Pulmonary Hypertension Questions With Answers

(A) is the false statement. Actually, women are twice as likely than men to contract PAH. Young women, approximately 36 years of age, are the women who are most prone to PAH.

(B) is a true statement. Relatively non-specific symptoms such as fatigue, edema, dyspnea, and angina/syncope present clinically, making the disease more difficult to diagnose.

(C) is also true. Right heart catheterization is utilized to measure the blood pressure of the heart and lungs. It is also called the "Swan-Ganz". This is especially crucial when PH is suspected.

(D) is also true. Multiple studies are required for evaluation, such as an echocardiography, pulmonary function tests, and a CT of the chest. PCWP or LVEDP will help distinguish the disease from pulmonary VENOUS hypertension. Recall that the PCWP of LVEDP must be less than or equal to 15 mmHg AND the mean PAP must be greater than or equal to 25 mmHg to be defined as PAH.

(B) is the false statement. Recall that the right ventricle pumps blood through the pulmonary arteries. These arteries carry deoxygenated blood to the lungs. In PH, the pulmonary arteries are constricted, leading to the right side of the heart having to pump harder to eject blood to the lungs. This can ultimately lead to right-sided heart failure.. It must be noted that left-sided heart failure is an etiology of PH.

(A) is correct because PH is a complex disease that can be precipitated by various diseases. For instance, cocaine and amphetamine use, parasites, and numerous pulmonary diseases can bring about PH.

(C) is true. By definition, the mean PAP must be greater than or equal to 25 mmHg and right-heart catheterization is needed to assess this.

It must be noted that for PAH, the mean PAP must be greater than or equal to 25 AND the pulmonary capillary wedge pressure or the the left ventricle end diastolic pressure is less than or equal to 15 mmHg.

(D) is true. PAH is merely a subset of PH, which will be discussed further in the next question.

(C) is the false statement here. There is actually no cure for PAH. While there are medications to help control the symptoms and provide life-saving therapies, there is still no cure.

(A) is true because vasoconstriction is emblematic of hypertension. Recall TPR in the lectures of "regular" hypertension.

(B) is also true.Vascular wall remodeling is especially problematic in the right ventricle. The right ventricle, as mentioned earlier, must work harder and thus must enlarge. This is atypical of the right ventricle and leaking and clots may emerge as a result.

(D) is true. And this is important. Vasoconstriction and vasodilation are in a balance. Thromboxane A2 and Endothelin-1 (ET1) promote vasoconstriction. Nitric oxide (NO) and prostaglandin I2 (prostacyclin) promote vasodilation. This is important because drugs have been created to alter this balance and tip the scales for vasodilation. That is, more vasodilation is preferred in this disease state.

(A) is the false statement here. Many of these drugs are "new" (within the past 20 years). for instance epoprostenol was approved by the FDA in 1996. There is limited long-term data.

(B) is true. Some are taken IV, some are inhaled, and some can be taken subcutaneously. All of these have their pros and cons and whichever is best for the patient will depend on numerous variables.

(C) is true. These drugs are expensive. To compare, the yearly cost for the drugs for heart failure amount to approximately $2,000. For PAH, that same number is almost $150,000. Clearly, it's important to manage the disease state correctly.

(D) is true. Of course pharmacists are important to direct and monitor therapy. These drugs are subtle and new and pharmacists understand these nuances to make sure the doses are correct and to avoid treatment failure.

(A) is the false statement. Like the other ET-1 receptor antagonists, macitentan is CONTRAINDICATED in pregnant women.

(B) is true, meaning that it dissociates slowly when it binds with the receptor.

(C) is true, and therefore LFTs must be monitored at baseline.

(D) is also true. Macitentan is a 3A4 substrate and must be used in caution (even avoided) with strong 3A4 inhibitors and inducers.

Interestingly, macitentan was very recently approved. It was approved by the FDA on October 18, 2013.

(B) is the false statement. Riociguat is avoided in patients whose CrCL is less than 15 mL/min or dialysis dependent. (A) is true. It is a soluble guanylate cyclase stimulator, which will convert GTP into cGMP, allowing for smooth muscle relaxation, which is desired. (C) is true. Riociguat is CONTRAINDICATED in pregnant women and therefore baseline and monthly pregnancy tests must be performed. Hepatotoxicity is also a concern. Those with severe hepatic impairment (Child Pugh C) will avoid this drug for treatment. (D) is also true. Since riociguat is a CYP and PGP substrate, strong inhibitors and inducers are avoided. Nitrates are avoided (riociguat works with NO). PDE-5 inhibitors are avoided (riociguat works with NO). Antacids are separated by at least 1 hour from riociguat due to a decreased absorption. And smoking actually increases the metabolism of drugs in 1A2. This drug also recently was approved by the FDA. Riociguat was approved on October 8, 2013.

This is a true statement. Treprostinil has two products: Remodulin and Tyvaso.

Tyvaso is an inhaled product that requires 4 treatments per day while awake. Its claim to fame is that it helps improve exercise capacity by improvign the 6 minute walking distance (6MWD). Because it has a more local effect, the adverse effect profile is significant for cough, throat irritation, and flushing.

(B) is the correct choice here. This is the goal INR range for a patient with PAH on warfarin. Recall that this is different than many other patients, who usually have INR goals of 2.0-3.0.

Warfarin can be used to prevent thrombosis due to dilation of the right heart chamber, which can occur with PAH, which is a major concern.

The problem is with the right ventricle and supportive measures can be taken, such as diuretics, digoxin (for the cardiac output), oxygen, and even surgery.

(C) is the false statement here. ILOPROST (written like this to distinguish "I" and "L") is actually given 6 to 9 times a day. Each inhalation session takes approximately 10 minutes, accounting for about an 1 to 1.5 hours a day.

(A) is true. This is a prostacyclin analog, meaning that it will promote vasodilation.

(B) is true. ILOPROST is indicated for sever symptoms. Recall that class 3 characterizes symptoms of less than ordinary exertion, so "around the house" activities. Class 4 characterizes symptoms at rest.

(D) is true. That is true with every other prostacyclin analog.

(B) is the false statement here and it must be noted. Maximum physiologic doses of CCBs must be used for the treatment of PAH. For instance, for diltiazem, 500-600 mg doses are not unheard of for this disease state.

(A) is true. Recall from the hypertension lectures that the CCBs selectively affect vascular smooth muscle because of the relevancy of calcium channels for contraction.

(C) is true all the time. The statement is even more relevant because of the maximum doses being utilized.

(D) is true. This may be surprising, but even when using the maximum doses of CCBs, the long-term response in PAH is less than 10%. Clearly, other drugs must be utilized.

(Sildenafil is also called Revatio and tadalafil is also called Adcirca. These are different formulations than Viagra and Cialis, respectively!)

(E) is the false statement here. Nitrates are contraindicated with PDE-5 inhibitors. Recall this from the hypertension lectures. Sildenafil is especially contraindicated with nitrates within 24 hours of nitrate administration (think 2 = S = sildenafil). Tadalafil is especially contraindicated within 48 hours (4 ~ T = tadalafil). Administration of both can lead to severe hypotension, which means less perfusion to the vital organs.

(A) is a true statement. This is especially seen with the dosing intervals.

(B) is true. Revatio is TID dosing (this is why it is considered shorter-acting) where as Adcirca is QD dosing.

(C) is true. Recall that these are PDE-5 inhibitors, meaning that vasodilation will occur and lead to flushing and hypotension. This is a nitric oxide mediated mechanism.

(D) is also true. These drugs have significant improvement in the 6MWD.

Of course! You already saw the small nuances between these drugs that were discussed. Many are contraindicated in pregnancy and some have hepatotoxicities. Drug interactions are major concerns with many of these drugs. Pharmacists can ensure that the drug and regimen are right for the patient. We can do it all!

(A) is the false statement. Compared to bosentan, ambrisentan is more selective for the ETa receptor. Once again, it will antagonize the ET-1 receptor and thus promote vasodilation, which is desired. (B) is true. Ambrisentan is contraindicated in pregnant women. This is such a concern that women must have a baseline pregnancy test and monthly pregnancy tests thereafter. Recall that PAH is most prevalent in women of child-bearing age. (C) is also true. While this may be less so than bosentan, there is still a concern for drug interactions with ambrisentan. Strong inhibitors (ketoconazole, ritonavir) and inducers (rifampin) must be used with caution.

(B) is the false statement here. Treprostinil is NOT shown to have a survival benefit. That is actually one of the major differences between treprostinil and epoprostenol. Recall that epoprostenol has the survival benefit.

(A) is a true statement. Treprostenol has a half-life of 4 hours while epoprostenol has a half-life of just under 3 minutes! Clearly, treprostinil is much better in that regard.

(C) is also true. With the better profile of half-life and stability at room temperature, it actually has a higher cost and that must be taken into account for a patient.

(D) is true. It is stable at room temperature but what makes it different from Veletri is that treprostinil does NOT need a back-up cassette.

(E) is also true. Again, prostacyclin analogs will promote vasodilation.

(D) is the false statement and is important clinically. Epoprostenol is NOT selective.Because epoprostenol is not selective, other drugs, such as other vasodilators, antiplatelets, and anticoagulants, have interactions with epoprostenol. In essence, epoprostenol acts on "regular" blood vessels in addition to the pulmonary vessels. This causes systemic problems and that certainly interacts with drugs that act in the systemic vasculature.

(A) is true. Recall that prostacyclin is one of the elements that will promote vasodilation, which is desired here. As an analog, it will act as endogenous prostacyclin.

(B) is also true and this is important. Two products, Flolan and Veletri, are on the market. And they each have their own characeristics. For instance, an infusion pump (CADD pump) is used in both products. This is how the patient administers epoprostenol at home. Flolan is particular in that it requires a sterile diluent that is unique for Flolan. Veletri can get away with sterile water and 0.9% sodium chloride as the diluent. Veletri doesn't need ice packs (Flolan does), and it is stable at room temperature (hence no ice packs). Both need back-up cassettes (just in case).

(C) is also true. "Improves mortality" means that there is a survival benefit from the drug. There are improvements in exercise capacity and quality of life. Naturally, there are adverse effects such as flushing headache, and nausea. This is expected because of the vasodilation of the arteries leading to the brain.

(D) is the true statement here. Drug interactions are a major concern for bosentan. It is a substrate of 3A4 (many, many drugs) and 2C9. On top of that, it is an autoinducer, meaning that it induces its own metabolism. There are contraindcations for bosentan including cyclosporine (3A4) and glyburide due to hepatotoxicity. Warfarin also has a decreased effect due to the autoinduction of 3A4.

(A) is a false statement. Remember: endothelin-1 is a receptor to promote vasoconstriction, so you want to ANTAGONIZE the receptor. Indeed, bosentan is an ET-1 ANTagonist.

(B) is false. Bosentan is pregnancy category X. Hepatotoxicity is such a concern with this drug that LFTs are monitored at baseline AND monthly.

(C) is false because it is NOT selective. It antagonizes ETa and ETb (though ETa to a greater extent. Selective ET-1 antagonists will be discussed later.