Medical

Glucagon/SQ- inj/ mini-dose/ 1 unit (10 mcg) per yr of age (…up to 15 yrs of age…)—for Hypoglycemia (when oral feeds cannot be tolerated, as in vomiting)—then, Check BS in 15 mts—if still hypoglycemic, double dose….Then, call the M.D., if needed.

http://www.jfponline.com/uploadedFiles/Journal_Site_Files/Journal_of_Family_Practice/supplement_archive/SupplJFP_clinicalconditions.pdf ( Incretins)

http://pi.lilly.com/us/humalog-pen-pi.pdf ( Humalog) ; http://www.medscape.com/viewarticle/581186 ( Liraglutide)

http://www.consultantlive.com/diabetes/article/10162/37734 ( DM--New Drugs)

http://www.consultantlive.com/diabetes/article/10162/37574 ( DM--11 treatment pitfalls)

http://jama.ama-assn.org/cgi/content/full/299/21/2590 ( DM & Preg)

http://www.medscape.com/viewarticle/578048 ( Prediabetes Management)

http://www.lillydiabetes.com/index.jsp (Insulin)

http://www.diabetesa1c.org/

http://www.guideline.gov/summary/summary.aspx?doc_id=6826 ( Care of children with Type DM)***

http://www.diabetes.org/for-parents-and-kids.jsp

http://www.medscape.com/viewarticle/559585 ( GLP 1 analogues; DPP4 Inhibitors)****

http://www.jfponline.com/uploadedFiles/Journal_Site_Files/Journal_of_Family_Practice/supplement_archive/JFPSupp_InsulinAnalogs_0107.pdf

( Appropriate use of Insulin Analogs)

http://www.jfponline.com/uploadedFiles/Journal_Site_Files/Journal_of_Family_Practice/supplement_archive/JFPSupp_InsulinFP_1206.pdf

( Practical Insulin Strategies)

http://www.jfponline.com/uploadedFiles/Journal_Site_Files/Journal_of_Family_Practice/supplement_archive/jfp_0505_00445.pdf

( DM 2--The role of Insulin)

http://professionaled.joslin.org/ ( CME)

http://cmejama-archives.ama-assn.org/cgi/quiz/amacme_quiz;jama_297_2_196?node_id=amacme_course;jama297/2/196 ***

http://www.medscape.com/viewarticle/550034 ( Oral GTT in CAD)

http://www.bcchildrens.ca/NR/rdonlyres/F0674005-EF69-4DAE-9A42-76D7DE69E17D/13009/dkaprt.doc ( DKA Protocol in Children)******

http://www.medscape.com/viewarticle/557783 ( Exenatide + Oral monotherapy, in DM2)

NEW PROTOCOL FOR DKA IN THE ED ( Peds/ ED---PICU)

http://www.medscape.com/viewarticle/547237 ( Pump Tx)

http://www.aau.edu.et/faculties/med/internalmed/Notes/DKA_protocol.htm ( DKA Protocol in Adults)

Insulin Drip Protocol ( Adults)

http://www.medscape.com/viewprogram/5997 ( Inpatient Insulin Tx) *******

BMJ Publishing House ( Summer/ 2006) ------Outpatient Tx in DM2 *********

Hospital Diabetes Plan: What Can We Do for Patients Admitted to the Hospital?

Hospital Diabetes Plan: What Can We Do for Patients Admitted to the Hospital? (cont'd)

Hospital Diabetes Plan: Protocol for Insulin in the Hospitalized Patient

Hospital Diabetes Plan: Protocol for Insulin in the Hospitalized Patient (cont'd)

Total Daily Dose(TDD) in Physiologic Insulin Replacement Therapy= Wt in Kg x 0.7= __Units of Insulin daily.

Basal & Bolus Insulin Requirements/ 24 hrs: 50 % Basal ( Detemir, Glargine); 50% Bolus ( Aspart, Glulisine, Lispro)..

For Post-Meal ( PP) Hyperglycemia: 1700/ TDD=X ( i.e., 1 Unit of Analog Insulin will decrease X mg/dl of Blood Glucose). Target correction 'to' not lesser than 150 mg/ dl, to avoid Hypoglycemia.

To prevent PP Hypoglycemia, based on the amount of Carbohydrate ingested: 450/ TDD=Y ( i.e, 1 Unit of fast-acting Insulin analog will cover the consumption of Y gms of carbohydrate).

Endocrine Consult

Diabetes Education and Discharge Planning

For Further Information

Insulin Analogs Are Preferred for Patients Who Are Eating

Additional Directions Are Attached to Specific Scheduled Insulin Orders, or Are Specified Under Protocols

Writing Orders for Basal Insulin for Patients Who Are Eating Discrete Meals

Writing Orders for Prandial Insulin for Patients Who Are Eating Discrete Meals

Sample

Basal Insulin in Type 2 Diabetes Is 40%-50% of the Usual Total Daily Dose

Answer

Estimating Combined Basal and Nutritional Coverage From Drip

One Acceptable Answer

Insulin Regimen, No Tube Feeds, for Patients Attempting to Eat (Transitional Meal Plan With

Example of a

Initial Insulin Calculation, Hospitalized Patient Type 2 Diabetes

During Continuous Nutritional Support or IV Dextrose Infusion

For Type 2 Diabetes

How Much to Start With?

Type 2 Diabetes, NPO, Continuous D5W

Requirement for Exogenous Insulin During Prolonged Fasting May Disappear in Type 2 DM, But Even During Prolonged Fasting it Is Absolute in Type 1 DM

'Locking In' Basal Insulin for Insulin-Deficient Diabetes When Not Eating

Type 1 Diabetes, Continuous Carbohydrate Exposure

Summary

Summary (cont'd)

Consider Intensification After Discharge

Continuous Variable-Rate IV Insulin Drip

Continuous Variable-Rate IV Insulin Drip (cont'd)

Converting to SC Insulin

Correction Bolus (Supplement)

Correction Bolus Formula

Initiating SC Basal Bolus

1. Data have shown that inpatient mortality in patients with previously undiagnosed diabetes was:

Answer: >15%
Newly discovered hyperglycemia was associated with a higher in-hospital mortality rate (16%) compared with patients with a history of diabetes (3%) and patients with normoglycemia (1.7%; both P < .01).

2. Of the following choices, 3-BG is a highly accurate indicator of blood glucose control for surgery patients that:

Answer: Averages discrete 24 measurements over 3 perioperative days
It is shown that 3-BG is a highly accurate indicator of blood glucose control for surgery patients that averages discrete 24 measurements over 3 perioperative days. It is measured starting on the day of surgery and the first 2 postoperative days. Blood is taken by arterial line drop, venous line drop, or capillary fingerstick methods.

3. According to data from the Portland Diabetic Project, the major risk factor for increased morbidity and mortality in cardiac surgery with diabetes is:

Answer: 3-BG
According to data from the Portland Diabetic Project, the major risk factor for increased morbidity and mortality in cardiac surgery with diabetes is 3-BG. They found that mortality was 4.4% among those with 3-BG greater than 200 mg/dl compared with 1.6% in those with 3-BG less than 200 mg/dl.

4. Use of GIK infusions to control blood glucose is no longer recommended because:

Answer: All of the above
GIK infusions to control blood glucose are no longer recommended because it is burdensome and it is difficult to control glucose especially in patients who are eating. Additionally, studies with GIK are complicated by varying degrees of glucose control, congestive heart volume, and volume of GIK infusion.

5. One of the key elements of continuous insulin infusion is:

Answer: Blood glucose must be controlled for all 3-BG to normalize the risk for surgery patients with diabetes
Researchers have found that duration of CII therapy matters and there is independent significance of daily glucose parameters on outcomes.

6. Diabetes increases acute MI mortality risk by about:

Answer: 50%
Diabetes increases acute MI mortality risk by about 50%.

7. Compared to subcutaneous insulin, continuous insulin infusion has been shown to reduce CABG mortality by:

Answer: 65%
Compared to subcutaneous insulin, continuous insulin infusion has been shown to reduce CABG mortality by 65%.

8. According to the ADA, the in-hospital target for glucose is:

Answer: FPG 90-130 mg/dL; peak postprandial <180 mg/dL
According to the ADA, the in-hospital target for glucose is FPG 90-130 mg/dL and <180 mg/dL peak postprandial.

9. What is the threshold for starting an insulin drip?

Answer: FPG 140 mg/dL
The threshold for starting an insulin drip is an FPG of 140 mg/dL.

10. For patients with diabetes and major surgery or NPO status, the recommended therapy for control blood glucose is:

Answer: Continuous variable rate IV insulin drip
For patients with diabetes and major surgery or NPO status, the recommended therapy to control blood glucose is continuous variable rate IV insulin drip. The starting rate can be determined by using the following formula: U/h = (BG ¨C 60) x 0.02 where BG is current BG and 0.02 is the multiplier. Glucose should be checked every hour and the drip adjusted. The multiplier should also be adjusted to keep blood glucose in desired target range (80-110 mg/dL in the ICU and 100-140 mg/dL on the floor).

11. When do you convert to SC basal from IV drip insulin?

Answer: When >0.5 units/hr IV insulin is required and glucose is in a stable range
IV drip insulin can be converted to subcutaneous basal insulin if > 0.5 U/hr of IV insulin is required with normal blood glucose. In this case, a long-acting insulin such as glargine can be initiated. However, if there is no prior DM and normal A1C, the patient may not need SC insulin. The SC insulin must be started at least 1 to 2 hours before stopping IV insulin.

12. IV drip insulin can be converted to subcutaneous basal insulin if more than 0.5 U/h of IV insulin is required with normal blood glucose. In this case, a long-acting insulin such as glargine can be initiated. However, if there is no prior DM and normal A1C, the patient may not need SC insulin. The SC insulin must be started at least 1 to 2 hours before stopping IV insulin.

Answer: All of the above
When converting to SC insulin, it is important to establish the 24-hour insulin requirement. Half the insulin should be given as basal and half should be given as total bolus.

13. A preferred SC insulin therapy in the hospital for a patient eating discrete meals uses:

Answer: About 50% basal insulin (glargine) and 50% rapid-acting insulin (glulisine/lispro/aspart)
A preferred SC insulin therapy in the hospital for a patient eating discrete meals uses about 50% basal insulin (glargine) and 50% rapid-acting insulin (glulisine/lispro/aspart).

14. During preadmission, it is recommended that oral agents are discontinued and the dose of basal insulin is modified as needed.

Answer: True
For patients with diabetes and major surgery or NPO status it is recommended that oral agents are discontinued and the dose of basal insulin is modified. The recommended therapy to control blood glucose is continuous variable rate IV insulin drip. Glucose should be checked every hour and the drip adjusted. The multiplier should also be adjusted to keep blood glucose in desired target range (80-110 mg/dl in the ICU and 100-140 mg/dl on floor).

15. Scheduled insulin analogs are preferred over sliding scale because they improve glycemic control without increasing the risk of hypoglycemia.

Answer: True
Scheduled insulin analogs are preferred over sliding scale for patients with diabetes and major surgery or NPO status, the recommended therapy to control blood glucose is continuous variable rate IV insulin drip. The starting rate can be determined by using the following formula: U/h = (BG ¨C 60) x 0.02 where BG is current BG and 0.02 is the multiplier. Glucose should be checked every hour and the drip adjusted. The multiplier should also be adjusted to keep blood glucose in desired target range (80-110 mg/dl in the ICU and 100-140 mg/dl on floor).

http://www.medscape.com/viewarticle/540775******

http://nursingceu.com/courses/37/index_nceu.html**********

http://www.medscape.com/viewarticle/546864#question ( Metformin/ Sulfonylurea---Single Tx...)

http://www.medscape.com/viewarticle/546303 ( SITAGLIPTIN)

http://www.medscape.com/viewarticle/546479 ( DM/ C-Peptide/ Coffee).

http://www.medscape.com/viewarticle/546503 ( Meds to prevent DM ---?)

http://www.medscape.com/viewarticle/543799

http://www.medscape.com/viewarticle/545463 ( Pramlintide)

http://www.medscape.com/viewarticle/545802 ( Diagnosis of Gestational DM)

http://www.medscape.com/viewarticle/545466 ***DM 1--Hypoglycemia

http://www.medscape.com/viewarticle/542296***

http://www.medscape.com/viewarticle/542292

http://www.medscape.com/viewarticle/544758 ( Prevention of DM in Impaired fasting Glucose...)

http://www.medscape.com/viewarticle/543558

http://www.diabetesnet.com/diabetes_control_tips/corr_factor.php?PHPSESSID=535fb9fc5f7d7cb938183553cb55c112 1800 rule

http://www.minimed.com.au/pump_therapy-highgluc.html (Insulin Pump/ Pt information)

http://www.medscape.com/viewarticle/541953 ( When to start Insulin Tx--the first time...)

http://www.medscape.com/viewarticle/533668_15**********

Recognizing Oral Therapy Inadequacy

Defining Goals of Therapy in DM

Estimated Pharmacokinetics of Current Insulin Preparations

http://members.aadenet.org/scriptcontent/map.cfm (Find a Certified Diabetes Educator)

http://www.nlm.nih.gov/medlineplus/directories.html (Find a Professional)

Persons who have type 2 diabetes and whose glucose exceeds 200 mg/dL have at least a 30% decrease in survival within 200 days.

Oral Therapy for Type 2 Diabetes: Sites of Action

ROSI/MET Fixed-Dose Combination Effective in Patients With Severe Hyperglycemia

A1c Change From Baseline: TZD + Met vs SU + MET

http://www.medscape.com/viewarticle/536351_5

(The best results came when you continued the rosiglitazone and you gave a 25 mg dose of Aldactone. So, that is something we can use).

http://www.medscape.com/viewarticle/536351_7

(...Do triamterene or amiloride work for edema caused by TZDs? Well, it turns out that triamterene is great if you want stones. Then you're finished. What is meant is that triamterene does very little. For some reason there is a rash of triamterene use and you could end up doing is switching patients to a thiazide diuretic and get miraculous blood pressure discoveries. Don't use triamterene. Amiloride is very good. Amiloride will work because, in fact, the epithelial sodium channel (EnaC) is the one that has been found to really be affected by the TZDs. So amiloride would be an excellent drug to use in combination; something like Moduretic (amiloride) would be brilliant in people on TZDs because you'd have the thiazide plus the amiloride working. Spironolactone is also very good, but if you've got issues with potassium or something and the patient has good enough kidney function, then Moduretic would probably be a better way to go. The loop diuretics are worthless, and they are not going to help you in that situation.

The other little thing in terms of edema in these patients, especially if they're susceptible, is if you start dosing the TZD slowly rather than blasting patients with 8 mg up front, you'll tend to get less edema than you will if you start at much higher doses early on).

(...What drugs are safe to use for diabetes treatment in people with chronic kidney disease stage III or beyond? You can't use metformin anymore. Sulfonylureas are no longer that safe because many are renally excreted and would lead to prolonged activity and hyperglycemia would be a risk. Insulin is the safest. It is a natural product, so remember that short-acting insulin becomes long-acting; long-acting becomes longer-acting. Dosage modification becomes critical.

Some of the newer agents like the secretagogue marketed as Starlix, whose pharmacologic name is nateglinide, are neutral in the setting of renal failure. Even in dialyzed patients, its pharmacokinetics are unaltered, so its secretion is by nonrenal mechanisms. Rosiglitazone, a TZD, can be used up to a certain stage in renal failure; we still have the ability to use it because it is not nephrotoxic. It does not accumulate like metformin does, and there is no toxicologic concern.

So there are agents that can be used, but we have insulin, at least some insulin onboard to hedge our bets, to make sure the A1c control is on target. But there are some oral agents, the ones that have been mentioned, that can be used in renal failure).

(...How many of the patients given Aldactone (spironolactone) developed hyperkalemia? Researchers used 25 mg, which is much lower than doses they use in cirrhosis of the liver and other conditions where we do not see a lot of hyperkalemia. Aldactone is used a lot in hirsute patients in whom you need to block androgen receptors -- the polycystic ovary population. We use up to 100 mg/day and hyperkalemia as a limiting problem.

In KD, you do not need to use high doses. In fact, 12.5 to 25 mg is more than adequate. Use a loop diuretic twice a day, if you USE them. As for tolerability, generally don't even blink until the potassium hits 5.8. If you do all that, hyperkalemia will be an issue, but it will not be a big issue in those patients).

(...What is the best treatment to prevent progression of diabetic neuropathy? The best treatment is glucose control. The Diabetes Control and Complications Trial (DCCT) showed 60% reduction in the rate of new-onset neuropathy, and 70% in progression of preexisting neuropathy.

All of the marketed drugs for "neuropathy" don't address the fundamental biology of the process. They block pain through projection from the dorsal column in the gracile bundle in the thalamic integration site. It is similar to the way Tylenol (acetaminophen) makes your headache go away, where you think you do not have that brain-based process. Tylenol resets the membrane potential for pain threshold, but the process is still there.

So do not really prescribe Neurontin (gabapentin) or any of those pain medications that are supposed to heal the nerves. They do not heal nerves. Glycemic control and then in the future when we have nerve growth factor based approaches or aldose reductase based approaches, but right now glycemic control is the winning move here).

(...A question here about the "negative effects" of thiazide diuretics on lipids and insulin resistance, and should those effects discourage their use in people with diabetes. The short answer is no, it should not discourage the use because every single person with diabetes is volume expanded, period, and you will not be able to unload them unless you put them on peritoneal dialysis when their glomerular filtration rate is 65. It's just not going to happen.

You need to be using the diuretics, and unfortunately, it was thought that the angiotensin-converting enzyme (ACE) inhibitors and the angiotensin-receptor blockers (ARBs) would protect you from the effects of the diuretics on metabolic control, but there is a paper in the Journal of the American Medical Association that -- in a very nicely controlled study looking at a number of things, including insulin levels and oral glucose tolerance tests, etc. -- actually probably does not support that theory.

This does not mean that if you have a patient with diabetes that you should avoid diuretics. Absolutely the contrary. They need to be used. You may need to go up on the diabetes medicine. You may need to reinforce lifestyle more. But you absolutely are going to have to use them. The key issue is to make sure the potassium doesn't go below 4. As long as the potassium stays above 4, you will be in good shape. Once it starts going below 4, you actually are starting to worsen insulin sensitivity, and in addition to that, by the way, you're going to see negative results because if a patient has hypokalemia, you are actually closing the potassium channels and worsening blood pressure independent of anything else. Minoxidil works in the exact opposite manner).

http://italia.medscape.com/viewarticle/532093

http://www.juri.dia-club.ru/eng/desc.php?go=e4 (Insulin Dose Calculator/ for the PT.).

http://www.mendosa.com/www-2aida-org/tutorial.htm (Insulin Dosing Tutorial/ for the Pt.)

http://www.diabetic-talk.org/dp.htm (Hyperglycemia in the FBS in the mornings/ Dawn phenomenon & Somogyi effect).

http://www.aafp.org/afp/20050501/1705.html (DKA)

http://www.medscape.com/viewarticle/546259 ( Use Metformin FIRST ?)

http://www.whhi.com/themeofthemonth.htm (Pt Education)**********

http://aadenet.org/ (Diabetes Educators).

http://www.postgradmed.com/issues/1997/02_97/skyler.htm (Insulin Therapy in T2DM).

http://www.medscape.com/viewarticle/525024 (When to add Insulin Glargine in Type 2 DM).

Switching Insulin Brands ; Mixing Insulin; Table 1

The initial dose of rapid-acting insulin may be calculated as 1 U of rapid-acting insulin for every 10 g of carbohydrate eaten plus an additional 1 U for every 30 mg/dL above the target self-monitoring blood glucose level of 100 mg/dL.

A GOOD LUNCH HAS ATLEAST 250 CALS OR 30 GMS OF CARBOHYDRATE.

Administer from one third to one half of that as basal insulin, and the remainder as rapid-acting insulin, distributed as 40% (8 U) at breakfast, 30% (6 U) at lunch, and 30% (6U) at supper. Consider adopting a carbohydrate-counting program to refine the premeal doses.

http://www.guideline.gov/summary/summary.aspx?view_id=1&doc_id=6826 (Care of Children & Adolescents in Type 1 DM).

http://emedmag.com/html/pre/cov/covers/021505.asp (Glucose Control in the Hospitalised Patient)

http://www.healthline.com/multumcontent/pramlintide PRALIMTIDE

http://www.diabetesnet.com/diabetes_treatments/insulin_inhaled.php INHALED INSULIN

http://www.diabetes.org.uk/infocentre/inform/insulin_detemir.htm INSULIN DETEMIR

http://www.drugs.com/mtm/insulin_glulisine.html INSULIN GLULISINE

-------------------------------------------------------------------------------

American Association of Diabetes Educators at (800) 832-6874 to find someone who can help you with your diabetes meal plans.

(BS of 1 mmol/ L= 18mg/dl);

1 unit of Reg Ins decreases BS by roughly 1.5 to 1.8 mmol/ Varies by Pt.-Pt;

2 units of Reg Ins needed for 12 gms of Carbohydrate).

---------------------------------------------------------------------------------

Early DM:

If after OAD don't work well, you need to initiate insulin Tx---start Insulin Gargine @ 10 units/d @ bedtime to maintain FBG @ 100-110 mg/dl. If FBG is not in target range, increase bedtime Insulin Glargine by 2 units Q 3 days.

To control the 2 hr PP glucose excursions, use 'prandial insulin' to 'main meal' ( 0.05-0.1 units/ kg). If the PPG is greater than 180 with the other largest meal, again use the same regimen ( Rapid acting Insulin 0.05-0.1 units/kg, to maintain 2 hr PPG lesser than 180.

*** ( Add 1 unit of insulin for every 25 mg/dl increase in Blood Sugar 'beyond' FBG greater than 130, or, PPBG greater than 200).

-----------------------------------------------------------------------------------

Late stage DM, or, IDDM:

Start with Insulin 0.5 units/kg/day ( for BMI lesser than 28 kg/ m2) & Insulin 0.7 units/kg/day ( for BMI greater than 28 kg/ m2). Divide this as basal (50 %), &, bolus (50%).

Basal Insulin ( LA Insulin 'like' glargine/ 0.35 units/ kg/day---QD---@ HS)

Bolus Insulin ( SA Insulin like 'lispro or aspart'/ 0.35 units/kg/day---divided TID, 15 mts before meal-time).

-------------------------------------------------------------------------------------

Basal Insulin Dose ( units) correction/ Using the Morning-Bld-Glucose ( mg/dL) of the 7-day average-sugars.

Less than 80 = -2, 80-110= 0 , 111-140= +2 , 141-180=+4 , Greater than 180= +6.

--------------------------------------------------------------------------------------

Carbohydrate Snack @ start of exercise------if Bld sugar is less than 100 mg/dL, & ,pt is taking Insulin or Insulin Secretagogues.

______________________________________________________________________________________________________________________________________

http://www.medscape.com/viewprogram/6309

1. Which one of the following statements is correct?

Answer: Type 2 diabetes is characterized by progressive loss of beta-cell function
Although insulin resistance is another feature of type 2 diabetes, it has not been shown to worsen over time. In clinical trials with a treat-to-target approach, near normalization of fasting glucose levels in patients inadequately controlled on oral agents by the addition of basal insulin will result in A1C levels of ¡Ü 7% in 60% of patients. Data from the UKPDS estimated that a 1% decrease in A1C would lead to a 25% risk reduction in the development of complications in subjects with type 2 diabetes.

2. Common reasons cited by providers as barriers to insulin initiation include all of the following except:

Answer: Fear that insulin use may promote injection drug use among patients
Concern about the promotion of injection drug use has not been cited by providers as a reason for failure to initiate insulin treatment in surveys.

3. The current American Diabetes Association (ADA) guidelines for goals of therapy in type 2 diabetes are as follows:

Answer: Preprandial blood glucose 90-130 mg/dL and peak postprandial blood glucose < 180 mg/dL
Current ADA guidelines are fasting blood glucose of 90-130 mg/dL and peak postprandial blood glucose < 180 mg/dL.

4. Mr. Smith, a 62-year-old mechanic with type 2 diabetes, is seen for routine follow-up. He is currently on glyburide 10 mg twice daily, metformin 850 mg twice daily, and rosiglitazone 4 mg once daily. His A1C at this appointment is 8.6%, and it has steadily increased over the last 2 visits. Review of his log reveals fasting glucose levels of 160-220 mg/dL and 2-hour postprandial values between 160 and 200 mg/dL. Which one of the following methods will best help Mr. Smith improve his glycemic control?

Answer: Add 1 injection of 10 U of insulin glargine at night to the current regimen and adjust to target fasting blood glucose levels
The most effective means of achieving a target A1C would be to add glargine insulin to his regimen. Addition of detemir or NPH would be equally effective. Lispro would not be effective for basal insulin coverage because it is a rapid-acting insulin.

5. Which one of the following statements in regard to rapid-acting insulin analogs is correct?

Answer: They rapidly dissociate into monomers after injection
Rapid-acting analogs begin to act within 25 minutes of subcutaneous injection and are taken right before meals. They rapidly dissociate into monomers and are quickly absorbed into the circulation. Duration of action is 4-5 hours.

6. According to an analysis of the 1999-2000 National Health and Nutrition Examination Survey (NHANES), the number of Americans with diabetes who have A1C levels < 7% is estimated to be:

Answer: 37%
Data from NHANES 1999-2000 revealed that only 37% of patients with diabetes achieved A1C levels < 7%, and 37.2% had A1C levels > 8%.

7. The following are contraindications to use of inhaled insulin except:

Answer: History of hypoglycemia with subcutaneous insulin use
Even though hypoglycemia is an adverse effect that can be seen with use of inhaled insulin (and all other insulin preparations), it is not a contraindication.

8. Which one of the following statements is true about the Treat-to-Target Trial, which randomized type 2 diabetes patients failing oral antiglycemic drugs (OAD) to the addition of NPH or glargine?

Answer: Glargine + OAD therapy was associated with fewer hypoglycemic events
Glargine and NPH were equally effective in terms of reduction in A1C level achieved and the percentage of subjects who achieved an A1C concentration of < 7%.

9. Which one of the following statements best describes normal endogenous insulin secretion?

Answer: Continuous pulsatile secretion at low levels with increased bursts of secretion with meals
Insulin is secreted continuously at low levels (basal secretion) coupled with increased bursts of secretion during mealtime.

10. All of the following scenarios are indications for the initiation of insulin in type 2 diabetes except:

Answer: A patient with a history of type 2 diabetes for 10 years with an A1C level of 7.2% treated with metformin 500 mg twice daily
Insulin therapy is indicated for pregnant women, newly diagnosed symptomatic patients with very high blood glucose levels, and those whose A1C level remains above goal on maximal oral therapy. Insulin therapy is not indicated for this patient because even though the patient may have had diabetes for a long time, he/she has relatively good control with lifestyle intervention and monotherapy. Intensification of therapy can be achieved by adding a second OAD.

http://www.medscape.com/viewarticle/548905#question ( Rosiglitazone, Metformin, Glyburide...DM2)*********

http://www.medscape.com/viewarticle/545155

1. Which one of the following medications must be given by injection?

Answer: Exenatide
As with many small polypeptides, exenatide can only be given by injection.

2. What is the mode of action of metformin?

Answer: Suppression of hepatic glucose production
The mechanism of action of metformin is via suppression of hepatic glucose production. The mechanism of action of the sulfonylureas is stimulation of insulin secretion by the pancreas. The mechanism of action of the short-acting insulin secretagogues is stimulation of prandial increases in insulin. The mode of action of the thiazolidinediones (TZDs) is the suppression of hepatic glucose production.

3. Which one of the following statements is true?

Answer: Imaging data have shown a reduction in visceral fat with TZD treatment
Imaging data have shown a reduction in visceral fat with TZD treatment. However, exenatide has been not been shown to have beta-cell protective effects in clinical trials; there are no head-to-head comparisons of the lipid effects of metformin, the TZDs, and exenatide; and 20% of patients receiving exenatide experience nausea.

4. What is the Third Report of the National Cholesterol Education Program (NCEP III) and American Diabetes Association (ADA) low-density lipoprotein cholesterol (LDL-C) target in patients with type 2 diabetes and no overt cardiovascular disease?

Answer: Less than 100 mg/dL
The NCEP II and ADA LDL-C target in patients with type 2 diabetes and no overt cardiovascular disease is 100 mg/dL.

5. Maximal doses of metformin will reduce glycated hemoglobin (A1C) levels by approximately what range?

Answer: 0.9% to 1.4%
Maximal doses of metformin will reduce A1C levels by approximately 0.9% to 1.4%.

Figure 1: Mean change in glycated hemoglobin (A1C) in selected glucose-lowering studies.

Figure 2: Mean change in weight in selected glucose-lowering studies.

Asthma / COPD/ RS

http://www.aanma.org/ http://www.aafa.org/ *************

http://www.fpnotebook.com/LUN.htm ( PULMONOLOGY) ***********************

http://www.medscape.com/viewarticle/530089

http://www.medscape.com/viewarticle/581937?src=mp&spon=34&uac=74821FZ ( Updated..)

http://www.jfponline.com/Pages.asp?AID=6494&issue=August%202008&UID=42445re

http://www.aafp.org/afp/20090501/761.html (Asthma Guidelines/ new changes)

http://www.emedmag.com/html/p/cov/covers/041506.asp ( Tx of Acute Asthma Exacerbations)/ Prednisolone Tx in Asthma--IP & OP/ Child & Adult

http://www.medscape.com/viewarticle/554557 ( 1200 mcg/ day, of ICS ,in adults with COPD)...

http://www.nationaljewish.org/pdf/Childhood_ACT.pdf (Childhood ACT) ****

http://thoracic.org/sections/copd/

"In people with chronic lung disease, distress with breathing is one of the most common and most distressing symptoms which impacts upon all aspects of people's lives"

http://www.jfponline.com/Pages.asp?AID=6648&issue=September_2008&UID=42445 ( Lung Age)

http://familydoctor.org/online/famdocen/home/articles/706.html ( COPD)

http://www.jfponline.com/Pages.asp?AID=6270&issue=June%202008&UID=42445 ( Oral or IV steroids for --Inpt COPD)

Handbook of Drug Interactions: A Clinical and Forensic Guide - Google Books Result

http://www.rxlist.com/cgi/generic/albut1_ids.htm http://www.rxlist.com/cgi/generic/albut1.htm

http://www.rxlist.com/cgi/generic/xopenex.htm http://www.rxlist.com/cgi/generic/leval_ids.htm

http://www.medscape.com/viewarticle/562258 ( Asthma Management)

http://www.ncbi.nlm.nih.gov/books/bv.fcgi?indexed=google&rid=asthma3.chapter.1871 ( Age group/ Guidelines)

http://www.ncbi.nlm.nih.gov/books/bv.fcgi?indexed=google&rid=asthma3.chapter.1913

http://www.medscape.com/viewarticle/556184 ( Asthma in Preg)

http://www.medscape.com/viewarticle/561419 ( Long term O2 in COPD)

http://www.jfponline.com/uploadedFiles/Journal_Site_Files/Journal_of_Family_Practice/supplement_archive/JFPSupp_COPD_1106.pdf

http://www.mesg.org/_files/ICS_NL_Part2.pdf ( Care of children with Persistent Asthma)

http://www.fpronline.com/files/supplements/M506.pdf ( Allergic Rhinitis)

http://www.jfponline.com/uploadedFiles/Journal_Site_Files/Journal_of_Family_Practice/supplement_archive/jfp_0305_00255(1).pdf ( CA--Pathogens)

http://goldcopd.com/ *******Guidelines/ COPD

http://www.medscape.com/viewarticle/549524 ( Allergic Rhinitis/ Asthma/ Allergic Conjunctivitis--Stepwise Tx) ***

http://www.medscape.com/viewprogram/6441_index ( Immunology in Asthma---NKT cells----IL & Cytokines; B Cells & IgE)---Both are allergen specific...?

http://www.medscape.com/viewprogram/6420 ( Allergies-- Immunotherapy) ***

http://www.lungusa.org/site/pp.asp?c=dvLUK9O0E&b=22542 (American Lung Association)

http://www.aaaai.org/patients/publicedmat/tips/travelingwithallergies.stm (Tips for Travel)

http://www.medscape.com/viewarticle/542598#question ( Child---PEFR/ FEV1 for Diagnosis).

http://www.acaai.org/ (American College of Allergy, Asthma and Immunology)

http://aafa.org/ (Student asthma action card)

http://ncbi.nih.gov/ (National Center for Biotechnology Information)

http://lung.ca/asthma/ (The Lung Association)

http://epa.gov/iaq/asthma/shs.html (Environment Protection Agency)

http://ginaasthma.com/ (Global Initiative for Asthma)

http://www.cdc.gov/nchs/about/major/slaits/nsa.htm (National Asthma Survey--Statistics)

http://www.cdc.gov/nchs/products/pubs/pubd/hestats/asthma/asthma.htm (Statistics)

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5217a2.htm (Self reported-Statistics)

http://www.nhlbi.nih.gov/health/index.htm (Information for the Patients and the Public)

http://www.nhlbi.nih.gov/health/prof/lung/asthma/astpreg.htm (Asthma Care Guidelines in Pregnancy)

http://www.cdc.gov/search.do?action=search&queryText=asthma+survey+questions (Asthma Survey Questions)

http://www.cdc.gov/search.do?action=search&queryText=asthma+questions (Asthma Questions)

http://www.cdc.gov/asthma/BRFSSasthmaquestions.pdf (Asthma survey questions)

http://www.protectingourhealth.org/newscience/asthma/asthmaknow.htm (Asthma Prevalence, morbidity, mortality---Statistics)

http://centerwatch.com/search.asp?qu=asthma&FreeText=off (Centerwatch.com; asthma clinical trials)

http://www.acrn.org/ (Asthma Clinical Research Network)

http://www.medscape.com/viewarticle/545732 ( Symbicort---Maintanance & Relief) **********

http://www.asthma-education.com/info16.html (The Children's Asthma Education Center)

http://www.asthma-carenet.org/ (Childhood Asthma Research Education Network)

http://njc.org/ (National Jewish Medical & Research Center)

http://www.nhlbi.nih.gov/about/naepp/ (NAEPP Guidelines)----********

allergyasthma.com

http://www.medscape.com/px/splash

http://www.clevelandclinic.org/; (Daily Asthma Diary) http://search.ccf.org/SCRIPTS/texis.exe/Webinator/search/

http://onlineallergyrelief.com/bedding/bedding.html (Allergy relief store)

http://www.allergycontrol.com/

http://www.allsupinc.com/ (Do you qualify for social security disability income?)

http://www.radix.net/~mwg/inhalers.html (Types of Inhalers)

http://www.nlhep.org/spirom1.html (Spirometry)

http://www.docguide.com/news/content.nsf/SearchResults?openform&Query=asthma&so=date&id=48DDE4A73E09A969852568880078C249 (Docguide.com; asthma)

http://www.emedicine.com/cgi-bin/foxweb.exe/searchengine@/em/searchengine?boolean=and&book=all&maxhits=100&HiddenURL=&query=asthma (emedicine.com; asthma)

http://www.fbhc.org/Patients/Modules/asthma.cfm (Frequently asked Questions)

http://www.medscape.com/viewarticle/543856 ( maintenance TX)

http://www.medscape.com/viewarticle/544332 ( Formoterol in Asthma).

http://www.medscape.com/viewarticle/544333#question ( COPD)

http://www.medscape.com/viewarticle/549746 ( Cosyntropin Test; Prevention of OP induced by Steroids...)***

http://summitcountyinternist.com/id228.htm

http://italia.medscape.com/viewarticle/532103

http://www.medscape.com/viewprogram/5321

http://www.mayoclinic.com/search/searchresults.cfm (mayoclinic.com; asthma)

http://www.medscape.com/viewarticle/530089

Pulmonology ************** Individualizing therapy for Adult Asthma/ Pediatric Asthma ( Pub Date---8/3/06) ****************

http://www.medscape.com/viewprogram/6166 ( COPD) http://goldcopd.org/Guidelineitem.asp?l1=2&l2=1&intId=989 ( COPD)

http://www.jfponline.com/uploadedFiles/Journal_Site_Files/Journal_of_Family_Practice/supplement_archive/IMS-J-1.pdf ( COPD)

( Medsite CME/ Pulmonology/6-13-06----Pub Date) ----COPD/ Role of Anti Inflammatory Meds

1. The estimated annual cost of chronic obstructive pulmonary disease (COPD) in the United States in 2002 was:

Answer: 32.1 billion dollars
The estimated annual cost of COPD in the United States in 2002 was 32.1 billion dollars. This figure was calculated by adding the 18 billion dollars spent in hospitals (direct cost) and 14.1 billion dollars spent indirectly (lost productivity/morbidity) due to the diagnosis and/or exacerbations of COPD. Overall, the chronic diseases asthma, diabetes, heart disease, and hypertensive disease cost the United States over 270 billion dollars in combined direct and indirect fees. Asthma cost 5.8 and 5.1 billion dollars in direct and indirect costs, diabetes cost 91.8 and 31.8 billion, heart disease cost 72 and 20.6 billion, and hypertensive disease figures were 5.5 and 7.2 billion in direct and indirect costs, respectively.

2. Studies show that most COPD patients often decrease their activity levels because of:

Answer: Dyspnea
COPD patients decrease their activity as a result of the unpleasant sensation of dyspnea and, as a result, become deconditioned, which leads to further impairment in exercise tolerance because of the high oxygen requirements of deconditioned muscles. As the effects on the lungs progress, dyspnea will become present with minimal effort or even at rest. Ultimately, quality of life will deteriorate to the point at which patients may become oxygen-dependent and finally completely immobilized.

3. At every patient visit, beginning with school-aged children, a __________should be recorded along with vital signs by the office staff.

Answer: Smoking history
At every patient visit, beginning with school-aged children, a smoking history should be recorded along with vital signs by the office staff. This history should include the number of cigarettes smoked per day, duration of smoking habit, exposure to passive smoking, and an estimate of total pack-years of smoking. Expanding the vital signs to include smoking status is a low-cost intervention that has been shown to increase the rate of identifying former or current smokers.

4. The hallmark of COPD is a decline in FEV1 to less than _______ of predicted, with relative preservation of the FVC.

Answer: 80%
The hallmark of COPD is a decline in FEV₁ to less than 80% of predicted, with relative preservation of the FVC. An FEV₁/FVC ratio of less than 70% of predicted identifies obstructive impairment. A normal FEV₁ and a normal FEV₁/FVC ratio usually exclude the diagnosis of COPD. While measurement of FEV₁ can determine the severity and staging of COPD, peak expiratory flow rate (PEF) is a less accurate gauge. A normal PEF does not exclude mild COPD. In general, this measurement underestimates the severity of COPD.

5. Clinical goals for the treatment of COPD include:

Answer: All of the above
The clinical goals in COPD treatment listed in the Workshop Report, Global Strategy for Diagnosis, Management, and Prevention of COPD -- 2005 Update include: symptom relief, increased exercise tolerance, improved health status, preventing and treating exacerbations, decreased mortality and/or prolonged survival, preventing and treating complications, and minimized treatment-adverse effects.

6. A patient who presents with an FEV₁ less than 80% with or without symptoms would be classified under the Global Obstructive Lung Disease (GOLD Initiative as:

Answer: GOLD Stage I: mild COPD
A patient who presents with an FEV₁ less than 80% with or without symptoms would be classified under the GOLD Initiative as GOLD Stage I: mild. The classification criteria are: GOLD Stage 0: at risk for COPD -- Chronic symptoms, exposure to risk factors, normal spirometry; GOLD Stage I: mild COPD - FEV₁ less than 80% with or without symptoms; GOLD Stage II: moderate COPD - FEV₁ 50% to 79%, with or without symptoms; GOLD Stage III: severe COPD - FEV₁ 30% to 49%, with or without symptoms; and GOLD Stage IV: very severe COPD - FEV₁ < 30% or presence of chronic respiratory failure or right heart failure.

Proposed Spirometry-Based Severity Classification System for COPD

http://www.medscape.com/viewarticle/549962 ( COPD Tx):

Severity	Postbronchodilator FEV₁/FVC	FEV₁ % Predicted
Mild	</= 0.7	>/= 80
Moderate	</= 0.7	50-80
Severe	</= 0.7	30-50
Very severe	</= 0.7	< 30

Table 2. Stepped Therapy of COPD

Stage	Characteristics	Recommended Therapy
All		Avoidance of risk factors Influenza vaccination
I: Mild COPD	FEV₁/FVC < 0.70 and FEV₁ >/= 80% predicted with or without symptoms	Short-acting bronchodilator when needed Active reduction of risk factor(s) Influenza vaccination
II: Moderate COPD	FEV₁/FVC < 0.70 and >/= 50% < FEV₁ < 80% predicted change to FEV₁ (between 50% and 80% predicted)	Short-acting bronchodilator when needed Active reduction of risk factor(s) Influenza vaccination Add regular treatment with 1 or more bronchodilators (when needed) Add rehabilitation
III: Severe COPD	FEV₁/FVC < 0.70 and >/= 30% < FEV₁ < 50% predicted	Short-acting bronchodilator when needed Active reduction of risk factor(s) Influenza vaccination Add regular treatment with >/= 1 bronchodilators (when needed) Add rehabilitation Add inhaled glucocorticoids if repeated exacerbations
IV: Very Severe	FEV₁/FVC < 0.70 FEV₁ < 30% predicted or presence of respiratory or right heart failure	Short-acting bronchodilator when needed Active reduction of risk factor(s) Influenza vaccination Add regular treatment with >/= 1 bronchodilators (when needed) Add rehabilitation Add long-term oxygen therapy if chronic respiratory failure is present Consider surgery Add inhaled glucocorticoids if repeated exacerbations

Using classically established criteria, Figure 2 enumerates current indications for LTOT. It is ideal to confirm these criteria during a time of clinical stability. Reassessment of oxygenation status after an exacerbation is recommended, although the optimal timing remains controversial.^[27] Criteria for LTOT.

HIV

http://www.cdc.gov/hiv/dhap.htm

http://www3.niaid.nih.gov/about/organization/daids/

http://www.who.int/hiv/en/

http://hivguidelines.org/Content.aspx

http://aidsinfo.nih.gov/ ***

http://idph.state.ia.us/adper/hiv_aids_programs.asp#prevention***

http://idph.state.ia.us/adper/common/pdf/disease_prevention_immunization/perinatal_guidelines_HIV_2007.pdf ( PN--Guidelines)

http://www.hivatis.org/

http://cdc.gov/mmwr/pdf/rr/rr5514.pdf ***

http://www.fpnotebook.com/HIV43.htm **********HIV LINKS

http://www.fpnotebook.com/HIVCh6.htm *********

http://drugtherapyinhivinfection.org/ ***

http://jama.ama-assn.org/cgi/content/full/300/5/614 ***

http://www.medpagetoday.com/ProductAlert/Prescriptions/tb/10251 ( Abacavir/ Genetic testing prior to prescribing)

http://www.hiv-druginteractions.org/ ****

http://en.wikipedia.org/wiki/Enfuvirtide ( Fusion Inhibitors)

http://en.wikipedia.org/wiki/Raltegravir ( Integrase Inhibitors)

http://en.wikipedia.org/wiki/Maraviroc ( CCR5 receptor inhibitor; Entry inhibitor )

http://www.medscape.com/viewarticle/706256 (Tx resistant HIV pts)

http://www.medscape.com/viewarticle/706251 (Integrase inhibitor MT)

http://www.medscape.com/viewarticle/706260 (Darunavir/ Ritonavir-- MT, in pts with undetectable HIV viral load)

http://cmejama-archives.ama-assn.org/cgi/content/full/jama;300/5/555?quiz_ans_id=5#5 ( Newer TXs)

http://www.medscape.com/viewarticle/578530 ( Tx Guidelines)

http://www.medscape.com/viewarticle/578584 ( Tx)

http://www.nccc.ucsf.edu/ ( HIV testing laws)

http://www.medscape.com/viewarticle/578659 ( HIV Screening/ Women 19-64 yrs)

http://www.medscape.com/viewarticle/578858

http://cmejama-archives.ama-assn.org/cgi/quiz/amacme_quiz;jama_300_9_1056?node_id=amacme_course;jama300/9/1056 ( Statins-- PI, Efavirenz)

http://www.medscape.com/viewarticle/581746 ( Tenofovir 300, Emtricitabine 200/ Atazanavir 400--QD)

http://www.medscape.com/viewarticle/567624 (Tx of HIV-1 in Teens, Adults)

http://www.thebody.com/content/art12718.html?mtrk=7461500 (HIV--Guidelines)

http://www.medscape.com/viewarticle/582922 (HIV Test, Prophylaxis to prevent MCT)

http://www.medscape.com/infosite/epzicom/article-3?src=0_nl_sm_0 (Abacavir/ HLA-B* 5701)

http://mail.live.com/default.aspx?wa=wsignin1.0 (Adverse effects of HIV meds)

http://www.medscape.com/viewarticle/705504 (Single tablet ART regimen to maintain Viral Suppression)

http://www.medscape.com/viewarticle/705577 (JCV Viruria--PML--HIV)

http://cmejama-archives.ama-assn.org/cgi/content/full/jama;296/7/827?node_id=amacme_course;jama296/7/827

( HIV +/- TB/ PREGNANCY/ HBV/HCV...)

http://www.medscape.com/viewarticle/570318 ( HIV/ TB---New Guidelines); http://jama.ama-assn.org/cgi/content/full/300/5/555

http://www.thebody.com/content/art12718.html?mtrk=7461500 ( Guidelines)

http://www.medscape.com/viewarticle/582679 ( Early HIV therapy improves survival)

http://www.advocatesforyouth.org/youth/index.htm

http://idsociety.org/

http://hivatis.org/

http://positive.org/

http://www.i-base.org.uk/questions/q2-150306.html ---HIV 1 &2 differences

http://www.medscape.com/viewarticle/545022#question **********

http://www.medscape.com/viewarticle/545812 ( HIV Dementia)

http://www.aids-ed.org/pdf/p02-et/et-02-01.pdf (MD Net Guide)

http://doctorfungus.org/ Fungal Infections

http://www.medscape.com/viewarticle/542919 ( In Pregnancy/ Hepatitis/ TB)

http://news.bbc.co.uk/2/hi/health/5021074.stm#endemic

http://www.aidsinfo.org/do/Associates

http://www.fantaproject.org/focus/preservice.shtml (Nutrition)

http://www.aidsinfo.nih.gov/ (guidelines)

http://hivinsite.ucsf.edu/(Rx, Prophylaxis)

http://www.hiv-druginteractions.org/

http://www.medscape.com/druginfo (search)

http://www.aidsmeds.com/ (post a question)

http://www.projinf.org/fs/drugin.html (Rx)

http://www.idsociety.org/

http://www.cdc.gov/nchstp/tb/TB_HIV_Drugs/TOC.htm (TB/HIV--CDC)

http://www.aids.com/official_aids_directory.htm

http://www.aids.com/ (statistics, news, links, providers)

http://hivdrugresistance.com/ (resistance testing)

http://www.avert.org/usa_aids.htm (Statistics)**********

http://www.cdc.gov/mmwr/PDF/RR/RR5314.pdf (Rx Guidelines for Opportunistic Infections)

http://www.aids.org/factSheets/index.html (Drugs/ Treatment Guidelines, including Opportunistic Infections)

http://content.nejm.org/cgi/content/full/353/16/1702/T1 (HIV......Initial Evaluation)*************

http://www.medscape.com/viewarticle/541163_1 ---Management of HIV Drug Resistence

http://www.medscape.com/viewarticle/504941 (2005--Update)

http://www.medscape.com/qna/AddResponses ---Pregnancy ; http://www.medscape.com/viewarticle/525167 ----MTCT

http://www.medscape.com/qna/AddResponses

http://www.medscape.com/qna/AddResponses----STDs

http://www.medscape.com/viewarticle/542617 ---Mental Health

http://www.medscape.com/viewprogram/6376

1. According to DHHS and ISA-USA guidelines, antiretroviral treatment should be started immediately for asymptomatic patients who have:

Answer: CD4 cell counts <200 and any viral load
There are several complications of HIV that may be avoided if therapy is started early for patients with low CD4 cell counts. Currently, the guidelines recommend offering and/or considering treatment for patients in the 2 middle groups and deferring treatment for those with CD4 cell counts >350 and viral loads <100,000 copies/mL.

2. Goals of HIV therapy include:

Answer: All of the above
In terms of HIV, the goals are viral suppression and, concomitantly, restoration or preservation of immune function. For patients, improvement in quality of life is the primary goal, as well as reductions in HIV-related morbidity and mortality.

3. It is advised that drug-resistance testing be performed at the first visit for treatment-naïve patients.

Answer: True
Even if treatment is not being initiated immediately, drug-resistance testing can identify primary or transmitted resistance and help in planning therapy.

4. Advantages of NNRTI-based regimens include:

Answer: Fewer drug interactions than with PIs
Resistance to NNRTIs can be conferred by a single mutation or a limited number of mutations, whereas multiple mutations confer resistance to PIs. Additionally, nevirapine has demonstrated hepatotoxicity. On the other hand, NNRTIs have fewer potential drug interactions than do PIs.

5. Potential disadvantages of PI-based regimens include:

Answer: All of the above
Several PI-based regimens may not be taken once daily; hence, adherence is less likely than with once-daily regimens. Also, PIs have documented adverse side effects, and they inhibit the CYP450 isoenzyme, resulting in a high likelihood of increased drug interactions.

6. The antiretroviral agent with a Category D classification in pregnancy is:

Answer: Efavirenz
Efavirenz has teratogenic properties in humans and is contraindicated for women who are pregnant or who may become pregnant.

7. It is acceptable to continue treatment in the presence of antiretroviral failure in the hope that the treatment will eventually be effective.

Answer: False
Continuing treatment in the presence of antiretroviral failure can result in accumulation of drug-resistance mutations, the development of cross-resistance within multiple drug classes, difficulty reestablishing virologic control with future regimens, and eventual decline in T cell counts and disease progression.

8. The criteria for defining treatment failure in antiretroviral-experienced patients include:

Answer: All of the above
Suboptimal viral suppression is a sign, along with virologic rebound after viral suppression, of virologic failure; decreasing CD4 cell counts indicate immunologic failure; and new, recurrent, or worsening AIDS-related opportunistic infections, along with other symptoms, are hallmarks of clinical failure and disease progression.

9. Phenotypic resistance testing can detect changes as small as _________-fold.

Answer: 1½

10. In patients with HIV and hepatitis coinfection, most elevations in aminotransferase levels are severe and permanent.

Answer: False

FDA-Approved Drugs for HIV Therapy: 2006

Recommended Regimens for Treatment-Naïve Patients: DHHS 2006

Choosing an Initial Regimen: Tolerability and Toxicity

DHHS Guidelines: Advantages and Disadvantages of NNRTI-Based Regimens

DHHS Guidelines: Factors to Consider When Starting Antiretroviral Therapy

Optimizing ARV Regimens in the Setting of Drug Resistance

HBV Flares That Are NOT Related to DILI, cont’d

Potential Mechanisms for Risk of DILI in HIV/HCV

Histologic Improvement With PEG/RBV in Virologic Nonresponders

Can We Prevent DILI by Avoiding Certain Drugs?

http://www.medscape.com/viewprogram/6288

1. Which of the following is/are characteristic of PIs but not of NNRTIs?

Answer: High genetic barrier to resistance
Among PI-naive patients treated with boosted PIs, the emergence of resistance is rare, and if it does occur, it typically takes a long time to emerge. In contrast, the risk of dyslipidemia is high with PIs and low with NNRTIs.

2. Data on once-daily treatment of treatment-naive patients can be extrapolated directly to treatment-experienced patients.

Answer: False
With once-daily treatment, trough levels may be lower than with twice-daily treatment. Because treatment-experienced patients may harbor resistance mutations, they may need the consistently higher drug levels seen with twice-daily treatment to maintain viral suppression.

3. The only PI approved for once-daily therapy in a nonboosted regimen is:

Answer: Atazanavir
Currently, fosamprenavir 1400 mg and lopinavir 800 mg are approved for once-daily dosing, but only when boosted with ritonavir 200 mg. Atazanavir 400 mg is approved for once-daily nonboosted administration, and boosted saquinavir (2000/100) is under evaluation for once-daily dosing.

4. If atazanavir is given with tenofovir, it must be boosted.

Answer: True
Tenofovir has been shown to reduce atazanavir levels significantly; therefore, nonboosted atazanavir should not be coadministered with tenofovir to treatment-experienced patients.

5. Factors that can increase pharmacokinetic variability of a drug include:

Answer: All of the above
In addition to the factors listed here, interpatient genetic differences, pregnancy, adherence rates, and drug-drug interactions may increase the pharmacokinetic variability of a drug.

6. The PIs that are least affected by acid-reducing agents are:

Answer: Lopinavir, fosamprenavir, darunavir, and saquinavir
Atazanavir and indinavir require stomach acid for maximal dissolution and absorption, and acid-reducing agents, particularly proton pump inhibitors, produce gastric pH levels above those needed for optimal levels of these PIs. In contrast, the dissolution and absorption of lopinavir, fosamprenavir, darunavir, and saquinavir are minimally affected by acid reduction. The effects of acid-reducing agents on tipranavir and nelfinavir are not fully known.

7. The statin safest to use with PIs is:

Answer: Pravastatin
Pravastatin levels decrease in the presence of PIs, whereas those of atorvastatin, lovastatin, and simvastatin are increased, raising the risk of rhabdomyolysis. Even pravastatin levels are increased by some PIs, notably darunavir; thus, pravastatin and, in some cases, atorvastatin, may be coadministered with PIs, but it is prudent to start with low doses and titrate up gradually.

8. Rifampin can lower PI levels as much as:

Answer: 98%
Rifampin, a very potent cytochrome P450 inducer, has been observed to lower levels of PIs, particularly atazanavir, by as much as 98%. Thus, rifampin should not be used with PIs. Rifabutin, at lower-than-typical doses, may be safe to use with PIs.

9. According to DHHS guidelines, the first thing to do for a treatment-naive patient with chronic HIV is:

Answer: Perform a drug-resistance genotype test
The DHHS recommends resistance testing before therapy is initiated, because increasing numbers of individuals are receiving resistant virus initially, and selection of appropriate therapy is facilitated by the awareness of the presence and type of resistance.

10. The most common reason for increasing viral load in a patient on ART is:

Answer: Poor adherence
Although drug interactions may attenuate the effect of PI therapy, the most common reason for lack of efficacy is patient nonadherence. Only if this is ruled out are other causes likely.

Consults for HIV: Depression, Substance Abuse, Diet, Exercise, Labs & Resistance, SE of Drugs, Smoking & Alcohol, Cancer Screening, Family Planning; LABS--for--Anemia/ Glucose/ Lipids/ LA;

Other Tests: Bone Densitometry.

http://www.medscape.com/viewarticle/536391 *********HIV Management 2006 ( Virological failure is inability to decrease Viral Load to less than 400 copies/ mL by 24 wks of Tx, OR,

to less than 50 copies/ mL by 48 weeks of Tx...

http://www.medscape.com/viewarticle/544409 http://www.medscape.com/viewarticle/544412 http://www.medscape.com/viewarticle/544411

Table. Current Recommendations for Treatment Initiation According to Disease Status: DHHS and IAS-USA

Disease Stage	DHHS Recommendation	IAS-USA Recommendation
Symptomatic	Recommend therapy	Antiretroviral treatment
Asymptomatic, CD4+ ¡Â 200 cells/mcL	Recommend therapy	Antiretroviral treatment
Asymptomatic, CD4+ > 200 cells/mcL, but ¡Â 350 cells/mcL	Offer therapy	Consider therapy^¢Ó
Asymptomatic, CD4+ > 350 cells/mcL	Defer therapy*	Defer and monitor^¢Ô

Ascites with lymphocyte predominance and negative bacterial cultures

Chronic lymphadenopathy (especially cervical)

CSF lymphocytic pleocytosis with elevated protein and low glucose

Exudative pleural effusion with lymphocyte predominance, negative bacterial cultures, and pleural thickening

Joint inflammation (monoarticular) with negative bacterial cultures

Persistent sterile pyuria

Unexplained pericardial effusion, constrictive pericarditis, or pericardial calcification

Vertebral osteomyelitis involving the thoracic spine

*Some clinicians may consider therapy if HIV RNA > 100,000 copies/mL

¢ÓStronger recommendation for therapy for patients with CD4+ cell counts closer to 200 cells/mcL, those with higher viral loads, and those with rapidly declining CD4+ cell counts

¢ÔConsider therapy for patients with high viral load or rapidly declining CD4+ cell counts

1. Which of the following statements regarding CD4+ cell counts and antiretroviral therapy is not supported by data?

Answer: If HIV RNA is suppressed in patients with CD4+ cell counts < 200 cells/mcL, there is little, if any, risk for disease progression
For patients presenting with CD4+ cell counts ¡Ã 200 cells/mcL, the data from both clinical trials and cohort studies are clear: Those who initiate therapy with lower CD4+ cell counts have worse outcomes than those who initiate therapy prior to this cut-off. Clinical studies have shown that those who initiate therapy with CD4+ cell counts ¡Ã 200 cells/mcL have a decreased likelihood of achieving virologic suppression. It is important to note that disease progression occurs even among patients in this CD4+ cell stratum who achieve virologic suppression following treatment initiation. Therefore, it is currently recommended that all patients initiate therapy as soon as possible if the CD4+ cell count is < 200 cells/mcL.

2. Which of the following is true regarding starting antiretroviral therapy during acute infection?

Answer: Preliminary data show that people who initiate antiretroviral therapy during acute infection have increased reconstitution in gut-associated lymphoid tissue relative to people with chronic HIV infection
The gastrointestinal tract is the site of the majority of CD4+ cells in the body. HIV preferentially infects CCR5+ CD4+ cells in the gastrointestinal tract during acute infection, causing rapid and profound damage to the immune system. For patients who start therapy during chronic infection, immune reconstitution in the gut appears to be limited, even following up to 5 years of successful HAART. Initial studies have indicated that initiation of therapy during primary infection is associated with increased immune reconstitution in the gut-associated lymphoid tissue; therefore, this may be a key intervention to prevent CD4+ cell loss and allow for reconstitution in this compartment. The effect of this preservation on disease course is not known, however. More studies need to be conducted in humans to fully determine the clinical importance of this issue.

3. Antiretroviral therapy should always be initiated given which of the following surrogate markers or clinical considerations?

Answer: The presence of HIV-associated symptoms, at any CD4+ cell count
According to the DHHS guidelines, treatment should be initiated at any CD4+ cell count when HIV-associated symptoms are present. Among asymptomatic patients, treatment should be initiated when CD4+ cell count falls below 200 cells/mcL, and offered when CD4+ cell count is in the range of 200-350 cells/mcL. Most clinicians would defer treatment among patients with CD4+ cell counts > 350 cells/mcL. Viral load is another important surrogate marker in persons with HIV, but CD4+ cell count and presence/absence of HIV symptoms are more critical determinants regarding the decision of when to begin treatment.

4. Among patients with HIV and a CD4+ cell count of 200-350 cells/mcL, a CD4 percentage below what value was shown to be independent prognostic factor for mortality?

Answer: Less than 15%
Moore and colleagues recently reported that the proportion of CD4+ cells among the total lymphocyte population may be another important indicator of whether to initiate therapy within the CD4 stratum of 200-350 cells/mcL. They reported that a CD4 percentage less than 15% of the total lymphocyte population was an independent prognostic factor for mortality among these patients.

5. Which of the following general statements about antiretroviral therapy, particularly in regard to its initiation, is FALSE?

Answer: Mistakes made early after antiretroviral treatment initiation -- whether the wrong regimen selection by the clinician or poor adherence on the part of the patient -- can always be overcome and rarely affect long-term outcome
Gallant noted several important points about antiretroviral therapy. Most important is that patients should receive care from clinicians with expertise, preferably as soon as HIV is diagnosed, as expert care improves survival and decreases cost. Early treatment decisions have a profound impact on the course of disease, and past mistakes are sometimes difficult to overcome. Resistance and failure of antiretroviral therapy are not random or inevitable, but are predictable outcomes of a number of controllable risk factors. Antiretroviral regimens should be based on potency, tolerance, convenience, and future options. Clinics are full of patients who exhausted future therapeutic options without understanding the importance of adherence.

6. Which one of the following statements about antiretroviral medication adherence is TRUE?

Answer: Nonadherence to antiretroviral therapy can result in drug resistance and treatment failure
Adherence to HIV therapy is of vital importance to the health of the individual patient as well as to public health, as nonadherence to HIV therapy is associated with increased mortality. The potential consequences of nonadherence to antiretroviral therapy include viral resistance and treatment failure in an individual patient as well as transmission of resistant virus, all of which can limit future therapeutic options for the individual and the community.

7. In the United States, what is the estimated number of people who are infected with HIV but are unaware of their status?

Answer: 250,000
The problem of persons who are HIV-infected and unaware of their serostatus is observed around the world. In the United States, the estimate is that about 250,000 people are infected with HIV and don't know it. Globally, about 90% or 95% of persons with HIV are unaware of their infection.

http://www.medscape.com/viewarticle/546785_5 ( Half-Lives of Anti-Retrovirals); A viral load of ≥ 1000 copies/mL is needed in order to accurately assess a patient's resistance profile. In general, determining viral phenotype or genotype may be useful for treating patients during acute infection, but may be more difficult for patients during chronic infection. Resistance testing is recommended in treatment failure and during suboptimal viral suppression, defined as HIV RNA > 400 copies/mL at 24 weeks or > 50 copies/mL at 48 weeks.^[1]

Table 2. Clinical Symptoms Associated With Extrapulmonary Tuberculosis

The use of rifampin with either nevirapine or PIs is generally not recommended because of the risk for additional drug-drug interactions. http://www.cdc.gov/nchstp/tb/tb_hiv_drugs/toc.htm ( TB + HIV Drug Guidelines) When to Start Treatment