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CardioPulm II > Pulmonary HTN > Flashcards

Pulmonary HTN Flashcards

1
Q

Definition of pulmonary arterial hypertension

A

Pulmonary Hypertension (PH): mean pulmonary artery pressure > 25 mmHg (leads to Right HF)

–> Diagnosed by invasive monitoring with a pulmonary artery catheter

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2
Q

Normal Pathophysiology:

A

High flow, low-pressure circulation

Has less resistance as compared to systemic circulation

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3
Q

Normal Pathophysiology:

Mediators

A

Endothelin- Vasoconstrictor; stimulate smooth muscle growth

o Prostacyclin- vasodilator; decrease platelet activation

o Nitric oxide-Vasodilator

o Serotonin- Vasoconstrictor

o Other: Thromboxiane: promotes clotting and increases cell proliferiation

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4
Q

PH Pathophysiology:

A

Imbalance of vasoconstrictors and vasodilators

Increased resistance:
->Thickening of the smooth muscle cells

->Growth of endothelial cells due to
cellular proliferation

->Thrombosis block the lumen of the
vessel

*Leads to enlarged right ventricle and HF

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5
Q

WHO

Causes/ Classification of pulmonary hypertension
Group I: Pulmonary arterial hypertension

A

Idiopathic

Familial

Related to HIV, drugs, congenital,
connective tissue disease

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6
Q

Causes/ Classification of pulmonary hypertension

Group II

A

Pulmonary hypertension with left heart disease

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7
Q

Causes/ Classification of pulmonary hypertension

Group III

A

Associated with hypoxemia

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8
Q

Causes/ Classification of pulmonary hypertension

Group IV

A

Due to chronic thromboembolic

For those who constantly have have pulmonary embolism.

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9
Q

Causes/ Classification of pulmonary hypertension

Group V

A

Miscellaneous

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10
Q

Group I: Pulmonary arterial hypertension

Drug Induced:

A

Definite: aminorex, fenfluramine, dexfenfluramine, phentermine (diet pills)

Possible: Amphetamines, cocaine, chemotherapy

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11
Q

Symptoms and Functional Classification

Common symptoms

A

Exertional dyspenea, Fatigue/weakness, Leg swelling, Angina, syncope

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12
Q

Symptoms and Functional Classification

Progressing disease

A

Worsening dyspenea, Abdominal fullness, increased edema, Profound fatigue, Anorexia

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13
Q

Symptoms and Functional Classification

Advance disease

A

Tricuspid regurgitation, peripheral edema, Hypotension, cool extremities, Cyanosis

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14
Q

Functional Classification:

A

I: often Asymptomatic
II:Slight limitation
III:marked limitation with physical activity
IV: Symptoms at rest (late stage)

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15
Q

Non-Pharmacologic treatment

A

Avoid pregnancy + contraceptive (avoid hormone )

Excercise

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16
Q

Supportive therapy

A

• Prophylactic oral anticoagulants (goal INR 1.5-2.5)

o Idiopathic PAH/inherited PAH/due to anorexigens

  • Diuretics
  • Oxygen
  • Digoxin (target concentration 0.5-0.8ng/ml)
  • Vaccines
  • ->Influenza
  • ->Pneumococcal
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17
Q

Targeted therapy: List

A
  • Calcium channel blockers
  • Synthetic prostacyclin and prostacyclin analogs
  • Endothelin receptor antagonists
  • Phosphodiesterase inhibitors
  • Guanylate cyclase activator
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18
Q

Targeted therapy:

Calcium channel blockers

A

Nifedipine extended release (Procardia/ Adalat CC)
tablet

Diltiazem (Cardia XT, Cardizem CD, etc.) capsule-
Avoid diltiazem in patients with left ventricular systolic
dysfunction

Amlodipine (Norvasc) tablet

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19
Q

Targeted therapy: Prostacyclins

All dispensed from specialty pharmacies only (Accredo and Curascript)

A

Agents used:
Epoprostenol - IV continuous infusion

Treprostinil - IV, SC continuous infusion

Treprostinil - inhaled four times daily

Treprostinil ER - tablet 2-3 times daily

Iloprost -inhaled 6-9 times daily

20
Q

Targeted therapy:
Special

Epoprostenol - IV continuous infusion

A

IV epoprostenol considered the most effective therapy

21
Q

Targeted therapy:

Special

IV/SC formulations:

Epoprostenol - IV continuous infusion

Treprostinil - IV, SC continuous infusion

A

Mixed by the patient at home and administered
through a central line by a special IV/SC pump

NOT compatible with other medications

** Abrupt withdrawal or interruption of infusion may lead to rebound pulmonary hypertension and possibly death!**

22
Q

Targeted therapy:

Endothelin receptor antagonists (ERAs)

PO ONLY

A

Bosentan (Tracleer) oral tablet

Ambrisentan (Letairis) oral tablet

Macitentan (Opsumit) oral tablet

23
Q

Calcium channel blockers

MOA

A

vasodilation but sustained response is rare

24
Q

Calcium channel blockers

Major adverse effects/warnings:

A

Peripheral edema, headache, fatigue, constipation

25
Q

Calcium channel blockers

Drug interactions:

A

Known inhibitors of CYP 3A4: e.g. amiodarone, erythromycin, azole antifungals, HIV medications

Known inducers of CYP 3A4: e.g. rifampin, carbamazepine, phenytoin, St. John’s wort

Simvastatin: 10mg diltiazem, 20mg amlodipine

26
Q

Prostacyclins

MOA

A

Potent vasodilator that affects the pulmonary and
systemic circulations

Known to cause a decrease in platelet aggregation

27
Q

Prostacyclins

Major /most common adverse effects:

A

Flushing, jaw pain, severe headache, hypotension,
thrombocytopenia (ALL)

Pain at injection site- (treprostinil SC)

Infection with IV continuous infusion due to central
line - Epoprostenol and Treprostinil

Throat irritation, cough, hemoptysis (Iloprost and Treprostinil)

28
Q

Endothelin receptor antagonists (ERAs)

o Major/most common adverse effects:

A

Headache, flushing, peripheral edema, increase in

liver enzymes, reduced hemoglobin

29
Q

Endothelin receptor antagonists (ERAs)

Drug interactions:

A

Avoid with cyclosporine, glyburide, rivaroxaban and apixaban

Bosentan: metabolized by CYP2C9, 3A4, inducer of 2C9, 3A4

Ambrisentan & macitentan: substrate of 2C19, 3A4

p-glycoprotein (ambrisentan only)

Inducers of CYP 2C9 (e.g. carbamazepine, azole antifungals, phenytoin, rifampin)

Inhibitors of CYP 2C9 (e.g omeprazole, voriconazole) Substrates of CYP3A4 (with bosentain only)

Substrates of 2C9 (e.g. warfarin, tamoxifen, glyburide)
(with bosentan only)

Inhibitors of CYP 2C19 (e.g. cimetidine, efavirienz)
(with ambrisentan/macitentan only)

30
Q

Bosentan (Tracleer) oral tablet

A

! Substrates of CYP3A4 (with bosentain only)
Substrates of CYP3A4 (with bosentain only)
! Substrates of 2C9 (e.g. warfarin, tamoxifen, glyburide)
(with bosentan only)

Bosentan and macitentan blocks ETA and ETB
receptors

FDA requires LFT monitoring monthly (Bosentan
ONLY)

31
Q

Ambrisentan (Letairis) oral tablet

A

Inhibitors of CYP 2C19 (e.g. cimetidine, efavirienz)
(with ambrisentan/macitentan only)

Ambrisentan & macitentan: substrate of 2C19, 3A4, p-glycoprotein (ambrisentan only)

Ambrisentan blocks ETA receptors only

Ambrisentan can be initiated in patients that
experienced asymptomatic LFT elevations to bosentan

32
Q

Macitentan (Opsumit) oral tablet

A

macitentan: substrate of 2C19, 3A4

Inhibitors of CYP 2C19 (e.g. cimetidine, efavirienz)
(with ambrisentan/macitentan only)

Alternative if Bosentan elevates LFTs

33
Q

Endothelin receptor antagonists (ERAs)

Other important points:

A

Pregnancy category X: pregnancy test is required
prior to initiation of therapy and then monthly

Women of child-bearing age should use 2 forms of
contraception

LFT monitoring prior to starting therapy

FDA requires LFT monitoring monthly (Bosentan
ONLY)

Avoid in patient with pretreatment moderate to severe
hepatic disease

Treatment should be stopped in patients with elevated
LFTs with accompanying signs of liver failure OR
bilirubin levels ≥ 2 times upper limit of normal

Ambrisentan can be initiated in patients that
experienced asymptomatic LFT elevations to bosentan

34
Q

Endothelin receptor antagonists (ERAs)

MOA

A

Endothelin is a potent vasoconstrictor

ETA Receptors: activation facilitates vasoconstriction
and proliferation of vascular smooth muscle cells

ETB Receptors: involved in clearance of endothelin,
may also cause vasodilation

Bosentan and macitentan blocks ETA and ETB
receptors

Ambrisentan blocks ETA receptors only

35
Q

Phosphodiesterase inhibitors:

A

Sildenafil (Revatio) oral tablet, IV

Tadalafil (Adcirca) oral tablet

36
Q

Phosphodiesterase inhibitors:

MOA

A

Promotes accumulation of cGMP therefore enhancing nitric-oxide mediated vasodilation in the lung

37
Q

Phosphodiesterase inhibitors:

Major/common adverse effects:

A

Headache, flushing, hypotension, nose bleeds, visual

disturbances, myalgia/pain in arms/legs (Tadalafil

38
Q

Phosphodiesterase inhibitors:

Drug interactions:

A

Inhibitors of CYP 3A4
Inducers of CYP 3A4
Contraindicated with nitrates

39
Q

Tadalafil ORAL ONLY –DOSE ADJUSTMENTS?

A

Tadalafil: Dose adjustment in kidney and hepatic

impairment

40
Q

Soluble guanylate cyclase stimulator:

A

Riociguat (Adempas)

1st line for PH with Chronic Thromboemoblic disease (IV)

41
Q

Soluble guanylate cyclase stimulator:

Mechanism of action:

A

stimulates soluble guanylate cyclase leading to increase NO and increased cGMP leading to vasodilation

42
Q

Soluble guanylate cyclase stimulator:

Riociguat (Adempas)

Major/most common adverse effects:

A

Hypotension, palpations, peripheral edema, dyspepsia, dizziness, headache, bleeding

43
Q

Soluble guanylate cyclase stimulator:

Riociguat (Adempas)

Drug interactions:

A

Riociguat is a substrate of CYP2C8, 3A4 and p-
glycoprotein

Contraindicated with nitrates and PDE-5 inhibitors

Metabolism induced by cigarette smoking

44
Q

Soluble guanylate cyclase stimulator:

Riociguat (Adempas)

Other important points

A

Contraindicated in pregnancy

Indicated for WHO class I PAH

 1st drug indicated for chronic thromboembolic
pulmonary hypertension (WHO IV)
45
Q

Deciding on therapy

A

! Non-pharmacologic therapy (all patients)

! Start supportive therapy (if appropriate)

! All positive responders to vasodilator testing → start
calcium channel blocker

! All non-responders and patients without sustained
response to CCB/Class III/IV):

• Start therapy according to functional class (II-IV)

• Choice of therapy depends on route of
administration, adverse effects, patient
preference, and clinical judgment

• IV Epoprostenol should be first line in
functional class IV

• Combo therapy should be used for those who
do not improve or deteriorate on monotherapy (use 2 drugs from different classes)

CardioPulm II (11 decks)

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