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615 Cards in this Set

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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
In which type of hep B infection is anti-HBc present? (A).Acute, resolved, (B).Chronic, (C).carrier
All three. This is the antibody to the core antigen. However, the antibody is not produced in vaccinated individuals who have never been exposed (because the vaccine doesn’t contain the core antigen?)
How does cirrhosis occur?
Cells are injured and destroyed, and in the process of regeneration, nodular fibrous tissue replaces normal lung parenchyma
Two types of changes to liver cell function in cirrhosis?
(intrinsic) = Metabolic dysfunction, and synthesis dysfunction (structural) = change in blood flow such as portal blood pressure change
Describe the liver lobule?
Has portal triad (actually four vessels) made of portal vein (from gut), hepatic artery (oxygenated blood from heart), bile duct (to collect bile) and lymphatic vessel (to collect lymphatic fluid)
What changes occur in sinusoids in cirrhosis?
NO and endothelin (and other vasoactive substances) should be in balance, but in cirrhosis, fibrous tissue in sinusoids can limit dilator function, so increases back-pressure
What’s Ascites?
Accumulation of lymph fluid in peritoneal cavity. More than half of patients develop asctites within 10 years of diagonosis of hepatic failure. Muscle wasting also occurs because source of glucose, which is the liver glycogen in a healthy liver, is muscle protein if liver failure
Pathogenesis of ascites?
Systemic vasodilation → decreased systemic resistance→ decreases MAP→increased CO (which doesn’t help because you’ve got back pressure throughout GI). Vasodilation activates kidney (decreased GFR and increased water and Na retention). Hyperaldosteronism results, and exacerbates the problem
What’s hepatic encephalopathy?
Increased GI nitrogenous substances bypass the liver and go to CNS. Ammonia (from gut bacteria and protein breakdown) either causes, or is a key player in causing encephalopathy
Other theories and factors affecting encephalopathy (besides just ammonia)
Accumulation of toxic metabolites, alteration of BBB, NT imbalance, altered cerebral metabolism, impaired neuronal membrane Na/K ATPase, increase of GABA/BDZs
Classification of encephalopathy severity?
sub-clinical (subtle changes that are not clinically apparent),
Acute (lasting <4 weeks and having full recovery),
chronic (≥4 weeks, with fluctuating severity).
What coagulation defects occur in cirrhosis?
Decrease in synthesis of coag factors, decreased clearance of activated clotting factors. This affects the vit K-dependent clotting factors and increases PT time
What is the significance of thrombocytopenia in liver disease?
An indicator of severity of liver disease. It is caused by three main factors:
(1) increased destruction of platelets in the spleen,
(2) increased immune mediated destruction of platelets,
(3) decreased bone marrow production of platelets.

It obviously leads to increased risk of bleeds.
Clinical presentation of liver cirrhosis?
Can be asymptomatic and have broad spectrum of effects. Some sxs include pruritis, dark urine, increased abdominal girth, decreased appetite, weight loss, jaundice, palmar erythema, spider angiomas, gynecomastia. Can results from EtOH abuse, and drug use, or occupational exposure to toxins
What’s hepatorenal syndrome?
Systemic complicaiton of cirrhosis. Vasoconstriction of afferent arteries to conserve lytes and fluid (in response to systemic vasodilation from liver failure)
What’s hepatopulmonary syndrome?
Ascities, intrapulmonary shunting
What’s endocrine dysfunction of liver cirrhosis?
Feminization, hypogonadism, hypothyroidism, gynecomastia
What is the effect of portal HTN on spleen?
Backflow pushes more blood to spleen, leading to increased platelet destruction (part of the clotting problem in liver failure)
What is effect of portal HTN on stomach and esophagus?
Backflow of blood goes through left gastric vein and causes varices. The varices go up through the esophagus, and can cause bleeding (life-threatening), It is the number one cause of death in hepatic failure. The extra blood being digested can also lead to encephalopathy. 70% of patients will re-bleed in one year
Important liver function tests
Alk phos, AST (aka SGOT), ALT (aka SGPT), GGT (gamma glutamyl transpeptidase), bilirubin, albumin
What is limit in utility of liver tests in cirrhosis?
Not as useful once liver failure has occurred, because most tests detect cellular damage (which already occurred in the past).

However, tests that are good to test for level of cirrhosis are Albumin and Clotting factors (synthesis activity). Factors I, II, V, VII, IX, X
Liver biopsy for hepatic failure?
Invasive, so done only when diagnosis is unsure. And false negative are common. Plus, bleeding is a problem for liver patients, so don’t want to puncture them
Child-pugh classification?
Assessment of degree in cirrhosis. It is based on bili levels, albumin levels, INR, ascites, encephalopathy

Child Class A: 5 to 6 points
Life expectancy: 15 to 20 years
Abdominal surgery peri-operative mortality: 10%
Child Class B: 7 to 9 points
Indicated for liver transplantation evaluation
Abdominal surgery peri-operative mortality: 30%
Child Class C: 10 to 15 points
Life expectancy: 1 to 3 years
Abdominal surgery peri-operative mortality: 82%
Goals of cirrhosis management?
Resolve acute complications, prevent complications, identify and treat the cause, assess risk for variceal bleeding, evaluate for ascites and spontaneous bacerial peritonitis (SBP), evaluate for encephalopathy, monitor of hepatorenal syndrome, pulmonary insufficiencyt, and endocrine
Goals of treatment of bleeding varices?
Primary prophylaxis, treat acute bleeding episosodes, and secondary prophylaxis
How do beta blockers help in varices, portal HTN?
Non-selective will decrease contractility of heart, and constrict blood vessels, to decrease overall flow to mesenteric vasculature
How can nitrates be used to treat varices and portal HTN?
Smooth muscle vasodilation (use isosorbide mononitrate)
What non-selective beta blockers are used to treat varices?
Propanolol 10mg TID (titrate to decrease resting heart rate 20-25% or 55-66)
Nadolol 20mg once daily (same titration)
Starting dose for isosorbide monnitrate for varices?
20mg BID. If tolerated (can cause severe headaches due to vasodilation), increase to TID in after one week
How to treat acute bleeding varices?
Resuscitation, correct coagulopathy, thrombocytopenia give FFP (fresh frozen plasma), platelets, and vit K, but vit K takes a day or so to work. Control bleeding, prevent re-bleeding. Know of risk factors (EtOH, NSAIDS, ASA, previous bleed)
What are components of general resuscitation in acute varices?
Airway (elective intubation), fluid resusciation (colloids and blood products, not crystalline products), maintain adequate systemic pressure (pressors). Colloids are dextrans, starch, and albumin
Mechanism and dosing of octreotide and somatostatin to treat acute varices bleeding?
Causes mesenteric vasoconstriction and decreases portal pressure. 50mcg bolus, then 25-50mcg/hr continuous infusion.
Mechanism and dosing for vasopressin in acute variceal bleeding?
Non-selective vasoconstriction, so increases systemic BP, and so has more side effects than octreotide and somatostatin. By constricting the mesentery, it decreases portal pressure. Dosing is 0.2-0.4 units/min continuous infusion.
What is Terlipressin?
A vasopressin analogue, used to constrict mesenteric vasculature to decrease portal pressure (control acute variceal bleeding). It is not available in the U.S.
Two surgical interventions for esophageal varices?
Esophagogastroduodenoscopy (EGD):
-Scleropathy (inject NS or something into the varices), or
-band ligation (tie varices off so they slough off)
Balloon tamponade for varices?
Balloons in stomach or esophagus can put direct pressure on bleeding varices in acute bleeds. Is only temporary or can cause cell death
What is TIPS?
Transjugular intrahepatic portosystemic shunt. A shunt put between portal vein and hepatic vein. However, it clots off after a year in half of patients.
What is advantage of portacaval shunt in liver failure?
In leaves portal vein intact, so can use it in future transplant. It just goes from portal vein to inferior vena cava
Treatments to prevent re-bleeding in varices?
Beta blockers (21% reduction), combo beta blockers and nitrates, endoscopy (more preferred), band ligation gives 45% reduction. Scleropathy give 27% reduction
Goals of treating ascites?
Improve QOL, prevent serious complications (spontaneous bacterial peritonitiis, rupture of umbilical hernia)
How to assess new cases of ascites?
Paracentesis (analyze fluid). Look at serum albumin gradient (SAG). If >1.1g/dL, then it’s probably due to portal HTN, and will respond to salt restriction and diuretics. If SAG<1.1g/dL, it’s probably not due to portal HTN, and will not respond to salt restriction and diuretics
Treatment for ascites?
Sodium restriction (2000mg/day), and diuretic therapy. Spironolactone + Furosemide. 100mg/40mg ratio, can increase to max of 400mg/160mg. Goal is 0.5kg weight loss per day (or more of peripheral edema as well). Other K-sparing diuretics not as useful because spironolactone is an aldosterone antagonist (remember high aldo in hepatic pts). Contraindicated if renal failure, encephalopathy, severe hyponatremia.

Just a side note: gynecomastia is a problem in liver failure, but it is made worse by spironolactone due to its inhibition of aromatase (less T, more Estradiol).
How to monitor ascites treatment?
Check urine electrolytes. In health, Na is higher than K, but in liver failure (and therefore hyperaldosteronism), K is wasted, and Na is reabsorbed. So, check urine lytes to se if K is being saved and Na excreted
When is paracentesis indicated?
If patient has respiratory distress. However, albumin needs to be given (if greater than 5L removed) to prevent post-paracentesis systemic collapse (keep fluid in the vasculature)
Ascites treatments other than meds or paracentesis?
Liver transplant, TIPS, peritoneal venous shunt
SBP?
Spontaneous bacterial peritonitis. Most common bacteria is E.coli, others. Occurs in 10-25% of ascites patients, and increases protein in ascitic fluid. Treated with abx
Risks of ascites treatments?
Lyte disturbances, hypovolemia, renal insufficiency, acid base disturbance, hepatic encephalopathy
Describe acute fulminant liver failure?
Rapid onset from drowsiness to coma in 24hrs. (severe encephaolopathy)
Problems associated with acute encephalopathy (from chronic liver failure)?
Reversible. GI bleed, infection, electrolyte inbalance, sedative, dietary (less aromatic AAs which act as false neurotransmitters in brain), renal failure.
Causes and associated factors with chronic encephalopathy?
Not reversible. From precipitating factors, post TIPS, PC shunt, etc..
Treat hepatic encephalopathy?
Reduce blood ammonia (drugs, dietary protein restriction), inhibit GABA-benzo receptors = flumazenil 0.2-15mg IV. Inhibit false neurotransmitters (give plant AAs instead of animal AAs)
How does lactulose work to treat encephalopathy?
At low pH, lactulose inhibits bacterial breakdown of protein. Also low pH favors NH4+ over NH3 (so less ammonia absorbed). Also is a cathartic, so empties colon faster to get rid of ammonia
How do antibiotics treat encephalopathy? Neomycin dose?
Neomycin, metronidazole, and vanco kill urease-producing bacteria, so less ammonia. Neomycin dose is 1-4g 4x daily
How can lactobacillus acidophilus treat encephalopathy?
Replace urease bacteria with non-urease bacteria
How does zinc help with encephalopathy?
Cofactor for removal of ammonia
Dosing for lactulose?
Oral: 30-60ml q 1-2hrs until bowel movement, then decrease to 15-30ml 4x daily. Titrate to 2-4 soft BM. Rectal: 300ml in 700ml water retention enema hold 30-60 minutes, then decrease q 6-8hrs
Pharmacokinetic changes in liver failure?
Absorption, distribution, elimination, protein binding. Less first pass effect, so higher systemic concentration. Fluid shifts can change Vd.
Pharmacodynamic changes in liver failure?
Increased sensitivity
How does decreased hepatic blood flow and decreased intrinsic activity of the liver in cirrhosis affect drug clearance?
High extraction drugs accumulate (example is lidocaine) due to low flow, and there is less metabolism of low extraction drugs (like warfarin) due to less intrinsic activity
Phase I and phase II metabolism changes in liver failure?
Phase I is P450 system, and is significantly reduced in cirrhosis. Phase II is conjugation, and is relatively unchanged in cirrhosis
Rules of thumb for dosage changes in liver failure?
Important for drugs that are primarily hepatically cleared. There are no specific recommendations for dose adjustment. Need to monitor the response and anticipate drug accumulation
What type of vascular access for hemodialysis is the best?
AV fistulas, as opposed to graft and catheter
Why is hemodialysis more common than other forms of dialysis in the U.S. than other countries?
It is reimbursed more, and Fellows are more trained in it, so it gets passed on. PD is a little more in a few other countries
Indications for RRT? (hemodialysis, PD, etc..)
AEIOU (acidosis, electrolytes, intoxication or ingestion, overload, uremia)
What acid/base state is an indication for RRT?
Acidosis <7.1
What electrolyte disorder is an indication for RRT?
Hyperkalemia (>6.5 mEq/L), or rapidly rising K levels
Ingestion or (intoxication) of what substances are an indication for RRT?
Salicylates, lithium, methanol, ethylene glycol, theophylline, pentobarbitol
What is meant by overload as an indication for RRT?
Fluid overload, post-operative fluid gain
Details of uremia as an indication for RRT?
High catabolism, leads to plasma creatinine >12 mg/dL, and/or BUN >100mg/dL. Signs of uremia include pericarditis, neuropathy, or unexplained decline in mental status
How do the principles of diffusion, osmosis, solvent drag, and convection apply to hemodialysis?
Solutes pass through membrane pores either by diffusion or convection (ultrafiltration). Diffusion depends on concentration gradient. Convection occurs when water is driven by hydrostatic pressure or osmotic force through a membrane. Solvent drag is when solutes are swept along with the water.
What procceses does intermittent hemodialysis use? How long is it, and what are goals based on? What should be Qd and Qb?
IHD. Diffusive clearance depends on concentration, convective clearance depends on pore size. Lasts 3-4 hrs, goal is based on dry weight. Pts can gain 1-4 kg between sessions. Dialysate Flow rate (Qd) = 500mL/min. Blood flow rate (Qb) = 350 mL/min, minimum 200mL/min.
What is the difference between high efficiency, high flux, and AN69 dialysis filters?
High efficiency filters are simply bigger (more surface area). High flux filters have bigger pore size, so can remove larger molecules. There is a reaction between AN69 filters and ACEIs, which can cause anaphylaxis due to negative charges activating bradykinin system.
What should potassium and calcium levels be in the dialysate used in IHD?
Calcium 2.5-3.5, and K 2-4.5. This will remove a lot of Ca and K from blood, which will cause significant hypokalemia immediately after dialysis, but do not treat it, because after 1-2 hours, it will rebound (shift from ICF?)
Anticoagulants for IHD? And what are choices if can’t use anticoagulators?
Heparin, and tight hepariniazation. Heparin bolus followed by continuous infusion (example 2000U, then 1200U/hr). Tight herparinization is for patients at risk for bleeding, so reduce dose to 750 unit bolus and 600U/hr infusion. Alternatives include saline flushes 100-250ml every 30 minutes, but not as effective. Or use trisodium citrate or calcium chloride.
What is disadvantage to fistula? Disadvantage to grafts?
Fistulas take months to develop. Grafts are temporary and subject to infection (same problem as catheters, which also have poor blood flow and poor dialysis)
What is Kt/V?
Clearance of urea (in dialysis). Kt is rate of urea clearance in dialyzer multiplied by duration of dialysis. V is Vd of urea in the pt. The minimum value for survival benefits is 1.2 (or 1.4 in diabetics)
What’s URR?
Urea reduction ratio (should be minimum of 65% for IHD). Basically the ratio of urea removed by dialysis
Complications associated with IHD (intermittent hemodialysis)?
line sepsis
hypotension/cramping
chest pain/HA
pruritis
N/V
How to prevent line sepsis in IHD?
Use AV fistulas, avoid long term catheter use, use broad spectrum abx with staphylococcal coverage
How to prevent hypotension and cramping in IHD?
(1) Trendelenburg position (head lower than body),
(2) NS 100-500mL,
(3) avoid excessive ultrafiltration (**reassess dry weight**),
(4) slow the ultrafiltration rate,
(5) perform isolated ultrafiltration.
(6) Can also increase dialsylate sodium (to prevent fluid shifts), it’s called sodium ramping in which you increase Na to 148mEq/L and decrease stepwise during dialysis.
(7) Switch from acetate to bicarb-buffered dialysate because acetate can inappropriately reduce total vascular resistance, increase venous pooling and O2 demand.
(8) reduce dialystate temp from 37 to 34-35.
(9) give midodrine 2.5-10mg po 30 minutes predialysis,
(10) hold anitHTNs before dialysis, (11) give oxygen.
Pharmacologic treatment for cramping in dialysis?
Quinine 200-300mg po QHS, or gabapentin 100mg po q 2 days to max 200mg po qhs, but gabapentin is cleared renally and causes drowsiness.
What are other complications of IHD besides line sepsis, hypotension and cramping?
N/V and pruritis. Treat with antiemetics like chlorpromazine or Ondansetron
How to treat pruritis in IHD?
(1) Regular intensive dialysis,
(2) hydrocortisone cream 1% tid-qid prn affected areas.
(3) diphenhydramine 25mg po or iv q 8-12 h prn,
(4) charcoal capsules 6g/day divided in 4-6 doses, to reduce bili in gut,
(5) cholstyramine 4g po BID, but space other meds 1 hr before or 4-6 hr after it.
How to treat chest pain and HA in IHD?
Set ultrafiltration to zero (don’t remove any water), nasal O2, Nitroglycerine sublingual if angina. Give Tylenol 650mg po q6h prn, not NSAIDS, not because of renal function but because of possible heart effect from high volume
Indications for CRRT?
Continuous renal replacement therapy. Hemodynanimc instability, ICU patients are catabolic, better control of azotemia, excessive volume overload, spesis, SIRS?
What is difference in Kt/V between CRRT and IHD?
CRRT gives 5.25-9.8 per week, compared to IHD of 3.6 per week. Same as a creatinine clearance of 30-40mL/min
What are advantages/disadvantages between arteriovenous and venovenous access?
Arteriovenous access uses patients own BP to maintain access, but has risk of bleeding, atheroembolic complications.
Venovenous accress uses external pump to maintain access, and has better performance due to constant flow. However, there is a risk of embolism if lines disconnect and with the longer lines, there is more risk of clotting
What is CVVH? How does it work?
Continuous venovenous hemoFILTRATION. It uses convective clearance with no dialysis solution. (as opposed to CVVHD which uses diffusive clearance and dialysate only) Replacement solution is given pre- or post-filter (25-50L)
What’s CVVHD?
Continous venovenous hemodialysis. It uses diffusive clearance (as opposed to CVVH which uses convective clearance), and uses dialysate only. Blood flow maintained by pump.
What is CVVHDF?
Continuous venovenous hemodiafiltration. It uses both convective and diffusive clearance with dialysate and replacement solutions (20L). blood flow in smaintained by a pump.
What not use heparin as anticoag in RRT?
Increased risk of thrombocytopenia, and bleeding
Key features of UCSD dialysis circuit?
Dialysate has zero Ca due to citrate (chelation risk)
Blood flow rate and dialysate and UF rate in UCSD dialysis circuit?
Blood flow is 100ml/min. Dialysate plus UF rate add up to about 30-40ml/min, which is an adequate creatinine clearance.
PD?
Perinoneal membrane is the dialyzer. So how well it works is different from person to person. Advantage is that it reserves RRF (residual renal function). So it is good if clearance is still>20mL/min
What determines diffusive clearance in PD?
Concentration gradient
What determines UF rate in PD?
Glucose concentration
How does CAPD work?
"continuous ambulatory peritoneal dialysis".
Clamp effluent bag for 4-6 hrs, then unclamp it to drain it. Dextrose concentration dictates how much fluid gets removed (based on osmosis), but so does glucose and other substances.
What is advantage to CCPD?
"continuous (or chronic) cycling peritoneal dialysis"
It pumps dialysate in, then out every 30-60minutes at night, and dwell of 500-1000ml during day (so bags don’t have to be hooked up constantly) APD (automated) is another name for this
What’s the PET in RRT?
How well someone’s peritoneal membrane can transport. Low transporters are better because glucose can’t cross the membrane as fast. High transporters have more permeable membrane (you’d think this is good), but they lose glucose fast, so need rapid cycling CCPD
How to prevent exit site infection for PD?
Daily cleansing, hand hygeine, and mupirocin cream (controversial due to efficacy against staph aureua, but resistance and allowing growth of pseudomonas aerruginosa
How to treat exit site infections?
Abx for 14 days
How to prevent peritonitis?
Prophylactic abx administered at time of catheter insertion. Good training and spiking techniques.
s/s peritonitis
Cloudy effluent, abdominal pain, N/V
How calculate ideal body weight?
Males=50 + 2.3(every inch over five feet). Females = 45.5 + 2.3(every lb over five feet)
How to classify urine output?
Anuria = <50ml./day. Oliguria = <400ml/day. Polyuria = >2500ml/day
Cockcroft gault equation?
Estimation of creatinine clearance, but alone not totally reliable Overestimates Cre clearance in low renal function. CrCl=[ (140-age)wt]/(72*Scre). If female, multiply by 0.85
What is MDRD equation for?
Calculate GFR based on Modification of Diet and Renal Disease. don’t need weight.
What’s the Jeliffe equation for?
Used to calculate GFR in quickly changing renal function
How to calculate CrCl from 24 hr urine collection?
(Ucr)(Uvolume/time)/(Plasma Cre)
Changes to absorption due to renal failure?
GI transit time, gastric acid (antacids, H2s), V/D, edema of GI tract, decreased 1st pass effect
Changes in distribution in renal failure? Which drugs most affected?
Change protein binding and tissue binding, Albumin and alpha 1 acid glycoprotein, decreased binding of acidic drugs, but normal or slightly changed binding of basic drugs. Be careful of central compartment effects. Dosing should be based on dry weight, since volume overload can result from retention.
Changes in metabolism in renal failure?
Change hepatic metabolism, problem in Chronic kidney disease rather than acute renal failure. There are CYPs in kidney, so metabolic clearance may be increased, unchanged, or decreased. Difficult to quantify effects of renal failure on hepatic metabolism.
Drug factors that affect their removal by dialysis?
Molecular weight (convection, but not diffusion, is independent of MW), Vd, protein binding, extent of renal and non-renal elimination. Clearance by RRT is significant when contributes >30% of total clearance
What consideration need to be
made regarding Vd of drugs in dialysis?
If large Vd, will not be removed by IHD. If Vd<1 L/kg, then more likely to be removed by RRT. If Vd>2 L/kg, less likely to be removed by RRT.
What is sieving coefficient, and how does protein binding affect removal of drugs by dialysis?
Sieving coefficient is the capacity of the drug to pass the membrane by convection. The main determinant is protein binding, so SC ~ (1-PB) if not published. However, estimations have been shown to be unreliable sometimes, so use published values when possible
How does peritonitis affect drug clearance in dialysis?
For PD, if peritonitis, get much higher clearance
How does the filter affect removal of drugs in dialysis?
High efficiency filters have higher urea clearance. High flux filters use lower pressue gardient, but can remove larger molecules like microglobulins
Aminoglycosides and AN69 dialysis filter?
Aminoglycosides bind to surface of AN69 filter, saturating after 30-60 minutes, so give drug after dialysis
How should post- or predilution in dialysis be considered in drug removal for dialysis?
Dilution needs to be calculated into calculation of clearance
What can use as a reference to know how to adjust drug doses in dialysis patients?
Can dose based on ClCr, serum concentrations, and/or pharmacodynamics. Consult literature.
How to calculate loading dose adjustment in renal failure?
Loading dose usually is unchanged, except for digoxin which is reduced 50-75%
How to adjust maintenance dose in renal failure/dialysis?
MIC is minimum inhibitory concentration
How well does CRRT emulate renal function in removing drugs?
For some RRT methods, equivalent creatinine clearances are between 5ml/min and 300ml/min, but for CRRT it’s about 20-22 ml/min.
What is problem with serum drug level monitoring in dialysis patients?
If pre-dialysis, need to account for subsequent removal by dialysis. If post-dialysis levels, need to beware of rebound effect in which re-equilibration occurs between compartments. Example: vanco takes 2-4 hours to re-equilibrate
Ways to reduce drug doses in dialysis patients?
Can reduce peak and raise trough for drugs that need to be maintained at an effective level constantly (abx, antiHTNs), Can change interval to keep same peak and trough for drugs that are peak-dependent (AMGs, Quinolones)
Difference between UC and CD in the patterns of effect on gut?
Crohn’s disease is patchy, skipping sections of gut, can be anywhere from mouth to anus, but is usually in terminal ileum. Ulcerative colitis affects long sections of gut, only in colon and rectum.
Who has highest rate of IBD?
Ashkenazi Jews, North Americans and Europeans, higher socioeconomic status, peaks in 20’s 30’s and 50’s to 80’s.
Possible etiologies for IBD?
Etiology is unknown. Westernization, improved sanitation, smoking is protective for UC, but increases risk for CD. Can be triggered by NSAIDS. Possibly wrong bacteria (inflammatory versus anti-inflammatory bacteria). They have more surface-adherent bacteria. High concordance for identical twins. Having an affected 1st degree relative increases risk 13 times. Some gene mutations have been identified. Other findings include leaky epithelium (leaky to bacteria), decreased immune defense, enhanced activation of macrophages and cytokines, and reduced tolerance to normal GI flora.
Characteristics of ulcerative colitis?
Confined to colon and rectum, inflammation affects mucosa and submucosa. Primary lesion is abcesses in crypts of liberkuhn, with ulcers extending into surrounding areas
Sxs of ulcerative colitis?
Frequent bowel movements with cramping, rectal bleeding, abdominal tenderness (rare), fever, weight loss, ocular problems like uveitis, episcleritis, conjunctivitis, and skin problems like erythema nodosum, pyoderma gangrenosum, aphthous ulcerations
Important lab values in ulcerative colitis?
Decreased HCT & Hb (bleeding), increased ESR, WBCs, hypoalbuminemia
UC or CD? Transmural inflammation
CD. rarely UC
CD or UC? Smoking is protective
UC. It increases risk for CD
How do NSAIDS affect IBD?
Can trigger disease flares by impairing mucosal defenses.
What is the bacterial infection theory for IBD?
Too little good bacteria, too much bad. Good bacteria turn off inflammatory genes, while bad bacteria turn on inflammatory genes.
What specific physiologic differences could possibly explain genetic susceptibility to IBD?
Defective GI lining (more permeable to bacteria), decreased immune defenses againt pathogenic bacteria, enhanced activation of macrophages and release of cytokines, reduced tolerance to normal GI flora
UC or CD? Primary lesion if abcess formation in mucosal crypts with ulcers extending into surrounding areas?
UC (remember the “crypt abcesses” that were unidentifiable on the histographs). CD exhibits cobblestone ulcers on inner bowel wall that narow the GI lumin, but CD can rarely have crypt abcesses
UC or CD? Frequent bowel movement
Both. However, UC is accompanied by cramping and bleeding, while CD is generally not associated with cramps, but can have intermitent bleeding if colon is involved.
UC or CD? Weight loss
Both. Fever and frequent bowel movements too
UC or CD? Fever
Both. Weight loss and frequent bowel movements too
UC or CD? Ocular involvement, uveitis, episcleritis, conjunctivitis
UC. UC also has skin symptoms of erythema nodosum, pyoderma gangrenosum, aphthous ulcerations
UC or CD? Skin problems like erythema nodosum, pyoderma gangrenosum, aphthous ulcerations
UC. erythema nodosum is raised red tender nodes on arms and legs, pyoderma gangrenosum is discrete skin ulcerations with necrotic center on any part of the body, aphthous ulcerations are canker sores. They occur in 5-10% of UC patients. UC also has Ocular symptoms of uveitis, episcleritis, conjunctivitis
UC or CD? Abdominal tenderness, pain?
CD. tenderness is rare in UC, but has cramping with bowel movements. CD has abdominal tenderness, pain, and even abdominal mass.
UC or CD? Frequent remission and exacerbations?
CD. UC tends to be relatively constant, but CD comes and goes in flares.
UC or CD? Increased WBCs and ESR (erythrocyte sedimentation rate)
Both. Other hematological changes in UC include hypoalbuminemia and decreased HCT and Hgb.
UC or CD? Complications of hemorrhoids, anal fissures, peri-rectal abcesses, colonic strictures, fistulas
UC. The way to remember this is that UC is more of a colon and rectum disease, and most of these things involve the rectum. In fact, the two complications that are not specifically rectal are rare in UC, but common in CD: strictures (but usually small bowel instead of colon) and fistulas
UC or CD? High risk of carcinoma
Both, but higher in UC.
UC or CD? Complications include arthritis (nondestructive and reversible), liver disease, gall stones?
Both. Liver disease can be fatty liver, cholangitis, biliary carcinoma, chronic hepatitis, cirrhosis. Arthritis is common, it is asymmetrical, and resolves after surgical resection of affected bowel.
UC or CD? Alkylosing spondylitis is a frequent complication?
UC (30 times more than general population). Most common in HLA-B27 genotype. It is unresponsive to therapy
What is 1st line therapy for IBD?
Sulfasalzine (Azulfidine), because it’s cheap. It is sulfapyridine combined with mesalamine, cleaved by gut bacteria. Sulfapyridine is absorbed and excreted. Mesalamine remains in colon to reduce inflammation (it’s a salicylate) and excreted in feces.
Tx goals for IBD?
Resolve acute inflammation, complications, systemic symptoms, maintain remission
Nutritional support for IBD?
Malnourishment is common due to lack of absorption (inflammation) or lack of absorptive area. No specific diet can improve sxs. Lactose intolerance is common. May need iron, folate due to blood loss and decreased absorption, and may need parenteral or enteral nutrition
UC or CD? Surgery (resection of bowel) is curative?
UC, but not for CD
When is surgery indicated for IBD?
For UC, when max pharmacologica therapy has failed. For CD, for severe complications, however, recurrence rate is high for CD
Sulfasalazine for IBD?
1st line for IBD. Contains sulfapyridine (abx) plus mesalamine in the same molecule. Cleaved by gut bacteria. Sulfapyrdine absorbed and excreted in urine. Mesalamine remains in colon to reduce inflammation (it’s a salicylic acid). It is cheap cheap, and works because mesalamine can get all the way to gut to work
Side effects of sulfasalizine?
Probably mostly due to sulfapyridine. N/V/D, anorexia, HA, arthralgias, impairment of folic acid absorption. Dose can be titrated up. Non-dose-related effects (for which drug must be discontinued) are sulfa allergy, rash, fever, hepatotoxicity, bone marrow suppression.
Dosing schedule for sulfasalazine?
Week 1 500mg daily, week 2 500mg BID, week 3 500mg TID, week 4 500mg QID, increase 500mg/day every week until 4-6g/day. Adverse effects limit how high it can go, and max effect may take 12 weeks
Mesalamine (alone, without the sulfapyidine) product choices?
Rowasa rectal enema and suppositories (good for sigmoid and rectum), Asacol 400mg coated tablet with delayed-release resin (so can get to distal colon). Pentasa capsules filled with encapsulated microgranules (dissolve in small bowel and colon)
When is Rowasa indicated for IBD?
Mesalamine enema (or suppositories), useful for rectum and lower colon. Used before bed, works while sleeping
Asacol versus Pentasa for IBD?
Both are mesalamine products (like Rowasa). Asacol is delayed-release tablet good for targeting distal colon. Pentasa is microgranules in a capsule, dissolves in small bowel and colon.
Olsalazine for IBD?
“Dipentum”. Very expensive. Two mesalamine molecules azo-linked, which is cleaved by bacteria. Acts in the colon. 250mg cap, dosed 2-3 grams per day in two doses
Balsalazide for IBD?
“Colazal” A mesalamine pro-drug, activated by bacterial enzymatic metabolism in colon. 750mg cap. Dose is 2250 mg TID. FDA approved for only 12 weeks. Never used
A) Rowasa enema, B) Asacol, C) Rowasa suppository, D) Steroid enema, E) Pentasa, F) Saulfasalazine. Which one(s) acts from terminal ileum down?
Asacol. Pentasa is only one that acts higher (from jejunum all the way down)
A) Rowasa enema, B) Asacol, C) Rowasa suppository, D) Steroid enema, E) Pentasa, F) Saulfasalazine. Which one(s) act only in distal colon and rectum?
Steroid and rowasa enemas. The only one that it limited to lower than this is the rowasa suppository
A) Rowasa enema, B) Asacol, C) Rowasa suppository, D) Steroid enema, E) Pentasa, F) Saulfasalazine. Which one(s) acts in all of the colon and rectum, but not in the small intestines?
Sulfasalazine. Remember, sulfasalazine must be cleaved by gut bacteria, which are (normally) limited in significant amounts to the large bowel.
A) Rowasa enema, B) Asacol, C) Rowasa suppository, D) Steroid enema, E) Pentasa, F) Saulfasalazine. Which one(s) acts only in the rectum?
Rowasa suppository. But Rowasa enema and Steroid enema can act in terminal colon and rectum
A) Rowasa enema, B) Asacol, C) Rowasa suppository, D) Steroid enema, E) Pentasa, F) Saulfasalazine. Which one(s) acts from jejunum all the way to the rectum?
Pentasa. It is microgranules of meselamine in a capsule that dissolve in small bowel and colon
Corticosteroids for IBD?
Oral (prednisone, budesonide), parenteral (hydrocortisone or methylprednisolone), rectal (hydrocortisone). Anti-inflammatory
Two types of rectal enemas for IBD?
Steroids (hydrocortisone) or Rowasa (mesalamine). Steroids are less effective than rectal mesalamine for inducing and maintaining remission
Budesonide for IBD?
The preferred oral corticosteroid for IBD, over prednisone. “Controlled ileal release formation” creates less systemic effects. It has high first pass. 9mg/day peak effect is at 2 weeks. More effective than 4g/day mesalamine. Very expensive, small market
When to use cyclosporine for UC?
Immunosuppression should only be used if refractory to corticosteroids, or severe, uncontrolled disease. For UC, use cyclosporine IV 4mg/kg/day, and can be switched to oral if responsive.
When to use cyclosporine for CD?
Immunosuppression should only be used if refractory to corticosteroids, or severe, uncontrolled disease. In Crohn’s only if need to heal rectal or perianal fistulas
How does cyclosporine work?
Immunospressant. Inhibits stimulation and prolifertion of IL-2 stiumulated Tcells. Binds to cyclophilin, which then binds to calcineurin, so blocks cytokine gene expression.
Adverse effect of cyclosporine?
Renal and hepatic toxicity, HTN, hyperlipidemia, hirsutism, infections. Interacts with CYP3A
Examples of immunosupressive agents to use in IBD, other than cyclosporine?
For refractory UC and CD, azathioprine, mercaptopurine, methotrexate, infliximab. They may decrease the need for steroids and prolong remission
How do azathioprine and 6-mercaptopurine work?
Immunosupressants. They are purine antimetabolites which inhibit de novo synthesis of purines. They are converted (multiple steps) into 6-thioguanine, and incorporated into DNA to stop proliferation. They can lead to bone marrow supression, lymphomas, skin cancers, pancreatitis, infections
Pharmacogenetics of azathioprine and 6-mercaptopurine?
0.1% of population is homozygous for dysfunctional thiopurine S-methyltranferase (TPMT), and so they cannot activate these drugs, but instead accumulate high concentrations, and have high risk of toxicity. Homozygotes should not receive them. Heterozygotes should be monitored closely
Methotrexate for IBD?
Inhibits DHFR, so can’t convert folic acid to active form FH4, which is required for DNA and RNA synthesis. But it can cause bone marrow supression, infections, liver and renal toxicity, and teratogenesis
Infliximab for IBD?
Chimeric human and murine anti-TNFalpha antibody to prevent its binding to TNF receptor on lymphocytes. Good for Crohn’s patients with high TNFalpha in their stools. VERY eexpensive. Can cause infections, lupus-like reactions, infusion reaction (fever, itching, hypotension, SOB)
What antimicrobials are used for IBD?
May be adjunctive in Crohn’s. Flagyl (metronidazole) 20mg/kg/day in divided doses, is good to kill anaerobic bacteria (gut bacteria). Ciproflaxacin 500-750mg/day has also been used. Cipro can lead to C.diff infections, and if flagyl therapy fails for that, C.diff can be very bad.
Nicotine for IBD?
Highest tolerated dose of nicotine patches may improve sxs in mild to moderate UC (the same condition for which smoking is protective).
Probiotics for IBD?
Good bacteria produce anti-inflamatory cytokines. Lactobacilllus, bifidobacteria and non-pathogenic strep show some efficacy
What is toxic megacolon?
Colonic dilation, distension (usually in UC patients). Sxs are fever, abdominal pain, bloody diarrhea, decreased bowel sounds, and dehydration
How to treat toxic megacolon?
IV fluids, high dose corticosteroids (IV), antibiotics covering anaerobes. Surgery (colectomy with ileostomy) may be lifesaving
Tx for systemic manifestions of IBD?
Arthritis: NSAIDS, salicylates, corticosteroids. Anemia: B12, folate (or transfusion if severe)
Pregnancy considerations for IBD?
While IBD does not impair fertility, it has increased risk of spontaneous abortion, and low birth weight (probably due to malnutrition). Sulfasalazine, mesalamine, and corticosteroids are safe, but immunosupressants and metronidazole are teratogenic. NSAIDS may be bad due to decreased mucosal protection against bacterial invasion
Questions (or types of questions) that seniors should be asked to begin evaluating their risk for MRPs (medication related problems)?
From the sheet Dr. Dirig uses in his business, here are 10 questions: (1) currently take more than 5 meds (Rx or OTC)? (2) currently take more than 12 doses daily? (3) take coumadin, quinidine, procainamide, digoxin, phenytoin, lithium, carbamazepine, theophylline, phenobarb? (4) take drugs for more than 3 conditions? (5) changed drugs or the way you take them 3 or more times this year? (6) more than 1 prescribing doctor? (7) scrips filled at more than one pharmacy or over internet? (8) someone else bring your drugs home for you? (9) difficulty or not want to follow medication instructions? (10) takeing drugs that you don’t know what they are for?
Above the age of 75, there is a very high risk of experiencing what conditions?
HTN, stroke, heart failure, arthritis, osteoporosis, memory impairment, depression, DM
What types of problems can result from taking multiple meds for multiple conditions?
Non-compliance, drug interactions, innapropriate or unnecessary meds, ineffective meds
What pharmacokinetic parameters change with increased age?
GI absorption, IM absorption, Vd (more fat, less water, less muscle), topical administration, decreased albumin, renal changes, hepatic changes. These changes require changing dose AND drug
What classes of drugs (on Beer’s list) do seniors exhibit increased sensitivity to?
(1) Anticholinergics (decreased cognition, increased constipation, increased risk of falls), (2) BDZs and CNS depressants (more receptor sensitivity), (3) vasodilators, TCAs, anti-HTNs, parkison meds (all cause more orthostatic hypotension due to decreased baroreceptor sensitivity), (4) antipsychotics, cause increased tardive dyskinesias and parkinsonian sxs, especially if dementia, (5) miscellaneous like muscle relaxants, barbiturates, amphetamines, long-acting chonic Rx NSAIDS
What problems occur more commonly in seniors that take anitcholinergics?
Congnitive impairment, constipation, increased risk of falls
What os the problem with seniors taking BDZs and CNS depressants (like opioid analgesics)?
Increased receptor sensitivity.
What is the problem with seniors taking vasodilators, anti-HTNs?
More orthostatic hypotension. This can also occur more by them taking TCAs and parkinsonian meds
What is the problem with seniors taking TCAs?
More orthostatic hypotension (like vasodilators and anti-HTNs and parkinsonian meds)
What is problem with seniors on parkinsonian meds?
More orthostatic hypotension (like vasodilators, TCAs, anti-HTNs)
What is the potential problem with seniors taking antipsychotics?
They are at increased risk for tardive dyskinesias, especially if suffering dementia too
How to think about polypharmacy?
Don’t count pills, count problems, risks, outcomes
What are the eight categories of MRPs (medication-related problems)? Know these for the test
ADRs, DDIs, dose too low, dose too high, improper drug, untreated condition, unnecessary drug, failure to receive (or take) drug. Any symptom in elderly should be assumed to be MRP unless proven otherwise
Common symtoms of MRPs in seniors?
Confusion, depression, delirium, insomnia, incontinence, parkinson’s, falls, loss of appetite (similar to typical problems seniors experience)
Characteristics of high risk seniors?
Multiple providers, drug interactions, improper drug, unnecessary drugs, inadequate monitoring, non-compliance, suboptimal outcomes
The “big picture” problem in geriatric pharmacotherapy?
A given dose of a particular medication produces a different and sometimes unexpected response in an elderly patient compared to a younger patient of the same gender and similar body weight.
High-risk factors MRPs in seniors?
Not consistent, but possibly, females, on medicaid, with increased number of medical problems, increases number of meds, older (than 80?), and poor self-rated health are correlated with particularly high risk for MRPs
What does the adrenal medulla do?
Makes up 10% of the adrenal gland. Produces and secretes epi and NE
What do each of the zones of the adrenal cortex do?
Makes up 90% of the gland. Zona glomerulosa secretes aldo. Zona fasiculata secretes cortisol. Zona reticularis secretes testosterone
What is problem with lowering XOL too much?
If get LDL down to 50-60, start limiting hormone production. So optimal goal for high risk groups is 70
How is cortisol production regulated?
Hypo releases CRH to ant pit, which releases ACTH, which causes secretion of cortisol from adrenal cortex. Cortisol negatively feeds back to limit ACTH and CRH release
Etiology of andogenous cushing’s syndrome?
Overproduction of ACTH from pituitary tumors (or from pancreatic, thyroid, or lung tumors). It can also be adrenal tumors secreting too much cortisol
Etiology of exogenous cushing’s syndrome?
Supraphysiologic corticosteroid administration
Clinical presentation of cushing’s syndrome?
Obesity, HTN, moon facies, glucose intolerance, stiae (stretch marks, even if no stretching), buffalo hump (from fat redistribution from extremities to trunk), myopathy, osteoporosis, psychiatric changes. And in females, menstrual irregularities and hirsutism
How to diagnose cushing’s?
Pages 1394-95 in DiPiro
How to treat endogenous hypercortisolemia (cushing’s)?
Removal or irradiation of tumor. But drug therapy is indicated if tumor cannot be removed, or before surgery
Four categories of drugs to treat cushing’s?
Steroid synthesis inhibitors, adrenolytic agents, neuromodulators of ACTH release, glucocorticoid receptor blockers
What is Metyrapone (Metopirone)? ADRs?
Steroid synthesis inhibitor treatment for cushing’s. CYP11B1 inhibitor, so it blocks conversion of1 11-deoxycortisol to cortisol. Poorly tolerated. Causes N/V, HA, dizziness, abdominal discomfort, rash
What is aminoglutethimide?
Steroid synthesis inhibitor treatment for cushing’s. Blocks very first step in conversion of XOL to pregnenolone (which leads to all the steroid hormones). It causes extreme sedation (like sedative hypnotic), nausea, ataxia, rash
What is ketoconazole?
Steroid synthesis inhibitor to treat cushing’s. Usually used as oral antifungal, but a potent inhibitor of many CYPs, inclusing the ones involved in steroid hormone synthesis. Specifically it blocks CYP11B1 and CYP17
What is Mitotane?
An adrenolytic agent. Cytotoxic, structure similar to DDT. Inhibits conversion of 11-OH-cortisol to desoxycorticosterone in the cortex. It can cause irreversible damage to zona fasiculata and reticularis, so less cortisol and testosterone. So, only for short-term use. If shot term, then minimal effect on zona glomerulosa (and therefore aldo), It usually requires corticosteroid supplementation afterward. Causes severe lethargy and somnolence in 40% of patiens. And causes Hypercholesterolemia
Examples of neuromodulators used in cushing’s syndrome, and how work?
They decrease ACTH secretion, but none are consistently effective, and response rates are low. 4 main ones are cyproheptadine (Periactin), bromocriptine (Parlodel), valproic acid (Depakote), octreotide (Sandostatin).
What is mifepristone?
Glucocorticoid receptor antagonist used to treat cushing’s/ Progesterone and glucocorticoid receptor antagonist, (RU-486), used mainly as abortifaciant, but also used in cushing’s syndrome, highly effective
What is addison’s disease?
Adrenal insufficiency, can be primary or secondary, acute ot chronic, and is symptomatic only after 90% function is lost
What is primary addison’s disease?
Results from acute or chronic physical destruction of adrenal gland, leading to deficiency in cortisol, aldo, testosterone
Symptoms of chronic symptoms of addison’s disease?
Weakness, weight loss, hyperpigmentation (and/or vitiligo), hypotension, N/V
What is the physiologic dose of prednisone?
5-7.5mg (which is also 20-30mg cortisol)
Main treatment for primary adrenal insufficiency?
Replace gluco- and mineralocorticoids. Hydrocortisone 20mg or prednisone 5mg QAM, plus 1/3 to ½ of morning dose QHS, plus Fludrocortisone 0.05 to 0.2 mg/day. Adjust as needed
What is secondary adrenal insufficency?
Usually too rapid d/c of therapeutic corticosteroids iin supraphysiologic doses. However, aldosterone secretion is not affected. it can be avoided by tapering corticosteroids properly
How to taper corticosteroids?
There is no perfect way to do it. Depends on what is being treated, and need for d/c. Slow is preferred while watching for disease exacerbation. If rapid d/c is needed, decrease by 50% per day until physiologic doses are met, continue on that dose, and evaluate with axis function tests, decreasing very slowly at the end (1mg/day/week)
What is acute adrenal crisis?
When patient’s system needs more steroids (due to physical stress, surgery, infection, trauma, etc.), and can’t make more because they have been suppressed from chronic steroid therapy, so can’t make more.
Symptoms of acute adrenal crisis?
Myalgias, anorexia, fever, weight loss, vomiting, hypotension, shock, hyponatremia, hypoglycemia, hypercalcemia
What is a “stress-dose” of corticosteroids?
Patients who are on steroid therapy (and so are ACTH-suppressed), need extra corticosteroids if going into undergo physical stress should receive corticosteroid to deal with extra stress
Difference between prednisone and prednisolone?
Prednisone is a prodrug that is converted to prednisolone
General treament strategy with steroid synthesis inhibitors? Examples of steroid synthesis inhibitors?
Usually used together to reduce side effects and improve tolerance, and are used until surgery can be perfomed or if surgery is not possible. Examples are Metyrapone, Aminoglutethimide, ketoconazole
Example of “stress dose” of corticosteroids?
Hydrocortisone 100mg IV q 6-8h x 24-48 hrs, or constant infusion of 10-15 mg/hr x24-48hrs or until stress is alleviated. Then, 50mg po q 8 h x 48 hrs, then taper back to dose prior to stress.
What adjustement should be made to corticosteroid dose if hyperkalemia is present?
Add 0.1mg fludrocortisone po daily (mineralocorticoid)
Which corticosteroids have mineralocorticoid potency?
Cortisone and hydrocortisone have twice as much as prednisone and prednisolone. The others are zero.
What dose of prednisone and prednisolone is equivalent to 25mg cortisone?
5.0 mg for each.
What dose of hydrocortisone is equvalent to 25mg cortisone?
20mg
What dose of tiamcinolone or methylprednisolone is equvalent to 25mg of cortisone?
4.0 mg
What dose of betamethasone is equivalent to 25mg cortisone?
0.6mg
What dose of dexamethasone is equivalent to 25mg of cortisone?
0.75mg
A. 0.6mg B. 0.75mg C. 1.0mg D. 3.0mg E. 4.0mg F. 5.0mg G. 10mg H. 20mg 25mg of cortisone is equivalent to how many mg of prednisone?
F. 5.0mg
A. 0.6mg B. 0.75mg C. 1.0mg D. 3.0mg E. 4.0mg F. 5.0mg G. 10mg H. 20mg 25mg of cortisone is equivalent to how many mg of triamcinolone?
E. 4.0mg
A. 0.6mg B. 0.75mg C. 1.0mg D. 3.0mg E. 4.0mg F. 5.0mg G. 10mg H. 20mg

25mg of cortisone is equivalent to how many mg of methylprednisolone?
F. 5.0mg
A. 0.6mg B. 0.75mg C. 1.0mg D. 3.0mg E. 4.0mg F. 5.0mg G. 10mg H. 20mg 25mg of cortisone is equivalent to how many mg of betamethasone?
A. 0.6mg
A. 0.6mg B. 0.75mg C. 1.0mg D. 3.0mg E. 4.0mg F. 5.0mg G. 10mg H. 20mg 25mg of cortisone is equivalent to how many mg of hydrocortisone?
H. 20mg
A. 0.6mg B. 0.75mg C. 1.0mg D. 3.0mg E. 4.0mg F. 5.0mg G. 10mg H. 20mg

25mg of cortisone is equivalent to how many mg of dexamethasone?
B. 0.75mg
A. 0.6mg B. 0.75mg C. 1.0mg D. 3.0mg E. 4.0mg F. 5.0mg G. 10mg H. 20mg 25mg of cortisone is equivalent to how many mg of prednisolone?
F. 5.0mg
What is PPRU?
Pediatric PK research units. They help do pediatric PK research to add to the little knowledge available about differences in pediatric populations
What is the rule of 1?
A way to classify or group the pediatric population. Under 36 weeks is premature. ≥36 weeks is TERM. Neonates up to 1 month, infants 1month to 1 year. Child 1 year to 11 years (young child 1-5, school age 5-11), adolescent 11-18.
What are the skin characteristics of neonates (birth to 1 month)?
Thin skin, delicate, highly permeable
How does APGAR scoring (of newborns) work?
Ranked at 1, 5, and 10 minutes after birth and is predictive of how they will do in first 24 hours. It assesses HR, respiratory effort, muscle tone, reflex, and skin color
In which age group does weight triple and height increases 50%? A) Neonate (0-1month), B) Infant (1mo to 1yr), C) Young Child (1yr to 5yr), D) School-age child (5yr to 11yr), E) Adolescent (11yr to 18yr)
Infant. It is in young children (at age 2), when birth weight has quadrupled and growth slows.
In which age group do kids particularly develop motor skills, trust, and language? A) Neonate, B) Infant, C) Young Child, D) School-age child, E) Adolescent
Infant. This is also the period in which their weight triples and height increases 50%, and they develop sleep/wake cycles.
In which age group are sleep/wake cycles established? A) Neonate, B) Infant, C) Young Child, D) School-age child, E) Adolescent
Infant. This is also the period in which their weight triples and height increases 50%, and they develop motor skills, trust, and language.
In which age group has birth weight quadrupled and growth slows? A) Neonate, B) Infant, C) Young Child, D) School-age child, E) Adolescent
Young child. At age two, birth weight has quadrupled. This is also the stage in which they develop an increased attention span, problem-solving skills, conceptualization, toilet training, and family centerdness
In which age group do kids develop an increased attention span, problem-solving skills, and conceptualization ability? A) Neonate, B) Infant, C) Young Child, D) School-age child, E) Adolescent
Young child. This is also the age at which birth weight has quadrupled (age 2), and they are toilet trained and family-centered.
In which age group does brain size reach nearly adult size, increased mental skills (memory, listening, problem-solving) are attained, and the ability to take pills (neuromuscular maturity) occurs? A) Neonate, B) Infant, C) Young Child, D) School-age child, E) Adolescent
School-age child. This is also the time in which they become peer-group oriented. They become fully coordinated at age 12
In which age group do kids become peer-group oriented? A) Neonate, B) Infant, C) Young Child, D) School-age child, E) Adolescent
School-age child. This is also when brain size reaches nearly adult size, increased mental skills are attained, and the ability to take pills (neuromuscular maturity) occurs.
In which age group is skin delicate, thin, and highly permeable? A) Neonate, B) Infant, C) Young Child, D) School-age child, E) Adolescent
Neonate. During this time, their vision is also poor, but can follow large objects,, and they respond well to sounds and changes in voice tone.
In which age group does 2nd growth spurt occur (including weight gain)? A) Neonate, B) Infant, C) Young Child, D) School-age child, E) Adolescent
Adolescent. This is also the period in which maximum learning ability and ability to understand complex ideas occurs. They also develop secondary sex characteristics (duh).
At what age and weight can smaller adult dosages be used (as opposed to using pediatric dosing calculations and dosage forms)?
Age 12 and 40kg
How does gastric pH change with child age, and how does this affect absorption of drugs?
pH high in neonates and declines to adult values by age 2. High pH increases absorption of basic drugs and decreases absorption of acidic drugs
How does gastric and intestinal motility change with child’s age, and how does this affect absorption of drugs?
Low motility in neonates and infants, but increases in older infants and children. These differences are cause for unpredictable absorption (and bioavailability) of drugs. Other factor leading to unpredictability is variable bicheistry of gastrourinary tract.
When does biliary pool and function fully develop in childhood?
Not until the first several months of life
Suitability of rectal administration of drugs in kids?
Depends on properties of the drug and duration of exposure to mucosa. Few drugs are suitable for this route
Two considerations tao make for percutaneous drug administration in kids?
Skin is thin and highly hydrated, so absorption is very high. Also. Neonates and infants have higher surface area to body weight ratio.
Suitability of intraocular drug administration in infants?
Eye membranes are thin in neonates and infants, so systemic side effects much more common than in older children and adults
Differences in BBB in children?
Neonates have underdeveloped BBB, so concentrations of drugs in the brain can be higher than expected. Can affect distribution
Differences in blood proteins in children?
Total protein concentration at birth is 80% that of adults, and reaches adult concentrations by age 1. Can affect distribution
How is body water and fat different in children compared to adults?
Body water higher in neonates, reach adults levels by age 12. Body fat (proportion of weight) is lower in children. Can affect distribution
How is metabolism of drugs different in children compared to adults?
At birth enzymatic microsomal systems for biotransformation are present, but activity is reduced. Liver maturity varies between individuals and each enzyme increases at different rates. By 2-3 months of age, metabolic rate is 2-6 times adult rates and stay high until about 8-10 years old.
Three main methods of elimination of drugs (after metabolism)?
Renal, Pulmonary (expired into air), Bile (into feces),
How does glomerular filtration in kids compare to adults?
GFR increases proportionally with age until adult values are reached by age 3
How is elimination in neonate affected by their renal function?
They have decreased renal blood flow, GFR, and tubular function, so elimination is prolonged. Dosing intervals need to be adjusted for this, especially drugs like aminoglycosides, cephalosporins, and penicillins
How to calculate Creatinine clearance in kids?
Traub and Johnson method. It applies if renal function is stable and age 1-18.
Do not use Cockroft Gault, or Jelliffe.

The Traub and Johnson method is:
Clcre = (0.48)*Ht(cm)/Scre
How to use child BSA to convert adult dose to child dose?
Peds dose = [BSA(m^2)/1.73m^2)]*Adult dose
Reasons for errors in pedatrics?
Calculations, lack of appropriate dosage forms, knowledge deficits. Critically ill neonates at highest risk. Outpatient also high risk.
Barriers to adherance in pediatrics?
Parents are responsible. Language, literaacy, chronic diseases, seeing different doctors, ferquent or complicated dosing schedules
Ways to improve pediatric adherence?
Educate (written, visual, show, tell), organization (decrease pt wait times), behavioral (reminders, self-monitoring, reinforcement, home visits)
Points on optimizing patient counseling for peds?
Brief, well-organized, keep on 6th grade level, give written info (50% oral is forgotten), engage child
OAP is important in what form(s) of glaucoma? theories for glaucoma etiology?
Definitely in CAG (10-20% of glaucoma), but not OAG (80-90% of glaucoma). One theory for glaucoma is retinal ischemia, or cytotoxic issue in which the NT glutamate builds up too high
Where is aqueous humor produced?
Ciliary epithelium through ultrafiltration AND secretion
What drug classes decrease aqueous humor outflow?
alpha2 blockers, beta-blockers, DA blockers, CAIs
What is route of aqueous humor outflow?
2 routes: 80% trabecular meshwork and 20% through uveoscleral outflow
What agents increase aqueous outflow?
Trabecular meshwork is opened by cholinergic agents, and uveoscleral pathway is opened by PGF2alpha analogues, beta blockers, and alpha2 agonists
Presentation of OAG?
Visual field loss “tunnel vision” with loss of visual acuity later on. It can be isolated scotomas, reduced contrast sensitivity, altered color vision
What is considered ocular hypertension (OHT)?
Average IOP is 15.5+/-2.5, and increases with age. Normo-tension glaucoma have IOP<21mmHg. If IOP>21mmHg without disk changes or visual field loss is observed in glaucoma suspects. If discovered early, prognosis is excellent.
What basis should be used in deciding who to treat in glaucoma?
All who have elevated IOP and disk changes AND/OR visual field defects. If OHT, but no signs are usually just monitored and not treated unless risk factors exist
Target for IOP reduction?
Initial target is 30% reduction. Normal tension glaucoma patients have a goal of <10-12mmHg.
Initial therapeutic approach for glaucoma?
Stepwise with one agent in one eye
Step therapy for OAG and OHT?
(1) topical beta blocker if no contraindication, (2) brimonidine, PG analogues, or topical CAIs, (3) pilocarpine, epinephrine (or dipivefrin), apraclonidine, (4) carbachol, topical AChEIs, oral CAIs, and combination therapies are last line
Presentation of CAG?
If untreated, there is intermittent prodromal symptoms like blurred vision, halos around lights and occasional HA. If there is closure, cornea is cloudy and edematous, and there is also ocular pain, N/V, and diaphoresis
Goal of therapy in CAG?
Rapid reduction of IOP to preserve vision and avoid surgery
Therapy for CAG?
The definitive treatment is surgical iridectomy. Drug therapy can be osmotic agent, secretory inhibitor (beta blocker, a2 agonist, PGF2 analogue, oral/topical CAI) with or without pilocarpine.
Osmotic agent used in CAG?
Usually mannitol 1/2g/kg IV or glycerin 1-2/gkg orally
Pilocarpine use in CAG?
Given immediately is controversial (since pupillary sphincter is paralyzed from IOP-induced ischemia), but after IOP is stable, may be given q 6 hrs until iridectomy is done
Epinephrine use in CAG?
Used with caution since it can precipitate acute CAG especially if used with beta-blocker
Drugs that can cause OAG?
Most common are ophthalmic CS and ophthalmic anticholinergics. Any Corticosteroids as well as fenoldepam and succinylcholine can also do it. Since CS can be used to treat OAG, should use lowest dose for shortest period possible
Drugs that can cause CAG?
TOPICAL sympathomimetics. Anticholinergics, heterocyclic antidepressants, low –potency phenothiazines, antihistamines, ipratropium, BDZs, theophylline
Examples and use of beta blockers in glaucoma?
1st line and most common for primary OAG. Reduces aqueous humor production 20-30% by blocking beta2 in ciliary epithelium. Examples are timolol, levobunolol, metipranolol, carteolol, betaxolol. Beta blockers can be combined with other glaucoma drugs. All the doses are 1 gtt BID except for timoptic and betimol which can also be given once daily. Carteolol has intrinsic sympathomimetic activity. Betaxolol has slight b1 selectivity.
Ocular side effects of beta blockers in glaucoma?
Burning, stinging, dry eyes, corneal anesthesia, blepharitis, blurred vision. Rare are conjunctivitis, uveitis, punctate keratitis
What does “-S” mean in beta blocker glaucoma drops? Why importnant?
It means suspension, and it can be half the strength
Caution and contraindications for glaucoma beta blockers
Pumonary disease, CHF, atherosclerosis, DM, myasthenia gravis, patients on beta-blockers, hyperlipidemia, thyroid dysfunction, athletes. Contraindicated in bronchial asthma, severe COPD, sinus bradycardia, 2nd and 3rd degree AV block, avert cardiac failure, cardiogenic block
Tachyphylaxis is common with what class of glaucoma drug?
Beta blockers. Need to switch to different agent
What are the a2 blockers used in glaucoma? How effective?
Apraclonidine, brimonidine, which reduce aqueous humor production. Lower IOP 18-27%. Brimonidine is 1st liine or adjunctive for POAG or OHT. Apraclonidine use has decreased due to high incidence of tachyphylaxis and severe ocular allergy. Can combine with otgher glaucoma agents
Pt ed for using eye drops?
Pull lower pouch down, instill drop, close eye, put finger on duct, so absorbed locally and more selectively. If more than one agent, separate by 10 minutes. If one is not a solution, solution should go first.
Ocular and systemic side effects of a2 agonists in glaucoma?
Allergic-type reaction with chronic use. Blurred vision, tearing (much less ocular effects with brimonidine (Alphagan), as compared to apraclonidine, but more systemic effects). Systemic effects are dizziness, somnolence, dry mouth, bradycardia, lower BP, HA, depression, fatigue. Alphagan-(P) means putite is added as a preservative, which turns into water and oxygen in the eye. It reduced allergic-type reactions by 40%
Conditions in which to use caution with a2 blockers?
CV disease, renal compromise, cerebrovascular disease, pts on antiHTNs and other CV drugs, patients on MAOIs and TCAs
What are the nonspecific adrenergic agonists used in glaucoma?
Epinephrine and dipivefrin. Increase AQ outflow anf reduce IOP 15-25%. Dipivefrin can be used at lower concentrations (0.1% compared to 1%) due to better ocular absorption. Can combine with other glaucoma drugs. Many ocular side effects
Ocular side effects of non-specific adrenergic agonists used in glaucoma?
Tearing, blurring, burning, conjunctival hyperemia, punctate keratopathy, blepharoconjunctavitis (allergic), loss of eyelashes (rare), stenosis of nasolacrimal duct, adrenochrome with prolonged use (>1yr), mydriasis (may cause CAG).
Systemic side effects of nonselective adrenergic glaucoma drugs?
HA, elevated BP, tachycardia, arrhythmias, tremor, pallor, anxiety, diaphoresis
When to use caution in using nonspecific adrenergic agonists in glaucoma?
CV disease, CAG, hyperthyroid, DM, contraindicated in aphakic patients (no lens)
What are the PGF2alpha analogues used in glaucoma?
Latanoprost, travoprost, brimatoprost, unoprostone.
How do the PGF2alpha analogues work in glaucoma?
Increase outflow and reduce IOP 25-35%. More effective with QHS dosing except for unoprostone (BID), so convenient. Excellent efficacy and safety, good 1st line or adjunctive therapy. Good for POAG or OHT. Latanoprost is only one that needs to be refrigerated, but okay for 4-6 weeks after opening without refrigeration. Travoprost best in African American population.
Ocular and systemic side effects of PGF2alpha analogues?
Punctate corneal erosions, conjunctival hyperemia, altered iris pigmentation if mixed coloe irises, hypertrichosis and increased eyelash pigmentation, uveitis, cystoid macular edema. Systemic effects are rare, but can be muscle and joint pain, allergic skin reactions. No CV effects
What are the topical CAIs for glaucoma?
Brinzolamide and dorzolamide. They decrease AQ production and reduce IOP by 15-26%. Used as monotherapy or adjunctive for OAG and OHT. Combo product available is timolol and dorzolamide. They are both dosed BID-TID
Ocular and systemic side effects of CAIs?
Burning, stinging, ocular discomfort, blurred vision, tearing, and rarely photophobia and conjunctivitis.

Systemic effects are ALTERED TASTE, HA, nausea, fatigue, contraindicated in sulfa allergy and hx of nephrolithiasis
What are the systemic CAIs used in glaucoma?
Azetazolamide, dichlorphenamide, methazolamide. Reduce AQ inflow and reduce IOP 25-40%. Considered 3rd line in POAG due to side effects. Dichlorphenamide is least well-tolerated
Systemic side effects of systemic CAIs?
Malaise, fatigue, nausea, anorexia, weight loss, altered taste, depression, decreased libido, renal calculi, blood dyscrasias (most serious), diuresis, myopia, increased uric acid.
Condition to use caution with in systemic CAIs for glaucoma?
Sulfa allergies, sickle cell disease, respiratory acidosis, pulmonary disorders, renal calculi, lyte imbalance, hepatic and renal disease, DM, addison’s disease. (all related to systemic acidosis)
Cholinergic agonists in glaucoma?
Pilocarpine and carbachol. They increase outflow and reduce IOP 20-30%. Pilocarpine is agent of choice in POAG and is available as solution, gel, ocular insert. Carbachol is more potent, but has frequent and severe ocular and systemic side effects
Ocular side effects of cholinergic agonists in glaucoma?
Meiosis (can be permanent), accommodative spasm, frontal HA, periorbital pain, eyelid twitch, cataracts (rare), CAG precipitation, retinal detachments.
Systemic effects of cholinergic agonists used in glaucoma?
Diaphoresis, N/V/D, cramping, urinary frequency, bronchospasm, heartblock (rare)
Cholinesterase inhibitors as glaucomas drugs?
Demacarium, echothiophate, physostigmine. Reserved for patients refractory or intolerant of other therapies. Often used only in aphakic or pseudophakic patients
Side effects of cholinesterase inhibitors used in glaucoma?
Severe fibrinous iritis, synechiae, iritic cysts, conjunctival thickening, nasolacrimal ducts occlusion, cararacts (common).
In what conditions should cholinesterase inhibitors in glaucoma be used with caution?
Asthma, retinal detachments, narow angle glaucoma, bradycardia, hypotension, heart failure, epilepsy, parkinsonism, ocular inflammation, d/c 2 weeks before use of succinylcholine
Reference Range for blood glucose?
65-110 mg/dL
Reference Range for BUN?
8-18 mg/dL
Reference Range for serum creatinine?
0.5-1.5 mg/dL
Reference Range for serum Na?
135-145 mEq/L
Reference Range for serum Potassium?
3.5-5.0 mEq/L
Reference Range for serum Chloride?
97-107 mEq/L
Reference Range for serum bicarb?
24-31 mEq/L
Reference Range for serum calcium?
9.0-10.6 mEq/L
Reference Range for serum phosphorous?
2.5-4.5 mEq/L
Reference Range for serum Mg?
1.8-2.5 mEq/L
Reference Range for serum total protein?
6.0-8.0 g/dL
Reference Range for serum albumin?
3.3-5.0 g/dL
Reference Range for serum bilirubin (direct and total)?
direct <0.2 mg/dL
total <1.2 mg/dL
Reference Range for serum AST (SGOT) and Alk Phos?
AST 10-46 Unit/L
Alk Phos 30-130 Unit/L
Reference Range for serum LDH?
25-175 Unit/L
Reference Range for creatinine clearance?
75-125 mL/min
Reference Range for urine specific gravity?
1.001-1.030
Reference Range for urine pH?
5.0 - 8.0
Reference Range for urine protein, glucose, ketones, blood, bilirubin, nitrite, leukocyte esterases?
negative
Reference Range for urine WBC/HPF and RBC/HPF?
0-2 for both. HPF stands for "high powered field" (of the microscope)
Reference Range for urine epithelial cells?
few
Reference Range for urine hyaline casts/LPF?
0-2 per LPF

LPF="low powered field" (of the microscope)
Reference Range for urine granular casts, RBC casts?
none
Reference Range for urine bacteria, mucus?
rare
Reference Range for WBC count?
4-11 (1000/mL)
Reference Range for Hgb?
male=14-17 g/dL
female=12-16 g/dL
Reference Range for Hct?
male=40-50
female=36-46
Reference Range for MCV?
82-98 cubic micrometers
Reference Range for MCH?
27-31 pgm
Reference Range for MCHC?
32-37%
Reference Range for platelet count?
130-400 (1000/ml)
Reference Range for neutrophils?
45-70%
Reference Range for lymphocytes?
20-40%
Reference Range for monocytes?
1-10%
Reference Range for Eosinophils?
1-3%
Reference Range for basophils?
0-2%
Reference Range for bands?
0-15%
bands are slightly immature neutrophils
Reference Range for reticulocytes?
0.3-2.3%
Reference Range for PT and PTT (or APTT)?
PT 9-12 seconds
PTT 25-33 seconds
effects on serum XOL levels of monounsaturated fats, polyunsaturated fats, partially hydrogenated fats?
monounsaturated have no significant effect
polyunsaturated reduce XOL
partially hydrogenated increase XOL
What are HBsAg, HBcAg, and HBeAg? and describe their changes in levels with acute and chronic hepatitis B?
hepatitis B surface antigen, core antigen, and envelope antigen.

Surface Ag rises and falls in acute hep B and recovery, but rises and stays high in chronic hep B

core Ag total ANTIBODIES rise and stay high in both chronic and acute hep B infection, but IgM anti-core antibodies rise and fall within 6-8 months in both cases.

envelope antigen is present for about 3 months in acute hep B, but can persist for years in chronic hep B