Therapeutics I > PAH > Flashcards

PAH Flashcards

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1
Q

What is the life expectancy of untreated PAH?

A

3 Y

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2
Q

What is the PAH?

A

HTN in pulmonary artery

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3
Q

What is the normal PAP? During exercise?

A

N: 8-20 mag at rest
PH: mPAP > at rest, >30 during excersise

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4
Q

Pathophysiology of PAH?

A
  1. Imbalance in vasoconstrictors and dilators
  2. Imbalance in cell proliferation and apoptosis
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5
Q

How are vasoconstrictors affected in PAH?

A

ET1 and TXA2 increase

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6
Q

How are vasodilators affected in PAH?

A

Prostocyclins increase inhibits platelet aggregation and antiproliferation

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7
Q

How can PAH cause imbalances in cell proliferation and apoptosis?

A

Increased smooth muscle cells in pulmonary artery → further artery narrowing → more difficult for right ventricle (RV) to pump blood into lungs → enlarged RV and right heart failure (HF)

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8
Q

What are risk factors of PAH?

A
  1. Anorexigens
  2. HIV infection
  3. increased pulmonary flow
  4. Portal HTN
  5. Connective tissue destruction
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9
Q

What are the diagnosis tests for PAH?

A
  1. Doppler Echo
  2. Echocardiography
  3. Right heart catheterization (RHC)
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10
Q

What is Doppler Echo?

A
  1. Noninvasive
  2. Detects increase pulmonary pressures
  3. Can’t definitively diagnose
  4. First if PH is suspected
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11
Q

What is echocardiography?

A
  1. Can detect specific cardiac causes
  2. Used to assess treatment effects and progression
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12
Q

What is RHC?

A
  1. Definitive
  2. Used to evaluate clinical worsening
  3. Asses vasoreactivity
  4. mPAP≥25 with PCWP≤15 and PVR≥3
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13
Q

What are the classification systems of PAH?

A

Clinical and functional

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14
Q

What is the difference between clinical and functional classifications?

A

Clinical: classifies etiologies (Groups 1-5)
Functional: classifies symptoms and severity (Class1-IV), increases as disease worsens

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15
Q

What falls under group 1 PAH?

A

Drug induced PAH

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16
Q

What is class 1?

A

Symptom free when physically active or resting

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17
Q

What is class 2?

A

No symptoms at rest but some discomfort and SOB

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18
Q

What is class 3?

A

Resting may be symptom free but limitations due to SOB or feeling tired

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19
Q

What is class 4?

A

Symptoms at rest and severe symptoms with activity

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20
Q

What is the purpose for monitoring parameters?

A

Determine baseline, functional classification, and monitor severity, response to therapy, risk level, prognosis, progression

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21
Q

How would we monitor parameters?

A
  1. Pulmonary unction tests
  2. ABGs
  3. 6MWD
  4. Serial biomarkers (bnp, LFTs)
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22
Q

What are the non-pharms for PAH?

A
  1. Sodium restriction <2.4 g/day
  2. Influenza and pneumonia vaccinations
  3. Oxygen to maintain sats >90%: Particularly if PaO2 <60
  4. Cardiopulmonary rehab
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23
Q

What are the types of pharm therapies?

A
  1. Supportive therapy
  2. Targeted therapy
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24
Q

What are examples of supportive therapies?

A
  1. Warfarin
  2. Loop diuretics for volume overload
  3. Digoxin to improve HR and CO
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25
Characteristics of warfarin supportive therapy?
1. Controversial (varies by MD) 2. INR goal 1.5-2.5 3. May consider if on long-term IV prostaglandins due to risk of catheter thrombosis 4. NOT recommended if portal HTN or HIV is the etiology
26
What is the rationale behind warfarin?
HF, immobility, thrombotic changes in pulmonary microcirculation
27
Characteristics of digoxin supportive therapy?
1. Adjunct with diuretics in R HF 2. Arrhythmias 3. Goal level 0.5-0.8 ng/mL
28
What are the classes of targeted therapy?
1. Prostacyclin Analogues and Agonists 2. Endothelin Receptor Antagonists 3. Phosphodiesterase-5 Inhibitors 4. Soluble Guanylate Cyclase Inhibitors 5. (supplement endogenous vasodilators, inhibit endogenous vasoconstrictors, reduce endothelial platelet interactions)
29
What is the purpose for targeted therapy? What do they include?
Addresses endothelial abnormalities seen in PH 1. Endogenous vasodilators 2. Inhibitors of vasoconstriction 3. Reducers of endothelial platelet interaction and thrombosis
30
What are loop diuretic used for?
Volume overload
31
What are therapeutic pathways affected by PAH?
1. Prostacyclin 2. Endothelian 3. Nitric oxide 4. guanylyl cyclase pathway
32
Mechanism of prostacyclin pathway?
33
Mechanism of endothelium pathway?
34
Mechanism of nitric oxide pathway?
35
Mechanism of guanylyl cyclase pathway?
36
What is the purpose for vasoreactivity testing?
Determine if patient will respond to treatment with calcium channel blockers
37
How do you administer vasoreactivity testing? Responders? Nonresponders?
Administer short acting VDs Responders: mPAP falls by at least 10 mm Hg to absolute value <40 mm Hg (treatable with CCB) Non: must treat with targeted therapies
38
What drugs are used for the vasoreactivity test?
1. inhaled NO 2. IV epoprostenol 3. IV adenosine
39
What are the preferred drugs for PAH? What class are they?
DHP (amlodipine and nifedipine)
40
What are the disadvantages of diltiazem? CIs?
1. Can use with concomitant tachycardia 2. Verapamil not recommended due to higher negative inotropic effects 3. Avoid all non-DHPs if LV systolic dysfunction present
41
What are the doses of amlodipine? Diltiazem? Nifedipine?
Amlodipine: 20-30 mg/d Diltiazem: 240-720 mg/d Nifedipine: 120-140 mg/d
42
What is the most common ADR for CCB?
Peripheral edema
43
What happens is CCBs stop working for PAH?
DC and switch to another agent Can add on another drug to enhance its effects
44
Contraindications of CCBs?
1. if RV dysfunction, reduced CO, or FC IV symptoms 2. if vasoreactivity testing not performed 3. Increase morbidity
45
Epoprostenol
Flolan, Veletri Class: III-IV Routes: IV
46
Treprostinil
Remodulin Class II-IV: IV, SC Class II-III: PO Class III: Inhaled
47
Iloprost
Ventavis Class: III-IV Form: Inhaled
48
Dosing of Selexipag?
Start with 200 mcg po BID; increase by 200 mcg BID weekly; max 1600 mcg BID
49
Effects of prostacyclin analogues?
vasodilations and platelet inhibiton 2. ↓ PGI2 synthase and ↓ excretion of PGI2 metabolites
50
Effects of prostacyclin analogues?
vasodilations and platelet inhibiton 2. ↓ PGI2 synthase and ↓ excretion of PGI2 metabolites
50
Advantages of inhaled prostacyclin analogues?
selective pulmonary vasodilation with fewer systemic effects
51
Class warnings with prostacyclin analogues?
Rebound PH with abrupt discontinuation, Increased risk of bleeding, CYP interactions
51
Class warnings with prostacyclin analogues?
Rebound PH with abrupt discontinuation, Increased risk of bleeding, CYP interactions
51
ADRs with prostacyclin analogues? Inhalation? Oral?
Flushing, HA, N/V/D, jaw pain, thrombocytopenia, hypotension Inh: cough, throat irritation, bronchospasm Oral: abdominal discomfort
51
Selexipag
Uptravi Class II-III ADRs: Anemia, hyperthyroidism Interruptions >3 days requires retitration
52
Endothelin receptor antagonist MOA? ADRs? BBW? Monitoring?
Prevents vasoconstriction HA, flushing, hypotension, increased LFTs, anemia, edema Teratogenicity (Greater dose=greater improvement) Monitoring: CBC, LFTs, bilirubin, pregnancy test
53
ERA types?
Bosentan Macitentan Ambrisentan
54
Bosentan
Tracleer Class II-IV BBW: hepatotoxicity CIs: glyburide or cyclosporine DDIs: CYP3A4 an 2C9 inhibitors/inducers
55
Macitentan
Opsumit Class II-IV DDIs: CYP3A4 an 2C19 inhibitors/inducers
56
Ambrisentan
Letairis Class II-III CIs: Idiopathic pulmonary fibrosis DIs: Cyp3A4, CYP2C19, Pgp
57
PDE5i MOA? CIs? Warnings? ADRs? DDIs?
Relaxation and vasodialtion CI: Nitrates, riociguat Warnings: hearing loss, vision loss, priapism, hypotension ADRs: HA, flushing, epistaxis, dyspepsia, diarrhea, myalgia DDIs: nitrates, CYP3A4 drugs, ED drugs
58
Sildenafil
Revatio Forms: PO, IV Class: II-III CIs: nitrates riociguat
59
Tadalafil
Adcirca Forms: PO Class: II-III CIs: nitrates riociguat
60
sGCS example?
Riociguat (Adempas)
61
Riociguat dosing
Adempas Dosing: Start with 0.5-1 mg TID; increase Q2 weeks by 0.5 mg TID if SBP >95 Max dose 2.5 mg TID with higher doses used in smokers
62
Riociguat
Adempas BBW: teratogenicity CI: pregnancy, nitrates, PDE5i Warnings: Hypotension, bleeding ADRs: HA, hypotension, hemoptysis, dizziness, dyspepsia, N/V/D, anemia DDIs: smoking, antacids, CYP3A4, 2C8, Pap drugs
63
How does Adempas differ from other PAH meds?
Only drug approved for Group 4 PH (CTEPH) with residual CTEPH after surgical treatment or inoperable CTEPH
64
What are PAH goals of therapy?
1. improve exercise tolerance 2. Improve symptoms 3. Improve QOL 4. Prevent progression 5. Improve survival 6. Preserve RV size and function 7. Normalize bnp
65
How do you improve exercise tolerance?
1. Preserve 6MWD to 380 m or more 2. Cardiopulmonary exercise testing goals: peak O2 consumption >15 ml/kg/min and ventilator equivalent for CO2 <45 L/min
66
How do you improve symptoms?
Achieve and maintain FC I or II
67
What is PAH therapeutic selection according to CHEST?
Severity should be evaluated using a combination of WHO FC
68
Med determination algorithm?
Therapeutics I
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