Transcript File

PULMONARY
HYPERTENSION
INTRODUCTION
BRIEF HISTORY
WHAT IS PH?
WHAT CAUSES PH?
SIGNS AND SYMPTOMS
DIAGNOSIS OF PH
TREATMENT OF PH
INTRODUCTION
In the human body, there are two types of circulation that enable
distribution of blood throughout the body.
The portion that pumps oxygenated blood from the left side of the
heart via the left ventricle to all parts of the body is known as the
SYSTEMIC CIRCULATION.
On the other hand, the portion that pumps deoxygenated blood from
the right side of the heart via the right ventricle into the lungs to
obtain oxygen is referred to as the PULMONARY CIRCULATION.
INTRODUCTION
Millions of people are affected by a condition known as high
blood pressure (hypertension) whereby the blood travels through
the body’s arteries at a pressure higher than normal.
PULMONARY HYPERTENSION is a far less common type of
high blood pressure that affects specifically the arteries in the
lungs. Pressures in the lung arteries are normally significantly
lower than the pressures in the systemic circulation. Pulmonary
hypertension occurs when the pressure in the pulmonary
circulation becomes abnormally elevated. It is a serious condition
that becomes progressively worse and eventually proves fatal.
INTRODUCTION
An estimated of 500 – 1000 new cases are diagnosed annually.
There is an incidence of about 2-3 per million per year and a
prevalence of 15 per million.
This disease can occur in men, women and children of all ages.
However, it is most common in females between 20 and 40 years
old, with twice as many cases reported in women then men.
The condition is rare in children but is sometimes seen in infants
born with heart defects. Pulmonary hypertension may be a primary
or secondary cause of hypoxia in neonates.
H
The first reported case – 1891
• E. Romberg, German doctor
I
S
T
• published description of a patient who, at autopsy, showed
thickening of the pulmonary artery but no heart or lung disease
In 1951, 39 cases were reported by Dr. D.T. Dresdale in the
United States. The illness received its name.
O
R
Y
Between 1967 and 1973, a 10-fold increase in unexplained
pulmonary hypertension was reported in central Europe. The rise
was subsequently traced to aminorex fumarate, an amphetaminelike drug introduced in Europe in 1965 to control appetite. It was
later removed from the market.
WHAT IS
PULMONARY
HYPERTENSION?
Ordinarily, blood vessels in the lungs provide less resistance to blood
flow than blood vessels in the rest of the body do. Hence, blood
pressure is usually much lower in the lungs. While pressure in
general circulation is about 120/80 mm Hg, in the pulmonary arteries,
it is only around 25/15 mm Hg.
Mean (average) pulmonary artery pressure
= number between highest and lowest pressures
Normal
at rest : 14 mm Hg
Pulmonary hypertension
at rest : 25 mm Hg
during exercise : 30 mm Hg
Primary Pulmonary Hypertension
• no underlying cause for the high blood pressure in lungs
• likely to begin with spasm of the muscle layer in pulmonary arteries
• patients are rather sensitive to substances that cause blood vessels
to constrict
• may have an inherited predisposition for the disease
Secondary Pulmonary Hypertension
• results directly from another medical problem
• most probable from diseases that impedes flow of blood through
lungs or that causes periods of low oxygen in blood
• eg. Chronic Obstructive Pulmonary Disease, scleroderma, sleep
apnea, pulmonary fibrosis, lung diseases such as asbestosis
Classification
I. Classification of PH based on etiology
Classification…
Abnormally high BP in pulmonary arteries
Increased pressure damages large and small pulmonary arteries
Blood vessel walls thicken
Cannot transfer oxygen and carbon dioxide normally
Levels of oxygen in blood fall
Constriction of pulmonary arteries
Further increase in pressure in pulmonary circulation
Pulmonary Hypertension
right side of heart must work harder
cor pulmonale
push blood through
pulmonary arteries to
lungs
right ventricle thickens
and enlarges
Heart Failure
In some people, the bone marrow will produce more red blood cells to
compensate for less of oxygen in blood leading
Polycythemia
Extra RBCs cause the blood to become thicker and stickier, further increasing
the load on the heart
Pulmonary Embolism
Functional Classification
A. Class I- Patients with pulmonary hypertension but without resulting
limitation of physical activity. Ordinary physical activity does not
cause undue dyspnoea or fatigue, chest pain, or near syncope.
B. Class II- patients with pulmonary hypertension resulting in slight
limitation of physical activity. They are comfortable at rest. Ordinary
physical activity causes undue dyspnoea or fatigue, chest pain, or
near syncope.
C. Class III- patients with pulmonary hypertension resulting in marked.
Limitation of physical activity. They are comfortable at rest. Less
than ordinary activity causes undue dyspnoea, fatigue, and chest
pain or near syncope.
D. Class IV -patients with pulmonary hypertension with inability to carry
out any physical activity without symptoms. these patients manifest
signs of right heart failure. Dyspnoea and /or fatigue may be present
even at rest. Discomfort is increased by any physical activity
WHAT CAUSES
PULMONARY
HYPERTENSION?
Although the exact cause of primary pulmonary hypertension is
unknown, scientists believe that most people who develop the
disorder are especially sensitive to substances that cause blood
vessels to constrict.
Cocaine and fenfluramine (fen-phen), which was withdrawn from
the market in 1997, are two of the substances that may contribute
to PH in many people.
Other people with PH have an inherited predisposition for the
disease. In these people, PH is triggered by another medical
condition such as chronic liver disease (cirrhosis), AIDS, sickle
cell anemia, scleroderma and lupus.
Pulmonary hypertension resulting directly from another medical
problem is called secondary pulmonary hypertension. Medical
conditions that may lead to secondary PH include :
 blood clots in the lungs (pulmonary emboli)
 chronic obstructive pulmonary disease such as emphysema
 connective tissue disorders, such as scleroderma
 sleep apnea – upper airway obstructed during sleep
 congenital heart disease
 obesity with reduced ability to breathe (Pickwickian syndrome)
 neuromuscular diseases involving respiratory muscles
 HIV infection
 lung diseases such as pulmonary fibrosis (causes scarring in
the tissue between the lungs’ air sacs)
Left-sided heart failure
• heart’s left ventricle weakens and cannot pump out enough blood
• increase in pressure backs up through pulmonary veins to
arteries in lungs
High Altitude
• above altitude of 8000 feet - may develop PH
• low blood oxygen (hypoxemia)
• constricts small pulmonary arteries
• climb to high elevations without first becoming acclimated
• risk of pulmonary edema too – air sacs filled with fluid instead of
with air, always associated with PH
The overall rise in blood pressure in PH is the end result of a
process which begins with changes in the endothelial cells that line
the lungs’ arteries.
Changes → causes formation of extra tissue → blockage in vessels
Scarring (fibrosis) usually also occurs → arteries stiff and narrow
These causes increased resistance to blood flow which raises
pressure in the pulmonary arteries.
Less often, PH is caused by extensive loss of lung tissue from
surgery/trauma.
Injury to endothelial cells leads to overproduction of endothelin – key cause
of blood vessel scarring and spasm & to reduced production of nitric oxide
and prostacyclins – 2 key body chemicals which keep blood vessels relaxed
and open.
The ‘Two-Hit’ Hypothesis
According to the hypothesis, vascular abnormalities characteristic of PPH
are triggered by accumulation of genetic and/or environmental insults in a
susceptible individual. A combination of germline BMPR2 mutation (‘first
hit’) and the ingestion of appetite suppressants (‘second hit’) were used to
generate the clinical disease.
A genetic cause of the familial form of primary PH has been discovered. It is
caused by mutations in a gene called BMPR2, as used in the ‘Two-Hit’
Hypothesis.
BMPR2 encodes a receptor (transforming growth factor beta type II
receptor) that sits on the surface of cells and binds molecules of the TGFbeta superfamily.
Binding triggers conformational changes → series of biochemical reactions
↓
affect cell’s behaviour
The mutations block this process. Hence, this discovery provides means of
genetic diagnosis and a potential target for the therapy with familial and
possibly, sporadic primary pulmonary hypertension.
SIGNS AND
SYMPTOMS
Like other forms of high blood pressure (hypertension), the
signs and symptoms of pulmonary hypertension are subtle in
the early stages of the disease and may not be apparent for
months or even years. As the disease progresses, these signs
become more noticeable. Also, the symptoms of PH are often
hidden by the underlying condition causing the disease.
Symptoms, however, tend to vary from patient to patient.
The diagnosis of PH are often overlooked by physicians. It is
sufficiently common and of such high impact that all patients
with scleroderma should be screened for its presence on a
regular basis.
 shortness of breath (dyspnea)
Initially, only short of breath when exert oneself physically but
eventually may be short of breath most of the time, even when
at rest.
 fatigue or light-headed upon exertion
 dizziness or fainting spells (syncope)
 swelling (edema) in ankles, legs and eventually in
abdomen (ascites) – fluid leak out of veins and into tissues
 bluish colour to lips and skin (cyanosis)
 coughing (sometimes with blood) and wheezing
 distended neck veins
 enlarged liver
 racing pulse or heart palpitations
 angina-like chest pain
 feel weak – body tissues not receiving enough oxygen
 achy joints (often developed years before apparent onset of
disorder)
Signs and Symptoms in Children
The symptoms of PH for children are similar to that of an adult,
though children are more likely to experience tiredness, dizziness
and breathlessness and for many, fainting is common.
 fail to put on weight like a normal child
 slowed growth
Children tend to be diagnosed earlier than adults, but just like
adults, they are often misdiagnosed several times before a correct
diagnosis is made. The commonest misdiagnosis is asthma.
Untreated PH in children worsens quicker than the same condition
in adults. However, with treatment, children appear to have an
overall better prognosis than adults.
DIAGNOSIS OF PH
It is often very difficult to initially diagnose PH. In fact, there is
often a lengthy delay between the time when patients first visit
their doctor and the time they receive specialist care at a hospital.
Since there is no single test that will tell the healthcare team if a
patient has PH, it is important to consider all associated diseases
as well as other causes of breathlessness, such as certain lung
and heart diseases and blood clots. The ruling out of different
diseases that are possible causes of particular symptoms is called
the differential diagnosis.
A definite diagnosis of PH usually requires passing a tube through
a vein in an arm or a leg into the right side of the heart to measure
the blood pressure in the right ventricle and the pulmonary artery.
For patients with suspected PH, there are several initial steps that
are commonly taken to confirm the diagnosis. These are first
discussed between the patient and the healthcare team :
• history of present illnesses
• past medical history
• family history
• any past or present medications that the patient may have taken
A thorough physical examination will also take place. After this, a
number of tests may be ordered to aid in assessment and
diagnosis of PH.
Chest X-Ray
Based on the symptoms, a doctor may suspect PH in people who
have an underlying lung disorder. A chest x-ray may show that the
pulmonary arteries are enlarged.
This imaging test offers the physician a picture of the general size,
shape and structure of the heart and lungs. One of the things the
physician will check is whether the right side of the heart is
enlarged.
Echocardiography (Ultrasonic Cardiography)
This test uses sound waves to track the structure and function of the
heart. It can compose images of a beating heart on a monitor and
detects:
• heart’s thickness, size and function
• motion pattern and structure of the four heart valves
→ revealing any potential leakage (regurgitation)
• thickening of right ventricle, enlarged right heart
• reversal of blood through tricuspid valve
• extent of lung damage
A specific echocardiogram, Doppler ultrasound, is sometimes used to
determine pulmonary artery pressure.
Exercise echocardiogram – determine how well heart works under stress
Electrocardiogram (ECG)
ECG is a record of the electrical activity produced by the heart. Abnormal
rhythms (arrhythmias) may indicate that the heart or part of the heart is
undergoing unusual stress.
Exercise ECG helps evaluation of performance of the heart during
exercise, for example, walking on a treadmill in the examination room.
Pulmonary Angiogram
Used to measure circulation in the lungs and to visualize clots in the lung
on x-rays. The test involves insertion of a thin catheter into the pulmonary
artery through which an iodine dye is injected.
Image of any blood clots present in the lung can be observed and
circulation of blood through lung’s blood vessels can be tracked.
Perfusion Lung Scan
Uses small amounts of radioactive tracers (radioisotopes) to study blood
flow in the lungs. Radioisotopes are attached to radiopharmaceuticals
which are then injected into a vein the arm. A gamma camera takes
pictures of blood flow in the lungs’ blood vessels. It is generally used to
determine whether blood clots may be causing symptoms of PH.
Pulmonary Function Tests
Non-invasive tests to measure how much air your lungs can hold and the
airflow in and out of your lungs. They can also measure the amount of
gases exchanged across the membrane between the lung wall and
capillary membrane. During the tests, the patient will be asked to blow
into a spirometer. An abnormality here may be amongst the first indication
of PH.
Computerized Tomography (CT)
Organs can be scanned in two-dimensional ‘slices’. Split-second
computer processing creates images as a series of very thin x-ray beams
pass through the body. A contrast medium is used to help visualization.
The fast CT machine can scan arteries in less than 20 seconds as
opposed to 20 minutes for a standard CT. Speed is important because it
allows the dye to be visualized while still in the arteries.
Magnetic Resonance Imaging (MRI)
Uses no x-rays but instead, a computer creates tissue ‘slices’ from data
generated by a powerful magnetic field and radio waves. Although not yet
routinely used to diagnose PH, it is showing great value in assessing the
pulmonary arteries. It cannot, however, measure artery pressure.
Other screening or diagnostic methods
 exercise testing
 ventilation-perfusion (V/O) scanning
 arterial blood gas studies
 central hematocrit count
 serum glucose and calcium levels count
 platelet count
 hyperoxia (100% oxygen) challenge test
TREATMENT OF PH
6 Minute walk Testing
In patients with PAH, serial determinations
of functional class and exercise capacity
assessed by the 6 minute walk test
provide benchmarks for disease severity,
response to therapy, and progression.
ACCP: QOE: good; Benefit: intermediate; SOR: A
Treatment Goals in PAH
Improved exercise capacity
Improved function
Improved hemodynamics
Improved survival
Prevention of clinical worsening
Therapy for PAH
Functional class II / III / IV
General Care
Oral anticoagulants ;B for IPAH, E/C for other PAH]  diuretics  O2 [E/A]  digoxin
Acute Vasoreactivity Testing [A for IPAH, E/C for other PAH]
YES
NO
Oral CCB [B for IPAH],
E/B for other PAH]
Sustained Response
YES
NO
Functional Class III
Functional Class IV
Endothelin Receptor Antagonists
(Bosentan) [A]
or
Chronic IV Epoprostenol [A]
or
Prostanoid Analogues
Chronic IV Epoprostenol [A]
Bosentan [B]
Treprostinil [B]
Chronic IV Iloprost [C]
SQ Treprostinil [B], Inh Iloprost [B], Beraprost [I]
No improvement
or deterioration
Continue CCB
PDE-5 Inhibitors (Sildenafil) [C]
Atrioseptostomy 
Lung Transplantation
Therapy Targets for PAH
Humbert M, Sitbon O, Simonneau G. N Engl J Med 2004;351:1425-36
Targeting the Mechanism of PAH
Calcium Channel Blockers
For patients (20%) with meaningful
reduction of PAP associated with
reduction of PVR on acute vasoreactivity
tests.
Nifedipine 240mg/day, 30 mg BID
Diltiazem 900mg/day, 60mg TID
Limiting factors for dose increase:
systemic hypotension and lower limb
peripheral edema
Pathophysiology in PAH
Deficiency of prostaglandin and an excess
of thromboxane in PAH patients
Christman et al, NEJM 1992
Decreased expression of prostacyclin
synthase in lungs from patients with
severe PAH
Tuder et al, AJRCCM 1999
Epoprostenol
 PGI2
 Potent vasodilator in both the pulmonary and
systemic circulation
 Has antiplatelet aggregatory activity
 Exogenously administered prostanoid analogues
 Unstable at acidic pH, not taken orally
 Very short half life,<6 mins
 For moderately severe to severe PAH
Epoprostenol
 Requires constant IV
administration
 Kept cold prior to infusion
 Initial dose: 1 – 2 ng/kg/min
 Gradually titrating in
increments of 1- 2
ng/kg/min, based upon side
effects and tolerance to
reach a “plateau” between
20 – 40 ng/kg/min
Epoprostenol
 Side effects: Flushing, headache, jaw pain with
first bite of food, diarrhea, nausea, blotchy
erythematous rash and musculoskeletal pain
(legs and feet )
 Chronic IV therapy: Line related infections,
catheter associated venous thrombosis,
thrombocytopenia
Treprostinil
 Stable prostacyclin analogue
 Half life of 3 hours
 Stable at room temperature
 Undergoing research: Inhaled treprostinil
Treprostinil
 Developed for SC
delivery
 Initially 1.25 ng/kg/min up
to maximum of 22.5
ng/kg/min
 Side effects: Headache,
diarrhea, nausea, rash,
jaw pain, infusion site
pain, erythema or
induration
Iloprost
 Prostacyclin analogue
 Stable at room temperature, at pH 7.4 and
normal light
 Serum half-life of 20 – 25 mins
 For functional class 3 – 4
Iloprost
 Administered via
nebulized aerosol
 Administered 6 – 9 times
a day, each inhalation
requires 10 – 15 mins
 Dose: 2.5 – 5 ug, median
inhaled dose of
30 ug/day
 Side effects: Cough,
headache and flushing
Beraprost
 First chemically stable and orally active
prostacyclin analogue
 Peak concentration is reached after 30 minutes
and elimination half-life is 35 – 40 minutes after
oral administration
 Median dose of 80 ug PO daily
 Approved therapy for PAH in Japan
Endothelin
Leu
Met
Ser
Ser
Cys Ser Cys
NH2
Asp
Lys
Glu Cys Val Tyr Phe Cys His Leu Asp Ile
Ile Trp
CO2
A 21-amino acid peptide released primarily from
the endothelium
Pathophysiology in PAH
 Endothelin 1 is a potent vasoconstrictor and
SM mitogen
 Increase in vascular tone and pulmonary
vascular hypertrophy
 2 distinct endothelin- receptor isoforms:
ETA – facilitates vasoconstriction and
proliferation of vascular SM cells
ETB – involved in clearance of endothelin and
cause vasodilatation and NO release
Expression of Endothelin in the
Lungs of PH Patients
Giaid A et al. N Engl J Med. 1993 Jun 17;328(24):1732-9.
Bosentan
 Orally active nonpeptide antagonist of both
endothelin receptor subtypes
 Prevents and even reverses the development of
PH, pulmonary vascular remodelling and right
ventricular hypertrophy
 Initial dose of 62.5 mg bid for first 4 weeks and
followed by target dose of 125 mg bid
 Side effects: Hepatotoxicity and teratogenicity
Sitaxsentan
Selective ETA antagonist
Has oral bioavailability and a long duration
of action (t 1/2, 5-7h) .
Approximately 6,500 fold more selective
as antagonist for ETA compared with ETB
receptors.
Side effects: ↑ INR and prothrombin time
due to inhibition of CYP2C9 P450 enzyme
Ambrisentan
ETA selective antagonist
Under research
Phosphodiesterase Inhibitors
Sildenafil
Potent and highly specific PDE5 inhibitor
Inhibits degradation of cGMP by
phosphodiesterases
Prevent rebound pulmonary
vasoconstriction after acute withdrawal of
inhaled NO
Revatio – contains sildenafil
same active ingredient used in Viagra
blocks the enzyme phosphodiesterase
accentuates actions of nitric oxide
opens blood vessels in the lungs - dilation
side effect - vision problems
Anticoagulant
 warfarin (Coumadin)
 prevent formation of blood clots within pulmonary arteries
 risk of bleeding complications – prevent normal blood coagulation
 periodic blood tests – check how well the drug is working
 more than 100 drugs can interact with anticoagulants
Diuretics
 water pills
 eliminate excess fluid from body
 reduces amount of work heart has to do
 limit fluid buildup in the lungs
 improve exchange of gases in lungs
Oxygen
 oxygen therapy
 especially for those who live in high altitude
or have sleep apnea
 continuous use of oxygen through
nasal prongs/oxygen mask
 relieve shortness of breath
Cardiotonics
 strengthen the contractions of the heart
 heart does not need to beat as often to circulate adequate
blood for body
Transplants
 surgical interventions – considered only in extreme cases
 treatment for severe secondary PH if treatment of the underlying
disorder fails
 surgically replace damage organs with healthy donated organs
 lung and/or heart transplantation
 most common : single-lung transplant, fewer complications than
double-lung or heart-lung transplant
 lung transplant - improvement in structure and functioning
of right ventricle
 major risks : rejection of transplanted organ, serious infection
 take immunosuppressant drugs for life – help reduce chance of
rejection
 survival rate is about 60% per year and 37% per 5 years
Nitric Oxide
 Inhaled form
 Acts as direct smooth
muscle relaxant via
activation of the
guanylate cyclase system
 Short therapeutic half life
 Ameliorates hypoxemia
and lowers PVR by direct
pulmonary vasodilatation
Anticoagulation
Rationale for use is based on the
presence of traditional risk factors for VTE,
such as heart failure and sedentary
lifestyle, thrombophilic predisposition,
thrombotic changes in the pulmonary
microcirculation and in the elastic
pulmonary arteries.
Dose adjusted according to INR 2 - 3
Supplemental Oxygen
 Low mixed venous
oxygen saturation caused
by low cardiac output and
low minimally altered
ventilation/ perfusion
matching.
 Improves quality of life
and ↓ mortality in patients
with PH due to chronic
respiratory insufficiency.
Surgical Interventions
 Atrial Septostomy
 Allow R L shunting to increase systemic output
that, in spite of fall in the systemic arterial
oxygen saturation, will produce an increase in
systemic oxygen transport.
 Shunt at the atrial level would allow
decompression of the RA and RV, alleviating s/s
of right heart failure.
 Considered after short term failure of maximal
medical therapy.
Heart / Lung Transplantation
1 year survival of 70%
5 year survival of 50%
International Society for Heart and Lung Transplantation
Registry
Effective therapy for patients with end
stage pulmonary vascular disease.
WHO Classification of Functional Status
of Patients with PH
Class
Description
I
Patients with PH in whom there is no limitation of usual physical
activity; ordinary physical activity does not cause increased
dyspnea, fatigue, chest pain, or presyncope.
II
Patients with PH who have mild limitation of physical activity.
There is no discomfort at rest, but normal physical activity causes
increased dyspnea, fatigue, chest pain, or presyncope.
III
Patients with PH who have a marked limitation of physical activity.
There is no discomfort at rest, but less than ordinary activity
causes increased dyspnea, fatigue, chest pain, or presyncope.
IV
Patients with PH who are unable to perform any physical activity
at rest and who may have signs of right ventricular failure.
Dyspnea and/or fatigues may be present at rest, and symptoms
are increased by almost any physical activity.
Chest 2004:126 (Suppl), JACC 2004:43 (Suppl)

Thank You
Until recently, nothing much could be done for people with
pulmonary hypertension. Before 1990, there were very few
treatments available for PH and the survival rate was
approximately two to four years. Since then, a number of exciting
new treatments that are able to slow progression of the disease
and may even reverse some of the damage to lungs and heart are
gradually becoming available.
Some people do well on drugs; others may need a transplant.
Some patients might also require supplemental oxygen delivered
through nasal prongs or a mask if breathing becomes difficult
whereas some need oxygen around the clock. In severely
affected cases, a heart-lung, single lung of double lung
transplantation may be appropriate.
PH patients respond differently to different medicines that are
prescribed to dilate or relax blood vessels and no one drug can
be said to be consistently effective in all patients. Because
individual reactions vary, different drug have to be tried before
chronic or long-term treatment begins.
During the course of disease, the amount and type of medicine
may also have to be changed. To find out which medicine works
best for a particular patient, the drugs should be evaluated via
cardiac catheterization. This way, they can see the effect of the
medicine on the patient’s heart and lungs. They can also adjust
the dose to reduce the side effects such as systemic low BP,
nausea, angina, headache etc that may occur.
To determine whether a drug is improving a patient’s condition,
both the pulmonary pressure and the amount of blood being
pumped by the heart (cardiac output) must be evaluated.
Calcium Channel Blockers
 blocks entry of calcium into muscle cells of heart & arteries
 improve ability of heart to pump blood
 relaxes smooth muscle in walls of heart and blood vessels
 amlodipine (Norvasc), diltiazem (Cardizem, Tiazac),
nifedipine (Adalat, Procardia), nicardipine (Cardene) etc.
 only small number of people with PH respond to them
 side effects – constipation, nausea, headache, rash, edema,
drowsiness, dizziness, low blood pressure
Blood Vessel Dilators
Prostacyclin
 substance that acts like a hormone (prostaglandin)
 imitates behaviour of natural prostacyclin
 powerful vasodilator and anti-clotting agent
 prevent blood clots from forming
 given intravenously through catheter
 bridge to help those waiting for transplant
 Epoprostenol (Flolan) - 1st vasodilator approved by FDA
 Ilopost - inhaled through nebulizer
 Treprostinil - injected under skin
 side effects - jaw pain, nausea, leg cramps etc
 need comprehensive follow-up care
Endothelin Receptor Antagonists
 available in pill form
 reverse effect of endothelin (blood vessels constriction)
 Bosentan (Tracleer) - may improve stamina of people with PH
 not for pregnant women
 need monthly liver monitoring - risk of liver complications
Phosphodiesterase Inhibitors
 Revatio – contains sildenafil
 same active ingredient used in Viagra
 blocks the enzyme phosphodiesterase
 accentuates actions of nitric oxide
 opens blood vessels in the lungs - dilation
 side effect - vision problems
Lung and heart for transplant
Other treatment procedures
Dilation Atrial Septostomy
 experimental procedure
 use in patient with severe PH
 makes a small hole in the heart, slowly enlarging it to
relieve some of the pressure in the heart’s right side
 shunts blood across the atrial septum and into the left side
of the heart
 similar to balloon atrial septostomy – naturally occurring
hole present at birth is enlarged to help those with
congenital heart defects
Other areas of research for treatment of PH includes gene
therapy and stem cell research.
Pregnancy and PH
The consensus of medical opinion is that PH and pregnancy is
very dangerous. The life of the mother and baby are put at
great risk. Pregnancy can really take its toll on a woman’s
body. For example, heart rate speeds up and the immune
system does not work quite as well. For a woman whose body
already has to deal with a severe illness, pregnancy can
actually have catastrophic consequences. The risk of
pregnancy-related death in women with PH is substantial –
reported to be as high as 30-50%.
Some drugs commonly used to treat PH can be harmful to the
developing fetus (e.g. warfarin). Because of this twofold risk to
both mother and baby, use of some form of birth control to
avoid pregnancy is strongly advised in women of childbearing
age with PH.
Children and PH
Unfortunately, there is no minimum age for
PH sufferers. Newborn, young children,
teenagers and even in early adulthood, PH
may occur.
Untreated PH in children worsens more quickly than the same
condition in adults. Children also change more quickly than
adults and have to be watched closely. However, with
treatment, children appear to have an overall better prognosis
than adults.
Children are responsive to the same treatments as adults.
Treatment for PH is lifelong. The treatment used has to be
individualized and adjusted according to how the child is
responding.
Children and PH
A child with PH can still go to school, dance, play sports or
ride a bike. Just like other children, a child with PH can help
themselves by eating a healthy and balanced diet and have
good rest periods.
It is really important to have a greater degree of caution in
allowing other non-PH doctors prescribe medication for a child
with PH.
It is hard but children with PH
should be treated as normally
as possible. The child will be
happier and feel safer if they
are treated just like the rest of
the family.
News From Home
KUALA LUMPUR : Siti Salmah Jasni is on a heartand-lung support machine and still in critical
condition.
A statement issued by the National Heart Institute
(IJN) said Siti Salmah is awake and able to
respond to doctors.
Siti Salmah underwent a six-hour heart and lung
transplant at 12.10am on Friday at IJN. She was
suffering from pulmonary hypertension. The 18year-old is the first in IJN's history to receive a
combined heart and lung transplant.
The organs were harvested by a 10-member IJN
team on Thursday night at the Sultanah Bahiyah
Hospital in Kedah from a woman donor who
became brain dead after a road accident
IJN thanked the donor's family for their generosity
during their hour of grief.
New Straits Times
2007/11/04
Recent advances in genetics and newer understandings in
cell biology are providing fresh insights into the nature of this
disease. New therapies offer an improved quality of life and
increased survival rates in both adults and children.
References
http://www.medicinenet.com/script/main/art.asp?articlekey=77244
http://www.medicinenet.com/pulmonary_hypertension/index.htm
http://www.medicinenet.com/calcium_channel_blockers/article.htm
www.merck.com/mmhe/sec04/ch054/ch054a.html
www.mayoclinic.com/health/pulmonary-hypertension/DS00430
www.nlm.nih.gov/medlineplus/pulmonaryhypertension.html
www.phassociation.org
www.americanheart.org/presenter.jhtml?identifier=11076
www.nhlbi.nih.gov/health/dci/Diseases/pah/pah_what.html
http://www.pha-uk.com/living_with_ph/
http://heart.health.ivillage.com/pulmonary/pulmonaryhypertension2.cfm
www.mater.ie/pha-ireland/html/what.htm.
http://www.medicalook.com/Lung_diseases/Pulmonary_hypertension.html
www-ermm.cbcu.cam.ac.uk/04007513h.htm.
home-2.tiscali.nl/~rsmid/index.html.
http://www.nst.com.my/
THANK YOU FOR YOUR ATTENTION!!
AND HAVE A PLEASANT DAY!!