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Old 06-09-2011
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Lungs How to treat this dyspnea case!

A 24-year-old woman is under your care for evaluation of progressive dyspnea of unknown etiology. Her shortness of breath first appeared 6 months ago. Subsequently, she developed a chronic nonproductive cough. There is a history of systemic lupus erythematosus (SLE). She is currently taking no medications but received 3 months of prednisone and methotrexate therapy for her last SLE exacerbation 1 year ago. Physical exam is unremarkable. Chest X-ray shows no interstitial or alveolar pathology. A high-resolution computed tomography (CT) scan and ventilation perfusion scan shows no evidence of pulmonary interstitial or thromboembolic disease. ECG shows right axis deviation, ST depression and T wave inversion in the anterior leads, and P wave morphology consistent with right atrial enlargement. Today, the patient has undergone cardiac catheterization that confirms her diagnosis and excludes any left-sided heart failure. Treatment with which pharmacological agent will likely provide the greatest improvement in this patient's prognosis?

Answer Choices
A. Calcium channel blockers
B. Corticosteroids
C. Glycoprotein IIb/IIIa inhibitors
D. Prostacyclin agents
E. Tumor necrosis factor inhibitors
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Default PAH

This patient has PAH. The answer is prostacyclin!

Out of the given options, CCB and prostacyclin are liscented! But only prostacyclin and newer one-endothelin receptor antagonists are shown to possibly have impact on survival! Sildenafil, also known as Viagra is also useful for symptom relief!

See below.
http://www.lunguk.org/you-and-your-l...pertension.htm

Prostacyclin
Prostacyclin is a steroid that is produced naturally in the body of a healthy person. It causes blood vessels in the lungs to relax and allows blood to flow through them more easily. People with pulmonary hypertension do not produce enough prostacyclin, so the blood vessels in the lungs are constricted. Prostacyclin, also known as epoprostenol, is used to treat this condition.
Prostacyclin therapy was initially used as a bridge to lung transplantation although it has also emerged as an alternative to transplantation in some patients. Prostacyclin, or its longer lasting derivatives, can be given by continuous infusion and sometimes by other routes. It has been shown to improve breathlessness and probably survival in patients with idiopathic PAH.

Endothelin receptor antagonists
These are a class of oral drugs that are now licensed for the treatment of pulmonary arterial hypertension. Endothelin is a peptide made by the body in the endothelium (a layer of cells which line the heart and blood vessels). It constricts blood vessels and increases blood pressure. It plays an important role in blood flow.
In PH, the body produces too much endothelin. This leads to the constriction of blood vessels and also affects blood pressure in the lungs.
Endothelin must connect with an endothelin receptor in order to be activated. Endothelin receptor antagonists block endothelin receptors. This limits the harmful excess endothelin in your blood vessels.
Controlled trials have demonstrated that endothelin receptor antagonists improve symptoms and quality of life in PH. They may also have a beneficial effect on survival.
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Option D (Prostacyclin agents) is correct. Untreated, idiopathic pulmonary arterial hypertension leads to right-sided heart failure and death with an overall survival of approximately 30% at 3 years. The use of long-term prostacyclin agents resulted in a 5-year survival rate greater than 65%.

Option A (Calcium channel blockers) is incorrect. Calcium channel blockers were, until recently, the most widely used class of drugs for idiopathic pulmonary arterial hypertension. The introduction of long-term prostacyclin agents for treatment of idiopathic pulmonary arterial hypertension has resulted in a improvement in survival from 30% at 3 years to a 5-year survival rate greater than 65%.

Option B (Corticosteroids) is incorrect. Corticosteroids clearly improve survival in patients with SLE. They have no effect on the relentlessly fatal progression of idiopathic pulmonary arterial hypertension and therefore provide no improvement in this patient's prognosis of 30% 3-year survival without prostacyclin therapy.

Option C (Glycoprotein IIb/IIIa inhibitors) is incorrect. Glycoprotein IIb/IIIa inhibitors such as abciximab, eptifibatide and tirofiban are potent inhibitors of platelet aggregation. They have no effect on the progression of idiopathic pulmonary arterial hypertension.

Option E (Tumor necrosis factor inhibitors) is incorrect. Tumor necrosis factor inhibitors, such as infliximab, etanercept, and adalimumab, are promising new agents in the treatment of several autoimmune mediated diseases including juvenile arthritis. There is no evidence that they improve survival in patients with idiopathic pulmonary arterial hypertension.

High-yield Hit 1

Prostaglandin I2 and Prostaglandin I2 Derivatives
Epoprostenol is a formulation of naturally occurring PGI2 (prostacyclin) that is used to treat pulmonary arterial hypertension (PAH). Epoprostenol acts on IP receptors to dilate pulmonary blood vessels and increase pulmonary blood flow, thereby counteracting the pathophysiologic consequences of pulmonary hypertension. The drug is administered by continuous intravenous infusion, and the dosage is titrated on the basis of clinical improvement and adverse effects. The most common adverse reactions include flushing, tachycardia, hypotension, diarrhea, nausea, vomiting, and flu-like symptoms.
Treprostinil is a stable analogue of prostacyclin which has a half-life of between 2 and 4 hours and can be safely administered by a continuous subcutaneous infusion, via a self-inserted subcutaneous catheter using a micro infusion pump designed specifically for subcutaneous drug delivery. It is approved to diminish the symptoms (e.g., shortness of breath) associated with physical activity in PAH patients.

From Pharmacology 2E by Brenner & Stevens
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Quote:
Originally Posted by 1TA2B View Post
This patient has PAH. The answer is prostacyclin!

Out of the given options, CCB and prostacyclin are liscented! But only prostacyclin and newer one-endothelin receptor antagonists are shown to possibly have impact on survival! Sildenafil, also known as Viagra is also useful for symptom relief!

See below.
http://www.lunguk.org/you-and-your-l...pertension.htm

Prostacyclin
Prostacyclin is a steroid that is produced naturally in the body of a healthy person. It causes blood vessels in the lungs to relax and allows blood to flow through them more easily. People with pulmonary hypertension do not produce enough prostacyclin, so the blood vessels in the lungs are constricted. Prostacyclin, also known as epoprostenol, is used to treat this condition.
Prostacyclin therapy was initially used as a bridge to lung transplantation although it has also emerged as an alternative to transplantation in some patients. Prostacyclin, or its longer lasting derivatives, can be given by continuous infusion and sometimes by other routes. It has been shown to improve breathlessness and probably survival in patients with idiopathic PAH.

Endothelin receptor antagonists
These are a class of oral drugs that are now licensed for the treatment of pulmonary arterial hypertension. Endothelin is a peptide made by the body in the endothelium (a layer of cells which line the heart and blood vessels). It constricts blood vessels and increases blood pressure. It plays an important role in blood flow.
In PH, the body produces too much endothelin. This leads to the constriction of blood vessels and also affects blood pressure in the lungs.
Endothelin must connect with an endothelin receptor in order to be activated. Endothelin receptor antagonists block endothelin receptors. This limits the harmful excess endothelin in your blood vessels.
Controlled trials have demonstrated that endothelin receptor antagonists improve symptoms and quality of life in PH. They may also have a beneficial effect on survival.
how did u reach to think it is
idiopathic pulmonary arterial hypertension
i didnt feel it is easy q to think in it in 72 sec am i right ?????
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Quote:
Originally Posted by miss patho View Post
how did u reach to think it is
idiopathic pulmonary arterial hypertension
i didnt feel it is easy q to think in it in 72 sec am i right ?????
There're clues in the question. Just need to pin down!

This patient has right heart failure. Common pathologies are secondary to lungs/vulvular lesions or recurrent thromboembolic diseases. They all been excluded. Also history of SLE helped to reach to the diagnosis!
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In casemof pul htn
first give sidenafil
bosenton then start iloprost,epoprostenol,teprostinil
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Old 06-16-2011
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what I have mentioned are given for all pul htn cases.SLE might lead to ILD which may lead to pul htn.I am a MD (INT MED) graduate from india ,I have treated many cases of pul htn so i could ans in 72 sec madam.
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