Pulmonary Hypertension Lehne Ch 107 Pulmonary Hypertension mean

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Pulmonary Hypertension Lehne Ch. 107

Pulmonary Hypertension Lehne Ch. 107

Pulmonary Hypertension • mean pulmonary artery pressure: >/= 25 mm. Hg at rest >/=

Pulmonary Hypertension • mean pulmonary artery pressure: >/= 25 mm. Hg at rest >/= 30 during exercise • can be primary (within the pulmonary arterial system) or secondary (within the pulmonary venous and capillary system) • Pathophysiology: – Vasoconstriction, proliferation of endothelial cells and pulmonary thrombosis within the pulmonary vascular system – Increased pulmonary vascular resistance – Endothelin-1 (PAH) • Diagnostic Tools: – Echocardiogram – Right Heart Catheterization

 • Clinical Manifestations: – Initially asymptomatic – 1 st signs: • Exertional dyspnea

• Clinical Manifestations: – Initially asymptomatic – 1 st signs: • Exertional dyspnea and exercise intolerance – Later signs: • • Progressive dyspnea Frequent episodes of syncope Peripheral edema Angina

1) Group 1 – PAH 2) Group 2 – PH due to left heart

1) Group 1 – PAH 2) Group 2 – PH due to left heart disease 3) Group 3 – PH due to chronic lung disease and/or hypoxemia 4) Group 4 – Chronic thromboembolic pulmonary hypertension (CTEPH) 5) Group 5 – PH due to unclear multifactorial mechanisms

Pulmonary Artery Hypertension • Idiopathic • Heritable – BMRP 2 • Drug/Toxin Induced –

Pulmonary Artery Hypertension • Idiopathic • Heritable – BMRP 2 • Drug/Toxin Induced – Appetite suppressants, amphetamines • Individuals w/… – HIV – Portal Hypertension – Connective Tissue Disorders – Congenital Heart Defects

Incidence Rates • Systemic Sclerosis (PAH) – 10 -15% • HIV (PAH) – 0.

Incidence Rates • Systemic Sclerosis (PAH) – 10 -15% • HIV (PAH) – 0. 5% • Portal Hypertension (PAH) – 1 -10% • Congenital Heart Disease (PAH) – 10 -30% • COPD (PH) – Up to 90% in advanced stages • Obstructive Sleep Apnea (PH) – 15 -20% • Left Heart Disease (PH) – Up to 100% in advanced stages

Primary Pulmonary Artery Hypertension • Progressive • Poor Prognosis • Requires Advanced Pharmacological Treatment

Primary Pulmonary Artery Hypertension • Progressive • Poor Prognosis • Requires Advanced Pharmacological Treatment – Prostacyclin Analogs, Endothelin-1 Receptor Antagonists, Phosphodiesterase Type 5 Inhibitors • Additional Treatments (symptom management) – Oxygen – Diuretics – Digoxin – Exercise conditioning

 • Treatment for Secondary PH: – Treat the underlying cause • • •

• Treatment for Secondary PH: – Treat the underlying cause • • • Diuretics Oxygen Anticoagulants Exercise conditioning Embolectomy

Prostacyclin Analogs • Prostacyclin – Causes venous relaxation – Suppresses smooth muscle growth –

Prostacyclin Analogs • Prostacyclin – Causes venous relaxation – Suppresses smooth muscle growth – Inhibits platelet aggregation

Epoprostenol • Oldest in drug category • Short half-life • Must be kept cold

Epoprostenol • Oldest in drug category • Short half-life • Must be kept cold and given as a continuous infusion • Adverse Effects: – Flushing – Headache – N/V – Catheter related infections

Treprostinil • Parental and Inhalation administration routes • Longer half-life; temperature stability • SQ

Treprostinil • Parental and Inhalation administration routes • Longer half-life; temperature stability • SQ infusion • Adverse Effects: – Parental • Injection pain, swelling, erythema • Jaw pain • GI distess – Inhalation • • Cough Throat irritation Headache Flushing

Iloprost • Oral inhalation • Adverse Effects: – Cough – Headache – Flushing –

Iloprost • Oral inhalation • Adverse Effects: – Cough – Headache – Flushing – Jaw pain – Hypotension

Endothelin-1 Receptor Agonists • Endothelin – Promotes vasoconstriction – Promotes proliferation of endothelial cells

Endothelin-1 Receptor Agonists • Endothelin – Promotes vasoconstriction – Promotes proliferation of endothelial cells

Bosentan • Non-specific blocking of ET(A) and ET(B) receptors • Oral administration w or

Bosentan • Non-specific blocking of ET(A) and ET(B) receptors • Oral administration w or w/o food • Adverse Effects: – Hepatotoxicity – Pregnancy Category X – Headache – Flushing – Anemia – Drug Interactions: • Warfarin, oral contraceptives, cyclosporine, glyburide

Ambrisentan • Same as bosenten except… – 1) Does not cause hepatoxicity – 2)

Ambrisentan • Same as bosenten except… – 1) Does not cause hepatoxicity – 2) Only blocks ET(A) receptors

Phosphodiesterase Type 5 Inhibitors Mechanism: -cyclic GMP promotes vasodilation -PDE 5 inhibits c. GMP

Phosphodiesterase Type 5 Inhibitors Mechanism: -cyclic GMP promotes vasodilation -PDE 5 inhibits c. GMP -sildenafil or tadalafil inhibits PDE 5 (Revatio/Viagra) sildenafil (Cialis) tadalafil PO/IV PO Adverse Effects: -flushing, headache, hypotension (nitro) -priapism -dyspepsia -visual disturbances -muscle pain