Aliskiren: Direct Renin Inhibitor. New Anti Hypertensive

(Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension: a randomised, double-blind trial, Prof Suzanne Oparil MD a , Steven A Yarows MD, The Lancet, The Lancet 2007; 370:221-229)

Q. What is Aliskiren and what is its role in hypertension ?

Aliskiren is the first orally available direct Renin inhibitor. The used earlier on Renin angiotensin system were ACE Inhibitors and Angiotensin receptor blockers. Aliskiren provides a new option in this pathway.

Q. Is combing ACE inhibitors and ARB useful ?

¬ Combining full doses of ACEI and ARBs has been tried in many studies including Val-HeFT, VALIANT, and CHARM

¬ The results of the same have been mixed.
¬ For example, CHARM-Added showed significant benefit of combining an ARB with ACE inhibitor treatment in patients with heart failure,
¬ whereas VALIANT showed no significant outcome benefit.
¬ Moreover, both trials showed that the combination therapies were less well tolerated than the respective monotherapies.
¬ Mechanistically, both ACE inhibitors and ARBs attenuate feedback inhibition of renin release by inhibiting the production or action of angiotensin II, resulting in increases in plasma renin concentration and plasma renin activity.

¬ Also the trials have showed that long-term dual renin system intervention with an ACE inhibitor and an ARB was associated with a higher rate of adverse events and an increased incidence of raised serum potassium and creatinine concentrations than was ACE inhibitor monotherapy.

Q. Is it a good idea to combine Aliskiren with ARBs ?

A recent trial published in LANCET combines Aliskiren and Valsartan (an ARB). The results according to the trial have been promising with minimal additional side effects. The authors recommended it to be better than coming ARB with ACEI.

Tricks of Trade: Small Little Things to make Practice of Medicine easier

As Featured in Journal "Emergency Medicine". Contributed by readers. Edited by Donald B. Middleton, MD

TETRA BEFORE LIDO
In Terrell, Texas, Dr. Amaha Hailey uses a few drops of a 3-ml bottle of 0.5% tetracaine solution for topical anesthesia for corneal injury. But rather than discarding the remainder, Dr. Hailey pockets the bottle for later application into open wounds to produce topical anesthesia prior to lidocaine infusion. He claims the tetracaine is usable for a couple of days. Although many claim that topical anesthetics like tetracaine help reduce the sting of lidocaine injection, I have found that one must wait 15 to 20 minutes for the drug to penetrate the tissue and that slow injection of the lidocaine, as an alternative, is almost painless. To each his own, in this case.

STEALTH APPENDIX
"Don't forget about the retrocecal or otherwise unusually placed appendix as a cause of nonclassical abdominal pain," warns Dr. Basil Rodansky of Lincoln Park, Michigan. Pain from acute appendicitis can be lateral or posterior, mimicking other diagnoses. On rare occasions, a long appendix may even result in pain localized to the left lower quadrant. If pain precedes fever and vomiting, appendicitis should enter the differential diagnosis even with an atypical pain site. A computed tomography scan can often clinch the diagnosis.

LIGHT TOUCH
From Paulding, Ohio, Dr. Quang Le reminds us to warm up mirrored instruments or otoscope shields before use to reduce the risk of fogging during the examination. He warms his mirror under hot or warm water and always tests it against his own wrist before using it on the patient. Others warm a mirror on a light bulb, again testing it first before using it.

SWEET SUCCESS
Recent studies have supported the idea that sucrose on an infant's pacifier or lips may have some analgesic effect. Dr. Scott McIntosh from Hartford, Connecticut, suggests sucrose as an alternative to more intense anesthesia for infants undergoing minimally painful procedures

NO-TEARS EYE DROPS

When administering ophthalmic medication to a sensitive patient like a child, the best technique is to lay the patient on his or her back with the eyes gently closed, then place a drop or two into the inner canthus spaces. Ask the patient to open the eyes while still lying down, and the drops will flow naturally into the eyes without a fuss. Thanks to Dr. Carol Gardner in Lakeland, Florida, for resurrecting this time-honored advice.

EXIT SPLINTER

When removing toothpicks or splinters from the skin, Dr. John Wipfler in Peoria, Illinois, anesthetizes the area properly. Then, before he pulls the splinter out, he uses a number-11-blade knife or perhaps the tip of an 18-gauge needle to incise the skin immediately adjacent to the foreign body. A 2-mm incision through to the dermis loosens the taut skin, allowing less resistance to extraction. If removal is attempted without this incision, the wooden foreign body may break off, thus making complete removal more difficult. After the procedure, if there is any doubt about whether the entire object was removed, Dr. Wipfler fully educates the patient about the signs and symptoms of a retained foreign body to watch for. Specialist referral is usually indicated in these suspect cases.

UNDER PRESSURE
In some circumstances, a basic task like taking blood pressure can be nearly impossible. To enhance the Korotkoff sounds, Dr. Jerome Lebovitz in Pittsburgh, Pennsylvania, inflates the cuff to above 180 mm Hg, tells the patient to open and close the fist and then relax, and slowly deflates the cuff. He claims that the sounds are then easily heard. Remember that blood pressure should be measured with the patient at rest for at least five minutes, sitting in a chair with the feet on the ground.

POSITIONAL PAIN CLUES
Pain in some illnesses changes with position, Dr. Brady Pregerson of Los Angeles reminds us with some examples. Worse lying down: pericarditis, epiglottitis, Ludwig's angina, asthma, congestive heart failure, gastroesophageal reflux disease. Better lying down: post-spinal tap headache, retropharyngeal abscess. Better lying on the left side: pancreatitis, pregnancy, pyelonephritis on the right, a kidney stone on the left. Better lying on the right side: pyelonephritis on the left, a kidney stone on the right

NOTHING TO SNEEZE AT
To prevent reflex sneezing during a cauterization and packing for epistaxis, Dr. Brian Collins of York, Maine, has his patient rub the nasal bones between a thumb and a forefinger. This technique prevents inadvertent expulsion of the nasal packing and further trauma to the bleeding site. The rubbing may work via the gate theory, by interfering with sensory input from the irritated nasal mucosa. Dr. Collins uses it on himself to stifle his own sneezes whenever the situation dictates.

EYE FEEL SOMETHING...
To remove a corneal foreign body, Dr. Stephen Acosta of Portland, Oregon, recommends eye spuds or a moist cotton-tipped applicator to pop the foreign body off the cornea. The cotton will not scratch if moistened, says Dr. Acosta. Ersatz eye spuds can be made by bending the tip of a 27-gauge needle on an insulin syringe (or a TB syringe if necessary) to a 45- to 90-degree angle with the needle bevel facing away from the eye surface.

PERCUSSION POINTER
The reflex hammer is good for more than just reflexes, writes Dr. Mike Lemanski of Springfield, Massachusetts. Tapping on his finger with the reflex hammer augments the percussion note
from the chest, heart, or abdominal exam, and the soft, round tip leaves his finger feeling fine.

FAMILIAR TWIST
To prevent twisting of the spine during a lumbar puncture, Dr. Jeff Metzger of Durham, North Carolina, puts a pillow or rolled blanket under the patient's knees. With the patient in a decubitus, fetal position, this support keeps the pelvis and shoulders perpendicular to the plane of the table. Perfect alignment leads to a simpler lumbar puncture.

THE GAG IS ON THEM
Some patients with pharyngitis and severe headache are simply too ill to allow a look into the throat. Interference from a heightened gag reflex may be too powerful to overcome by force of will. Before ordering more expensive, complex tests and to get a less time-consuming evaluation, Dr. Stephen Fahey of Kensington, Maryland, puts a dollop of viscous lidocaine on the end of a tongue depressor and asks the patient to flip it so the gel sits on the tongue. The patient slowly "walks" the gel-coated tongue blade as far back on the tongue as possible, coating the tongue itself. The result is an easily depressed tongue and a reduced gag reflex that permits a better visualization of the pharynx and facilitates more specific therapy.

MULTITASKING TEST
Asterixis, also known as the "liver flap," is more than just a bedside assessment of hepatic encephalopathy. It tests for any type of encephalopathy due to a metabolic cause, including renal failure, drug toxicity, and—probably the most useful—elevated pCO2. To remember the causes of asterixis, Dr. Brady Pregerson in Los Angeles, California, uses an ABCD mnemonic: A for ammonia; B for BUN (renal failure); C for pCO2, CVA, CNS infection (malaria, encephalitis), or CNS tumor; and D for drugs (aspirin, antidiabetics, seizure medications, and psychiatric medications).

THE TOPIC OF TOPICAL ANESTHESIA
Everyone wants local anesthetics to work without injecting; in my experience, topical products often fall short. In Overland Park, Kansas, Dr. Dan Harpt claims that dripping several drops of an anesthetic into a wound and waiting a few minutes will provide some decent anesthesia. That effect combined with slow injection during wound infiltration largely eliminates pain, he says. I believe that gauze soaked with anesthetic is even better, especially if left in place for 10 to 15 minutes. Others favor LAC or TAC (lidocaine or tetracaine with adrenalin and cocaine) or lidocaine gels. Trial and error may help you find your favorite.

TEA FOR TOOTH
For a bleeding socket after tooth loss or extraction or even a simple lip or gum laceration, Dr. Michael Jaeger in Tivoli, New York, suggests a teabag moistened with cold water as an astringent compress to quickly stop the bleeding.

API Guidelines for Management of Hypertension in Indian Patients

INDIAN HYPERTENSION GUIDELINES-II

Click Here http://www.apiindia.org/hypertensionguidelines/hyperhome.htm

API Guidelines for Management of Diabetes Mellitus in Indian Patients

API Guidelines for managament of DM in Indian patients. Click the link below to download this very useful document. It is a PDF file, you would need an Adobe Acrobat Reader.

http://www.japi.org/july2007/IDGM.pdf

New England Medical Journal Free Online for 21 days

Free Trial of New England Medical Journal for 21 days

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Links to top journals of the World

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Rimonabant : New Novel anti-obesity agent.

(Endocannabinoid System- A Novel target for Cardiometabolic Risk, Review Article, Shashank Joshi, JAPI Vol 55 June 2007 , Page 439)

Q. What is Rimonabant and how does it act ?

Rimonabant is a new anti-obesity agent. It acts on the Endocannabinoid system. It is a CB1 Endocannabinoid system Antagonist. It was invented by Sanofi.

Q. What is the Endocannabinoid system and what is its role in Obesity ?

• Endocannaboid system comes from the research on action of Cannabis on human body.
• Cannabis and its effects are known since ancient times and it is consumed in various forms likeGanja etc.
• The Cannabinoid system increases Sexual drive, increase appetite, and modulates addiction to various substances like tobacco.

Since it has a role in increasing Appetite and inducing the desire to eat, the drug Rimonabant breaks this drive by acting on the CB1 receptor.

Q. Are there any other drugs which act on this system ?

• DRONABINOL is an antiemetic that is a Endocannabinoid receptor agonist.
• NABILONE is a CB1 stimulant used as an appetite stimulant
• CB1 agnosit also used in muscle spasticity in Multiple Sclerosis

Q. What are the Endocannabinoid receptor ?

There are two types of Endocannabinoid receptors.

1. CB1 Receptor on which ligand ANANDAMIDE acts (derived from the Sanskrit word 'Anand' meaning pleasure ) on which RIMONABANT Acts.

2. CB2 receptor which is found in the immune system and ligand 2-AG acts on it.

Q. In which group of patients should Rimonabant be given with caution ?

Obesity is often associated with Depression. It is prefreble to avoid this drug in patients with Depression because data of safety are currently not avaiable and there have been reports of worseing iof depression with this agent.

Q. Is there any other use of Rimonabant ?

Rimonabant has potential to be used in Tobacco deaddiction. STRATUS trial is currently on for finding out the same.

Q. What is the dose of Rimonanbant ?

Rimonabant is given in dose of 20mg Once daily before breakfast. It causes an average wieght loss of 4 Kg in one year of use. Studies for use more than 2 years is not avaiable.

ARTICLE OF THE MONTH: THE ROSIGLIZATONE STORM: Rosiglitazone and Increase Risk of Coronary Artery Disease.

This is one of the biggest controversies medical science has seen in recent times. There have been reports that the popular Anti Diabetic Drug ‘Rosiglitazone’ increases the risk of Myocardial Infarction. Dr. Om Lakhani analyzes the background and the current status of this controversy.

Sources

• “The Rosiglitazone Controversy: Indian Perspective” : V Mohan, S. Joshi: Editorial JAPI Volume 55: July 2007
• Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007;356:2457-71.
• Psaty BM, Furberg CD. Rosiglitazone and cardiovascular risk. N Engl J Med 2007; June 5:[Epub ahead of print]
• Krall RD. Cardiovascular safety of rosiglitazone. Published online
• Home PD, Pocock SJ, Beck-Nielsen H, Gomis R, Hanefeld M, Jones NP, Komajda M, McMurray JJV. For the RECORD Study Group. Rosiglitazone Evaluated for Cardiovascular Outcomes - An Interim Analysis. N Engl J Med 2007; June 5:[Epub ahead of print]
• Drazen JM, Morrissey S, Curfman GD. Rosiglitazone – Continued Uncertainty about safety. N Engl J Med 2007; June 5:[Epub ahead of print]
• Nathan DM. Rosiglitazone and cardiotoxicity – weighing the evidence. N Engl J Med 2007; June5:[Epub ahead of print].

Psaty BM, Furberg CD. The Record of rosiglitazone and the risk of myocardial infarction. N Engl J Med 2007; June 5:[Epub ahead of print].


Q. What are “Glitazones” or “Thiazolines” and why have they been always in the news ?

Ø “Glitazone” or “Thiazolidines” the popular anti diabetics have always been in the news for reasons right or wrong
Ø Glitazones are wonderful antidiabetic drugs because they reduce the Insulin Resistance. Insulin Resistance as we know is the main pathological factor in Type 2 Diabetes Mellitus.
Ø It was widely used after its introduction but then came the first big controversy.
Ø About 63 deaths were reported in US due to hepatotixicity caused by earlier products from this family. The US FDA withdrew the drug from the market.
Ø But popular demand made this group of drugs come back in newer safer versions as ‘Rosiglitazone’ and ‘Pioglitazone’
Ø Because of their history they were always viewed with suspicion and the FDA had asked the doctors to regularly monitor the hepatic functions of their patients who were prescribed these medications.
Ø But the drugs turned out to be safe and did not cause hepatotoxicty.
Ø Because of this new found safety this group of drugs widely rose in prominence.
Ø In recent time two trials DREAM and ADOPT have went on to suggest that it is time we start using them as first line agents.
Ø But then came the big storm after a meta analysis submitted in New England Journal of Medicine questioned the safety of Rosiglitazone once again. (more on in it is given below)

Q. What are the know side effects of Rosiglitazone ?

Rosiglitazone and Pioglitazone are known to cause the following side effects.

Pedal Odema
Weight gain
Reduced Hematocrit
Fluid Retention.

Q. What is the recent controversy about Rosiglitazone that created a storm in the medical circles ?

Ø The recent controversy about Roiglitazone came forward after a meta analysis published in New England Journal of Medicine by Nissen et al reported an increase risk of Coronary Artrey disease and Myocardial Infarction on usage of Rosiglitazone.
Ø They concluded on studying 42 trials that

Rosiglitazone Increases risk of MI by 42%
It increases the risk of Death due to Cardiovascular event by 64 %

Ø This study was widely reported in Lay press and hence created a lot of anxiety in patients already taking this drug.

Q. Why was this reported viewed with suspicion ?

Ø Meta-analysis by nature are two weak to conclude anything major
Ø Many question Meta-analysis per se and even those who do believe in them have questioned the way this one was carried out.
Ø Analyses of the 42 studies showed that 40 of them were small and all these put together did not yield statistically significant difference for myocardial infarction (MI) between groups.


Ø Responding quickly to the metaanalysis by Nissen et al , the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD) study investigators did an unplanned interim analysis of their results two years before the study was scheduled to conclude.
Ø The results indicated no statistically significant differences in the overall risk of hospitalization or death from cardiovascular causes between the study groups

Ø The results were (not surprisingly) inconclusive as this is an interim analysis after 3.75 years of median follow up and thus lacked adequate power as the original analysis was planned to be done after 6 years of median follow up.

Ø From a purely statistical perspective, these results would indicate a slight increase in risk for MI / coronary artery disease among subjects on rosiglitazone.
Ø However, a closer analysis of these data would indicate that the presently available data are not conclusive as none of the studies had cardiovascular disease (CVD) as primary end-points except RECORD.
Ø In the RECORD study, only an interim analysis was published which had inadequate power to assess CVD outcomes.
Ø Several Societies like the American Diabetes Association, Endocrine Society in the US, American Association of Clinical Endocrinologists have come out with statements urging physicians and patients not to panic and stop the medication but to undergo a reevaluation by their treating physicians and make decisions with them.
Ø Even the US FDA has not withdrawn the drug but asked for strict review and some changes have been made on the prescription label.
Ø The EU regulatory agencies have also not withdrawn the drug.


Q. So what should the conclusion and what should be done now ?


The Editorial in recent edition of JAPI advices the following for the Indian Physicians:

1. Reassure patients and physicians that there is nothing to panic.
2. Advise patients not to abruptly stop their medications but discuss it with their physician and under medical supervision of experts decide on case to case basis a plan which meets patient’s safety and therapy concerns.
3. Ensure that current glycemic control & non glycemic comorbid conditions are validated by not just fasting and postprandial blood glucose but do a glycosylated hemoglobin test, lipid profile,hematocrit and electrocardiogram(with or without an echocardiogram)
4. If they have established heart disease, it may be worthwhile to discuss with their physician / cardiologist about stopping the drug and appropriately adjusting their anti-diabetic medications.
5. If the physician is convinced about any concern then there are other options available in the same class, other class as well as Insulin. Both options need patient education and physician supervision to ensure patient safety risk as well as the glycemic control is well balanced as well as monitored periodically.
6. New patients with type 2 diabetes at risk of heart disease could probably be given alternate drug therapies until further evidence emerges with respect to the safety of this class of drugs.
7. Strict adherence to CVD risk reduction i.e. Aspirin (or Clopidrogel), Statin, ACE (or ARB) inhibitors, weight reduction, tighter glucose and BP control and stricter cardiac evaluation in all diabetic patients.
8. Individualized comprehensive evaluation and cardioprotective measures can be re-addressed and its an ideal opportunity for patient education to ensure that they are in control of their diabetes and vascular risk.

Guidelines for Use of Antiretroviral Therapy for HIV Infected Individuals in India (API ART Guidelines) 2007

Guidelines for Use of Antiretroviral Therapy for HIV
Infected Individuals in India (API ART Guidelines)
2007

Click the link below to Download the LATEST pdf file. A Summary Version of This coming soon.

http://www.japi.org/july2007/api_Art_Guidelines_new.pdf

How Common Is Needlestick Injury ?

(Needlestick Injuries among Surgeons in Training, Martin A. Makary, M.D., M.P.H. et al, New England journal of Medicine. Volume 356:2693-2699 June 28, 2007 Number 26 )

How Common is needlestick injury amongst Residents ? Here are some intersting facts about needlestick injury collected from an article published in New England Journal of Medicine .

1. 99% of Surgical Residents have reported atleast 1 needlestick injury in their period of training
2. As expected Surgical Residents are more likely to have an injury than Medical Residents
3. A Shocking 51% of Injuries are not reported.
4. Double Gloving reduces the risk of exposure to blood significantly.
5 .Sharpless surgical practices are new methods for reducing this menace
6. If anti retroviral therapy is taken within 24-36 hrs , it reduces the incidence of Needlestick injury by 81%