Pulmonary Arterial Hypertension Flashcards
1
Q
Pulmonary Arterial Hypertension
A
- PAH: sustained elevated pulmonary arterial pressure (>= 25 mmHg) with a mean PCWP or LVEDP =< 15 mmHg
- Ultimately leads to right ventricular failure and death
2
Q
PAH Symptoms
A
- Fatigue
- Dyspnea
- Weakness
- DOE
- Less common symptoms: chest pain, near-syncope/syncope, peripheral edema, and palitations
3
Q
WHO Group 1 PAH
A
- Idiopathic PAH
- Familial PAH
- Associated with APAH: connective tissue disease, portal HTN, HIV, drugs
- Associated with significant venous or capillary involvement
- Persistent PAH of newborn
4
Q
WHO Group 2 PAH
A
- PAH with left heart disease
- Left-sided atrial or ventricular heart disease
- Left-sided valvular heart disease
5
Q
WHO Group 3 PAH
A
- PAH associated lung disease and/or hypoxemia
- COPD
- Interstitial lung disease
- Sleep-disordered breathing
- Chronic exposure to high altitude
- Developmental abnormalities
6
Q
WHO Group 4 PAH
A
- Due to chronic thombotic disease or embolic disease (CTEPH)
- Thromboembolic obstruction or proximal or distal pulmonary arteries
- Nonthrombotic pulmonary embolism
7
Q
WHO Group 5 PAH
A
- Sarcoidosis
- Pulmonary Langerhans
- Lymphangiomatosis
- Compression of pulmonary vessels
8
Q
PAP
A
- Pulmonary Arterial Pressure
- PAP is generated by right ventricle, ejecting blood into pulmonary circulation
- Acts as a resistance to output from RV
- Pulmonary vasculature is low resistance system
- PAP = (CO * PVResistance) + PVPressure
- PAP ~ 15, PVP ~8
9
Q
Pulmonary Vascular Changes
A
- Vasoconstriction - imbalance between vasodilators and vasoconstrictors
- Smooth muscle cell and endothelial cell proliferation: imbalance between growth inhibitors and mitogenic factors
- Thrombosis: imbalance between antithrombotic and prothrombotic determinants
10
Q
PAH Diagnostic Evaluation
A
- History: family and physical examination
- Electrocardiography, chest radiography, pulmonary-fxn test
- Echocardiography
- Ventilation/perfusion scan, chest CT
- CBC, HIV-1 antibody, LFTs, thyrotropin, antinuclear antibody
- Exclude other secondary causes
- Right heart catheterisation with vasodilator testing: NEEDED to confirm PAH
11
Q
WHO Functional Classifications
A
- I: No limitation of physical activity
- II: Mild limitation: no discomfort at rest, normal activity causes increased dyspnea, fatigue, chest pain presyncope
- III: Marked limitation of physical activity, no discomfort at rest, less than ordinary activity causes dyspnea, fatigue, chest pain, presyncope
- IV: unable to perform any physical activity, signs of RV failure, dyspnea/fatigue present and rest and symptoms increases by most activity
12
Q
PAH Markers for Disease Severity
A
- BDI (Borg Dyspnea Index): 0 = no impairment, 10 = severe impairment
- 6-MWT (6 minute walk test): measure of exercise level reflective of everyday life
- Cardiopulmonary hemodynamic variables: mPAP, PVR, CO via right heart catheterization
13
Q
NonPharm General Treatment Measures
A
- Oxygen: want to maintain O2 saturations >90%, helps fight hypoxic vasoconstriction
- Diet: Na (<2500 mg/day) strongly encouraged and fluid restriction when necessary
- Immunizations: influenza, pneumococcal
14
Q
Pharm General Treatments
A
- Diuretics: indicated in patients with evidence of RV failure (edema, ascites, elevated JVD), maintain normal volume status is the goal
- Monitor: vitals, renal fxn, and serum electrolytes
-Digoxin: may be beneficial to patients with refractor right ventricular failure and/or atrial dysrrhythmias
15
Q
Oral Anticoagulants
A
- Microscopic thrombosis has been documented with IPAH and right-sided HF increases risk of PE
- Patients with IPAH should receive anticoagulation with warfarin
- Still consider anticoagulation if PAH is related to other conditions like scleroderma or congenital HD
- Use other anticoagulants if PAH patient has an indwelling catheter
- Target INR: 1.5-2.5
16
Q
Acute vascular Testing
A
- Vasodilator testing to determine response to vasodilators
- If responsive, better survival with long-term CCB use
- Acute vasodilator testing must be done during a right heart catheterization
- Positive response defined as a drop in PAP >= 10 mmHg to =< 40 mmHg with unchanged to increased CO
- Patients with IPAH should undergo this testing as well
- Use short-acting agents like IV epoprostenol, IV adenosine, or inhaled NO for testing
17
Q
CCB
A
- ~10% have favorable vasodilator response
- Nifedipine XL, diltiazem, or amlodipine used the most (avoid verapamil, (-) inotrope)
- Start low and titrate dose as tolerated
- Monitor: @ 3 months for symptoms/vitals/edema,
- Sustained response to CCB therapy is defined as being FC I or II
18
Q
ERAs
A
- Endothelin-1 Receptor Antagonists
- ET-1 is a potent, endogenous vasoconstrictor and smooth-muscle mitogen that is overexpressed in plasma and lung tissue of PAH patients
- Two receptors: ETa and ETb
- Eta: activation facilitates vasoconstriction and proliferation of vascular smooth-muscle cells
- ETb: involve clearance of ET-1, may cause vasodilation and NO release
19
Q
Bosentan
A
- Tracleer
- Block Type A and B receptors
- CI: pregnancy (test monthly), hepatotoxicity, glyburide and cyclosporin
- Check LFTs every month
- CYP2C9 and 3A4 substrate
20
Q
Ambrisentan
A
- Letairis
- Selective for ETa receptor
- CI: pregnancy (test montly)
- CYP3A4 (major), 2C19 (minor), and P-gp substrate
21
Q
Macitentan
A
- Opsumit
- Non-selective A/B receptor antagonist
- CI: pregnancy (test monthly)
- CYP3A4 (major) and 2C19 (minor) substrate
22
Q
ERA Warnings/AE/Monitorign
A
- Warnings: DEcrease Hgb/HCT, fluid retention, decreased sperm counts
- AE: headache, URI, flushing, hypotension
- Monitoring: LFTs, Hgb/Hct, pregnancy tests
23
Q
PDE5-I + PAH Treatment
A
- NO is a pulmonary vasodilator which is mediated trough cGMP and rapidly degraded by PDE
- PDE5 is a predominate isoform in the lung that metabolizes cGMP (upregulated in PAH)
- By inhibiting PDE5, increases of cGMP occur and enhance NO vasodilation
24
Q
Sildenafil
A
- FDA-indicated for PAH WHO Group I to improve exercise ability
- Monitor: BP, symptoms, vision, hearing
- Interacts with nitrates, CYP3A4 inhibitors/inducers, and alpha-blockers/other vasodilators (hypotensive effects)
25
Q
Tadalafil
A
- Indicated for treatment of PAH (WHO Group I) to improve exercise ability
- Monitor: BP, symptoms, vision, hearing
- DI: nitrates, CUP3A4 inhibitors/inducers
- Reduce dose by 1/2 in renal insufficiency (CrCl 31-80)
26
Q
Riociguat
A
- Adempas
- Guanylate cyclase (sGC) stimulator
- Acts in synergy with and independently of endogenous NO to stimulate sGC
- Indicated for those with CTEPH (WHO Group 4) and WHO Group 1 to increase exercise capacity
- Available through REMS program
- Start at lower dose if hypotensive
27
Q
Riociguat AE/Monitoring
A
- AE: Headache, dyspnea, dizzy, N/V, diarrhea, anemia, GERD, Pregnancy Category X
- Monitoring: BP, bleeding, symptoms, preggo test monthly
- PK: Metabolized y CYP 1A1, 3a, 2C8, and 2J2
- DI: CYP inhibitors and inducers, P-gp/BCRP inhibits, antacids, tobacco smoking
- CI: nitrates, specific or non-specific PDE5I
28
Q
Prostanoids
A
- Prostaglandin I2: prostacyclin induces relaxation of vascularsmooth muscle by stimulating cAMP production
- Powerful inhibitor of platelet aggregation
- [PGI2] are decreased in PAH
29
Q
Epoprostenol
A
- Flolan
- Naturally occuring prostaglandin with potent vasodilatory activity and inhibitory activity of platelet aggregation
- Indicated for long-term IV treatment of IPAH and PH associated scleroderma in Class III-IV patients who don’t respond to conventional therapy
30
Q
Epoprostenol Administration
A
- Given continuously IV through central venous catheter
- Keep cold during infusion and protectfromlight
- Veletri formulation is more stable and can last 2-3 days at times, protect from light still
- Avoid abrupt D/C, symptom deterioration and perhaps death
31
Q
Epoprostenol DI/CI/AE
A
- Start lose with dosing and slowly titrate up based on SE/tolerability (usually dose max between 20-40 ng/kg/min)
- DI: risk of hypotension with other HTN drugs, antiplatelets/anticoagulants increase bleed risk, increases [digoxin]
- CI: HFrEF
- AE: HA, jaw pain while chewing, flushing, diarrhea, nausea, rash, aches/pains
- Rare Delivery AE: sepsis, cellulitis, hemorrhage, and pneumothorax
32
Q
Treprostinil
A
- Remodulin
- Synthetic prostacyclin analog
- Indicated for PAH patients with Class II-IV symptoms
- Can be continuous IV or SC
- Start slow and increase doses over first for weeks
33
Q
Treprostinil AE/Monitoring
A
AE
- SC Infusion: infusion site pain/rxn, often severe and could need narcotics/D/C
- IV infusion: line infections, sepsis, arm swelling, hematoma, and pain
- General: diarrhea, jaw pain, vasodilation, and edema
- Monitor: AEs, vital signs, and PAH symptoms
34
Q
Inhaled Trepostinil
A
- Tyvaso
- Indicated to PAH WHO Group I to improve exercise (mainly studied in FCIII group with bosentan or sildenafil use)
- Use only with Tyvaso inhalation system
- QID, separated 4 hours
- Target maintenance dose: 9 breathes per session
- AE: Cough, HA, throat irritation, nausea, flushing, syncope, bleeding, hypotension
35
Q
Oral Treprostinil
A
- Orenitram
- ER tablet who WHO Group 1 to improve exercise
- Available in several dosing strengths
- Increase dose every 3-4 days to max tolerability/symptom response
36
Q
Orenitram DI/Counseling
A
-DI: increased bleeding with anticoag, increased hypotension with anti-HTN, strong CYP2C8 inhibitors
Counseling
- Avoid abrupt D/C (worsens symptoms)
- Take with food
- Swallow tablets whiole, don’t split/crush/chew
- Tablet shell remains intact during GI transmit and will be eliminated in feces
- Don’t take with alcohol
37
Q
Iloprost
A
- Inhaled, Ventacis
- Synthetic analog of prostacyclin’
- For WHO Group I with Class III or IV symptoms
- Given 6-9 times per day and slowly titrate to max tolerated dose
- AE: vasodilation (Flushing), cough, HA, trismus (lockjaw), and insomnia
- Monitoring: AE, vital signs, and PAH symptoms
38
Q
Selexipag
A
- Uptravi
- Non-prostanoid, IP prostacyclin receptor agonist
- Different structure than prostacyclin, metabolized by CYP2C8 and 3A4
- Oral tablet for WHO Group I to delay disease progression and reduce hospitalization risk
- DI: Strong CYP2C8 inhibitors (gemfibrozil)
- AE: HA, flushing, nausea, diarrhea, myalgia, jaw/extremity pain
39
Q
Combination Therapy
A
- Ambrisentan + Tadalafil
- Trial studied its use in naive PAH patients
- Improved outcomes versus monotherapy of either medication on its own
40
Q
PAH Longitudinal Eval
A
- Follow up based on therapy
- IV: by phone in 1-3 weeks then qweek until symptoms subside
- Oral: F/U every 1-2 months
- Combination: F/U every 2-4 weeks
- Assess: WHO-FC,, 6-MWT, Chem-7, AST/ALT if on ERAs INR if on warfarin, NT-proBNP
