT use as monotherapy - must use a vasopressor
Terlipressin, NE, Midodrine (commonly seen)
Treatment of choice: midodrine + octreotide (100-200mcg SQ TID) + Albumin |
|
|
Term
In hepatorenal syndrome, why is using a vasopressor useful in treatment?
-Must use it with albumin
-Would think it might decrease renal blood flow further |
|
Definition
The vasoconstrictor will constrict the splanchnic and systemic vasculature
-This INCREASES ARTERIAL PRESSURE (key)
-This in turn decreases RAAS, SNS, ARP (arterial renal pressure)
-Therefore it decreases the vasoconstriction of the renal system, which will increase GFR
-Increased arterial pressure also increases renal perfusion pressure (which increases GFR too!) |
|
|
Term
| What are three options for use of vasopressors to be used for treatment of hepatorenal syndrome? |
|
Definition
1. Terlipressin (0.5-2 mg IV q4-12h): vasopressin analog, safest
2. NE (0.5-3 mg/hr IV): alpha agonism has the vasoconstrictor action; increases GFR (used most in ICU)
3. Midodrine (7.5-15 mg PO TID): alpha agonist |
|
|
Term
| Why does coagulopathy occur in cirrhosis? |
|
Definition
-Hepatocyte loss: less ability to synthesize clotting factors
-Thrombocytopenia |
|
|
Term
| General treatment approach to coagulopathy due to cirrhosis? |
|
Definition
1. Blood products: FFP (fresh frozen plasma) and platelets
2. Vitamin K
**Remember, they cant make these/use these |
|
|
Term
| T or F: coagulopathy does NOT protect against venous TE in patients with chronic liver disease. |
|
Definition
T
Even if INR is good (>2) there was still equal incidence of VTE in patients with liver disease |
|
|
Term
| Cirrhosis can lead directly to [1] portal HTN and [2] liver insufficiency - which complications of cirrhosis do each of these two contribute to? |
|
Definition
Portal HTN:
Variceal hemorrhage
Ascites -->SBP and Hepatorenal syndrome
Liver Insufficiency:
Jaundice
Coagulopathy
BOTH: encephalopathy |
|
|
Term
| What are the two most common etiologies of upper GI bleed? |
|
Definition
1. Esophageal varices (associated with alcoholic liver disease)
2. PUD (NSAID induced or H.pylori) |
|
|
Term
| Which GI bleed has the highest mortality: PUD or esophageal varices? |
|
Definition
|
|
Term
| T or F: a common sign/symptom of all GI bleeds is blood in stools or vomiting blood. |
|
Definition
|
|
Term
| What are common signs/symptoms of a GI bleed? |
|
Definition
Anemia-like
Melena (black, tarry stools, can be upper or lower origin)
Hematochezia (bright red blood per rectum) bleed from diverticulum, other colonic disease, or anal disease
Upper: hematemesis (bright red to coffee grounds color) |
|
|
Term
|
Definition
Usually from esophagus, stomach, duodenum
-PUD: can be asymptomatic until first bleed
-Esophageal varices: due to portal HTN secondary to chronic EtOH consumption
-gastritis (esp from EtOH)
-Mallory-Weiss tear from prolonged retching (generally self-limiting)
-Swallowed blood from epistaxis or other source |
|
|
Term
| Besides bleeding, what are other potential causes of black, tarry stools? |
|
Definition
Ingestion iron
Licorice
Bismuth |
|
|
Term
| What are some causes of hematochezia? |
|
Definition
(Bright red blood per rectum)
Anal disease: hemorrhoids, rectal fissure
Bleeding diverticulum, other colonic disease: Crohn's disease, UC, carcinoma, dysentery (esp amebiasis, Campylobacter, Shigella, and other organisms) |
|
|
Term
| General treatment for lower GI bleeds? |
|
Definition
| Usually more surgical intervention, few drug therapies |
|
|
Term
| Why is it important to know the source of bleeding when a patient presents? |
|
Definition
Will help decide which way to go (through mouth or rectum) when doing an endoscopy.
Also important in deciding what to treat with |
|
|
Term
| What is the 'mainstay' of therapy for GI bleeding due to ulcers? |
|
Definition
| Endoscopy (gold standard for diagnosis and treatment) |
|
|
Term
| T or F: most patients will stop bleeding spontaneously without recurrence with nonvariceal upper GI bleed. |
|
Definition
| T - 80% will stop bleeding spontaneously without recurrence |
|
|
Term
| What are some risk factors that might indicate a patient with a nonvariceal GI bleed may be at high risk for an adverse outcome? |
|
Definition
Clinical Variables: age, shock, comorbid conditions
Lab Variables: Hgb<10 g/dL, coagulopathy
Endoscopic variables (presentation) |
|
|
Term
| What is the typical treatment of a nonvariceal upper GI bleed once diagnosis has been confirmed with endoscope? |
|
Definition
| Cautery (electrocoagulation) of the site of bleeding (must be done with an endoscope, so will treat immediately upon diagnosis) |
|
|
Term
| What are some risks factors for post-endoscopic rebleeding? |
|
Definition
Active bleeding
Visible vessel
Presence of clot
Ulcer size (>2 cm)
Ulcer location |
|
|
Term
| What can/should be given in addition to endoscopy in patients where there is a nonvariceal upper GI bleed expected? |
|
Definition
PPI (IV bolus followed by continuous infusion)
-Can give (high dose PPI) empirically if patient is awaiting endoscopy
Why:
1. Decrease rebleeds (less need for repeat transfusions)
2. Prevent need for surgery/increase healing rate
3. Decrease mortality |
|
|
Term
| Can you use H2RAs in patients with nonvariceal upper GI bleeds? |
|
Definition
|
|
Term
| Can you use somatostating and octreotide (analog) in nonvariceal upper GI bleeds? |
|
Definition
|
|
Term
| What do you need to test for in patients with UGI bleeding |
|
Definition
| H.pylori (and should receive eradication if present) |
|
|
Term
| If it is unknown whether the Upper GI bleed is due to variceal or nonvariceal causes, how should the patient be treated empirically? |
|
Definition
Treat for both:
Endoscopy
PPI (nonvariceal)
Octreotide (variceal)
-D/C whichever one is not needed after endoscopy |
|
|
Term
| What are the goals of post-endoscopic acid suppression with nonvariceal GI bleeds? |
|
Definition
pH>6 (helps maintain clot) - must use much higher PPI dose than us usual
platelet formation and aggregation
Prevention of clot digestion
Inhibit activity of pepsin |
|
|
Term
| Why are PPIs preferred over H2RAs for nonvariceal GI bleeds? |
|
Definition
| PPIs are more effective at keeping pH >6 |
|
|
Term
| What PPIs are commonly used in nonvariceal upper GI bleeds? |
|
Definition
Data only for IV omeprazole
Can use pantoprazole (used most in US, but not indicated for this)
-80 mg bolus then 8mg/hr CI |
|
|
Term
|
Definition
| symptoms or mucosal damage produced by the abnormal reflux of gastric contents into the esophagus. |
|
|
Term
| T or F: with GERD, symptoms are well-correlated with the degree of tissue damage/complications |
|
Definition
| F - symptoms are poorly correlated with degree of tissue damage |
|
|
Term
| What are some mechanisms by which meds that exacerbate GERD? What some examples? |
|
Definition
Decrease LES tone: anticholinergics, dihydropyridine CCBs, barbiturates, estrogen and progesterone, opioids, theophylline
Direct Contact Irritants: ASA, Iron, NSAIDs, KCl, Bisphosphonates |
|
|
Term
| What are some lifestyle causes of GERD? |
|
Definition
Diet: EtOH, Fat, peppermint, caffeine, chocolate, tomato products (acid)
Smoking
Pregnancy
Running
Tight Clothes
Lifting
Obesity |
|
|
Term
| What are some complications that can develop from GERD? |
|
Definition
1. Esophagitis which can lead to Esophageal stricture
2. Esophageal bleeding and ulceration
3. Barrett's Esophagus
4. Esophageal adenocarcinoma |
|
|
Term
| What is the prevalence of Barrett's esophagus amongst those with chronic reflux? |
|
Definition
| 5-15% of chronic reflux patients |
|
|
Term
| Describe Barrett's Esophagus |
|
Definition
Normal squamous epithelium is replaced with specialized columnar epithelium
1/250 will develop adenocarcinoma of esophagus if have Barrett's esophagus |
|
|
Term
| What are some typical and atypical symptoms of GERD (aka NOT alarm symptoms)? |
|
Definition
Typical:
-Heartburn/retrosternal pain
-Acid or food regurgitation
-Dyspepsia
Atypical:
-Pulmonary symptoms
-Dental erosions
-Hoarseness (vocal chords)
-Chest pain (may need to rule GERD out if suspecting something else) |
|
|
Term
|
Definition
GI Bleeding
Early satiety
Dysphagia or odynophagia (painful eating)
Unexplained weight loss
Iron deficiency anemia
Vomiting |
|
|
Term
| What are some diagnostic tests that can be done to determine GERD? |
|
Definition
Endoscopy
Upper GI radiography
H.pylori testing
pH testing
Therapeutic trial
Barium swallow test |
|
|
Term
| What is the step-up and step-down therapy for GERD and when do you chose one over the other? |
|
Definition
Lifestyle modifications < Antacids < H2RA < PPI < Surgery
If severe start with PPI then go down, and if mild start at lifestyle modifications then go up if still need more |
|
|
Term
| Possible lifestyle modifications for GERD |
|
Definition
Smaller, more frequent meals (avoid eating close to bedtime ~3hr)
Elevate head of bed ~6-8 inches
Avoid foods that lower LES tone (chocolate, fats, peppermint, caffeine, acidic juice)
Lose weight, avoid tight clothes
Reduce/eliminate alcohol and smoking
Dont recommend everything at once, just a bit at a time |
|
|
Term
| Potential drug interactions with antacids? |
|
Definition
Tetracyclines
Quinolones
Levothyroxine
Isoniazid
Sulfonylureas |
|
|
Term
|
Definition
Constipation (Ca and Al)
Diarrhea (Mg)
Acid rebound with Ca-containing agents |
|
|
Term
| T or F: antacids affect acid secretion. |
|
Definition
F - no effect on acid secretion
They neutralize gastric acid, inactivate pepsin |
|
|
Term
| What cells produce HCl in the stomach and what stimulates its secretion? |
|
Definition
Parietal cells
Stimulated by: histamine, acetylcholine, and gastrin |
|
|
Term
| What is the final step of gastric acid secretion and what drug class acts at this step? |
|
Definition
H/K ATPase pump
PPIs inhibit this
This is why they are a more effect at acid secretion than H2RAs which only inhibit one (of the three [histamine, Ach, gastrin]) pathways of acid secretion |
|
|
Term
| Over a long period what often develops with H2RA use? |
|
Definition
| tachyphylaxis (decrease in response with prolonged use at same dose) |
|
|
Term
| What are potential drug interactions to watch for with H2RAs? |
|
Definition
Warfarin, Phenytoin, Alcohol, and Theophylline
(+some have different enzymes they inhibit - ex: cimetidine) |
|
|
Term
| What are some ADRs associated with H2RAs? |
|
Definition
Generally well-tolerated
HA, dizziness, constipation/diarrhea, somnolence |
|
|
Term
| What is the drug of choice for healing esophagitis? |
|
Definition
|
|
Term
| What is the goal pH for PPI use in the treatment of GERD? |
|
Definition
|
|
Term
| What time of day should PPIs be taken? |
|
Definition
|
|
Term
|
Definition
HA
diarrhea
constipation
abdominal pain
Long-term potential risks: increased fractures, gastroenteritis, C.diff risk doubles
Consider dose reduction in severe hepatic disease |
|
|
Term
| Drug interactions with PPIs? |
|
Definition
Clopidogrel
Atazanavir
Itraconazole
Iron |
|
|
Term
| What are some promotility agents? |
|
Definition
Metoclopramide
Cisapride
Domperidone (not in US) - increases LES tone
may be considered as adjuncts in GERD |
|
|
Term
| Why is metoclopramide not used as much in GERD? |
|
Definition
| QID dosing and limited by CNS effects |
|
|
Term
| Why is cisapride not used very much in the treatment of GERD? |
|
Definition
|
|
Term
| Who gets PUD more, men or women? |
|
Definition
| Equal prevalence but affects the elderly more |
|
|
Term
| Does PUD have a high level or recurrence? |
|
Definition
|
|
Term
|
Definition
group of ulcerative disorders of the upper GI tract that require acid and pepsin for their formation
Deeper into the mucosa than gastritis and other erosions |
|
|
Term
| What is the overall cause of PUD? |
|
Definition
1. Disruption of mucosal defenses
-Mucus and bicarbonate secretion
-Intrinsic epithelial defense
-Mucosal blood flow (Ex: hyperemia)
-Prostaglandin synthesis by COX-1/-2
2. Disruption of mucosal repair mechanisms (restitution, growth, regeneration) |
|
|
Term
| What are the three major classifications of PUD? |
|
Definition
1. H.pylori associated
2. NSAID-induced
3. Stress ulcers (common in ICU) |
|
|
Term
| Which type of PUD is associated with the most pain? |
|
Definition
| H.pylori associated (epigastric pain) |
|
|
Term
| Which of the classifications of PUD has the most severe GI bleeding? |
|
Definition
BOTH NSAID and Stress-related ulcers
NSAID has the deepest ulcers
(H.pylori is less severe) |
|
|
Term
| Where do H.pylori PUD and NSAID PUD commonly occur |
|
Definition
H.pylori: duodenum> stomach
NSAID: Stomach> duodenum |
|
|
Term
| What is the primary risk factor and other risk factors for PUD associated with H.pylori? |
|
Definition
1. H.pylori (Primary)
2. Smoking
3. Alcohol
4. Diet: Coffee, tea, soda, milk, spices
5. Psychological stress |
|
|
Term
| Describe H.pylori morphology, transmission, how it lives in stomach. |
|
Definition
Spiral-shaped, pH sensitive, G-, anaerobic bacteria with flagellum
Transmitted via fecal-oral
Flagellum allows it to burrow into neutral mucus layer of GI tract and releases ureases to survive low pH
-It isnt removed via cell turnover or mucus production |
|
|
Term
| Pathophysiology of H.pylori PUD (how it causes ulcers) |
|
Definition
1. Directly damages mucosal layer (burrows)
2. Alters host immune/inflammatory response
3. May increase acid production
4. May enhance carciogenic conversion of susceptible gastric epithelia
5. Gastric PAIN |
|
|
Term
| What are some diagnostic tools used for PUD? |
|
Definition
1. Endoscopy
-Histology is the gold standard (but invasive)
-Biopsy urease is test of choice (still invasive and painful)
-Culture - used to determine sensitivities after 2nd failure (slow)
2. Non-endoscopy
-Antibody Detection (Lab) - better than office test
-Antibody Detection (Office) - faster
-Urea Breath Test - 95% sensitivity for active infection (better than antibody detection)
-Stool Antigen use to confirm eradication |
|
|
Term
| What is the ideal treatment of H.pylori? |
|
Definition
3 drug regimen: PPI + Abx1 + Abx2
PPI + Clarithromycin + Amox OR Metronidazole
ALL BID x 10-14 days (except PPI) |
|
|
Term
| What is the alternative treatment for H.pylori PUD? |
|
Definition
Four drug regimen
PPI or H2RA
Bismuth Subsalicylate
Metronidazole
Tetracycline, Clarithromycin, or Amoxicillin
All QID x 7 days (except PPI) |
|
|
Term
| When deciding on a treatment regimen for H.pylori PUD, which antibiotic has been found to be less effective than others? |
|
Definition
Amoxicillin
Tetracycline and Clarithromycin are better to combo with Metronidazole |
|
|
Term
| How do NSAIDs induce PUD (aka ulcers)? |
|
Definition
1. They inhibit PG synthesis (by blocking COX-1/2)
2. Directly irritate epithelia (due to acidic properties - ASA is the worst) |
|
|
Term
| T or F: Enteric coated NSAIDs will be less likely to cause an ulcer. |
|
Definition
|
|
Term
| What the the most common presentation of a PUD due to NSAIDs |
|
Definition
Asymptomatic
must be aware of signs of underlying bleeding |
|
|
Term
| Which are more likely to cause PUD, non-selective or selective NSAIDs? |
|
Definition
| Non-selective NSAIDs cause it more frequently but either type is capable of causing PUD |
|
|
Term
| What is the treatment of NSAIDs related PUD? |
|
Definition
1. D/C NSAIDs (if can NOT do this, then decrease dose, change to selective COX-2 inhibitor, or ADD a PPI)
2. ADD PPI, H2RA, or Sucralfate
-Decrease acid to promote healing
-PPI is the fastest |
|
|
Term
| What should be used to prevent ulcers in the future (prophylaxis)? |
|
Definition
PPIs
H2RAs (only good for duodenal ulcer prevention)
Misoprostal 200 mcg QID (limited by diarrhea and cramping) |
|
|
Term
| About how many people in the ICU will develop a stress ulcer in less than 24 hours? |
|
Definition
>75%
This will increase length of stay |
|
|
Term
| Who should get prophylaxis for Stress ulcers in the ICU? How should they be treated? |
|
Definition
1. Intubated >48 hr
2. coagulopathy
3. 2+ risk factors (Ex: burns, sepsis, HF, acute renal failure)
Usueally if a patient in the ICU is extubated many of their previous risk factors for stress ulcer have resolved and they can be taken off the PPI (or whatever med was added for prophylaxis)
Treat them prophylactially - ex: PPI or H2RA; sucralafate [mucosal protectant] |
|
|
Term
| What are some additional risk factors/meds that a patient may be one that will increase their risk for NSAID associated PUD? |
|
Definition
1. Concomitant use of ASA
2. Age >60
3. 2x increased risk when used with corticosteroids
4. Anticoagulants
5. SSRIs (unknown why, but can potentially promote bleeding)
Consider adding a PPI if these risk factors and patient is on an NSAID |
|
|
Term
| What are some complications seen with PUD? |
|
Definition
1. GI Bleed
2. Perforation: sudden pain, potentially masked in elderly
3. Obstruction: usually takes about 4 months to develop; associated with early satiety, anorexia, bloating, N/V
4. Gastric Cancers |
|
|
Term
| T or F: PPIs limit gastric acid secretion of a dose dependent basis. |
|
Definition
|
|
Term
| What might you be concerned with if someone is planning on stopping Nexium after long-term use? |
|
Definition
| Rebound hypersecretion of gastric acid |
|
|
Term
| If you want to use an H2RA for prophylaxis for PUD, how can it be dosed? |
|
Definition
Can do QD dosing after dinner or at bedtime
But can also dose multiple times a day for daytime pain |
|
|
Term
| When might you need to decrease the dose of an H2RA? |
|
Definition
|
|
Term
| Why must sucralfate be taken on an empty stomach? |
|
Definition
It will prevent binding to dietary protein/phosphate
MOA: coats the stomach |
|
|
Term
| What are some medications that interact with sucralfate? |
|
Definition
Will decrease bioavailability of:
FQ, Phenytoin, Digoxin, Warfarin |
|
|
Term
|
Definition
Constipation
Beozar formation (accumulation of food in stomach)
Potential for seizure in dialysis patients (in combo with aluminum antacids) |
|
|
Term
| MOA of misoprostol for ulcer protection |
|
Definition
Moderately inhibits acid secretion and enhances mucosal effect (like normal prostaglandins in GI)
Ulcer dosing: 200 mcg QID or 400 mcg BID |
|
|
Term
| What are some precautions/ADRs with misoprostol |
|
Definition
-Dose dependent diarrhea, abdominal pain, nausea, flatulence, HA
Preg Cat X: must have a documented pregancy test within 2 weeks |
|
|
Term
| What two actions does Bismuth have to help with GI ulcers? |
|
Definition
1. Local antibacterial effect
2. Gastroprotective: antisecretory, anti-inflammatory |
|
|
Term
| What are some precautions/ADRs seen with bismuth? |
|
Definition
Black tongue or stool
Tinnitus
N/V
Caution in renal failure and with salicylate therapy (ex: no kids, caution with ASA use)
Increases anticoagulation effect
Decrease tetracycline absorption |
|
|
Term
| What are the two different salt forms of bismuth? |
|
Definition
Subsalicylate
Subcitrate potassium |
|
|
Term
| What are the potential risk factors for a stress ulcer in the ICU |
|
Definition
Patient will need two of these risk factors to get treated prophylactically for ulcers (or be intubated or coagulopathy)
hypotension
sepsis
hepatic failure
acute renal failure
multiple trauma; head or spinal cord injury
history of GI bleed
severe burns (>35%) |
|
|
Term
|
Definition
| Increased frequency and decreased consistency of fecal discharge as compared to an individuals normal bowel pattern |
|
|
Term
| How is the duration of diarrhea classified |
|
Definition
Acute < 3 days
Chronic >14 days |
|
|
Term
| What is the most common cause of acute diarrhea? |
|
Definition
Bacteria
Shigella, Salmonella, Staph, E.coli, Campylobacter |
|
|
Term
| What are the four types of diarrhea? |
|
Definition
Secretory
Osmotic
Exudative
Altered intestinal transit time |
|
|
Term
| What are some potential mechanisms for diarrhea pathophysiology? |
|
Definition
1. Change in active ion transport
2. Change in intestinal motility
3. Increase in luminal osmolarity
4. Increase in tissue hydrostatic pressure |
|
|
Term
| Pathophysiology of secretory diarrhea |
|
Definition
INCREASED secretions and DECREASED absorption of large amounts of water and electrolytes
Etiology: PANCREATIC tumor, unabsorbed dietary fat, hormones, bacterial toxins, excessive bile salts
-BIG stool volume
-Fasting does NOT help |
|
|
Term
| Pathophysiology of osmotic diarrhea |
|
Definition
DECREASED absorption of substances which increases intestinal fluid
Etiology: Malabsorption, lactose intolerance, Meds (ex: Mg, lactulose), unabsorbed dietary fat
-Fasting helps fix problem |
|
|
Term
| Pathophysiology of exudative diarrhea |
|
Definition
INCREASED mucus, protein, exudate, and blood in gut
Etiology: inflammatory diseases (IBS, Crohns, UC, Celiac Disease) |
|
|
Term
| Pathophysiology of altered intestinal transit diarrhea |
|
Definition
Chyme moves too quickly through the gut for components to be absorbed due to INCREASED peristalsis or altered anatomy
Etiology: Gastric bypass, short gut syndrome, DM, Meds (ex: metoclopramide) |
|
|
Term
| What medications can cause diarrhea? |
|
Definition
Laxatives
Mg-containing meds (antacids)
Anti-neoplastics: Ironotecan, capecitabine, cisplatin, 5-FU (their dose limiting toxicity is diarrhea)
ABX: Clindamycin (Black Box), Broad spectrum
Central-acting anti-HTN
Cholinergics
Colchicine
Anti-arrhythmics
NSAIDs
Misoprostol (increases contractions)
PPI/H2RA (altered flora)
Narcotic withdrawal |
|
|
Term
| Complications from diarrhea |
|
Definition
Dehydration
Vitamin deficiencies
Electrolyte abnormalities: hypo-K, bicarb wasting |
|
|
Term
| If someone is dehydrated what fluid replacement should and should not be used? |
|
Definition
Pedialyte and WHO solution is good
(Gatorade + water in a 1:1 is ok)
NOT apple juice |
|
|
Term
| T or F: if a patient presents with diarrhea they should not eat for 24 hours. |
|
Definition
F - only d/c food and milk if patient has known osmotic diarrhea
NEVER stop feeding kids |
|
|
Term
| How is dehydration classified? |
|
Definition
Based on body weight loss
4-5% loss: Mild - home treatment
6-9% loss: Moderate - seen by doctor
>10% loss: Severe - may need IV fluids and electrolytes
Fluid deficit = Wt loss (kg) x 1000 mL/kg |
|
|
Term
| What are some alarm symptoms that would indicate a patient would need to be seen if they have diarrhea? |
|
Definition
FEVER
vomiting blood
dramatic weight loss
Do not treat these patients symptomatically - figure out underlying cause |
|
|
Term
| Which two nutrients/ions still get absorbed even when a patient has diarrhea? |
|
Definition
glucose and sodium
giving a fluid replacement solution that has enough of both of these components can help decrease some of the water in the GI tract |
|
|
Term
| What is the MOA of the opiate derived anti-diarrheals? What are some examples? |
|
Definition
Inhibits peristalsis, prolongs transit time, increases gut capacity
Loperamide, Diphenoxylate/Atropine, Opiate tincture |
|
|
Term
| What is the typical dosing schedule for loperamide and how is it different for chemo patients? |
|
Definition
Normal: 4 mg initially, the 2 mg after each loose stool Max of 16mg/day
Chemo: 4 mg then 2 mg q2h until 12 hours have passed without a loose stool (NO MAX) |
|
|
Term
| What is first line for the treatment of diarrhea? |
|
Definition
|
|
Term
| Lomotil: dose, administration |
|
Definition
Diphenoxylate 2.5 mg/Atropine 0.025 mg: 5 mg QID Max of 20mg/day
C-V
Atropine present to deter abuse |
|
|
Term
| ADRs with opioid derived anti-diarrheals |
|
Definition
Dizziness
Constipation
Atropinism: blurred vision, dry mouth, urinary hesitancy
Potential addiction |
|
|
Term
| What are absorbents used for and what are some examples? |
|
Definition
Diarrhea treatment
MOA: absorb nutrients, toxins, drugs, and digestive juices
Polycarophil (Fiber-Con), Kaolin-Pectin |
|
|
Term
| Besides bismuth subsalicylate, what is another drug that can be used for diarrhea that has an antisecretory agent? |
|
Definition
Octreotide
MOA: synthetic analog of somatostatin, inhibits secretion of gastrin, VIP, and secretin + decreases splanchnic blood flow |
|
|
Term
| What is octreotide's role in the treatment of diarrhea? (including ADRs) |
|
Definition
Symptomatic treatment of carcinoid tumors/peptide-secreting tumors (pancreatic)
IV only
ADRs: local rxns, reduced dietary fat absorption, cholelithiasis, nausea, abdominal pain |
|
|
Term
|
Definition
Lactobacillus and Bifidobacterium
Evidence of reduction in C.diff and antibiotic associated diarrhea
ADR: flatulence
Wide variation of doses |
|
|
Term
| T or F: most acute cases of diarrhea will not require systemic therapy |
|
Definition
| T - usually just rehydration and dietary modifications |
|
|
Term
| T or F: constipation occurs more commonly in women than men |
|
Definition
|
|
Term
| T or F: constipation increases with age |
|
Definition
| Not necessarily, but self-reported laxative use has been shown to increase with age (and with sex(female), number of meds, abdominal pain, and hemorrhoids) |
|
|
Term
| T or F: constipation is a disease |
|
Definition
| F - it is usually a symptom of an underlying problem |
|
|
Term
| What are some possible etiologies (causes) of constipation |
|
Definition
Lack of fiber
GI disorders: IBS, tumors
Metabolic and endocrine disorders (DM, hypothyroid)
Pregnancy
Neurogenic causes (spinal cord injury)
Psychogenic causes
Medication induced |
|
|
Term
| What are some drugs that can cause constipation? |
|
Definition
Opiates
Anticholinergics (Antihistamine, Anti-parkinsonians, TCAs)
Antacids (Ca, Al)
Also: Fe, NSAIDs, sodium polystyrene (Kayexelate) |
|
|
Term
| T or F: if constipation is acute, then it is mild. |
|
Definition
F - not necessarily
Both acute and chronic constipation can be either mild or severe |
|
|
Term
| What two things are warning signs with constipation and warrant immediate referral to MD? |
|
Definition
-Bleeding
-Severe discomfort |
|
|
Term
| What are some lifestyle modifications that can be implemented for the treatment of constipation? |
|
Definition
Fiber: at least 10-15 gm/day (must treat for atleast 1 month to see improvement)
Increase exercise
Increase fluid intake
Schedule regular and adequate time to respond to the urge to defecate |
|
|
Term
| What constipation agents are fast acting vs slow acting |
|
Definition
Fast (1-6 hr): saline cathartics, PEG-ELS, glycerin
Moderate (6-12 hr): bisacodyl, senna, MgSO4
Long (1-3 Days): Bulk forming agents, emollients, PEG 3350, lactulose, sorbitol |
|
|
Term
| MOA of bulk forming agents |
|
Definition
| increases stool bulk, retention of stool water, rate or transit through intestine faster, increase frequency of defecation |
|
|
Term
| ADRs of bulk forming agents |
|
Definition
Abdominal distention, flatus
Inhibited absorption of meds (space meds either 2 hours before, or 4 hours after)
Watch SUGAR CONTENT for diabetics |
|
|
Term
| What is emollients role in constipation treatment |
|
Definition
| not generally used in the treatment of constipation, but rather for prevention and avoidance of straining |
|
|
Term
|
Definition
emollient
mix of aqueous and fatty materials within the GI tract |
|
|
Term
|
Definition
increased intestinal absorption of some agents
electroyte imbalance |
|
|
Term
| Why is mineral oil not recommended in the elderly? |
|
Definition
can cause lipoid pneumonia (via aspiration)
Other ADRs: decreased absorption of fat soluble vitamins, leakage |
|
|
Term
| MOA and drug class of mineral oil |
|
Definition
MOA: inhibits colonic absorption of water, increases stool weight, decreases transit time, coats stool to allow for easier passage
Lubricant (stool softener) |
|
|
Term
| What are some saline cathartic agents? |
|
Definition
Magnesium citrate
Milk of Magnesia
Sodium phosphate (Fleets)
Enema or PO |
|
|
Term
| Mechanism of saline cathartics |
|
Definition
poorly absorbed ions cause osmontic retention of fluid int he GI tract
Mg stimulates bowel motility and fluid secretion |
|
|
Term
| What are some ADRs of Magnesium Citrate? |
|
Definition
(and other saline cathartics)
Fluid and electrolyte depletion
Caution in renal and CV disease |
|
|
Term
|
Definition
used for constipation
Non-absorbable large molecules results in osmotic retention of fluid in colon and increases peristalsis |
|
|
Term
| Examples of osmotic agents |
|
Definition
Lactulose
Sorbitol
Gylcerin
PEG products (Miralax, PEG 3350) |
|
|
Term
|
Definition
1. Hepatic Encephalopathy (can decrease ammonia content)
2. Constipation
Can be PO or PR
Costly |
|
|
Term
| Which agent for constipation is okay to use in children? |
|
Definition
|
|
Term
| Patients with ________ should use caution when using PEG3350 |
|
Definition
|
|
Term
| What is the role of stimulants in the treatment of constipation? |
|
Definition
| NOT recommended for regular use - may be used in a bowel prep regimen |
|
|
Term
| MOA of stimulants for constipation |
|
Definition
| Stimulate the nerve plexus |
|
|
Term
| What are two stimulant agents used for constipation? |
|
Definition
Bisacodyl (Dulcolax)
Senna (Sennakot): dose dependent on indication (for constipation relief or bowel evacuation) |
|
|
Term
| ADRs of senna and bisacodyl |
|
Definition
| Severe cramping, fluid and electrolyte abnormalities (with chronic use), dependence (can get rebound constipation if d/c) |
|
|
Term
| When should enemas be used for treatment of constipation? |
|
Definition
For simple constipation
Many different kinds
MOA: liquid innfused in the bowel loosens stool |
|
|
Term
|
Definition
Amitiza (Rx only for constipation or IBS-C)
Uses:
Chronic idiopathic constipation: 24mg BID
IBS (constipation type) in females>18: 8mg BID
**Adjust for hepatic dysfunction
In general will decrease bloating and cramping
Pregnancy Category C |
|
|
Term
| What is the MOA of lubriprostone? |
|
Definition
Chloride channel activator
Stimulates chloride-rich intestinal fluid secretion and accelerates GI transit time, delays gastric emptying |
|
|
Term
|
Definition
|
|
Term
| What is methylnaltrexone? |
|
Definition
Relistor (Rx only)
For the treatment of OPIOID-induced constipation in advanced illness receiving pallative care with inadequate response to conventional laxative regimens
Administered SQ with dose based on weight QOD (max of 1 dose/day) |
|
|
Term
|
Definition
| Blocks opioid binding at the mu receptor in the periphery (NOT CNS) |
|
|
Term
| ADRs of methylnaltrexone? |
|
Definition
| Abdominal pain, flatulence, nausea, dizziness, diarrhea |
|
|
Term
| What is initially recommended in IBS-C? |
|
Definition
|
|
Term
|
Definition
Functional bowel disorder characterized by abdominal pain/discomfort and associated with change in bowel habits
-Constipation, Diarrhea, Mixed (equal prevalence) |
|
|
Term
| What is the most common functional bowel disorder? |
|
Definition
IBS
(~10-20% of population, but less than 20% of these seek dr help) |
|
|
Term
| T or F: if someone is diagnosed with IBS, they probably will/have been diagnosed with an anxiety or depression disorder. |
|
Definition
| T - >66% of IBS patients have a diagnosis of these |
|
|
Term
| What three disorders is IBS also linked to? |
|
Definition
1. Fibromyalgia (or chronic fatigue syndrome)
2. Anxiety/Depression
Childhood trauma is also associated with IBS |
|
|
Term
| Possible factors/etiologies that lead to the development of IBS? |
|
Definition
Genetic
Infection
GI motor disturbances - not enough to explain symptoms of abd.pain
Visceral hypersensitivity - leads to sensations of bloating/distention, noted inflammatory mediators present
Abnormal central processing of sensations
Serotonin-Type Reactions: 5HT responsible for secretion, sensation, and motility
Psychological disturbances
Inflammation and bacterial overgrowth
Abuse history
Food
Stress |
|
|
Term
| In what form of IBS are 5HT-3 levels elevated? |
|
Definition
| Diarrheal IBS (increases motility) |
|
|
Term
| What must be present for a diagnosis of IBS ususally? |
|
Definition
|
|
Term
| What are some red flags to look out for when trying to determine if someone has IBS? |
|
Definition
Older age (could be colon cancer)
Family history of colon cancer
Bloody stools
No pain
Weight loss (>10 lb)
Iron Deficiency Anemia
Recent ABX use
Family history (GI cancer, IBD, celiac)
Only nocturnal symptoms of pain and abnormal bowel function
Severe persistent constipation that is unresponsive to treatment |
|
|
Term
| What is the Rome III Criteria? |
|
Definition
Used to identify IBS
1. Symptoms originate for 6 months prior to diagnosis, and are currently active for 3 months
2. Characterization into the constipation, diarrhea, or mixed subtype have also been revised
Supportive symptoms: feeling of incomplete evacuation, mucus in stool, abdominal fullness/bloating, Constipation- <3 BM/week, Diarrhea >3 BM/day
Currently active symptoms must include 2/3: abdominal discomfort relieved upon defacation; onset associated with change in stool frequency; onset associated with change in stool appearance |
|
|
Term
| What are some differential diagnoses that must be ruled out when confirming IBS |
|
Definition
-Malabsorption (intestinal, pancreatic insufficiency)
-Dietary factors (lactose intolerance, fat-contianing/gas-producing foods, caffeine, EtOH)
-IBD
-Infection (bacteria, parasites)
-Psychological disorders (panic, depression)
-Colon cancer
-Misc: HIV, med-related |
|
|
Term
| What are some potential diagnostic tests used in IBS? |
|
Definition
Routine diagnostic testing (CBC, BMP, thyroid function, stool ova and parasites, abdominal imaging) are NOT recommended in typical IBS
-Serologic screening for Celiac sprue (IBS-D, IBS-M)
-Lactose breath test if maldigestion considered
-Colonoscopy if >50
*Also if >50: CBC, electrolyes, LFTs |
|
|
Term
| What are some non-pharmacologic treatments for IBS? |
|
Definition
Avoidance diets + Fiber
Exercise
Psychological therapy |
|
|
Term
| What are some treatment options for IBS-C (constipation)? |
|
Definition
Symptomatic: Bulking agents, laxatives Antispasmodics/Anticholinergics SSRIs
(Tegaserod) Lubriprostone Probiotics (bifidobacterium) |
|
|
Term
| Use of anticholinergics/antispasmodics in the treatment of IBS |
|
Definition
Smooth muscle relaxants via direct anticholinergics
Used for symptomatic pain relief (IBS-D predominant)
Ex: dicyclomine and Hyoscyamine sulfate
NO BENEFIT with diarrhea or constipation
Use PRN or Short Course (Long term use is not adequately studied) |
|
|
Term
| What anti-depressants are used in IBS-C and IBS-D? |
|
Definition
IBS-C: SSRIs
IBS-D: TCAs (think ADR profile- anticholinergic) |
|
|
Term
|
Definition
Used in the treatment of IBS-D (unapproved indication)
Non-absorbable antibiotic (RNA synthesis inhibition) Improves pain and betters GI motility -Associated with persistent improvement in IBS symptoms and QOL measures $$$$$ and not approved for this indication so might be hard to get it covered by insurance |
|
|
Term
| What agents could be used in IBS-D? |
|
Definition
| Antidiarrheals (Loperamide, Diphenoxylate)- dose titrated to reduction of symptomatic diarrhea Antispasmodics/Anticholinergics Rifaximin TCAs Alosetron (Lotronex) Probiotics |
|
|
Term
| Which probiotic is proven to have some benefit? |
|
Definition
Bifidobacterium infantis
Immunomodulating properties, reduce bacterial overgrowth
Improved global symptoms |
|
|
Term
|
Definition
Reduction in visceral pain, altered GI transit time
Can use lower doses than with depression treatment
Also, helps stabilize mood which can improve symptoms and has analgesic properties (facilitates endorphin release thru 5HT and NE) |
|
|
Term
| Role of serotonin in IBS? |
|
Definition
5HT3 receptors play a role in GI motility, sensation, and secretion
-Concentrations are elevated in IBS-D
-Concentrations are decreased in IBS-C |
|
|
Term
| What drug class is Alosetron and what is it used for? |
|
Definition
5HT3 receptor antagonist
Used for IBS-D
Improves diarrhea and global symptoms in women
Recently re-approved for use, but very restricted (REMS) |
|
|
Term
| What is tegaserod and what is it used for? |
|
Definition
5HT4 receptor agonist
Used for IBS-C
MOA: Stimulates increased colonic motility (increased defactory frequency and improved global symptoms and QOL)
**REMOVED FROM MARKET** |
|
|
Term
| When the primary symptom of IBS is pain, what is first line agent and what are some alternatives? |
|
Definition
Antispasmodics
(Alt: TCAs, SSRIs) |
|
|
Term
| When the primary symptom of IBS is diarrhea, what is first line agent and what are some alternatives? |
|
Definition
Loperamide
(Alt: 5HT3 antagonist, TCA) |
|
|
Term
| When the primary symptom of IBS is constipation, what is first line agent and what are some alternatives? |
|
Definition
Fiber
(Alt: Lubriprostone, SSRI) |
|
|
Term
| When the primary symptom of IBS is bloating, what is first line agent and what are some alternatives (both with and without distention)? |
|
Definition
Distention: Dietary manipulation
Without distention: Antispasmodics
Alt: Probiotics/Rifaximin |
|
|
Term
| What is considered unexplained unintentional weight loss that would warrant being seen by a physician? |
|
Definition
|
|
Term
| Which viral hepatitis is/are a chronic infection? |
|
Definition
| Hep B and C are chronic (A is acute) |
|
|
Term
| What is the most common reason for a need of a liver transplant? |
|
Definition
|
|
Term
| What is a HUGE reason for the spread of Hep A, especially in the rest of the world? |
|
Definition
| Contaminated water supply (transmitted oral-fecal route) |
|
|
Term
| What are some HAV risk factors? |
|
Definition
Personal contact: household, daycare, sexual contact
Contaminated water or food sources: food handlers, raw shellfish
Blood exposure (rare): needlestick, IV drug use, transfusion |
|
|
Term
| What are the phases of Hep A infection? |
|
Definition
1. Incubation: ~28 days
2. Preicteric Phase: flu-like symptoms, anorexia, N/V, right upper quadrant pain
3. Icteric Phase: YELLOW, dark urine (orange/brown), acholic stools (gray), worse systemic symptoms, pruritis
4. Fulminant failure (rare) or Recovery
NOTE: kids<6 are often asymptomatic |
|
|
Term
| What are some manifestations of high bilirubin? |
|
Definition
YELLOW
acholic stools (gray)
pruritis (cant fix this with antihistamines) |
|
|
Term
| What do IgM and IgG levels look like during a hepatitis A infection? |
|
Definition
HAV IgM + at onset
HAV IgG + after 3-12 months (long-term immunity) |
|
|
Term
| General treatment of HAV infection? |
|
Definition
Symptomatic relief/supportive care
Avoid hepatotoxic drugs (EtOH, APAP) |
|
|
Term
| What are some things that can be done to prevent the spread of HAV? |
|
Definition
Wash hands
Improve water source handling
No raw foods in endemic areas of the world
IMMUNIZATION |
|
|
Term
| What are the two HAV vaccines? |
|
Definition
|
|
Term
| Effectiveness of the HepA vaccines? |
|
Definition
~90-95% of patients will receive immunity with one shot, but second dose is given to increase likelihood
Doses are given ~6-18 months apart (IM) |
|
|
Term
| Who is recommended to get the HepA vaccine? |
|
Definition
Kids
Travelers
MSM
Drug users
Occupational risk (day care)
Person with clotting factor disorders (need transfusions)
Chronic liver disease |
|
|
Term
| If someone is known to have been exposed to Hep A what can be done for them? |
|
Definition
Give HAV Immune Globulin within 14 days post-exposure
Ex: give to household and other intimate contacts and childcare staff/attendees if a child is known to have this; institutions (hospitals, offices, schools); and common source exposures (ex; food prepared by infected food handler) |
|
|
Term
| What type of ethnicity is Hep B most commonly seen in? |
|
Definition
|
|
Term
| What are some risk factors for contracting HBV? |
|
Definition
-Blood or body fluid transfer!
-Sex
-IV drug abuse
-Perinatal transfer from mom to kid (increased risk of chronic HepB and need of liver transplant compared to those contracting it later)
-Healthcare workers
-Household contact |
|
|
Term
| What body fluids is Hep B most concentrated in? |
|
Definition
High: blood, serum, wound exudates
Moderate: Semen, vaginal fluid, saliva |
|
|
Term
| After contracting Hep B, how long will it take to see signs? |
|
Definition
| 1-6 months (incubation period) |
|
|
Term
| T or F: damage to hepatocytes in HepB is due to the direct effect of toxins of the virus. |
|
Definition
F - damage is related to the body's immune response
-Cytotoxic T-cells lyse infected hepatocytes-->Fulminant failure
(HBV most common cause of fulminant failure) |
|
|
Term
| Who is at greatest risk of complications due to Hep B |
|
Definition
| Patients who get it when they are younger (will have a greater risk of chronic HBV infection and greater risk of hepatocyte carcinoma) |
|
|
Term
|
Definition
| "flapping tremor" - put your arms our straight in front of you and tremor up and down |
|
|
Term
| What are some physical findings seen with HBV presentation? |
|
Definition
-Fatigue, malaise
-jaundice, ascites, encephalopathy
-asterixis
-spider angioma (especially if lots of ascities)
-scleral icteris
(increased INR; decreased platelets) |
|
|
Term
| In an acute HBV infection, what antigens will be present? |
|
Definition
|
|
Term
| In a chronic HBV infection, what antigens will be present? |
|
Definition
HBsAg
HBcAb
HBeAg can be + or -
-if + then the virus is actively replicating
HBV DNA can be + or - |
|
|
Term
| If a patient clears a Hep B infection what will there blood tests (titers) for Hep B look like? |
|
Definition
HBsAb +
HBeAb +
HBcAb +
HBV DNA -
Long term immunity |
|
|
Term
| If someone had an acute infection of Hep B, will they be able to get it again? |
|
Definition
|
|
Term
| If got vaccinated for Hep B, what will a patient's titers look like? |
|
Definition
|
|
Term
| If someone knows they have been exposed to Hep B, what can be done? |
|
Definition
Give Hep B immunoglobulins within 48 hours
(anti-sAg) |
|
|
Term
| Who should be vaccinated for Hep B? |
|
Definition
All infants (after 1991)
Adults at risk (ex: healthcare workers)
Adults can be vaccinated if they wish |
|
|
Term
| What are some criteria considered when deciding to treat for hepatitis B? |
|
Definition
-HBsAg + for >6months (aka chronic infection)
-Persistent elevation in LFTs
-evidence of viral replication (HBeAg, HBV DNA)
-signs of chronic hepatitis on liver biopsy
(treatments mainly inhibit viral replication - so pointless to give if not an active infection) |
|
|
Term
| What are some treatment options for HBV? |
|
Definition
Interferon (alpha-2b) [Intron] 5 mil units SQ/IM QD (or 10 mil units 3xweekly) x16 weeks
-Pegylated IFN preferred now!!
Nucleoside/Nucleotide analogues:
Adefovir
Entecavir
Lamivudine
Telbivudine
Tenofovir |
|
|
Term
| What are some ADRs of Interferon? |
|
Definition
Alopecia
Depression
Mood swings
Insomnia
Impaired concentration
Thyroid alterations
Worsening DM
Autoimmune disorders
Injection site rxns |
|
|
Term
|
Definition
nucleotide analogue that inhibits viral polymerase
Spectrum: HBV, herpes (activity against HIV, but dose nephrotoxic at levels required for HIV) |
|
|
Term
| Resistance with the nucleoside/nucleotide analogues used in HBV |
|
Definition
Adefovir: Resistance rarely seen with first yr of therapy (but more with chronic); used in lamivudine-resistant strains but ADD ON (dont d/c L)
Lamivudine: resistance is common (15-30%)
Telbivudine: do NOT use in lamivudine resistant cases
Tenofovir: can use in Adefovir resistance (b/c much higher dose) |
|
|
Term
| What are patients usually on entecavir for life once they start? |
|
Definition
Discontinuation can cause severe acute exacerbations of Hep B
-if decide to d/c, liver function should be monitored |
|
|
Term
| Black box warning for entecavir |
|
Definition
Potential risk of causing LACTIC ACIDOSIS and severe LIVER ENLARGEMENT with STEATOSIS - which can be fatal
Severe acute exacerbations of Hep B can occur upon d/c'ing therapy |
|
|
Term
|
Definition
| Guanosine nucleoside analogue which is an potent selective inhibitor of Hep B virus |
|
|
Term
| Which two nucleotide/side analogues used in HBV are very similar and shouldn't be used together? |
|
Definition
| Lamivudine and Telbivudine |
|
|
Term
| What other drug is tenofovir similar to? |
|
Definition
Adefovir
Is active against HIV because much higher doses can be used b/c nephrotoxicity is decreased |
|
|
Term
|
Definition
| nucleoside reverse transcriptase inhibitor that inhibits the replication of human retroviruses (spectrum HIV-1, HIV-2, HepB) |
|
|
Term
|
Definition
nuclosdie analogue that inhibits reverse transcriptase and DNA polymerase
(only active against Hep B) |
|
|
Term
|
Definition
Generally it is very safe but can cause:
-pancreatitis
-peripheral neuropathy
-RESISTANCE |
|
|
Term
| T or F: nucleoside analogues will cure Hep B? |
|
Definition
|
|
Term
| Why is Hep C incidence decreased? |
|
Definition
| Screening of the blood bank supply |
|
|
Term
| What is the most common reason for a liver transplant? |
|
Definition
|
|
Term
| What are some risk factors for HCV infection? |
|
Definition
Blood to blood transfer:
-IV drug use
-Transfusion or transplant from infected donor (before 1992)
-Hemodialysis
-Accidental needle stick
-Sex (especially if multiple partners)
-Birth to HCV-infected mother
-Tattoos |
|
|
Term
| Who should undergo HCV Screening |
|
Definition
| -Current or past IV drug use -HIV co-infection -Blood transfusion (before 1992) -Clotting factors prior to 1987 -Hemodialysis -Unexplained ALT increases or evidence of liver disease -Needle stick/exposure -kids born to HCV + mothers -Sexual partners who are HCV + |
|
|
Term
| T or F: HCV has post-exposure prophylaxis, like in HIV? |
|
Definition
|
|
Term
| How does an acute Hep C infection present |
|
Definition
Like other acute hepatitis infections
Flu-like symptoms, N/V, right upper quadrant pain, jaundice |
|
|
Term
| How long will it take to develop cirrhosis from Hep C? |
|
Definition
| ~30 years - long term disease |
|
|
Term
| Who are candidates for HCV treatment? |
|
Definition
-Chronic HCV
-Elevated AST
-Circulating HCV RNA
-Inflammatory or significant fibrosis on liver biopsy
-Compensated liver disease
-Symptomatic cryoglobulinemia (abnormal proteins gel up under cold conditions in the bloodstream) |
|
|
Term
| What are some contraindications to the treatment of HCV? |
|
Definition
-Autoimmune hepatitis
-Decompensated liver disease
-Pregnancy (or unwilling to use contraception)
-Untreated thyroid disease
-Serum creatinine >1.5 mg/dL or on hemodialysis
-Major uncontrolled DEPRESSION
-Severe comorbidities (heart problems, DM, renal failure)
-Solid organ transplant (relative) |
|
|
Term
| What are the types of HCV? |
|
Definition
Genotype-1: more common in US, harder to treat
Genotype-2 and -3
**Require different drugs/dosages |
|
|
Term
| What is the treatment for Genotype-1 HCV infection? |
|
Definition
Peginterferon + Ribavirin (1 g if <75 kg; 1.2 g if >75 kg) x48 weeks
PLUS telaprevir (preferred) 750 mg Q8H x12 weeks OR boceprevir 800mg Q8H (timing varies based on response)
MONITOR for virologic response at 12 weeks |
|
|
Term
| Treatment of HCV Genotypes-2/-3? |
|
Definition
Peginterferon + Ribavirin 800 mg x24 weeks
Ribavirin dose is shorter and shorter overall treatment duration than genotype-1 |
|
|
Term
|
Definition
unknown, but potentially:
-Modulates unknown host cell targets that trigger cytokine changes
-RNA viral mutagenesis to make it a non-survivable virus
-Inhibition of HCV RNA dependent RNA polymerase
Reduces relapse rates and enhances sustained viral response |
|
|
Term
|
Definition
HEMOLYTIC ANEMIA
TERATOGENICITY (male and female)
-HA
-Cough/SOB
-GI: Diarrhea, Nausea, Dyspepsia, Anorexia
-Pharyngitis
-Pruritis
-Rash
-Insomnia |
|
|
Term
| Which type of Interferon is used to treat HCV |
|
Definition
PEG interferon alpha-2a (Pegasys) 180 mcg/week SQ x24-48 weeks (based on genotype)
OR
PEG interferon alpha-2b (PEG-Intron) 1.5mcg/kg/weeks SQ |
|
|
Term
| Which type of PEG interferon is associated with fewer ADRs and what is the one ADR that is more common with that PEG-interferon? |
|
Definition
alpha-2a (Pegasys) - increased risk of neutropenia
(Intron: flu-like sx, rigors, inj rxns, thrombocytopenia/neutropenia - ?) |
|
|
Term
| Benefits of PEG-interferon over interferon? |
|
Definition
1. Enhanced solubility
2. Reduced immunogenicity
3. Increased half-life (makes it 1Qweek)
4. Reduced renal clearance
5. Increased circulation |
|
|
Term
| Is PEG-interferon more or equally effective at treating HCV than regular interferon? |
|
Definition
More effective (~8-10% better)
(along with Ribavirin and telapravir) |
|
|
Term
| How common is it for people with HCV infections to clear the infection on their own? |
|
Definition
|
|
Term
| What needs to be monitored with treatment of HCV? |
|
Definition
1. CBC with differential platelets Q2weeks x1 month then monthly
2. LFTs every 1-2 months
3. Renal panel, blood glucose, A1c, TSH Q3 months
4. Urine pregnancy tests monthly
5. HCV RNA at 4, 12, 24, and 48 weeks |
|
|
Term
| What type of patient is required for telaprevir therapy |
|
Definition
COMPLIANT
For HCV dosed: 750 mg Q8H with food x12 weeks (must take within 1 hour of the dosing schedule) |
|
|
Term
| For HCV, if viral load is undetectable at 4 and 12 weeks, how does the treatment change versus if the viral load was detectable? |
|
Definition
If viral load detectable: continue therapy for 48 weeks
If viral load undetectable at 4 and 12 weeks, then duration in 24 weeks (will get same response) |
|
|
Term
| When treating HCV, how does treatment regimens differ when using telaprevir vs boceprevir? |
|
Definition
Telaprevir starts with start the interferon
Boceprevir: start 4 weeks into treatment with interferon; duration also varies based on response (less preferred because of more complicated regimen) |
|
|
Term
| What are some ADRs of Telaprevir? |
|
Definition
VERY POTENT CYP3A4 inhibitor (ex: tacrolimus is usually 2-5 mg QD, when on telaprevir too, it is dosed 0.5 mg qweek)
-Rash (56%)
-Increased risk of anemia (adds to risk associated with ribavirin |
|
|
Term
| T or F: in previously treated HCV patients a second course of therapy will never be effective |
|
Definition
| F - with telaprevir and boceprevir, sustained virologic response has been seen with untreated and previously-treated patients |
|
|
Term
|
Definition
Potent CYP3A4 inhibitor
-Anemia worsened
-Abnormal taste |
|
|
Term
| Which test will detect lower levels of viral load: qualitative or quantitative tests? |
|
Definition
| Qualitative tests will detect lower viral loads because will just be looking to see if the virus is there, not trying to determine how much is actually present |
|
|
Term
| T or F: there is a cure for IBD? |
|
Definition
| F - only can minimize recurrence and improve QOL |
|
|
Term
| What are the different types of IBD? |
|
Definition
Crohn's Disease: ANY part of the lining of the GI tract
Ulcerative Colitis: transmural inflammation resulting in abdominal pain, diarrhea, and weight loss (localized)
Indeterminable or intermediate colitis (~10% of cases) |
|
|
Term
| Which type of IBD is increasing over time? |
|
Definition
|
|
Term
| When is the peak age of onset of IBD? |
|
Definition
15-30 years old
smaller peak 60-80 |
|
|
Term
| What type of patient is more likely to have IBD? |
|
Definition
| White, urban, runs in families |
|
|
Term
| What can trigger or worsen IBD? |
|
Definition
NSAIDs - worsen IBD (alterations of epithelial barrier)
Smoking - more likely to develop Crohn's (less likely to develop UC, smoking cessation can exacerbate UC)
Dietary antigens may also contribute to ongoing inflammation
Luminal bacteria - may stimulate intestinal inflammatory response (not associated with a particular organism)
Proinflammatory cytokines (IL-1, -6, TNF)
Genetics (NOD2/CARD15) |
|
|
Term
| Difference between Crohn's and UC? |
|
Definition
CD: anywhere in GI tract (simultaneously in different areas - patchy); COBBLESTONE appearance
UC: in COLON and RECTUM; Crypt abcesses |
|
|
Term
| What is the most common type of Crohn's Disease? |
|
Definition
Ileo-colic (50%)
Also possible: Ileum and Colon only |
|
|
Term
| What does transmural mean |
|
Definition
| Existing/occurring across the entire wall of a vessel or organ (aka more than just superficial) |
|
|
Term
|
Definition
1. Ulcerative proctitis (rectum only, rectan bleed, tenesmus
2. Limited to distal colitis (left side of colon, diarrhea, bleed pain)
3. Universal aka pancolitis (entire colon; fulminant colitis -->toxic megacolon -req. surgical intervention) |
|
|
Term
| Which IBD is more associated with colon cancer? |
|
Definition
|
|
Term
| What are common presenting symptoms of both UC and Crohn's? |
|
Definition
-Fever
-*Abdominal pain/tenderness (but unusual in UC)
-Diarrhea (bloody, watery, mucopurlent)
-Rectal bleeding
-Weight loss |
|
|
Term
| Which IBD usually has fistulas more likely to be present? |
|
Definition
|
|
Term
| What are some signs of IBD outside of the GI tract? |
|
Definition
1. Dermatologic:
-erythemia nodosum, pyoderma gangrenosum, aphthous stomatitis (ulcers)
2. Ocular:
-uveitis, iritis, scleritis, episcleritis
3. Musculoskeletal:
-ankylosing spondylitis, peripheral arthritis, osteoporosis
4. Hepatobiliary:
-primary sclerosing cholangitis, hepatitis/cirrhosis |
|
|
Term
|
Definition
1. Hemorrhage
2. Obstruction
3. Perforation
4. Abcess
5. Fistulas (common, esp perianal and perirectal)
6. Fulminant colitis -> toxic megacolon
7. Carcinoma |
|
|
Term
|
Definition
Lab: anemia, LFT, antibody
Imaging: endoscopy, colonoscopy
Scan: CT, WBC
Stool Samples
CRP may help predict short-term relapse
Fecal markers (calprotectin - neutrophil protein; good for detecting disease activity/predicting relapse) |
|
|
Term
| Classification of severity of Crohn's |
|
Definition
Mild-Moderate: can take PO, no systemic signs (fever, anemia, dehydration, abdominal tenderness); <10% weight loss
Moderate-Severe: failed treatment for mild; systemic signs (N/V, pain, weight loss, fever)
Severe-Fulminant: no response to out-patient steroids; high fever/pain; persistent vomiting |
|
|
Term
|
Definition
Mild: <4 stool/day (no systemic signs)
Moderate: 4-6 stools/day (minimal systemic disturbance)
Severe: >6 stools/day (fever, HR>90, ESR>30, HB<75% of normal, pain)
Fulminant: >10 stools/day with continuous blood |
|
|
Term
| What is the main goal of treatment of IBD? |
|
Definition
| maintaining the patient's QOL |
|
|
Term
| What are some treatment options with IBD? |
|
Definition
1. Aminosalicylates
2. Corticosteroids (topical, PO, IV)
3. Immunomodulators
4. ABX/probiotics
5. Biologics
6. Others: nicotine, antidiarrheals, pain management, supplements
7. Surgery |
|
|
Term
| What is another name for 5-aminosalicylate (5-ASA)? |
|
Definition
|
|
Term
|
Definition
Anti-inflammatory effects due to inhibition of leukotriene production, anti-prostaglandin and antioxidant effects
Activates a coloncyte differentiation factor and has other anti-proliferative effects (may protect against colon cancer assoc. with UC) |
|
|
Term
| What helps to target different areas of the GI tract with mesalamine? |
|
Definition
The different dosage forms can be used to target certain areas.
(Ex: original PO mostly absorbed in sm. intestine and doesn't reach colon |
|
|
Term
| Aniosalicylate use in the two types of IBD? |
|
Definition
UC: FIRST LINE for maintenance and remission
CD: used off-label and only modestly more effective than placebo (ineffective for ileal CD) |
|
|
Term
|
Definition
First aminosalicylate used for IBD
Contains 5-ASA (mesalamine) and sulfapyridine
-Cleavage of connecting azo-bond by bacteria
-MOST ADRS DUE TO SULFAPYRIDINE (ex: allergy to sulfa) |
|
|
Term
|
Definition
4-6 g/day for induction
2-4 g/day for maintenance
-Dosing is based on mesalamine component
available as immediate release and enteric coated
-Titrate dose at beginning (~500-1000 mg to start) - TAPER UP AND DOWN |
|
|
Term
|
Definition
Dose related: GI upset, HA, arthralgia, folate malabsorption
-Some suggest folate supplementation
Non-dose related: rash, fever, hepatotoxicity, bone marrow suppression, hemolytic anemia, pancreatitis |
|
|
Term
| Primary site of action of sulfasalazine action? |
|
Definition
|
|
Term
| What is a major advantage of mesalamine products? |
|
Definition
| Non-sulfa containing - better tolerated |
|
|
Term
| What is considered first line for mild-to-moderate UC/Crohns? |
|
Definition
|
|
Term
| Dosage forms of mesalamine? |
|
Definition
Topical (enema)
Suppository (proctitis)
PO (slow release can deliver to small intestine and colon) |
|
|
Term
| What is Lialda and how does the drug get to the site of action? |
|
Definition
Mesalamine (2-4g QD) in UC
The tablet reaches basic pH (terminal ileum) it dissolves
Hydrophilic matrix swells to form an outer viscous gel mass (designed to slow diffusion of the active drug into the colonic lumen)
Lipophilic matrix is added to slow the penetration of aqueous fluids into the tablet core (decreases rate of drug dissolution) |
|
|
Term
| What are some different mesalamine products? |
|
Definition
| Lialda, Pentasa, Asacol, Apriso |
|
|
Term
| What is olsalazine used for and what is a major ADR? |
|
Definition
prodrug converted to 5-ASA
-used for IBD
ADR: secretory diarrhea (~25%) |
|
|
Term
| What is the difference between controlled release and delayed-release mesalamine? |
|
Definition
CD: releases throughout GI tract
DR: releases in distal ileum/colon |
|
|
Term
| What mesalamine products only release drug in colon? |
|
Definition
Besalazide (prodrug)
Olsalazine (prodrug)
sulfasalazine |
|
|
Term
| What is the purpose of using corticosteroids in IBD? |
|
Definition
To induce remission in moderate to severe disease
NOT FOR MAINTENANCE THERAPY (risk of steroid dependency)
-not effective at preventing relapses/decreasing disease progression |
|
|
Term
| ADRs of corticosteroid use? |
|
Definition
adrenal suppression
glucose intolerance
HTN
Na/water retention
osteoporosis
cataracts
impaired wound healing |
|
|
Term
| What are typical doses of prednisone used for IBD? |
|
Definition
0.5-0.75 mg/kg/day QD or BID
Max:40-60 mg/day
-higher doses (1mg/kg) have higher response rates
Once in remission - taper by decreasing ~5-10 mg weekly until at 20 mg then taker by 2.5-5mg weekly |
|
|
Term
| What should be monitored during treatment with corticosteroids (during IBD)? |
|
Definition
BONES
Baseline DEXA scan
supplementation of Ca and vit D
Consider bisphosphonate |
|
|
Term
| What type of IBD is budesonide good for? |
|
Definition
| Disease in terminal ileum and treats ONLY terminal ileal/ascending colonic disease |
|
|
Term
| Dose of budesonide. Is it more or less potent than prednisone? |
|
Definition
9 mg/day
15x more potent than prednisone |
|
|
Term
| What helps decrease the ADRs associated with budesonide (compared to prednisone)? |
|
Definition
High first pass metabolism allows for high ratio of local anti-inflammatory effect to systemic effects
BUT less effective than conventional PO steroids in inducing remission |
|
|
Term
| What are two steroids that can be given IV for IBD? |
|
Definition
Hydrocortisone
Methylprednisone
(Use for 7-10 days then change to PO) |
|
|
Term
| What are some topical steroids that can be used for IBD? |
|
Definition
Cortenema
Cortifoam
Anucort/Proctocort |
|
|
Term
| What are the immunomodulators role in IBD? |
|
Definition
Induction in steroid dependent or patients who cant be tapered without recurrence (when steroids fail)
-Use may result in steroid-sparing effect |
|
|
Term
| What are some examples of immunomodulators (used in IBD)? |
|
Definition
1. Azathioprine
2. 6-mercaptopurine
3. MTX
4. Cyclosporine
5. Tacrolimus (limited data) |
|
|
Term
| What two drugs are metabolized by thiopurine methyltransferase and why is this important? |
|
Definition
1. Azathioprine
2. 6-MP
There are genetic variations in this enzyme
-The FDA recommends genetic testing for this to optimize dose and avoid ADRs (ex: bone marrow suppression) |
|
|
Term
| What are some ADRs of Azathioprine and 6-MP? |
|
Definition
Pancreatitis (3-15%)
Bone marrow suppression
Nausea
Diarrhea
Rash
Hepatotoxicity |
|
|
Term
| What are some ADRs of MTX? |
|
Definition
Bone marrow suppression
Nausea
Rash
Diarrhea
Pulmonary toxicity
Hepatotoxicity |
|
|
Term
| What is a major ADR of cyclosporine? |
|
Definition
| Long-term risk of renal toxicity and infection |
|
|
Term
| What antibiotics can be used for the treatment of IBD? |
|
Definition
Metronidazole - CD only unless UC with pouchitis
Cipro
Rifaximin: either UC or CD |
|
|
Term
| Metronidazole use in IBD? |
|
Definition
Crohn's with perianal or fistulas
UC ONLY if with pouchitis
suppresses cell-mediated immunity
10-20mg/kg |
|
|
Term
|
Definition
Peripheral neuropathy
Paresthesia
Reversible upon d/c med |
|
|
Term
| What type of IBD can rifaximin be used for? |
|
Definition
Either UC or CD
it is a non-absorbable antibiotic |
|
|
Term
| What do biologics target? |
|
Definition
TNF-alpha
(associated with inflammation) |
|
|
Term
| What are some biologics used for the treatment of IBD? |
|
Definition
Infliximab (Remicade)
Adalimumab (Humira)
Certolizumab (Cimzia)
natalizumab (Tysabi) |
|
|
Term
| Why is using TNF-alpha inhibitors an effective therapy for IBD? |
|
Definition
TNF-alpha - plays a role in inflammation
-direct tissue injury from induction of matrix metalloproteinases
-Activation and recruitment of inflammatory cells to the mucosa/submucosa
-Enhanced cytokine secretion
-Direct apoptosis of mucosal epithelial cells |
|
|
Term
| Infliximab as IBD treatment? |
|
Definition
Indicated for both UC and Crohn's disease -moderate-severe active disease
-fistulizing Crohn's
-maintenance of moderate-severe disease |
|
|
Term
| PK/Administration/Dosing of Infliximab |
|
Definition
IV ONLY ($$)
chimeric monoclonal antibody that binds to TNF-alpha
-human constant and murine variable region
LONG half-life (~1 wk - 10 days)
-Induction week 0, 2, and 6; then Q8weeks
(5 mg/kg) |
|
|
Term
| ADRs associated with infliximab (biologics in general)? |
|
Definition
Infusion related: hypotension, fever, chills, urticaria, pruritis
-INFUSE OVER 2 hours and pretreat with APAP/antihistamine
Delayed hypersensitivity: fever, rash, myalgia, HA, sore throat (3-10 day after administration)
Infection - reactivation of latent infections
HF exacerbations (CI in Class III/IV HF)
Ab induction
Bone marrow suppression, lymphoma, hepatitis, vasculitis |
|
|
Term
| Why does adalimumab not cause the body to develop antibodies to it? |
|
Definition
|
|
Term
| Indication of adalimumab? |
|
Definition
| induction and maintenance of moderate-severe active Crohn's in patients unresponsive to conventional therapy or infliximab |
|
|
Term
| Which biologic has a better response rate: infliximab or adalimumab? |
|
Definition
Infliximab (40-80%)
[adalimumab - 20-50%] |
|
|
Term
| Administration of adalimumab? |
|
Definition
|
|
Term
| Indication of certolizumab? |
|
Definition
| induction and maintenance of moderate-severe active IBD disease with no response to treatment |
|
|
Term
| What patients are found to have the best response to certolizumab? |
|
Definition
| patients with CRP>10 mg/L |
|
|
Term
| Administration of certolizumab? |
|
Definition
|
|
Term
| T or F: major ADRs for biologics appear to be a class effect? |
|
Definition
| T - risk of lymphoma, CHF, and infection for all biologics |
|
|
Term
| How is natalizumab different than other biologics? |
|
Definition
| It is a humaninze monoclonal antibody that antagonized integrin heterodimers and inhibits integrin-mediated leukocyte adhesion |
|
|
Term
| Role of natalizumab in IBD treatment? |
|
Definition
for patients with moderate-severe active Crohn's who have inadequate response to conventional treatment or TNF-alpha inhibitors
-Use TNF inhibitors first |
|
|
Term
| What must be monitored during natalizumab therapy? |
|
Definition
| Mental status changes (progressive multifocal leukoecepholopathy) |
|
|
Term
| Can loperamide be used in IBD? |
|
Definition
Yes - but use caution because will reduce mortality
- may be useful in proctitis/diarrhea |
|
|
Term
| Antispasmodics role in IBD? |
|
Definition
| Can help with the pain in IBD |
|
|
Term
| How can cholestyramine be used for IBD? |
|
Definition
| possible for bile-salt induced diarrhea after ileal resection - will decrease bile acid |
|
|
Term
| How can nicotine be used in IBD? |
|
Definition
ONLY UC (not crohn's)
-used for treatment after smoking cessation - it may improve symptoms in mild-moderate disease of active UC |
|
|
Term
| What kind of surgery may be seen in IBD? |
|
Definition
Bowel resection
Indicated if:
-failure on drugs/nutritional therapy
-steroid toxicity
-obstruction, hemorrhage, perforation, fistula
UC - Removal of diseased colon |
|
|
Term
| Which biologic agent is especially good at treating fistulizing IBD? |
|
Definition
|
|
Term
| What do the delta cells of the pancreas produce? |
|
Definition
|
|
Term
| What are the exocrine functions of the pancreas? |
|
Definition
Secretes 1.5-3 L of fluid/day
Acinar Cells: secrete pancreatic enzymes
Alkaline secretion (pH >8) to neutralize gastric acid and activate enzymes |
|
|
Term
| What are the pancreatic enzymes? |
|
Definition
Trypsinogen: proteolytic
Amylase: amylolytic
Lipase: lipolytic
**There are protective enzymes in the pancreas that prevent activation of these in the organ (autodigestion) |
|
|
Term
| Where do enzymes go when they leave the pancreas? |
|
Definition
Through the common bile duct into the duodenum
it is in the intestine that the enzymes get activated |
|
|
Term
| How does pancreatitis occur? |
|
Definition
Mechanisms to prevent trypsinogen activation are overwhelmed
Activation of trypsin in pacreatic acinar cells (autodigestion)
SPINK1(usually inhibits trypsin activation) ->inhibited by chronic EtOH and gallbladder disease -> trypsin gets activated in pancreas
Gallstones
CFTR seen in cystic fibrosis (increased pressure) |
|
|
Term
| Signs and Symptoms of pancreatitis that can help diagnose. |
|
Definition
Abdominal pain (90%)- midepigastric
N/V (associated with pain)
Anorexia
Abdominal distention (decreased bowel sounds)
Epigastric tenderness
Low grade fever
Tachycardia (due to pain)
Grey-Turner's sign (bruising on flank)
Cullen's sign (bruising on stomach) |
|
|
Term
| What lab tests can help diagnose pancreatitis? |
|
Definition
1. Amylase: (early) elevated in 2-12 hr of onset and remains high for up to 5 days
-non-specific (could also be biliary tract disease, salivary adenitis)
-suggestive of gallstone pancreatitis
2. Lipase: (later) elevated for 5-7 days, more sensitive
3. ALT: gallstone etiology
Imaging tests: Ultrasound (to check for cholelithiasis, psuedocyst; preferred b/c easier), CT Scan (to id necrosis) |
|
|
Term
| How is pancreatitis classified? |
|
Definition
Mild: without necrosis
-no organ dysfunction
Severe (any of the following):
-Organ failure
-Local complications: necrosis, pseudocyst, abscess |
|
|
Term
| What is Ranson's criteria used for and what are some general trends? |
|
Definition
It is to measure risk of pancreatitis
Older age
High WBC
High glucose
High LDH
High AST |
|
|
Term
| What are the main causes of pancreatitis? |
|
Definition
1. Gallstones (45%)
2. Alcohol (35%) - can be higher in urban areas - due to direct toxic effects and decreased pancreatic tubule permeability
3. Idiopathic (10%)
4. Misc: Drugs (didanosine, azathioprine, mercaptopurine); trauma; metabolic abnormalities; infection |
|
|
Term
|
Definition
Endoscopic Retrograde Cholangiopancreatography
Procedure to remove gallstones - can cause acute pancreatitis by retrograde flow |
|
|
Term
| What metabolic abnormalities can cause acute pancreatitis? |
|
Definition
Hypertriglyceridemia
Hypercalcemia |
|
|
Term
| What drugs can cause acute pancreatitis? |
|
Definition
1. Didanosine: possible accumulation of toxic metabolite (delayed onset - up to months after initiation; dose related)
2. Azathioprine; Mercaptopurine: hypersensitivity rxns; usually about 1 month after initiation
Others: metronidazole, thiazies, valproic acid, estrogens, mesalamine, tetracycline, sulfonamides |
|
|
Term
| Treatment of Acute Pancreatitis? |
|
Definition
1. Supportive care
2. Fluid resuscitation
3. NPO - b/c food stimulates pancreatic enzymes
4. Pain control
5. Nutrition: enteral> parenteral
6. Prevent infection
7. Surgery |
|
|
Term
| Why do fluids need to be replaced in acute pancreatitis? |
|
Definition
Volume loss for third spacing, internal bleeding, and vomiting
Need to maintain urine output |
|
|
Term
| T or F: giving an IV H2RA or PPI in acute pancreatitis will help to 'rest the pancreas' |
|
Definition
F - just do NPO
no benefit found with H2RA or PPI |
|
|
Term
| Nutrition during pancreatitis |
|
Definition
NPO
Place feeding tube beyond duodenum
-enteral feeding is best in most cases (over parenteral) + less infections |
|
|
Term
| Pain control during pancreatitis |
|
Definition
Why - sphincter of Oddi spasms and constricts (increases biliary-tract pressure and worsens pain)
GIVE: morphine, fentanyl, hydromorphone
-Consider PCA
NOT: meperidine (accum of normeperidine -seizures, short duration of action, muscle fibrosis [IM inj], drug interactions[MAOIs]) |
|
|
Term
| What are the two major complications we are worried about with pancreatitis? |
|
Definition
1. Pseudocysts
2. Pancreatic necrosis
3. Infection
(Shock/CV collapse, coagulopathy, respiratory failure, acute renal failure) |
|
|
Term
| Pseudocysts due to pancreatitis |
|
Definition
Collection of pancreatic secretions (2-10% of patients)
-Appears 2-3 weeks after onset of acute pancreatitis
-50% of cases resolve without treatment
-if persistent will need drainage |
|
|
Term
| Pancreatic necrosis due to pancreatitis |
|
Definition
Sterile tissue - due to hypoperfusion, autodigestion
Risk of INFECTION is high
Associated with high mortality (10-25%)
-Can see this on a CT Scan - so if patient isnt improving check for this |
|
|
Term
| Pancreatic infection due to pancreatitis |
|
Definition
Develops in 40-70% of patients with PANCREATIC NECROSIS
LEADING CAUSE of morbidity/mortality in pacreatitis
-Diagnosis: CT scan and signs/symptoms
1-4 weeks after onset of pancreatitis
TX: ABX and drainage |
|
|
Term
| Should antibiotics be given prophylactically to patients with pancreatitis? |
|
Definition
NO, unless they have necrosis (severe >30% of pancreas)
- can increase risk of fungal infections
- unnecessary in mild cases |
|
|
Term
| What organisms need to be covered in antibiotics used for pancreatitis with necrosis? |
|
Definition
Enteric gram negative rods +/- anaerobes
Enterococcus |
|
|
Term
| What is also commonly required in patients with necrotizing pancreatitis or psuedocysts? |
|
Definition
| Debridement and drainage in addition to abx |
|
|
Term
| What agents should be used empirically for the treatment of pacreatic infections from pancreatitis? |
|
Definition
Carbapenems (DOC): Imi, Mero, Dori
Beta-lactams (later generation): Zosyn, 3rd gen ceph
FQ (+ Metronidazole) (less effective) |
|
|
Term
| What would be the needed treatment for shock or CV collapse (as a complication to pancreatitis) |
|
Definition
| Aggressive volume replacement and pressors |
|
|
Term
| Signs of acute hepatic failure |
|
Definition
-Elevations in AST, ALT, Bilirubin, INR
-Nausea
-Jaundice
-Encephalopathy
-Coma |
|
|
Term
| _________ levels are prognostic for mortality in acute hepatic failure. |
|
Definition
| Bilirubin - larger elevation = more liver failure |
|
|
Term
| Signs of chronic liver toxicity? |
|
Definition
-Elevation in ALT and AST: May be minimal or dramatic (esp if chronic)
-No overt signs until jaundice develops (usually what brings them into hospital)
MOST are reversible if caught early |
|
|
Term
| What are some types of hepatotoxicity? |
|
Definition
Centrolobular Necrosis
Steatohepatitis
Hepatocellular Necrosis
Toxic Cirrhosis
Cholestatic Injury |
|
|
Term
| Presentation of Centrolobular necrosis? |
|
Definition
Elevation in aminotransferases: mild reaction, most patients recover
(ALT, AST, LDH)
Signs: N/V, jaundice, abdominal pain if severe rxns
Once fibrosis occurs, it isnt reversible |
|
|
Term
| What are some common causes of centrolobular necrosis? |
|
Definition
APAP!! (depletes glutathione stores and leads to free radical formation via NAPQI)
Valproic acid, ASA (reye's ->fever escalation) |
|
|
Term
|
Definition
Accumulation of fat in hepatocytes
-too much fat will cause rupture and fibrosis
-inflammation occurs from hepatocyte lysis |
|
|
Term
| What can cause steatohepatitis? |
|
Definition
ALCOHOL!
-NASH (Non-Alcoholic Steatohepatits): mainly due to obesity, type 2 DM
Drugs: Tetracycline, valproic acid |
|
|
Term
| How can you tell a difference between Alcoholic fatty liver disease and NASH? |
|
Definition
| Only by the patient history, looks the same on histology |
|
|
Term
| Hepatocellular necrosis - what can cause it? |
|
Definition
Isoniazid, ketoconazole
-They appear as a hapten the in immune system and trigger an attack
ultimately caused by collateral damage
Variations based on genetic differences
Changes are similar to that of viral hepatitis |
|
|
Term
|
Definition
Decreased flow of bile through the ducts - sludging or obstruction
- acute or chronic
"vanishing bile duct syndrome" |
|
|
Term
| What are some signs of cholestasis? |
|
Definition
Increased Alk phos and bilirubin, GGT
Hepatocyte necrosis
Nausea
Jaundice |
|
|
Term
| What are the two forms of alk phos? |
|
Definition
| Bone and biliary - if there is an elevation can be due to bone or liver disease |
|
|
Term
| Common Drug causes of cholestasis |
|
Definition
TPN -glucose to fast and nothing in GI tract to stimulate bile release(BIG ONE)
Augmentin
Erythromycin |
|
|
Term
| What is the marker for significant liver disease (aka end-stage disease)? |
|
Definition
INR elevation (autoanticoagulated)
high: bilirubin
normal/low: AST and ALT |
|
|
Term
| General treatment of liver toxicity |
|
Definition
Removal of offending agent (if TPN can slow rate)
Specific antidote if available (N-acetylcysteine for APAP)
Dialysis (if acute tox)
Supportive Care
Liver transplant - wont be able to do if intentional OD |
|
|
Term
| What is the most common cause of acute liver failure? |
|
Definition
|
|
Term
| How to determine if APAP OD needs to be treated |
|
Definition
| Rumack-Matthew Nomogram (after 4 hours from OD) |
|
|
Term
|
Definition
IV N-acetylcysteine that can be given over 24 hours (vs PO over 72 hours)
-generally have ~24 hr window to treat APAP OD |
|
|
Term
| If someone depressed and tries to commit suicide with drug OD what should be done? |
|
Definition
Counseling!
Give anti-depressant, but NOT TCA (easy for another OD) |
|
|
Term
| What will be the last thing to go with liver disease? |
|
Definition
| gluconeogenesis - watch for this drop if patient is on insulin drip! |
|
|
Term
|
Definition
Underweight: <18.5
Normal: 18.5-24.9
Overweight: 25-29.9
Obese Class I: 30-34.9
Obese Class II: 35-39.9
Obese Class III: >40
**disease risk will increase with weight and WAIST CIRCUMFERENCE |
|
|
Term
| What is a 'bad' waist circumference? |
|
Definition
|
|
Term
| What are the indications for bariatric surgery? |
|
Definition
Severe obesity >40
BMI >35 + serious comorbid conditions |
|
|
Term
| What are the seen benefits from bariatric surgery? |
|
Definition
Sig sustained weight loss for >5 years
Improved:
HTN
DM
HLD
sleep apnea
fertility
mobility
QOL |
|
|
Term
| What are some risks seen with bariatric surgery? |
|
Definition
GI leaks
Respiratory failure
PE (because of immobility) |
|
|
Term
| What is an example of gastric restriction bariatric surgery? |
|
Definition
Gastric banding - forms a 30-60 ml pouch - can change the size of the band once in place and shrink stomach
-also helps to slow peristalsis
(vertical banded gastroplasty isnt as common anymore - staple stomach) |
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Term
| What is the only reversible bariatric surgery? |
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Definition
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Term
| What is an example of intestinal malabsorptive bariatric surgery? |
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Definition
Bilopancreatic diversion
Distal gastric bypass |
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Term
| What is Roux-en-Y Bypass? |
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Definition
| Combination bariatric surgery that is both restrictive (takes the fundus of stomach) and bypass/malabsorptive (attaches fundus after duodenum) |
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Term
| What are some changes that may affect drug delivery due to bariatric surgery? |
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Definition
1. Surface area for drug absorption decreases (less time for drug absorption)- no ER tablets
2. Less time for disintegration so use liquids when possible
3. pH: increases - may need to give a drug with acid if needs acidic environment for absorptions
4. Some drugs need enzymes for absorption that are found thru GI tract (ex: cyclosporine) - not as big of issue |
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Term
| What are some drugs that require an acidic environment for absorption? |
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Definition
Rifampin
Iron (give with vit C)
Digoxin
Calcium (use citrate) |
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Term
| How will bariatric surgery affect diabetes? |
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Definition
A decrease in food intake will decrease insulin requirements
May need to avoid PO hypoglycemics (not as well controlled and if need glucose quickly and something already in stomach wont be able to react quickly enough) |
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Term
| How will bariatric surgery affect HTN? |
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Definition
| increased monitoring b/c with weight loss the need for hypertensives should decrease (AND many are ER - change to IR) |
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Term
| How will bariatric surgery affect hyperlipidemia? |
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Definition
| Cholesterol should improve (b/c less cholesterol intake) and may need to decrease dose |
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Term
| Which nutrients are prone to deficiencies with bariatric surgery? |
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Definition
-Fat soluble vitamins: patients will need more of these daily than normal patients (ex: vit D RDA = 400, with surgery recom 600-50,000)
-Ca
-Fe
-B-12 |
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Term
| Calcium and bariatric surgery |
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Definition
Usually absorbed in duodenum and jejunum
Blood levels frequently remain in normal range
Elevated PTH is much more common
-This means that while Ca may appear normal, it is actually being drawn from bones and thus should be supplemented
Ca Citrate: 1500-1800 mg/d |
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Term
| Vitamin D and Bariatric surgery |
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Definition
Principally absorbed in the jejunum and ileum
Most are deficient post-op
Helps to cause lower Ca absorption in gut which stimulates bone to breakdown to keep Ca levels up |
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Term
| Iron deficiency and bariatric surgery? |
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Definition
Reported in about half of cases
Leads to MICROCYTIC ANEMIA
The primary site of absorption (duodenum) is bypassed in Roux-en-Y
Needs acidic environment so supp with VitC (absorbed in FERROUS state Fe2+) |
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Term
| B-12 deficiency in bariatric surgery |
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Definition
1/3 of patients by may take up to 5 years to see
Complications: macrocytic anemia, leukopenia, thrombocytopenia, glossitis, irreversible neuropathies
MOST LIKELY: Roux-en-Y
Least likely: gastric banding (b/c no effect on acid or intrinsic factor) |
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Term
| What type of bariatric surgery is B-12 deficiency most common in? |
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Definition
| Roux-en-Y: b/c decreases gastric acid and intrinsic factor |
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Term
| How should B-12 supplementation be given post-op with bariatric surgery? |
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Definition
Can be given PO (350-600 mcg/d) [Compared to 2mcg/d RDA]
Alternative: Sublingual or IM injection |
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Term
| What are some of the less common possible deficiencies patients can experience post-bariatric surgery? |
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Definition
1. Thaimine - Wernicke's
2. Zinc - hair loss
3. Magnesium - no signigicant complications reported
4. Vit A - reversible blindness |
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Term
| NSAIDs and bariatric surgery |
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Definition
nonselective NSAIDs associated with an increased risk of stomach ulcers (same with bisphosphonates)
Change to something else, potentially use selective COX-2 |
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