Pulmonary Hypertension

Question 1

Definition of Pulmonary Hypertension (PH)

Answer 1

A hemodynamic and pahtophysiological condition defined as: An increase in mean pulmonary arterial pressure >25 mmHg at rest as assessed by heart cath

Question 2

Definition of Pulmonary Arterial Hypertension (PAH)

Answer 2

A clinical condition characterized by precapillary PH in the absence of other causes (lung disease, chronic thrombo-embolic PH)

Question 3

Changes in these 2 things affect pulmonary blood flow

Answer 3

Cardiac Output and pleural/alveolar pressure

Question 4

Drugs that definitely cause PAH

Answer 4

Aminorex, fenfluramine, dextenfluramine, toxic rapeseed oil, benfluorex

Question 5

Drugs that are likely to cause PAH

Answer 5

Amphetamines, L-tryptophan, mephamphetamines

Question 6

Drugs that are UNLIKELY to cause PAH

Answer 6

OC, estrogen, cigarettes

Question 7

Drugs that possibly cause PAH

Answer 7

cocaine, phenylpropnolamine, St. John’s wort, chemotherapic agentis, SSRI, pergolide

Question 8

WHO Class I

Answer 8

No symptoms with normal daily activities

Question 9

WHO Class II

Answer 9

Symptoms with strenuous normal daily activities. Slightly limit functional status and activity level

Question 10

WHO Class III

Answer 10

Symptoms of dyspnea, fatigue, syncope and chest pain with normal daily activities that severely limit functional status and activity level

Question 11

WHO Class IV

Answer 11

Symptoms at rest, cannot conduct normal daily activities w/o symptoms

Question 12

Risk factors for PAH

Answer 12

history of smoking/ ETOH/ recreational drug use, systemic htn, cyanosis/ murmur as a child, Joint/ musculoskeletal pain, Raynaud’s syndrome, previous DVT, use of appetite suppressant drugs

Question 13

Clinical Presentation of PAH

Answer 13

Dyspnea on exertion (DOE), Fatigue, weakness, chest pain, syncope, LE or abdominal swelling

Question 14

Evaluation of PH

Answer 14

ECG, Chest x-ray, PFT, exercise oximetry, echo, right heart cath w/ vasodilator testing, labs (CBC, CMP, INR, ANA, HIV, TFTs)

Question 15

Reassessment of PAH

Answer 15

functional class determination and 6 minute walk test every 3-6 months

Question 16

Treatment of PAH (5 basics)

Answer 16

1. Supportive care
2. Oxygen
3. Oral anticoagulation
4. Immunizations
5. Birth control

Question 17

Supportive care for PAH

Answer 17

Treat hypoxemia, avoid dehydration, pain fatigue, high altitude, smoking, pregnancy and iron deficiency

Question 18

Oxygen for PAH

Answer 18

Maintain O2 sat above 90% use a diuretic if peripheral edema or ascites

Question 19

Oral Anticoag for PAH

Answer 19

Warfarin (INR 1.5-2.5) +/- digoxin, +/- diuretics (anticoag to prevent catheter thrombosis and VTE)

Question 20

Immunizations for PAH

Answer 20

Flu and pneumococcus

Question 21

CCB use in PAH

Answer 21

Class II PAH (should not be used empirically without positive response to acute vasodilatory response testing)

Question 22

Selecting a CCB

Answer 22

If tachycardic (>90) use diltiazem; if bradycardic choose amlodipine or nifedipine

Question 23

Endothelin’s role in PH

Answer 23

exerts vasoconstrictor mitogenic effects by binding to 2 distinct receptor isoforms in the pulmonary vascular smooth muscle cells Endothelin A and B receptors

Question 24

Bosentan (Trade name, class, Indication, dose)

Answer 24

Tracleer, Nonselective ETa and ETb receptor blocker, Class III and IV PAH, 62.5-125 mg PO BID

Question 25

Bosentan Considerations

Answer 25

Severe interaction with glyburide and cyclosporine, potential teratogen (use 2 forms of birth control)

Question 26

Monitering paramaters with Bosentan

Answer 26

Monitor LFTs monthly, Monitor hemoglobin/ hematocrit every 3 months, pregnancy test monthly

Question 27

Ambrisentan (Trade, Class, Indication, Dose)

Answer 27

Letairis, ETa blocker, Class II or III PAH, 5-10 PO QD

Question 28

Considerations with Ambrisentan

Answer 28

Caution with cyclosporine, Monitor LFTs monthly, potential teratogen

Question 29

Macitentan (Trade, Class, Indication, Dose)

Answer 29

Opsumit, Nonselective ETa and ETb blocker, PAH (maybe class III?), 10 mg PO QD

Question 30

Macitentan Considerations

Answer 30

Pregnancy precautions (REMS program), may cause severe anemia, Hepatotoxicity may occur, PVOD may occur

Question 31

PDE-5 Inhibitors

Answer 31

Enhance NO-cGMP pathway, slowing cGMP degradation

Question 32

sGC Stimulators

Answer 32

Enhance cGMP production and are potentially effective also in conditions in which endogenous NO is depleted

Question 33

Riociguat (Trade, Class, Indication, Dose)

Answer 33

Adempas, sGC stimulator, CTEPH (WHO group 4), 1mg PO QD)

Question 34

Riociguat Considerations

Answer 34

Pregnancy precautions, Renal impairment, Hepatic impairment

Question 35

Sildenafil (Trade, Class, Indication, Dose)

Answer 35

Revatio, PDE-5i, Class II-IV PAH, 20 mg PO TID

Question 36

CI of Sildenafil and Tadalafil

Answer 36

CI in patients using nitrates

Question 37

Tadalafil (Trade, Class, Indication, Dose)

Answer 37

(Adcirca, PDE-5i, Class II-IV PAH, 40mg PO QD)

Question 38

Prostacyclin Pathway

Answer 38

Produced by endothelial cells, induces vasodilation, inhibits platelet aggregation, dysregulation of prostacyclin shown in pts with PAH

Question 39

Eprostenol (trade, class, indication, dose)

Answer 39

Flolan + Veletri, prostanoid, Class III-IV, 2-40 mg/kg/min IV

Question 40

Eprostenol Considerations

Answer 40

Considered a medical emergency if infusion interrupted (spare drug cassette and infusion pump should be kept available)

Question 41

Treprostinil (Trade, class, Indication, dose)

Answer 41

Remodulin + Tyvaso, Prostanoid, Class II-IV PAH, 1.25-40 ng/kg/min IV

Question 42

Treprostinil ADE

Answer 42

Severe erythema (83%) and injection site pain (85%) (have hot/cold packs and topical analgesics available) (move infusion site every 3 days)

Question 43

Inhaled iloprost (Trade, Class, Indication, dose)

Answer 43

Ventavis, Prostanoid, Class III-IV, 5 mcg by nebulizer 6-9 times a day