Managment ypertensionPulmonary H
Pulmonary hypertension (PH) is a disease characterized by elevated pulmonary artery
pressure (mean pulmonary artery pressure ≥20 mmHg at rest with a pulmonary vascular
resistance ≥3 Wood units).
Risk factor:
Drug- and toxin like appetite suppressants, toxic rapeseed oil, and benfluorex
and possibly cocaine, phenylpropanolamine, St. John's Wort, dasatinib, and
interferon.
Heart failure (preserved LVEF or reduced LVEF)
Restrictive lung disease Obstructive lung disease
Hypoxia without lung disease
Developmental lung disorders
Chronic thromboembolic PH
Sign and Symptoms:
Dyspnea and fatigue
●Symptoms of right ventricular (RV) failure like
•Exertional chest pain
•Exertional syncope
•Weight gain from edema
•Anorexia and/or abdominal pain and swelling.
•exertion intolerance
Diagnostic tests:
Echocardiography
Doppler echocardiography
pulmonary function testing: Full PFTs (spirometry, lung volumes, diffusing capacity)
Chest radiography
Arterial blood oxygenation
Treatment
are to alleviate symptoms, improve the quality of life, The goals of treatment
slow the progression of the disease, and improve survival
Nonpharmacologic Therapy:
Oxygen therapy: Continuous oxygen administration remains the cornerstone of
therapy in patients with group 3 PH Oxygen should be considered for all patients with
PH plus hypoxemia, the goal of oxygen therapy to maintain the O2 sat above 90 % at
rest.
Vaccinations: Pulmonary hypertension is considered a chronic disease and as such,
patients should be immunized with all age-appropriate as well as influenza and
pneumococcal pneumonia vaccines.
Exercise, training was consistently associated with improved exercise capacity,
muscular function, quality of life, and possibly right ventricular function and
pulmonary hemodynamics, resulted in improved exercise capacity, and health-related
quality of life
Pharmacologic Therapy:
PRIMARY THERAPY FOR PH
Primary therapy refers to treatment that is directed at the underlying cause of the PH.
It is warranted in nearly all patients with PH. The disease severity should be
reassessed following primary therapy, in order to determine whether advanced
therapy is indicated.
Group 1 PAH: Patients with group 1 pulmonary arterial hypertension (PAH):
There are no effective primary therapies for most types of group 1 PAH. As a result,
PH-specific therapy is often needed
Group 2 PH: Patients with group 2 PH have PH secondary to left heart disease with
chronic left atrial and pulmonary venous hypertension:
rimary therapy for group 2 PH consists of treatment of the underlying heart disease
Group 3 PH: Patients with group 3 PH have PH secondary to various causes of
hypoxemia:
Primary therapy for group 3 PH consists of treatment of the underlying cause of
hypoxemia and correction of the hypoxemia with supplemental oxygen
Group 4 PH: Patients with group 4 PH have PH due to thromboembolic or other
occlusion of the proximal or distal pulmonary vasculature:
Anticoagulation is primary medical therapy for patients with group 4 PH. The value
of anticoagulant therapy for group 4 PH is an extrapolation of the clinical evidence
that anticoagulation prevents recurrent pulmonary embolism. Data suggesting that
anticoagulation is beneficial in patients with group 4 PH are lacking.
Surgical thromboendarterectomy is primary surgical therapy for selected patients with
thromboembolic obstruction of the proximal pulmonary arteries . Prior to proceeding
with this invasive approach, a three-month period of anticoagulation is required and
patients must remain severely incapacitated due to PH
Balloon angioplasty of the pulmonary artery is also a consideration in patients who
are not suitable candidates for surgery.
Group 5 PH: Group 5 PH includes PH with unclear multifactorial mechanisms.
1-Diuretics
Patients with fluid retention from PH-related right ventricle failure (RV) may benefit
from diuretics. Diuretics diminish hepatic congestion, peripheral edema, and pleural
effusions and may be of particular benefit in those in whom interventricular sepal
deviation from elevated RV pressure impairs left ventricle output.
However, diuretics should be administered with caution. Since patients with PH are
pre-load dependent, over-diuresis may result in under-filling of the RV, and a decline
in RV stroke volume, thereby reducing left ventricle (LV) stroke volume resulting in
systemic hypotension and sometimes shock. In addition, diuretics can be associated
with arrhythmias induced by hypokalemia, and metabolic alkalosis (which can
depress ventilation).
Most diuretic is administered orally in the chronic setting. However, intravenous
diuresis may be more effective in the acute setting, when it can be given as a bolus
dose or a continuous infusion (which may be better tolerated hemodynamically in
those with borderline blood pressure).
Occasionally, the increased right ventricular pressure is so severe that diuretics are
ineffective; in such cases, ultrafiltration may be beneficial.
2-Oxygen therapy:
Continuous oxygen administration remains the cornerstone of therapy in patients with
group 3 PH Oxygen is generally administered at 1 to 4 L/min via nasal prongs and
adjusted to maintain the oxygen saturation above 90 percent at rest and, if possible,
with exercise and sleep
3-Anticoagulation:
Anticoagulation is indicated in patients with group 4 PH and not typically
administered to those with group 2, 3, or 5. However, anticoagulation in patients with
group 1 PAH is controversial; in general anticoagulation has fallen out of favor in this
population and we suggest that anticoagulant therapy be administered on a case-by-
case basis according to the clinician's assessment of the risks and benefits
.Limited experience was with direct oral anticoagulants (eg, direct thrombin or factor
Xa inhibitors) makes warfarin the anticoagulant of choice, with a therapeutic goal of
an international normalized ratio (INR) of approximately 2.0. Many centers in the US
target a range of 1.5 to 2.5 with no bridging for temporary interruptions. The risk of
bleeding on anticoagulation (warfarin) may differ among patients with different types
of PH.
Patients with PH frequently have other risk factors for thromboembolism (eg, atrial
fibrillation, severe left heart failure) that may warrant anticoagulation.
Anticoagulation for these conditions should be assessed independently
4-Digoxin:
Digoxin therapy has been shown to have both beneficial effects and drawbacks:
Digoxin improves the left ventricular EF of patients with group 3 PH due to COPD
and biventricular failure However, these patients may be more sensitive than most
patients to digitalis toxicity and require close monitoring.
Digoxin helps control the heart rate of patients who have supraventricular
tachycardias associated with right ventricular dysfunction Verapamil is preferred for
multifocal atrial tachycardia, unless there is concurrent left ventricular failure. No
data are available on the long-term effects of digoxin in patients with group 1 PAH.
5- Exercise
6- Vaccinations
SPECIFIC THERAPY-PULMONARY HYPERTENSION
specific therapy is directed at the pulmonary -Pulmonary hypertension (PH)
targeted therapy), rather than the underlying cause of the -hypertension (PH) itself (PH
PH.
specific therapy should not be administered unless a diagnostic right heart -PH
ation (RHC) and extensive investigations for the etiology of PH have been catheteriz
performed. Additionally, most patients with group 1 PAH, in particular, those with
induced PAH, should also undergo -idiopathic PAH, heritable PAH, and anorexigen
ng during RHC which facilitates agent selection vasoreactivity testi
specific therapy is widely accepted for many patients with group 1 pulmonary -PH
-by-arterial hypertension (PAH). In contrast, it should only be administered on a case
group 4 PH, or group 5 PH, after carefully case basis for patients with group 3 PH,
weighing the risks versus the benefits. Advanced therapy should NOT be
administered to most patients with group 2 PH.
After initiating therapy, most patients are followed up within four to six weeks to
he clinical and hemodynamic response. Patients with refractory PAH may evaluate t
require alternate or combination therapy
For those who are refractory to all medical interventions, lung transplantation or
tionscreation of a right to left shunt by atrial septostomy are op
Some patients who are vasoreactive and receive CCB : Calcium channel blockers-1
can achieve prolonged survival, sustained diltiazem or Amlodipinetherapy with a
rovement.functional improvement, and hemodynamic imp
-CCB therapy can be initiated with either long
then increased to the mg/day), (120 diltiazem or mg/day) (30 nifedipine acting
maximal tolerated dose.
acting nifedipine should NOT be used.-Short
Prostacyclin pathway agonists: -2
hemodynamic ) improves 2(prostacyclin; PGI epoprostenol Intravenous Epoprostenol:
parameters, functional capacity, and survival in patients with IPAH
continuously through a permanently implanted central venous catheter Delivered
per min ng/kg using a portable infusion pump. It is usually initiated at doses of 1 to 2
per min every one to two days as tolerated. ng/kg eased by 1 to 2and incr
can be given intravenously or subcutaneously or inhaledTreprostinil
: Inhaled iloprost has theoretical advantages in targeting the lung vasculature Iloprost
administration the main disadvantage is the need for and does not require intravenous
frequent administration (six to nine times per day)
prostanoid prostacyclin receptor (IP receptor) -is an oral selective non exipagSel
n of the pulmonary vascular bed.agonist that results in vasodilatio
3- Endothelin receptor antagonists:
There are two receptors (endothelin receptor A and B) that are targeted by endothelin
receptor antagonists (ERAs). ERAs that have been tested in clinical trials include:
bosentan and macitentan –Nonselective dual action receptor antagonists
ambrisentan and –Selective receptor antagonists of endothelin receptor A
.sitaxsentan
4- Nitric oxide-cyclic guanosine monophosphate enhancers:
PDE5 inhibitors: Sildenafil, tadalafil, and vardenafil are orally administered cyclic
GMP phosphodiesterase type 5 (PDE5) inhibitors that prolong the vasodilatory effect
of nitric oxide that improves pulmonary hemodynamics and exercise capacity in
patients with group 1 PAH.
sGC to ) increase the sensitivity ofRiociguat( Guanylate cyclase stimulantSoluble stimulate the receptor to mimic and directly endogenous nitric oxide, a pulmonary vasodilator
the action of NO.
* Refer to individual Lexicomp drug monographs included with UpToDate.
¶Choice of calcium channel blocker is based upon the patient's heart rate. Refer to text.
specific -best approach to selecting an agent for PHThere is no single Agent selection
therapy.
to choose an agent based on multiple factors including: WHO functional class, right
ventricular function, hemodynamics, vasoreactivity test, and patient characteristics
and preferences.
vasoreactivity test: administration of a short-acting vasodilator followed by
The test is considered . measurement of the hemodynamic response using an RHC.positive or negative
Treatment of pulmonary arterial hypertension algorithm
Organization; IV: intravenous; SC: subcutaneous; INH: inhaled.WHO: World Health
5 inhibitor combination is preferred by some experts. Combining -phosphodiesterase-* Endothelin receptor antagonist
ould be avoided due to the high risk of 5 inhibitors and guanylate cyclase stimulants (riociguat) sh-phosphodiesterase
hypotension.
¶ Options for agents include ambrisentan, bosentan, macitentan, sildenafil, tadalafil, or riociguat. Riociguat is best
studied in patients with chronic thromboembolic pulmonary hypertension.
ts are not approved for this use by regulatory agencies.Δ These agen
5 inhibitor-Some experts use initial combination therapy with a prostanoid and a phosphodiesterase ◊
FOLLOW-UP Patients should be seen every three months (or more frequently) if they are receiving
parenteral or combination therapy. The same is true of patients who have advanced
symptoms, right heart failure, or advanced hemodynamic abnormalities. Less ill
patients should be seen every three to six months.
The frequency of right heart catheterization (RHC) is made on a case-by-case basis. It
is common to repeat a RHC early after the initiation of therapy (3, 6 or 12 months),
when the patient deteriorates, and when combination therapy is initiated
SPECIAL POPULATIONS
Pregnancy Endothelin receptor antagonists (eg, bosentan) and guanylate cyclase
stimulants (riociguat) are absolutely contraindicated in pregnancy (FDA category X)
and in women who may become pregnant. A negative pregnancy test is required prior
to treatment, monthly during treatment, and at one month after discontinuation of
treatment. most women who are pregnant and have pulmonary arterial hypertension
(PAH) should be treated with a prostanoid (functional class III, IV), usually
epoprostenol. Consultation with an expert is warranted in these women to prevent
adverse events (eg, fetal hypoxia, acute cardiovascular collapse).
For women of childbearing age with known PAH, pregnancy should be avoided due
to the risk of worsening pulmonary vascular hemodynamics. In addition, estrogen-
containing contraceptives should be avoided. Surgical (patient or partner) methods of
contraception are preferred but dual barrier contraception (eg, progesterone implanted
intrauterine device) is an acceptable alternative
Altitude and air travel Patients with exposure to high altitude or patients planning
air travel should continue their routine PH medications. Supplemental oxygen (2 to 4
L per minute) can also be administered to maintain oxygen saturations above 90
percent.
Surgical risk Patients with pulmonary hypertension, in particular those with
pulmonary arterial hypertension (PAH) and significant right ventricular dysfunction,
are at high risk of complications and death when undergoing anesthesia, mechanical
ventilation, and major surgery The perioperative management can be complicated by
hemodynamic instability resulting in severe hypoxemia, acute right heart
failure/circulatory collapse and death In addition, medication-related complications
can increase surgical risk of bleeding (eg, anticoagulants and prostanoids)
Surgical interventions.
RIGHT TO LEFT SHUNT
Creation of a right to left shunt is not routinely recommended as therapy for the
treatment of pulmonary arterial hypertension (PAH). However, in adults with severe
symptomatic PAH, such a procedure can be considered
TRANSPLANTATION
Transplantation has been performed in patients with idiopathic pulmonary arterial
hypertension (IPAH) and is considered by some to be the final effective treatment for
selected patients with IPAH. Bilateral lung or heart-lung transplantation is the
procedure of choice.
Guidelines for when to refer a patient for transplan :
1-Rapidly progressive disease
2-Use of parenteral targeted pulmonary arterial hypertension (PAH) therapy
regardless of symptoms or New York Heart Association (NYHA) functional class
3-Known or suspected pulmonary veno-occlusive disease (PVOD) or pulmonary
capillary hemangiomatosis
eference:R
Hopkins, W. , Rubin ,L. (2019). Treatment of pulmonary hypertension in adults. In
G. Finlay (Ed.) ,UpToDate .Retrieved April 2,2019,from
adults-in-hypertension-pulmonary-of-www.uptodate.com/contents/treatment
Done by Pharm D Students: Waad mahajneh
Dania habashneh
Fairouz rayyashi
Supervised by: Dr. Eshraq Al-Abweeny
