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Warfarin and Dabigatran, Similarities and Differences

Author and Curator: Danut Dragoi, PhD

 

What anticoagulants do?

An anticoagulant helps your body control how fast your blood clots; therefore, it prevents clots from forming inside your arteries, veins or heart during certain medical conditions.

If you have a blood clot, an anticoagulant may prevent the clot from getting larger. It also may prevent a piece of the clot from breaking off and traveling to your lungs, brain or heart. The anticoagulant medication does not dissolve the blood clot. With time, however, this clot may dissolve on its own.

Blood tests you will need

The blood tests for clotting time are called prothrombin time (Protime, PT) and international normalized ratio (INR). These tests help determine if your medication is working. The tests are performed at a laboratory, usually once a week to once a month, as directed by your doctor. Your doctor will help you decide which laboratory you will go to for these tests.

The test results help the doctor decide the dose of warfarin (Coumadin) that you should take to keep a balance between clotting and bleeding.

Important things to keep in mind regarding blood tests include:

  • Have your INR checked when scheduled.
  • Go to the same laboratory each time. (There can be a difference in results between laboratories).
  • If you are planning a trip, talk with your doctor about using another laboratory while traveling.
Dosage

The dose of medication usually ranges from 1 mg to 10 mg once daily. The doctor will prescribe one strength and change the dose as needed (your dose may be adjusted with each INR).

The tablet is scored and breaks in half easily. For example: if your doctor prescribes a 5 mg tablet and then changes the dose to 2.5 mg (2½ mg), which is half the strength, you should break one of the 5 mg tablets in half and take the half-tablet. If you have any questions about your dose, talk with your doctor or pharmacist.

What warfarin (Coumadin) tablets look like

Warfarin is made by several different drug manufacturers and is available in many different shapes. Each color represents a different strength, measured in milligrams (mg). Each tablet has the strength imprinted on one side, and is scored so you can break it in half easily to adjust your dose as your doctor instructed.

https://my.clevelandclinic.org/health/drugs_devices_supplements/hic_Understanding_Coumadin

Today, on the basis of 4 clinical trials involving over 9,000 patients, PRADAXA is approved to treat blood clots in the veins of your legs(deep vein thrombosis, or DVT) or lungs (pulmonary embolism, or PE)in patients who have been treated with blood thinner injections, and to reduce the risk of them occurring again.

In these trials, PRADAXA was compared to warfarin or to placebo (sugar pills) for the treatment of DVT and PE patients.

https://www.pradaxa.com/pradaxa-vs-warfarin?gclid=CMaRq7al9ssCFUxZhgodZuoC5w

Warfarin (NB-which goes by the brand name Coumadin, see link in here) reduces the risk of stroke in patients with atrial fibrillation (NB- atrial fibrillation (also called AFib or AF) is a quivering or irregular heartbeat (arrhythmia) that can lead to blood clots, stroke, heart failure and other heart-related complications. Some people refer to AF as a quivering heart, see link here) but increases the risk of hemorrhage and is difficult to use.

Dabigatran is a new oral direct thrombin inhibitor (NB-direct thrombin inhibitors are a class of medication that act as anticoagulants by directly inhibiting the enzyme thrombin). Some are in clinical use, while others are undergoing clinical development), see link in here.

Some international large clinical trials, see link in here,  show results for patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage.

Picture below shows a deep vein thrombosis which is a blood clot that forms inside a vein, usually deep within the leg. About half a million Americans every year get one, and up to 100,000 die because of it. The danger is that part of the clot can break off and travel through your bloodstream. It could get stuck in your lungs and block blood flow, causing organ damage or death, see link in here.

Blod Clot

Image SOURCE: http://www.webmd.com/heart-disease/guide/warfarin-other-blood-thinners

The behaviour of blood thinning drugs is dependent on their physico-chemical properties and since a significant proportion of drugs contain ionisable centers a knowledge of their pKa (NB-pKa was introduced as an index to express the acidity of weak acids, where pKa is defined as follows. For example, the Ka constant for acetic acid (CH3C00H) is 0.0000158 (= 10-4.8), but the pKa constant is 4.8, which is a simpler expression. In addition, the smaller the pKa value, the stronger the acid, see link in here ) is essential, see link in here. The pKa is defined as the negative log of the dissociation constant, see link in here:

pka=-log10(Ka)              (1)

where the dissociation constant is defined thus:

Ka=[A][H+]/[AH]

Most drugs have pKa in the range 0-12, and whilst it is possible to calculate pKa it is desirable to experimentally measure the value for representative examples. There are a number of instruments that are capable of measuring pKa utilising Sirius T3 instrument, see link in here .

Table 1 below shows the pka values for warfarin, see link in here  and dabigatran, see link in here.

Table 1

==========================

Anticoagulant           pka          

warfarin                     4.99

dabigatran                 4.24        11.51*

==========================

* dabigatran possess both acidic and basic functionality.

Both groups are at ionized at blood pH and exist as zwitterionic

structures, see link in here.

Adding physico-chemical features of anticoagulants utilized in “dissolving” blood clots is important for better understanding the de-blocking process within the veins utilizing anticoagulants.

SOURCE

http://theochem.chem.rug.nl/publications/PDF/ft683.pdf

http://www.rsc.org/chemical-sciences-repository/articles/article/dr000000003197?doi=10.1039/c5ra04680g

http://pubs.rsc.org/en/content/articlelanding/2015/ra/c5ra11623f#!divAbstract

http://www.cambridgemedchemconsulting.com/resources/physiochem/pka.html

http://www.webmd.com/heart-disease/guide/warfarin-other-blood-thinners

https://www.google.com/#q=define+atrial+fibrillation

https://www.researchgate.net/profile/Lars_Wallentin/publication/26777612_Dabigatran_versus_Warfarin_in_Patients_with_Atrial_Fibrillation/links/02bfe50c8c2fa639c0000000.pdf

http://www.webmd.com/heart-disease/guide/warfarin-other-blood-thinners

 

Other related articles published in this Open Access Online Scientific Journal, include the following:

Coagulation N=69

https://pharmaceuticalintelligence.com/?s=Coagulation

Peripheral Arterial Disease N=43

https://pharmaceuticalintelligence.com/?s=Peripheral

Antiarrhythmic drugs

https://pharmaceuticalintelligence.com/?s=Antiarrhythmic+drugs

A-Fib

https://pharmaceuticalintelligence.com/?s=a-fib

Electrophysiology N = 80

https://pharmaceuticalintelligence.com/?s=Electrophysiology

 

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Normal and Anomalous Coronary Arteries: Dual Source CT in Cardiothoracic Imaging

Reporters: Justin D Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

Coronary anatomy and anomalies

“Coronary” describes the crown-like position of arteries on the heart that provide its nutrient blood supply. The heart does not live off of the blood in its chambers, but rather receives its nutrient perfusion from branches of the aorta, like all other organs. The most relied on method to exam coronary artery anatomy is angiography – xray image movies obtained while the blood is opacified by injection of iodine (high atomic number to block xrays) to provide a contrast between arterial flow channel (the lumen) and the surrounding tissues. Computed tomography is providing a second-best alternative with 3D reconstructions that can be obtained less invasively (no catheters), but it often fails to see the posterior descending artery (PDA) well, and is lower in resolution (point-discrimination detail) than xray angiography (XRA). Magnetic resonance angiography (MRA) comes in as a distant third place method for examining coronary anatomy (lower quality, lower reliability), but non-invasive with no ionizing radiation. A major goal of defining coronary anatomy in individual patients is to identify coronary artery disease (CAD) and to clarify best options for management – to relieve angina and to avoid adverse consequences, e.g., heart attacks (myocardial infarction), heart failure (CHF) and death. The COURAGE trial showed that for many, aggressive medical management with statins and blood pressure control may obviate need for percutaneous or surgical interventions to control angina and minimize the risk of adverse outcomes. Patients with blockage of the left main coronary artery, or two vessel blockage including proximal left anterior descending (LAD) especially with below normal ejection fraction may be better off in the long run with bypass surgery. Therefore less invasive imaging sufficient to rule out left main disease and proximal LAD disease may suffice for decision making (except that the BARI trial results have not been overturned in favoring bypass surgery for diabetics).

On the left an overview of the coronary arteries in the anterior projection.

Coronary anatomy and anomalies

  • Left Main or left coronary artery (LCA)
    • Left anterior descending (LAD)
      • diagonal branches (D1, D2)
      • septal branches
    • Circumflex (Cx)
      • Marginal branches (M1,M2)
  • Right coronary artery
    • Acute marginal branch (AM)
    • AV node branch
    • Posterior descending artery (PDA)
RCA, LAD and Cx in the anterior projection

On the left an overview of the coronary arteries in the lateral projection.

  • Left Main or left coronary artery (LCA)
    • Left anterior descending (LAD)
      • diagonal branches (D1, D2)
      • septal branches
    • Circumflex (Cx)
      • Marginal branches (M1,M2)
  • Right coronary artery
    • Acute marginal branch (AM)
    • AV node branch
    • Posterior descending artery (PDA)

RCA, LAD and Cx in the right anterior oblique projection
On the left an overview of the coronary arteries in the lateral projection.

  • Left Main or left coronary artery (LCA)
    • Left anterior descending (LAD)
      • diagonal branches (D1, D2)
      • septal branches
    • Circumflex (Cx)
      • Marginal branches (M1,M2)
  • Right coronary artery
    • Acute marginal branch (AM)
    • AV node branch
    • Posterior descending artery (PDA)

RCA, LAD and Cx in the lateral projection

Left Coronary Artery (LCA)

The left coronary artery (LCA) is also known as the left main.
The LCA arises from the left coronary cusp.

The aortic valve has three leaflets, each having a cusp or cup-like configuration.
These are known as the left coronary cusp (L), the right coronary cusp (R) and the posterior non-coronary cusp (N).
Just above the aortic valves there are anatomic dilations of the ascending aorta, also known as the sinus of Valsalva. The left aortic sinus gives rise to the left coronary artery.
The right aortic sinus which lies anteriorly, gives rise to the right coronary artery.
The non-coronary sinus is postioned on the right side.

Left coronary (LC), right coronary (RC) and posterior non-coronary (NC) cusp
The LCA divides almost immediately into the circumflex artery (Cx) and left anterior descending artery (LAD).
On the left an axial CT-image.
The LCA travels between the right ventricle outflow tract anteriorly and the left atrium posteriorly and divides into LAD and Cx.

On the image on the left we see the left main artery dividing into

  • Cx with obtuse marginal branch (OM)
  • LAD with diagonal branches (DB)

On volume rendered images the left atrial appendage needs to be removed to get a good look on the LCA.
In 15% of cases a third branch arises in between the LAD and the Cx, known as the ramus intermedius or intermediate branch.
This intermediate branche behaves as a diagonal branch of the Cx.
Left Anterior Descending (LAD)
The LAD travels in the anterior interventricular groove and continues up to the apex of the heart.
The LAD supplies the anterior part of the septum with septal branches and the anterior wall of the left ventricle with diagonal branches.
The LAD supplies most of the left ventricle and also the AV-bundle.Mnemonic: Diagonal branches arise from the LAD.

CT image of the LAD in RAO projection
The diagonal branches come off the LAD and run laterally to supply the antero-lateral wall of the left ventricle.
The first diagonal branch serves as the boundary between the proximal and mid portion of the LAD (2).
There can be one or more diagonal branches: D1, D2 , etc.
Circumflex (Cx)
The Cx lies in the left AV groove between the left atrium and left ventricle and supplies the vessels of the lateral wall of the left ventricle.
These vessels are known as obtuse marginals (M1, M2…), because they supply the lateral margin of the left ventricle and branch off with an obtuse angle.
In most cases the Cx ends as an obtuse marginal branch, but 10% of patients have a left dominant circulation in which the Cx also supplies the posterior descending artery (PDA).Mnemonic: Marginal branches arise from the Cx and supply the lateral Margin of the left ventricle.

Circumflex and LAD seen in Lateral projection
Right Coronary Artery (RCA)
The right coronary artery arises from the anterior sinus of Valsalva and courses through the right atrioventricular (AV) groove between the right artium and right ventricle to the inferior part of the septum.
In 50-60% the first branch of the RCA is the small conus branch, that supplies the right ventricle outflow tract.
In 20-30% the conus branch arises directly from the aorta.
In 60% a sinus node artery arises as second branch of the RCA, that runs posteriorly to the SA-node (in 40% it originates from the Cx).
The next branches are some diagonals that run anteriorly to supply the anterior wall of the right ventricle.
The large acute marginal branch (AM) comes off with anacute angle and runs along the margin of the right ventricle above the diaphragm.
The RCA continues in the AV groove posteriorly and gives off a branch to the AV node.
In 65% of cases the posterior descending artery (PDA) is a branch of the RCA (right dominant circulation).
The PDA supplies the inferior wall of the left ventricle and inferior part of the septum.
RCA, LAD and LCx in Anterior projection
On the image on the far left we see the most common situation, in which the RCA comes off the right cusp and will provide the conus branch at a lower level (not shown).
On the image next to it, we see a conus branch, that comes off directly from the aorta.
LEFT: RCA comes off the right sinus of Valsalva
RIGHT: Conus artery comes off directly from the aorta
The large acute marginal branch (AM) supplies the lateral wall of the right ventricle.
In this case there is a right dominant circulation, because the posterior descending artery (PDA) comes off the RCA.
Coronary Anomalies

Coronary anomalies are uncommon with a prevalence of 1%.
Early detection and evaluation of coronary artery anomalies is essential because of their potential association with myocardial ischemia and sudden death (3).
With the increased use of cardiac-CT, we will see these anomalies more frequently.

Coronary anomalies can be differentiated into anomalies of the origin, the course and termination (Table).

The illustration in the left upper corner is the most common and clinically significant anomaly.
There is an anomalous origin of the LCA from the right sinus of Valsalva and the LCA courses between the aorta and pulmonary artery.
This interarterial course can lead to compression of the LCA (yellow arrows) resulting in myocardial ischemia.

The other anomalies in the figure on the left are not hemodynamically significant.

Interarterial LCA

On the left images of a patient with an anomalous origin of the LCA from the right sinus of Valsalva and coursing between the aorta and pulmonary artery.
Sudden death is frequently observed in these patients.

ALCAPA

On the left images of a patient with an anomalous origin of the LCA from the pulmonary artery, also known as ALCAPA.
ALCAPA results in the left ventricular myocardium being perfused by relatively desaturated blood under low pressure, leading to myocardial ischemia.
ALCAPA is a rare, congenital cardiac anomaly accounting for approximately 0.25-0.5% of all congenital heart diseases.
Approximately 85% of patients present with clinical symptoms of CHF within the first 1-2 months of life.

Myocardial bridging

Myocardial bridging is most commonly observed of the LAD (figure).
The depth of the vessel under the myocardium is more important that the lenght of the myocardial bridging.
There is debate, whether some of these myocardial bridges are hemodynamically significant.

Fistula

On the image on the left we see a large LAD giving rise to a large septal branch that terminates in the right ventricle (blue arrow).

Left to right shunt: septal branch of LAD teminates in right ventricle
REFERENCES
  1. Introduction to cardiothoracic imaging
    by Carl Jaffe and Patrick J. Lynch
  2. Cardiology Site
    by M. Abdulla
    This site includes instructional movies, 3-D animation, panoramic views, online quiz, interactive video-clips, interactive heart sounds & murmurs and interactive echocardiograms.
  3. Visualization of Anomalous Coronary Arteries on Dual Source Computed Tomography
    by G.J. de Jonge et al
    European Radiology, Volume 18, Number 11 / November, 2008, 2425-2432

SOURCE

Robin Smithuis and Tineke Wilems
Radiology department of the Rijnland Hospital Leiderdorp and the University Medical Centre Groningen, the Netherlands.
http://rad.desk.nl/en/48275120e2ed5 

 

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