Tag: Treatment of Pulmonary Hypertension

Treatment of Pulmonary Hypertension

TREATMENT OF PULMONARY HYPERTENSION

Q. 1

Drug NOT used in pulmonary hypertension ‑

 A

Calcium channel blocker

 B

Endothelin receptor antagonist

 C

Alpha blocker

 D

Prostacyclin

Q. 1

Drug NOT used in pulmonary hypertension ‑

 A

Calcium channel blocker

 B

Endothelin receptor antagonist

 C

Alpha blocker

 D

Prostacyclin

Ans. C

Explanation:

alpha blockers [Ref- Harrison 17th/e p 1577, 1578] Pulmonary hypertension

General management

  • Diuretic therapy may be useful as it relieves pulmonary edema.
  • Anticoagulant therapy is advocated for all patients.

Specific management

Calcium channel blockers

  • Patients who have substantial reductions in pulmonary arterial pressure in response to short acting vasodilators at the time of cardiac catheterization should he initially treated with calcium channel blockers.

Endothelin receptor antagonist

  • Bostenan is a non-selective endothelium receptor antagonist, is an approved t/t ,for patients who are NYHA .functional classes III and IV.

Phosphodiesterase-5 inhibitors

  • Slidenafil is used for patients who are NYHA functional classes II and

Prostacyclins

  • Iloprost is a prostacyclin analogue used in PAH patients who are NYHA functional classes III and IV.
  • Pulmonary circulation is unique in that it accommodates a blood flow that is almost equal to that of all the other organs of body but still maintains low pressure.
  • The factors responsible for low pressure in pulmonary circulation (even with large volume of blood) are:- – Larger diameter of pulmonary vessels due to thin wall of pulmonary artery and arterioles.

– Greater compliance (distensibility) of pulmonary vessels.

numoral factors responsible for maintaining pulmonary circulation:?

Normally

  • NO causes vosodilation and proliferation of smooth muscles by r in the conc. of cGMP —) this increases the diameter of pulmonary vessels.
  • causes vosodilation and decreased proliferation of smooth muscles by increasing the conc. of cAMPincrease in the diameter of pulmonary vessels. Prostaglandin also decreases coagulation.

Endothelin causes vasoconstriction and increase smooth muscle proliferation si lumen of pulmonary vessels. – Normally the vasodilators and antiprolifeave effects of NO and PGI7 dominate 

In Pulmonary hypertension

 

  • There is l production of NO (and cGMP) and PGI2 (and cAMP), t vasoconstriction and proliferation of smooth

 

muscles, st lumen of pulmonary vessel. Decreased production of PGI2 also causes increased coagulation.

 

  • There is T production of endothelin, /vasoconstriction and smooth muscle proliferation, .1 lumen.
  • Drug therapy in puhnonan, hypertension is targetted at these growth factor pathways which are involved in the pathogenesis of pulmonary hypertension:

Endothelium receptor antagonist

  • Bostenan is an endothelin receptor antagonist. It prevents endothelin mediated contraction of vessels. Phosphodiesterase-5 inhibitors
  • Nitric oxide mediates its action through increasing cGMP concentration. Increased cGMP relaxes the vessels. cGMP is degraded by an enzyme phosphodiesterase-5 (PDE-5).

– Slidenafanil is a phosphodiesterase 5 inhibitor. It reduces the degradation of cGMP, thus causing vascular relaxation and reducing pulmonary hypertension.

Prostacyclins

  • In pulmonary hypertension, the level of prostacycline is reduced.
  • This causes pulmonary constriction as prostacyclin causes dilatation of pulmonary vessels.



Q. 2

All are used for treating Pulmonary hypertension except:

 A

Endothelin receptor antagonists

 B

Phosphodiesterase inhibitors

 C

Calcium Channel Blockers

 D

Beta blockers

Q. 2

All are used for treating Pulmonary hypertension except:

 A

Endothelin receptor antagonists

 B

Phosphodiesterase inhibitors

 C

Calcium Channel Blockers

 D

Beta blockers

Ans. D

Explanation:

Beta blockers [Ref Harrison 17th/e p 1577, 1578] Repeat .from May10 Q no.69


Q. 3

Which of the following is the best inotrope agent for use in Right Heart Failure secondary to pulmonary hypertension?

 A

Dobutamine

 B

Digoxin

 C

Milrinone

 D

Halothane

Q. 3

Which of the following is the best inotrope agent for use in Right Heart Failure secondary to pulmonary hypertension?

 A

Dobutamine

 B

Digoxin

 C

Milrinone

 D

Halothane

Ans. C

Explanation:

Phosphodiesterase III inhibitors (Milrinone) acts via a non-beta receptor pathway to effect a decrease in pulmonary vascular resistance while improving left and right contractility. Such interventions are the treatment of choice in conditions of Right Heart Failure secondary to high pulmonary vascular resistance (pulmonary hypertension).

Ref: Review of Clinical Anesthesia By Neil Roy Connelly, Page 218.

Quiz In Between


Q. 4

Which cardiovascular condition during pregnancy has the highest maternal mortality rate ?

 A

Primary pulmonary hypertension

 B

Marfan’s syndrome

 C

Coarctation of the aorta

 D

Mitral stenosis

Q. 4

Which cardiovascular condition during pregnancy has the highest maternal mortality rate ?

 A

Primary pulmonary hypertension

 B

Marfan’s syndrome

 C

Coarctation of the aorta

 D

Mitral stenosis

Ans. A

Explanation:

Primary pulmonary hypertension


Q. 5

Inhaled nitric oxide is used –

 A

For stabilizing systemic heamodynamics

 B

In case of jaundice

 C

To prevent CNS complication

 D

For reducing pulmonary hypertension

Q. 5

Inhaled nitric oxide is used –

 A

For stabilizing systemic heamodynamics

 B

In case of jaundice

 C

To prevent CNS complication

 D

For reducing pulmonary hypertension

Ans. D

Explanation:

Ans. is ‘d’ i.e., For reducing pulmonary hypertension

According to Goodman Gilman

“Inhaled nitric oxide has been approved by FDA for use in newborns with persistent pulmonary hypertension and has become the first line therapy for this disease. In this disease state NO inhalation has been shown to reduce, significantly, the necessity for extracorporeal oxygenation”


Q. 6

The only FDA approved application of nitric oxide is ?

 A

Primary pulmonary hypertension

 B

Newborn with pulmonary hypertension

 C

Congestive cardiac failure

 D

HAPE

Q. 6

The only FDA approved application of nitric oxide is ?

 A

Primary pulmonary hypertension

 B

Newborn with pulmonary hypertension

 C

Congestive cardiac failure

 D

HAPE

Ans. B

Explanation:

Ans. is ‘b’ i.e., Newborn with pulmonary hypertension

Quiz In Between


Q. 7

Sildenafil acts by inhibiting –

 A

Phosphodiesterase – 2

 B

Phosphodiesterase-5

 C

Adenyl cyclase

 D

Guanyl cyclase

Q. 7

Sildenafil acts by inhibiting –

 A

Phosphodiesterase – 2

 B

Phosphodiesterase-5

 C

Adenyl cyclase

 D

Guanyl cyclase

Ans. B

Explanation:

Ans. is ‘b’ i.e., Phosphodiesterase -5

o Sildenafil inhibits phosphodiesterase-5 and is used for erectile dysfuction.


Q. 8

Among the following, which of the following 5-PDE inhibitor has the longest duration of action?

 A

Sildenafil

 B

Vardenafil

 C

Tadalafil

 D

Udenafil

Q. 8

Among the following, which of the following 5-PDE inhibitor has the longest duration of action?

 A

Sildenafil

 B

Vardenafil

 C

Tadalafil

 D

Udenafil

Ans. C

Explanation:

Ans. is ‘c’ i.e., Tadalafil

o Tadalafil is the longest acting phosphodiesterase inhibitor used for erectile dysfunction. Its half life is 17.5 hours.


Q. 9

Drug NOT used in pulmonary hypertension

 A

Calcium channel blocker

 B

Endothelin receptor antagonist

 C

Alpha blocker

 D

Pro stacyc lin

Q. 9

Drug NOT used in pulmonary hypertension

 A

Calcium channel blocker

 B

Endothelin receptor antagonist

 C

Alpha blocker

 D

Pro stacyc lin

Ans. C

Explanation:

Ans. is ‘c’ i.e., Alpha blockers

Drug for pulmonary hypertension

1.  By increasing the effect of NO/cGMP

o This can done by increasing the concentration of cGMP by preventing its degradation.

o This can be achieved by inhibiting phosphodiesterase-5 by phosphodiesterase -5 inhibitors like sildenafil, Tadalofil.

2.  By increasing the effect of Prostacyclin (cAMP)

o This can be achieved by using prostacyclins like epoprostenol, Treprostinil, Iloprost.

3.  By decreasing the effect of endothelin

o This can be acheived by using endothelin receptor antagonists like Bosentan, ambrisentan.

By having direct vasodilatory effect on pulmonary vessels. o Calcium channel blockers like nifedipine dilate both systemic and pulmonary vascular bed.

Quiz In Between


Q. 10

Iloprost in Pulmonary Arterial Hypertension is administered:

 A

Intravenous

 B

Intramuscular

 C

Oral

 D

Inhalation

Q. 10

Iloprost in Pulmonary Arterial Hypertension is administered:

 A

Intravenous

 B

Intramuscular

 C

Oral

 D

Inhalation

Ans. D

Explanation:

Answer is D (Inhalation):

European Society of Cardiology (ESC) Guidelines for the diagnosis and treatment of pulmonary hypertension

Iloprost is a Prostacyclin analogue approved via inhalation for treatment of Pulmonary Arterial Hypertension (PAH).


Q. 11

Mechanism of action of sildenafil is:           

March 2012

 A

5 alpha reductase inhibitor

 B

Antiandrogen

 C

Phosphodiesterase-5 inhibitor

 D

Androgenic

Q. 11

Mechanism of action of sildenafil is:           

March 2012

 A

5 alpha reductase inhibitor

 B

Antiandrogen

 C

Phosphodiesterase-5 inhibitor

 D

Androgenic

Ans. C

Explanation:

Ans: C i.e. Phosphodiesterase-5 inhibitor

Drugs and mechanism of action

  • Finsateride is a competitive inhibitor of the enzyme 5 alpha reductase (which converts testosterone into more active dihydrotestosterone)
  • Flutamide is a non-steroidal drug having specific anti-androgenic, but no other hormonal activity
  • Sildenafil acts by selectively inhibiting PDE-5 and enhancing nitric oxide action in corpus cavernosum
  • Danazol is an orally active ethisterone derivative having weak androgenic, anabolic and progestational activities.

Q. 12

Tadalafil acts on Phosphodiesterase 5 and causes accumulation of‑

 A

cAMP

 B

cGMP

 C

PAF

 D

IL 10

Q. 12

Tadalafil acts on Phosphodiesterase 5 and causes accumulation of‑

 A

cAMP

 B

cGMP

 C

PAF

 D

IL 10

Ans. B

Explanation:

Ans. is ‘b’ i.e., cGMP


Q. 13

Which of the following is not true about bosentan

 A

Used in pulmonary hypertension

 B

Used in malignant hepatitis

 C

Endothelin receptor antagonist

 D

All are true

Q. 13

Which of the following is not true about bosentan

 A

Used in pulmonary hypertension

 B

Used in malignant hepatitis

 C

Endothelin receptor antagonist

 D

All are true

Ans. B

Explanation:

Ans. is ‘b’ i.e., used in malignant hepatitis

Endothein receptor antagonists

  • There are two endothelin receptor subtypes – ETA and and ETB.
  • Bosentan is a nonselective endothelin antagonist – blocks both ETA and ETB.
  • Bosentan is active intravenously and orally.
  • Bosentan is currently approved for use in pulmonary hypertension.
  • Tezosentan another nonselective antagonist is used investigation for the treatment of acute heart failure.
  • Sitaxentan and ambrisentan are selective ETA antagonists.
  • Phosphoramidon inhibits formation of endothelin by inhibiting endothelin converting enzyme. Remember
  • Bosentan can cause severe hepatotoxicity – monthly liver function tests should be done.
  • It is contraindicated in pregnancy.

Quiz In Between



Treatment of Pulmonary Hypertension

TREATMENT OF PULMONARY HYPERTENSION


TREATMENT OF PULMONARY HYPERTENSION

A) TREATMENT OF IDIOPATHIC PULMONARY HYPERTENSION:

Management of specific cases:

1. First-line therapy:

  • If respond to intravenous vasodilators: Oral calcium channel blockers (including amlodipine, diltiazem & nifedipine).
  • If vasodilators are ineffective/irresponsive: Therapy depends on function.

2. Patient with WHO Class 2 symptoms:

  • Phosphodiesterase inhibitors:
    • Sildenafil or tadalafil.
  • Endothelin receptor blockers:
    • Bosentan or ambrisentan

3. Patient with WHO Class 3 symptoms:

  • Prostacyclin analogs:
    • Epoprostenol intravenously
    • Iloprost by inhalation
    • Beraprost or treprostinil subcutaneously.

4. Patients with WHO Class 4 symptoms:

  • Epoprostenol or iloprost – As sole agent therapies.
5. In newborns:
  • Nitric oxide (NO) – Only FDA-approved NO application.

6. Other conjugant therapies:

  • Long-term oral anticoagulation.
  • Supplemental oxygen – Particularly at night, to improve symptoms & helps reduce pulmonary pressure.
  • Diuretics – In right heart edema.
  • Pulmonary transplantation:
    • Viable option in selected centers.
    • Operative mortality is high (around 20–25%).

B) MANAGEMENT OF 1° PULMONARY HYPERTENSION:

1. Endothelin receptor antagonists:

  • Bosentan & sitaxentan – Non-specific antagonist of endothelin receptors, both ETA & ETB.
  • Phosphoramidon – Non-specific inhibitor of endothelin converting enzyme.

2. PGI2 analogs:

  • Particularly with vasodilator action preferred.
  • PGE2 & PGI2 – Vasodilators {Note: PGF2α and TXA2 – Vasoconstrictors}.
  • Drugs:
    • Epoprostenol – PGI2
    • Treprostinil – Longer acting PGI2 analog.

3. Soluble guanylate cyclase (sGC) stimulator:

  • Riociguat
  • Soluble guanylate cyclase (sGC), an enzyme in CVS & nitric oxide (NO) receptor.
  • Helps arteries relax increasing blood flow & decreases BP.
  • Specifically indicated for persistent/recurrent chronic thromboembolic pulmonary hypertension.

General precautions:

  • Women with significant pulmonary hypertension not advised for pregnancy.
  • Permanent birth control measures should be considered.

Future of therapy:

  • Possible use of angiogenesis inhibitors, growth factor inhibitors, endothelial stem cells or progenitor cells.

Exam Important

TREATMENT OF PULMONARY HYPERTENSION

  • First-line therapy for pulmonary hypertension treatment includes oral calcium channel blockers (including amlodipine, diltiazem & nifedipine), only if patients respond to intravenous vasodilators.
  • First-line therapy for pulmonary hypertension treatment mainly depends upon function & patient’s status if patients don’t respond to intravenous vasodilators.
  • Patient with WHO Class 2 symptoms are treated using phosphodiesterase inhibitors (Sildenafil/tadalafil) & Endothelin receptor blockers (Bosentan/ambrisentan).
  • Patient with WHO Class 3 symptoms are treated using prostacyclin analogs particularly epoprostenol intravenously, iloprost by inhalation & beraprost/treprostinil subcutaneously.
  • Patient with WHO Class 4 symptoms are treated with epoprostenol or iloprost, as sole agent therapies.
  • Pulmonary transplantation has high operative mortality (around 20–25%).
  • Bosentan & sitaxentan are useful in treating pulmonary hypertension, which is a non-specific antagonist of endothelin receptors, both ETA & ETB.
  • Phosphoramidon is a non-specific inhibitor of endothelin converting enzyme, which is useful for treating pulmonary hypertension.
  • PGI2 analogs, particularly with vasodilator action is preferred for treating pulmonary hypertension like epoprostenol & longer acting PGI2 analog Treprostinil.
  • Soluble guanylate cyclase (sGC) stimulator like Riociguat is specifically indicated for persistent/recurrent chronic thromboembolic pulmonary hypertension.
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