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Glossary of Therapeutics Final Spring 2nd year UCSD SSPPS

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Components of lipoproteins?
Outer layer is phospholipid and apolipoproteins and XOL. the inside is XOL esters and TGs
Percentage of blood XOL that is VLDL?
15-20%
How to estimate amount of VLDL?
TG/5
What does LPL do to VLDL?
Removes TGs from VLDL and puts it into adipose for storage, so VLDL becomes VLDL remnants (XOL more concentrated), and becomes IDL and then LDL
Where does LDL come from?
VLDL becomes depleted of TGs, and more concentrated with XOL
What is difference in apoproteins between VLDL, VLDL remnants, IDL, LDL?
VLDL has B-100, E, and C;
VLDL remnants and IDL just have B-100 and E;
LDL just has B-100
What is the reverse XOL transport?
HDL picks up XOL esters from peripheral cells using LCAT (activated by cofactor A1 on HDL), and then either goes back to the liver or turns into VLDL via CETP (XOL ester transfer protein)
What percentage of serum XOL is LDL?
60-70%, and greater contribution to atherosclerosis.
How much of LDL does liver remove?
½. The other half is taken up by peripheral cells and macrophages
What percentage of serum XOL is HDL?
20-25%
What happens in CETP deficiency?
Can’t make VLDL and IDL from HDL, so HDL goes very high, and have very low incidence of CHD
Characterisitics of chylomicrons?
High in TGs, transport gut fats to liver
What do apolipoproteins C-II and C-III do?
C-II is a cofactor for LPL. C-III is a marker for high risk of atherosclerosis
High apo B is a marker for what?
High CHD risk (because B is on LDL and VLDL)
What does lipoprotein A-I do?
Activates LCAT → esterify free XOL
Characteristics of polygenic hyperXOLemia?
Most common lipid disorder, due to genetic and environmental factors. Has moderate LDL (130-250), and 20% have hx of premature CAD. Managed well with diet and drugs
Characteristics of atherogenic dyslipidemia?
Responsible for 25% of patients with a lipid disorder, TGs 150-500, low HDL (<40). Commonly have obesity, metabolic syndrome, DM. Low LPL makes TG-rich VLDL, which is exchanged for XOL
Outward signs of FH?
Arcus senilis, tendon xanthomas
What is hypoalphalipoproteinemia?
HDL<40, but no elevated TG. Rare, but higher CHD. Primary goal is decreasing LDL. Low A-1 means can’t do reverse XOL transport as well.
What is the problem caused by inflammation in atherosclerotic patient?
Inflammation, among other things, can weaken atherosclerotic plaques
Basic steps in plaque formation?
LDL accumulates in intimal space. Oxidized LDL, macrophage ingestion, foam cells, fatty streak, collagen synthesis, lesions stronger
What change in blood XOL corresponds with what % increase risk of CHD?
1% more XOL means 1-2% higher risk of CHD
Incidence of CHD in women compared to men?
Lower in women up to menopause, then equal or increased
What did ASTEROID study show?
March 2006, JAMA, showed statins can shrink and stabilize plaques
How do statins shrink plaques?
Decrease lipid component and increase fibrous component, so less chance of rupture
Effect of lower LDL on vascular function?
Reverse endothelial damage, so more NOS function, and better vasodilation
What does CRP indicate?
c-reactive protein is a measure of inflammation in atherosclerosis
How often should check lipid profile in adults >20yo?
Every 5 years according to the NCEP ATP III
Classifications of LDL levels?
Optimal is <100, near optimal is ≤129, borderline is ≤159, high is ≤189, very high is ≥190
What are the classsifications of total XOL?
Desirable is <200, borderline is <240, high is ≥240
Classifications for HDL levels?
Low is <40. High is ≥60
List the 5 major risk factors defined by ATP III guidelines?
(1) Smoking
(2) HTN, which means on anti-HTN meds or BP >140/90)
(3) low HDL (<40)
(4) Family hx of CHD (if male, 1st degree relative <55, female <65)
(5) Age (men ≥45, women ≥55)
What is significance of metabolic syndrome in lipid disorders?
It is equivalent to CHD as a risk factor
What is significance of DM in lipid disorders?
It is equivalent to CHD as a risk factor
LDL goal for ATP risk factors?
If CHD or equivalent (DM or metabolic syndrome), then goal is <100, but 70 is better. If 2+ risk factors, goal is <130. If zero or 1 risk factors, then goal is <160.
What is significance of HDL as risk factor in lipid disorders?
If high HDL (>60), it is a negative risk factor
What ATP III categories correspond to what % chance of Coronary event in the next 10 years?
CHD or equivalent is a 20% risk.

2+ risk factors is ≤20% risk of heart event

0-1 risk factor is <10% risk of event in the next 10 years
What scoring system is most accurate for calculating risk of cardiac event?
Framingham risk scores. The system calculates a 10yr % risk based on points for age, gender, total XOL, HDL, smoking status, and systolic BP.
What are categories of TG levels?
Normal is <150. Borderline is <200. High is <500. Very high is ≥500
TGs as a risk factor?
High TGs is a risk factor for CHD
Diagnosis of metabolic syndrome?
3 or more of:
waist circumference >40in (men), >35in (women).
TGs ≥150,
HDL <40 (men), <50 (women),
BP ≥130/85
fasting glucose ≥110
Causes of secondary dyslipidemia?
DM, hypothyroid, obstructive liver disease, chronic renal failure, drugs (progestins, anabolic steroids, corticosteroids, cyclosporins, sirolimus, beta-blockers, protease inhibitors, thiazides, isotretinoin, mirtazapine).
Effect of EtOH on lipids?
Increase TGs and HDL
appropriate medical hx and procedures to assess lipid patient?
Look for atherosclerosis (if in one artery, probably in many or all), hx of MI, angina, stroke. Do treadmill for ischemia on ECG, exercise thallium, electron beam CT to look for Ca buildup, carotid bruit or stenosis>50%, AAA (abdominal aortic aneurysm), DM
Gemfibrozil interaction with statins?
Increase statins 2-4 times (except for Flu)
When to consider lifestyle changes versus drug treatment for high lipids?
For each risk category, initiate drug therapy if 30 LDL points above goal (e.g. CHD or equivalent goal is <100, but if ≥130, use drug therapy. If 100-129, try TLC first)
4 main TLCs for lowering lipids?
Low sat fat in diet, increase physical activity, weight reduction, smoking cessation
What fats should replace saturated fats in the TLC diet?
Monounsaturated (canola, olive oil, avocados), and Omega-3
What is unique about the mediterranean diet?
Daily physical activity
Key food choices in the TLC diet?
Lean meat, grill or broil, smaller portion. Skim or 1% milk, butter-substitutes, low-fat soft cheese instead of hard cheese, frozen yogurt instead of ice cream, avoid sauce, cream, and fatty foods
What effect does viscous fiber, soluble fiber, and plant sterols have on XOL?
Can lower LDL 5-15% by decreasing absorption of XOL in the gut
Examples of foods and products that have plant sterols for reducing LDL?
Benecol spreads (1.7g), Avocado, soybeans, chickpeas, almonds, corn oil, olive oil (from 132 to 30mg)
How do stanols and sterols decrease XOL absorption?
By competing with XOL for incorporation into mixed micelles, but are absorbed much less. So, with less being absorbed, LDL receptors are upregulated. Benecol (sterols) lowers XOL 10-15% even in patients already taking statins
Steps in TLC treatment for lipid patient?
Begin lifestyle changes (reduce sat fat, increase physical activity), after 6 weeks assess XOL intensify therapy (reinforce low fat diet, add sterols/stanols, increase fiber intake), then after six weeks if goal not achieved, consider drug treatment (treat for metabolic syndrome, increase weight management and physical activity), and then reassess every 4-6 months
Goal for rate of weight loss in TLC?
10% over 6 months
Goal for BMI?
18.5-24.9
Desired waist circumference in TLC?
<40 males, <35 females
What are the Statins in order of potency for decreasing LDL?
generic: Rosu, Ator, Sim, Lo, Pra, Flu
brand: crestor, lipitor, zocor, mevacor, pravachol, lescol
Which dosing level gives biggest bang for the buck in statins?
Lowest dose
Which statins do not necessarily need to be taken at night?
Rosu and Ator (they are the most potent and also have the longest half-lives)
Adverse effects of statins?
HA, GI (pain, constipation, dyspepsia), Myalgia, increase LFTs, and rarely rhabdomyelysis, myoglobinuria, acute tubular necrosis (more with higher doses)
Which statins interact CYPs?
3 interact with 3A4: Ator, Lo, Sim.

2 interact with 2C9: Flu (and Rosu slightly)

Pra is the only one of the six we learned that doesn't inhibit CYPs
Examples of drugs that inhibit 3A4 (so can be a problem with Ator, Lo, Sim)?
Clarithromycin, erythromycin, diltiazem, verapamil, felodipine, ketoconazole, miconazole, ritonavir, Nefazodone, Alprazolam, Midazolam, Triazolam, Cyclosporine, Estradiol, Loratidine, Terfenadine
Examples of drugs that inhibit 2C9 (so can be a problem with Flu and Rosu)?
Alprenolol, Diclofenac, Hexabarbital, Tolbutamide, Warfarin. Especially look out for warfarin and Flu
Which statins cannot be used with warfarin?
Flu and Rosu (2C9 interaction)
Statins in the elderly?
Should have smaller dose due to smaller frame, less renal function, and multiple medications
Which statin is okay to take with Warfarin?
Pravastatin (not metabolized). Flu and Rosu can be a problem with warfarin due to CYP2C9 inhibition
Effect of bile acid resins on lipid profile?
Decrease LDL 15-27%, and increase VLDL, TGs from liver by 3-10%
Bile acid resins on the market?
Cholestyramine (Questran)
Colestipol (oderless, tasteless powder or tablets)
Colesevelam ("Welchol" tablets, best tolerated)
Bile acid resins adverse effects? How to minimize them?
Decreased fat soluble vitamins absorption, GI (bloating, constipation, flatulence, epigastric fullness, nausea).

Reduce effects by Increasing fluid and fiber intake, mix in juice, minimize air entrapment (use straw), educate patient. Tablet better than powder
Drug drug interactions with Bile acid resins?
Older BARs interfere with absorption of dig, warfarin, b-blockers, HCTZ, thyroxine, iron, nicotinic acid, loperamide, and other ionic drugs. However, Colesevelam (Welchol) appears to be okay
How does Ezetimibe work? Effectiveness?
Block XOL absorption in the gut. Even though it increases XOL synthesis 90%, circulating LDL decreases about 20%. Comes in only one strength, once daily 10mg tab which can lower LDL 18-22%, with no effect on HDL or TGs. Is combined with simvastatin in Vytorin as 10/10, 10/20, 10/40, 10/80
Adverse effects of Ezetimibe?
Diarrhea, cough, fatigue, arthralgias
What is Niacin, and what is the effect on the lipid profile?
Vitamin B3, lowers LDL 15-30%, increases HDL 20-35%, decreases TGs 30-60%, and decreases Lp(a) 30%
What is the only drug that can lower Lp(a)?
Niacin
Adverse effects of Niacin?
Flushing is the major one, bit occurs more with immediate release (OTC). Sustained release (OTC) has less flushing, but has increased risk of liver tox. Extended release (Rx) has nice balance with less flushing and less liver tox
Difference in Niacin products in lowering lipids?
ER (Rx) and IR (OTC) lower XOL same. But, IR lowers TGs and increases HDL more than ER.
Two pathways for metabolism of niacin that explains adverse effects?
Pathway I is high affinity but low capacity, and leads to Nicotinamide which causes liver tox.
Pathway II is high capacity, leads to nicotinuric acid which causes flushing.
Slowing the release (Rx ER formulation) helps to balance the two pathways, so less of each effect. The liver tox is reversible
Pt education for Niacin?
To prevent flushinf, take with food, aspirin 30 minutes before morning dose. For Niaspan, give dose before bed.
Side effects of Niacin besides flushing and liver tox?
GI upset (nausea, activate peptic ulcer, dyspepsia), transient increase in glucose levels (bad for DM), darkening of skin
Effect of fibric acid derivatives on lipid profile?
Decrease LDL 10-25%, increase HDL 10-30%, decrease TGs 30-60%
Examples of fibrates?
Gemfibrozil (Lopid), Fenofibrate (Tricor), Clofibrate (Atromid S)
How do Fibrates work?
Activated PPAR-alpha (peroxisome proliferator activated receptors, and nuclear hormone receptor) to increase A-I, A-II (apoproteins for HDL), which increases HDL. It also decreases C-III, which decreases VLDL. It also increases LPL to increase lipolysis. So, catabolize TG-particles and decrease VLDL secretion
ADRs of fibrates?
Well-tolerated, but can cause mild GI symptoms, muscle pain, weakness (do not use with statins), cholelithiasis (due to increased bile output). Fenofibrate can cause rash (2-4%)
Safety of fibrates?
Clofibrate and Gemfibrozil decrease MIs, but same or increase in overall mortality. There is not data for fenofibrate
Possible combination therapies for lowering LDL?
Stain + ezetimibe (vytorin);
statin + BAR;
statin + Niacin + BAR (decrease LDL 45-61%).
What is Vytorin?
Simvastatin + Ezetimibe
What is Advicor?
ER Niacin (Niaspan) + lovastatin
What is Caduet?
Atorvastatin + amlodipine (Ca channel blocker)
What is Pravigard PAC?
Pravastatin + ASA
Effect of omega-3s on lipids?
Lowers TGs 30-60%
Estrogen for lipid disorders?
Can lower LDL and increase HDL, but no change in CHD death, but actually increases CHD events and death at first, then possibly some improvement after 4-5yrs
Considerations for treating lipids in elderly?
They benefit more than young persons do from decreased LDL. But, elderly are more prone to ADRs due to differences in body composition, renal function, other physiological changes. Start low doses, titrate up
Considerations for treating lipids in women?
HDL a better indicator of CHD risk. During pregnancy, XOL and TGs increase, but there is no need for Rx. If high risk, condider BARs. Statins are contraindicated in pregnancy (and liver disease)
Considerations for treating lipids in children?
Drug therapy not until 10yo
Which niacin product should never be used for lowering TGs? Why?
Sustained release (OTC) due to liver tox at doses necessary for TG lowering
Max dose for niacin?
2g for ER, 3g for IR
Titration schedule for Niacin?
For IR, start at 125mgBID, and every week increase to 250, 500, 500, 1000, 1500 (max 3g). For ER, every 4 weeks increase from 500 to 1000 to 1500 if tolerated. Take QHS with food (max 2 g daily)
Endocrine function of kidney?
Renin, PGs, kinins, eythropoietin
Metabolic activities of kidney?
Insulin and glucagon metabolism, Acvitates vit D3
Excretory function of kidney?
Glomerular filtration, tubular secretion and reabsorption
Homeostatic function of kidney?
Removes waste, maintains fluid and lyte and acid/base balance, regulates BP
Major events in PT of nephron?
70% reabsorption of filtered load (AA, glucose, HCO3, water)
Major events in LOH of nephron?
Reabsorption of K, Mg, Ca, and mainenance of osmotic gradient
Major events in DT of nephron?
Reabsorption of water, HCO3, secretion of K and H
Appearance of abnormal urine?
Cloudy, foamy, turbid, or any change in color
What can cause acidic urine?
Ammonium, ascorbic acid, acetic acid bladder irrigation, cranberry juice, DKA

reference range for urine pH is 5-8
What can cause alkaline urine?
Acetazolamide, bicarb, thiazide, citrate and acetate salts, UTI

reference range for urine pH is 5-8
What does leukocytes in the urine mean?
UTI or urethritis
What does RBCs in urine mean?
Infection, coagulopathies, glomerulonephritis, necrosis, tumors, renal stones
What do hyaline casts in urine indicate?
Dehydration, strenuous exercise, fever, proteinuria, CHF
What does cellular casts in urine indicate?
Intrinsic kidney disease (can be from WBC, RBCs, tubular cells
What do waxy/granular casts in urine mean?
Not pathogenic
Relationship between urea clearance and BUN?
If urea clearance decreases, BUN will increase, and vice versa. However, BUN can rise and fall with dietary changes and high catabolic rate, without affecting urea clearance
BUN/Scre ratio?
Normally 10:1 – 15:1, but can initially rise to >20:1 in acute renal failure
List of medications that are associated with elevated Scre? KNOW THIS LIST!
ACEIs, Acyclovir, AMGs, amphotericin B, Cephalosporins, Cisplatin, cyclosporins, dextran, foscarnet, mannitol, NSAIDS, pentamidine, rifampin, tacrolimus, tetracycline, vanco
Why is CrCl not a good measure of GFR in renal impairment?
With decreased filtration, the secretory component of CrCl is a bigger fraction of the total (which is normally about 10%, but may increase to 100% due to nephron hypertrophy in renal insufficiency), so it greatly overestimates renal function
Factors that can affect variability in CrCl (but not necessarily GFR)?
Age, weight, gender, exercise, diet (protein), diurnal variation, elderly, malnourished, children
What things can affect Scre, but not CrCl?
Vigorous prolonged exercise, muscle wasting, muscle growth.
What weight should be used in Cockcroft-Gault calcualtion?
Ideal body weight

The equation is (140-age)(kg wt)/(72*plasma creatinine)

If female pt, multiply result by 0.85
3 classifications of azotemia?
Pre-renal, renal, or post-renal
Difference between azotemia and uremia?
Azotemia is high nitrogenous stuff in blood. Uremia is a syndrome with sxs of N/V, mental status change
What is pre-renal azotemia?
Rapidly revesible form caused by decreased perfusion. Responsible for 50% of ARF cases. Nephrons functionally intact. It occurs from anything that has low blood flow or volume. But, it can also be from hypercalcemia, which can constrict afferent arteriole. It can also happen from vascular thrombus or medications like ACEIs, cyclosporine, NSAIDS, osmotic diuretics, catecholamines
What is intra-renal (or renal) azotemia?
Actual damage to nephrons. In ICU, usually from acute tubular necrosis, which occurs from prolonged hypoperfusion to kidney (so it can result from untreated pre-renal azotemia). Also, nephrotoxic substances can cause it.
What are some endogenous toxins that can cause intra-renal azotemia?
Myoglobin, hemoglobin, uric acid, Ca-Phos compounds.
What are some exogenous toxins (drugs) that can cause intra-renal azotemia?
AMGs, penecillins, cephalosporins, acyclovir, ampho B, cisplatin, methotrexate, cipro, IV dyes
Miscellaneous causes of intra-renal azotemia?
Inflammation from acute glomerulonephritis, pyelonephritis, infection, tumors, myeloma
What is post-renal azotemia?
Reversible form resulting from any obstruction to urine flow. It is uncommon (<10% of renal failure cases). It can be caused by BPH, malignancy, urethral stricture, ureteral obstruction, trauma, spinal cord dysfunction
What are the phases of acute renal failure?
(1) insult to oliguria or nonoliguria, (2) diuretic phase, (3) recovery phase
What is the insult to oliguria phase of acute renal failure?
Oliguria, lasts 8-14 days, seen often with ischemic acute tubular necrosis, and has higher mortality/morbidity than nonoliguric insult
What is the insult to nonoliguric phase of renal failure?
Normal urine flow (>400ml.day), with elevated BUN/Cr. Lasts 5-8 days with high urine output, but high serum Na and K. seen most often with nephrotoxic acute tubular necrosis (as opposed to ischemic ATN). It has a better prognosis that oliguric insult
What is the diuretic phase of acute renal failure?
Urine output of >400ml.day, lasts 2-8 days, lab values stop rising and stabilize. If pt gets RRT, may not see diuresis phase
What is the recovery phase of acute renal failure?
Lasts 3-12 months, labs first stabilize then return to normal, 15% of pts have residual renal insufficiency and 5% will require RRT
Clinical signs of acute renal failure?
Fluid retention, Gi bleeding, confusion, seizures, coma
How to treat acute renal failure?
Remove nephrotoxic agent, start diuretics, hydrate (increase perfusion and decrease tubular workload)
How to manage and monitor acute renal failure?
Dialysis, renal imaging, renal biopsy
how to manage post renal transplant with ATN?
d/c tacrolimus and start thymoglobulin, renally adjust all meds, give NS boluses, lasix, renal ultrasound, biopsy
When do dialysis in acute renal failure?
AEIOU:
Acidosis
Electrolytes (hyperkalemia)
Intoxication/overdose
Overload (fluid)
Uremia or azotemia (BUN>100 or Cr>2 or rise more than 1 in 24 hrs.
What is chronic renal failure?
Progressive deterioration of kidney function leading to uremia, occurs slowly, and is IRREVERSIBLE.
Most common causes of chronic renal failure?
un- or under-treated HTN, and/or DM, especially type I.
What are characteristics of stage I chronic renal failure?
Renal function decreased 40-60%, asymptomatic, with exocrine and regulatory function intact. Creatinine elevates to twice normal.
What amount of kidney function must be lost before s/s manifest?
60%. Although serum Cr starts to rise before this
Characterisitics of stage II chronic renal failure?
Renal function is 20-40% of normal, incerased BUN/Cr, with polyuria, nocturia, anemia. Creatinine rises to 4x normal, and hormone secretion starts to decline
Characteristics of stage III chronic renal failure?
aka ESRD. Renal function is <15%, excretory, regulatory, and hormonal functions are severely impaired, creatinine is >10, can’t keep homeostasis, uremia develops affecting all body symptoms
Clinical CNS manifestations of chronic renal failure?
Fatigue, malaise, HA, drowsiness, dementia, insomnia, stupor, coma
Clinical CV manifestations of chronic renal failure?
Edema, lyte imbalance, HTN, hypotension, pericarditis, atheromatosis, cardiomyopathy
Clinical GI manifestations of chronic renal failure?
N/V, gastritis, anorexia, GI ulcers, Gi bleeding, stomatitis, pancreatitis
Miscellaneous clinical manifestations of chronic renal failure?
Anemia, oliguria/anuria, muscle twitches, cramps, bone disease, thirst, yellow skin, pruritis, poor wound healing, sleep disorders, decreased libido, impotence
Major risk factors for developing CRF?
DM, BP, dyslipidemia, smoking, anemia, Ca and Phos
How manage HTN and CRF in diabetes?
Reduce BP to <130/80, use multiple HTN drugs, minimize proteinuria, LDL<70, HgbA1C<7%, modest dietary protein restriction (0.8-1g/kg/day), low salt (<2g/day), stop smoking
How manage hyperkalemia (a major risk factor for developing CRF)?
-Calcium gluconate IV (protect heart from high K),
-Glucose and insulin (activates Na/K ATPase),
-NaHCO3 (shift K into cells),
-Na polystyrene sulfonate (SPS), to exchange Na for K, po or pr.
-Dialysis
How to manage Ca and Phos imbalace (a major risk factor for developing CRF)?
Caused by decreased Vit D activation in kidney, and high phos due to low GFR and high PTH resistance in bone. Give aluminum antacids, Ca salts, Sevelamer, Calcitriol (1,25-dihyroxy-vitD3) 0.25mf/day, ergocalciferol (activated ergosterol, vit D2) at 500mcg/day
How to treat anemia (a major risk factor for developing CRF)?
Epo 50-100U/kg TIW IV or SQ. goal is Hct of 30-35%. Can also do blood transfusion, iron, and folate
Common sxs of acute viral hepatitis?
Myalgia, N/V, fatigue and malaise, change in smell and taste, right upper abdominal pain, coryza (cold), photophobia, HA, diarrhea (may have pale stool and dark urine)
AST or ALT more specific for liver?
ALT
Chronic hepatitis is asssociated with what major risks within 5 years of infection?
There is a 5 yr risk of hepatic decompensation (ascities, jaundice, variceal bleeding)
Incubation of hep A?
14-45 days, average 30 days.

hep B is 45-180 days
hep C is 2-26 weeks (as short as hep A and as long as hep B)
Complications of hepatitis A?
Fulminant hepatitis, cholestatic hepatitis, relapse, anicteric jaundice in kids, and icteric jaundice in adults. Almost all have chronic sequelae
Risk factors for hep A outbreak?
-usually occurs in context of community outbreaks associated with poor sanitation
-infection common from person to person in same household (which is facilitated by asymptomatic infection in kids)
-in 40-50% of cases, not risk factor is identifiable
HAV clinical presentation?
-preicteric: flu-like sxs
-abrupt onset of anorexia, N/V, right upper quadrant pain, and flu-like sxs
-Icteric hepatitis accompanied by dark urine, acholic (light colored) stools, worse systemic sxs, and pruritus.

PE: icteric sclera, skin, and secretions, mild wt loss, hepatomegaly

Lab:
-positive IgM anti-HAV, mildly high bili, gamma-globulins, ALT, AST (twice normal).
-If cholestatic disease, alk phos, GGT, and total bili rise
When in sequence of hep A infection are each of the following most prominent? IgM, ALT, viremia, HAV in stool, IgG, symptoms?
Viremia and HAV in stool in weeks 1-5.
ALT and IgM high in weeks 4-6.
IgG rises throughout the illness and beyond (at least 13 weeks).
Sxs are in weeks 2-8.
Treatment for hep A?
Supportive (usually self-limiting, diet, rest, fluid, avoid alcohol, hepatotoxic drugs). Post-vaccination and IG 0.02ml/kg IM once within 14 days, 85% effective
How to prevent hep A?
-Avoid tap water when traveling internationally,
-practice good hygeine,
-hep A vaccine,
-immune globulin (pre- and post-exposure. For short travel, 0.02ml/kg IM once. For long travel or continued exposure without vaccination (such as in household members), 0.06ml/kg IM Q 5 months
Indications for hepA IG?
Foreign travel to highly endemic areas, or post-exposure
Indications for hep A vaccine?
Anyone >2 yo in highly endemic areas, travelers to endemic areas, MSM, illegal drug users, occupational exposure, blood product recipients, chronic liver disease
Important lab tests to diagnose hep B infection?
Bilirubin, AST, ALT, alk phos, PT, albumin, serum globulin, CBC, coagulation
Cancer and hep B?
Liver cancer common in areas of the world where hep B is common
How common is symptomatic manifestation of acute hep B infection? Fulminant?
30% syptomatic. 70% are asymptomatic, with fulminant consisting of 0.1-0.5%.
Percentage of hep B infections that becomes chronic?
5-10% (defined as lasting more than 6 mos)

15-40% of those cause liver failure
Of hep-B-caused chronic infectious cases, how many lead to liver failure?
15-40%

but only 5-10% of hep B infections turn chronic (last more than 6 mos)
Relative ease of transmission of HBV, HCV, and HIV in IV drug use, sexual contact, perinatal, and occupational exposure?
HBV is most easily transmitted in each case except IV drug use, in which HCV is slightly more easily transmitted.
What is the most common way to get infected with HBV, HCV, or HIV in the U.S.?
Through contact with body fluids and blood
Steps taken to prevent hep B?
Vaccination, management of HBaAg+ patients (test all family members, vaccinate, test sex partner after hep B sequence for antibodies, educate family members)
Difference in serology between acute Hep B with recovery and progression from acute to chronic hep B?
In both cases, antiHBc IgM goes up then down over about 8 months, and total HBc goes up and stays up. However, in recovery, HBe and Hbs go away within 3 & 6 months (respectively), followed by appearance of anti-HBe and anti-HBs. But in chronic, HBe stays around a long time, until anti-HBe shows up maybe years later.
Which HBV genotype is most common is N. America? SouthEast Asia?
GT-A in america (A for America)
GT-B and C most common is SouthEast Asia
Which HBV genotype is most associated with positive outcome? With necroinflammation and hepatoma?
GT-A has best outcome. GT-C has highest necroinflammation and hepatoma (HCC) in older patients
Which HBV genotype responds best to interferon?
GT-B better than GT-C
What stage of hepB infection is likely if HBsAg is positive?
Acute or chronic or carrier hep B. (but not in past exposure or immunized)
What stage of hepB infection is likely if positive anti-HBsAg?
Past exposure (not acute, since not enough time to make it)
What stage of hepB infection is likely if positive for HBeAg?
Acute or chronic hep B (same reasoning as HBs). Not from immunization or past exposure
What stage of hepB infection is likely if positive for anti-HBcAg?
Acute or chronic or carrier or past exposures, but not immunization (vaccine doesn’t give HBc)
What stage of hepB infection is likely if positive for IgM anti-HBcAg?
Acute infection. It rises and falls within 6 months or so after infection. But total anti-HBc will be present in either acute infection or past exposures, but not from vaccination
What stage of hepB infection is likely if positive for HBV DNA?
Acute and possibly chronic and carrier. But not from past exposure or vaccination
What stage of hepB infection is likely if ALT is elevated?
Acute and chronic infection, but not past exposure or vaccination
What lab tests increase/decrease in liver disease?
Increased ALT, AST, bili, PT. decreased albumin. Liver histology and ultrasound can also be used to identify disease stage and grade, and tumors/cirrhosis
Goals of chronic Hep B treatment?
Sustained suppression of HBV replication and remission of liver disease. Want normal ALT, negative HBV DNA, loss of HBeAG +/- anti Hbe, improvement in liver histology, loss of HBsAG+/- HBsAG
Dosing for chronic hepB IG?
For post exposure prophylaxis. 0.06ml/kg IM, or 0.5ml for <12mo of age
Definition of HBV response to therapy?
Reduction in inflammation and fibrosis on biopsy, normal ALT, suppressed HBV DNA, disappearance of HBe and appearance of anti-HBe. Especially important to monitor ALT and HBV DNA
IFN treatment for Hep B?
subQ for 16 weeks. Then watch for seroconversion to HBe- or anti-HBe.
Has significant side effects and high cost, but no risk of resisitance. 90% normalization of LFTs, 25-40% loss of HBe and HBV DNA at 6 months. Maintains response for 2-11 years. Better response in women, adults, HIV negative, symptomatic acute infection, high ALT. can cause decompensation in cirrhotic pts
Lamivudine for hep B treatment?
Oral for 12 months. needs renal dose adjustment in renal insufficiency. Has high risk of resistance to YMDD mutant. Lamivudine is also used in HIV, but at a much higher dose. A prodrug, a nucleoside analogue (like entecavir), must be triphophorylated to be active. Directly inhibits viral replication.
Adefovir treatment for heb B?
Oral daily for 12 months. needs renal dose adjustment in renal pts. Has low incidence (2-3% at 2 years) of resistance. A nucleotide analogue also a prodrug. Active against wild type and YMDD mutant.
Entecavir for hep B treatment?
Oral for 12 months, needs renal adjustment (QOD for 20-48ml/min or q72h for 10-19ml/min, or even q weekly if on dialysis). Best histological improvement, but also most expensive. Nucleoside analogue (like lamivudine), triphosphorylated to be active. Not active against HIV, directly inhibits viral replication.
Lamivudine resistance?
YMDD mutant is less virulent than wild-type, and occure 14-32% after 1 year, or up to 50% after 3 years. Test for elevated LFTs and HBV DNA. If needed, start adefovir and then d/c lamivudine when HBV DNA goes down
Adverse effects of entecavir?
HA, insomnia, N/V, NASH, lactic acidosis and severe hepatomegaly with steatosis

Entecavir provides best histological improvement, but also most expensive. Nucleoside analogue (like lamivudine), triphosphorylated to be active. Not active against HIV, directly inhibits viral replication.
How is response to hep C treament defined?
Liver enzymes (ALT), histology (biopsy), virology (HCV load), and SVR (sustained virologic response) 24 weeks after treatment cessation. EVR (early virologic response) is considered a negative HCV RNA or 2-log drop at week 12-24. If this doesn’t happen, then continued treatment has 97% failure rate, so reponse at 12 weeks predicts longterm response
Which hep C genotype is most common is U.S.?
Type 1 by far (75%), which is also the most difficult to treat.
difference between protectiveness of antibodies in HCV and HBV?
Anti-HCV is not protective in hep C like anti-HBV is in hep B
Interferon treatment for hep C?
Mechanism unclear (maybe immunomodulatory) give 50% initial dose, or gradual titration. d/c if intolerable side effects. Give TIW or pegylated once weekly
How is treatment for hep C based on hep C genotype?
If genotype 1, treat with IFN and ribavirin for one year. If genotype 2, treat with IFN and ribavirin for 6 months
For treating genotype 1 hep C, what does the algorithm say should be done at any time starting at week 12, all the way up to 24 months post treatment, if HCV RNA is detected?
At week 12, if RNA hasn’t dropped at least 2 log units, or if at any other time after that, RNA is detectable, the algorithm says to stop therapy, follow clinically, enroll in clinical trial, consider alternative therapies, or consider maintenance pegylated IFN monotherapy if advanced fibrosis
For treating genotype 1 hep C, when does the algorithm say HCV RNA should be tested, and what is dose of ribavirin?
Dose of ribavirin is 1000mg or 1200mg daily if <75kg or >75kg. Check HCV RNA at 12 weeks on therapy, 24 weeks, 48 weeks (end of therapy), and 24 weeks post-therapy. Only continue therapy if RNA is undetectable (or has dropped more than 2 log units after first 12 weeks).
Algorithm for IFN and ribavirin treatment for genotype 2 or 3 hep C infection?
Pegylated or standard IFN and ribavirin 800mg for 24 weeks. Check RNA at end of therapy and 24 weeks post-treatment. In either case, if RNA is detectable, follow clinically, enroll in clinical trial, consider alternative treatments, or consider maintenance IFN monotherapy if advanced fibrosis
Indications for hep C treatment?
≥18yo, high ALT, significant hepatitis with fibrosis, compensated liver disease (no ascites or encephalopathy), prior treatment for HCV, hx of depression, but controlled.
Contraindications for hep C treatment?
Major, uncontrolled depression (IFN-induced), renal, heart, or lung transplant recipient, automimmune hepatitis, untreated hyperthyroidism (IFN can mess up thyroid function), pregnancy, or no contraception use, severe co-morbidity, <3yo, hypersensitivity to HCV drugs..
Key side effects of interferon?
Flu-like and depression, MANY others
Adverse effects of lamivudine treatment?
Rash, insomnia, HA, N/V, pancreatitis, peripheral neuropathy, rare non-alcoholic steatic hepatitis (NASH) with nucleoside analogues
Adverse effects of adefovir?
N/D, flatulence, abd pain, HA, neuropathy, asthenia, nephrotoxic (fanconi type picture increase Cr, PO4). Beware of hepatic flares, renal tox, HIV resisitance, lactic acidosis
How know when not to treat Hep B?
Don’t treat acute. Wait and see. In chronic and carrier, HBs is positive for more than 6 months. But, if HBe is negative and HBV DNA is negative, then pt is carrier, and there is not need for therapy.
How to establish whether hep B pt has gone from acute to chronic (and not carrier) status? And what to evaluate next?
Chronic and carriers are HBs positive. But, if also HBe positive and HBV DNA positive, then it is a chronic case, and must see if ALT is >200 and if DNA is <200. If yes, treat with IFN x16 weeks. If not, then treat with lamivudine or entecavir. And in both cases, monitor seroconversion from HBe to anti-HBe. If stay or become DNA positive, consider adefovir, tenofovir, or investigational drugs.
If chronic hep B pt has received IFN or lamivudine therapy, and assessment of seroconversion from HBe to anti-HBe has been made, what steps are next in the treatment algorithm?
If conversion hasn’t happened, continue therapy maybe indefinitely or consider lamivudine or entecavir. If seroconversion has occurred, stop therapy and continue to monitor.
% of exposed hep C pts that resolve after acute phase?
25%.

75% turn into chronic infection (0f which 80% become stable, and 20% get cirrhosis)
% of chronic hep C cases that become stable (as opposed to cirrhotic)?
80% (of the 75% of cases of HCV that become chronic. The other 25% resolve after acute infection).
% of hep-C cirrhotic pts that disease progresses slowly?
75%.

So, it starts with infection. 75% of those turn chronic. 20% of those develop cirrhosis. And in 75% of those, the disease develops slowly while the other 25% go quickly into liver failure and death (usually facilitated by alcohol and/or HIV)
% of hep C cirrhotic pts that go into liver failure, HCC, transplant, or death?
25% (usually exacerbated by HIV and/or EtOH)

The other 75% have cirrhosis develop slowly
What group(s) have highest hep C infection rate in U.S?
Hemophilia, IVD users, and hemodialysis pts. (all from blood products)
Difference in serology between recovery from acute hep C and chronic hep C infection?
In both, anti-HCV rises then plateaus. And in both, sxs occur in months 1-5, or longer. But, in chronic, HCV RNA persists instead of dropping off like in recovery. And ALT is sporadically high in chronic, but goes to normal in recovery
Key monitoring parameters for hep C treatment?
Baseline ALT, CBC monthly, TSH, pregnancy monthly, genotype, HCV RNA every 3 months, liver biopsy, HIV. Then monthly ALT, CBC. Q 3 months TSH, HCV RNA at week 12, 24, and 48. Monitor depression
4 negative predictors of response to hep C treatment?
Cirrhosis, male, HCV RNA>10^6 copies/ml, genotype 1
3 therapeutic options to treat treatment relapse of hep C?
Higher dose IFN monotherapy, combo for 24 weeks, longer treatment duration (48 weeks), or pegylated IFN monotherapy
Contraindications for pegIFN treatment?
Creatinine clearance <50ml/min, severe depression, psychiatric instability, active substance abuse, uncontrolled autoimmune disorder (thyroid, DM, RA, etc)
Contraindications for ribavirin?
Unstable cardiac disease, severe COPD, asthma, renal dysfunction, hemoglobinopathies, pregnancy (or risk of)
Side effects of ribavirin?
Hemolytic anemia, teratogenicity, cough and dyspnea, rash, pruritus, insomnia, anorexia
Anemia and SVR?
SVR is sustained virologic response. It is decreased in anemia because hemolysis from ribavirin is worse and bone marrow is suppressed from IFN, so side effects are worse, and compliance goes down the tube. So, in anemia, ribavirin dose needs to be decreased or d/c’d
Nucleic acid is RNA. Hep A and/or B and/or C?
A and C, not B. HBV is a DNA virus.
Major source of the virus is blood/body fluids. Hep A and/or B and/or C?
Hep B and C, but not A. Major source of A is feces
Becomes a chronic condition about 70% of the time. Hep A and/or B and/or C?
Hep C. Hep B becomes chronic 5-10% of the time, and Hep A does not turn into a chronic infection
Can cause acute hepatitis Hep A and/or B and/or C?
Hep A and B, but very rarely from Hep C
Which acute infection is treated? Hep A and/or B and/or C?
HAV can only be acute, never chronic, and the only treatment is supportive. HBV infection isn’t treated unless/until it turns chronic. HCV infection is very rarely acute.
Treated with IFN for 16 weeks. Hep A and/or B and/or C?
HBV infection if HBe+ is treated with 16 weeks of IFN subQ, or 12-18 months is HBe-. IFN alone or in combination with ribavirin is used to treat hepC infection too, but either for 6 months (if genotype 2 or 3), or 1 year (if genotype 1). HAV is not treated pharmacologically.
Treated with ribavirin alone? Hep A and/or B and/or C?
None of them. However, Ribavirin is used in combination with IFN to treat HepC infection (for 6 months if HCV is genotype 2 or 3), (or 1 year if HCV is genotype 1). Alternatively, IFN can be used alone in the same way.
Vaccine available. Hep A and/or B and/or C?
A and B, not C
Can cause HCC (hepatocellular carcinoma). Hep A and/or B and/or C?
All three
Good hygeine is critical in preventing transmission. Hep A and/or B and/or C?
Hep A mostly (avoid food and water in highly endemic areas). Hep B transmission is likely with needles, tattoos, piercings, and sex. Hep C is prevented from screening blood donors, and risk behavior modification.
Transmitted perinatally (from mother to infant). Hep A and/or B and/or C?
Hep B, and rarely hep C.
Transmitted sexually. Hep A and/or B and/or C?
A and B, and rarely C
Incubation time is as little as 2 weeks. Hep A and/or B and/or C?
A and C. Hep A incubation is 14-45 days. Hep B is 45-180 days. Hep C is 2-26 weeks.
Is anicteric in 75% of patients. Hep A and/or B and/or C?
Hep C. However, Hep A is anicteric in kids but not adults, and Hep B is anicteric in 70% of kids <5yo and 50-70% in individuals ≥5yo.
When to use which dose of Ribavirin: 800mg, 1000mg, or 1200mg?
800mg daily, in combination with IFN should be used for six months (24 weeks) of treatment for genotype 2 or 3 hep C infection. The higher doses are used to treat genotype 1 hep C infection for one year. 1000mg is for pt weighing <75kg, and 1200mg is for patient weighing ≥75kg.
When are lamivudine or adefovir or entecavir used to treat hepatitis?
If after six months, patient is HBs positive AS WELL AS HBe positive AND HBV DNA positive, then check ALT and DNA. If ALT is >200 and DNA is <200, treat with IFN x16 weeks. If not, then treat with lamivudine or adefovir or entecavir. All three are oral 12 months, and must be adjusted in cases of renal insufficiency
Can cause fulminant (precipitous, aggressive, and rapid) hepatitis. Hep A and/or B and/or C?
Relatively common is Hep A, but only 0.1-0.5% of Hep B infections. (no info for Hep C)
Cholestasis and relapse hepatitis are common complications. Hep A and/or B and/or C?
Hep A. However, Hep C commonly leads to cirrhosis and liver failure.
Symptoms include flu-like sxs, dark urine, pale stools, pruritus, upper right quadrant pain. Hep A and/or B and/or C?
Hep A. Hep B presents with fatigue, anxiety, malaise, ascities, jaundice, variceal bleeding, encephalopathy, vomiting, seizures, icterus
What is included as supportive therapy in hepatitis A infection?
Diet, rest, fluids, no EtOH or hepatotoxic drugs
Indications for hepA vaccine?
Adults and children ≥2yo in highly endemic areas, or if illicit drug use, MSM, chronic liver disease, liver transplant, or chronic exposure
Indications for Hep B vaccine?
(1) if exposed, (2) all infants, kids, adolescents, (3) sex partners, household contacts, MSM, IV drug use, travel to highly endemic areas, occupational exposure, inmates
Goals of Hep B therapy?
Sustained suppression of HBV replication, remission of liver disease, normal ALT, negative or low HBV DNA, loss of HBe and HBs, improvement in liver histology (biopsy)
In which type of Hep B infection is HBsAg present for >6 mos? (A).Acute, resolved, (B).Chronic, (C).carrier
B and C, but negative after six months in acute resolved case.
In which type of hep B infection is ALT normal? (A).Acute, resolved, (B).Chronic, (C).carrier
A and C, but not B. In chronic state, ALT is intermittently elevated beyond 2 times the upper limit of normal.
In which type of hep B infection is serum HBV DNA present in >10^5 copies per ml? (A).Acute, resolved, (B).Chronic, (C).carrier
B.chronic. In carrier status, it is present, but less than 10^5 copies per ml. In acute resolved, it is undetectable
In which type of hep B infection is histology biopsy inflammation score <4? (A).Acute, resolved, (B).Chronic, (C).carrier
C.carrier. In chronic cases, score is ≥4, and in acute resolved, there is no significant inflammation on liver biopsy

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