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Therapeutics Pulmonary Fan
Final PAH
28
Business
Graduate
04/28/2010

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Cards

Term
WHO Classification of PH
Definition
  • Idiopathic PAH
  • Familial PAH
  • Secondary PAH (connective tissue, congenital, portal HTN, portal HTN, HIV, Drugs/toxins)
  • Pulmonary HTN with left heart disease, lung diseases, chronic thrombotic/embolic diseases
Term
Chemical Mediators involved in the pathophysiology of PAH
Definition

Prostacyclin

NO

Endothelin-1

Thromboxane

Von Willebrand

Autoantibodies

Pro-Inflammatory Cytokines

Term
Clinical Manifestations of PAH
Definition

Symptoms

  • Dyspnea
  • Fatigue
  • Exercise intolerance
  • Weakness
  • Chest pain
  • Syncope

Signs

  • Pulmonary regurgitation
  • Tricuspid regurgitation
  • JVD
  • HJR
  • Peripheral edema
Term
Diagnostic Criteria for PAH
Definition

Mean Pulmonary Artery Pressure (mPAP) > 25 mmHg at rest

+

Pulmonary Capillary Wedge Pressure (PCWP) < 15 mmHg

+

Pulmonary Vascular Resistance (PVR) > 3 wood units

Term
Assessment of Severity for PAH
Definition

WHO Classification

Class I -- No limitations of usual physical activity

Class II -- Mild limitation; strenuous normal daily activity causes increased symptoms

Class III -- Marked limitation; less than normal physical activity increases symptoms

Class IV -- Unable to perform any physical activity; symptoms at rest

 

6-Minute Walk Test

 

Hemodynamic Parameters (mPAP, PVR, CO)

 

Survival

Term
Non-Pharmacological Supportive Therapy for PAH
Definition
  • Na+ and fluid restriction
  • Maintain normal Hemoglobin/Hematocrit
  • Cardiopulmonary rehabilitation
  • Immunization
  • Avoid air travel and high altitude
  • Avoid pregnancy
  • Support group and counseling
Term
Pharmacological Supportive Therapy for PAH
Definition
  • Oxygen supplementation
  • Diuretics (loop, metolazone, K-sparing diuretics)
  • Warfarin (INR 1.5-2.5)
  • Digoxin (usually in patients with comorbidities -- Afib, right sided heart failure)
Term
Vascular-Targeted Treatments
Definition
  • Calcium Channel Blockers
  • Prostacyclin analogs
  • Endothelin Receptor Antagonists
  • Phosphodiesterase-5 Inhibitors
  • Combination therapy
Term
When can Calcium Channel Blockers be used?
Definition
  • Must show vasoreactivity in response to vasodilator testing
  • Response is defined as decreased mPAP by > 10 mmHg to a value of < 40 mmHg without decrease in CO
Term
When a patient is on Calcium Channel Blockers and he/she has not improved, what should you do?
Definition
  • If no improvements to Class I or Class II after 3 months, consider additional or alternative PAH therapy
Term
What Calcium Channel Blockers can be used in PAH?
Definition

Nifedipine

Amlodipine

Diltiazem

Term
Which Non-Dihydropyridine Calcium Channel Blockers can be used in PAH?
Definition

Diltiazem

 

Because of Verapamil's negative inotropy effects, NOT recommended for PAH

Term
Prostacyclin Analogs: MOA
Definition
Vasodilation, inhibition of platelet aggregation, anti-proliferative
Term
Prostacyclin Analogs: Available Agents
Definition
  • Epoprostenol
  • Treprostinil
  • Iloprost
Term
Epoprostenol: Administration, Clinical Pearls, and Place in Therapy
Definition
  • Must be given as continuous IV
  • Improves 6-MWT, hemodynamics, QOL, and survival
  • Approved for Classes III and IV
  • First line for Class IV
Term
Treprostinil: Administration, Clinical Pearls, and Place in Therapy
Definition
  • May be given SC, IV, or Inhaled
  • Improves 6-MWT and hemodynamics
  • Approved for Classes II, III, and IV
  • First line for Class IV
Term
Iloprost: Administration, Clinical Pearls, and Place in Therapy
Definition
  • Inhaled frequently
  • Improves 6-MWT and WHO-FC
  • Approved for Classes III or IV
Term
Advantages/Disadvantages of Epoprostenol
Definition

Adv

 

Most data

Effective in unstable and severe PAH

 

Disadv

 

Complicated drug preparation and delivery

Risk for line infections and sepsis

Term
Advantages/Disadvantages of Treprostinil
Definition

Adv

 

Longer half-life

Easier administration

 

Disadv

 

Infusion site pain limits use of effective dose

Term
Advantages/Disadvantages of Iloprost
Definition

Adv

 

Inhaled route

 

Disadv

 

Frequent inhalations

Term
Endothelin Antagonists: MOA
Definition
Inhibits endothelin-1 (ET-1) --> vasodilation
Term
Endothelin Antagonists: Available Agents
Definition
  • Bosentan
  • Ambrisentan
Term
Bosentan: Clinical Pearls, Place in Therapy, and Monitoring
Definition
  • Dual receptor antagonist (ETA >> ETB)
  • Improves 6-MWT, WHO-FC, hemodynamics, and time to progression
  • Approved for Classes II-IV
  • First line for II and III
  • Monthly LFT and monthly pregnancy test required
Term
Ambrisentan: Clinical Pearls, Approved Classes, and Monitoring
Definition
  • Selective ETA receptor antagonist
  • Improves 6-MWT, WHO-FC, hemodynamics, and time to progression
  • Approved for Classes II or III
  • First line for II and III
  • Monthly LFT and monthly pregnancy test required
Term
Phosphodiesterase Inhibitors: MOA
Definition
Inhibit PDE-5 --> inhibit breakdown of cGMP --> increased cGMP --> vasodilation
Term
Phosphodiesterase Inhibitors: Available Agents
Definition

Sildenafil

Tadalafil

Term
Phosphodiesterase Inhibitors: Place in therapy
Definition
  • First line as monotherapy for Classes II and III
  • Add-on therapy for Class IV
Term
Surgical Interventions for PAH
Definition

Indicated only in patients who failed pharmacologic therapy

  • Balloon Atrial Septostomy
  • Pulmonary Thromboendarterectomy
  • Lung or heart/lung transplant should be evaluated at the time of IV prostacyclin analog
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