Anwardeen Sirajuddin*

Clinical Pharmacist-CST, Kauvery Hospitals, India

*Correspondence: Tel.: +91 9578038232; email: [email protected]

Pulmonary Hypertension and Portal Hypertension

Pulmonary-Hypertension-1

Pulmonary Hypertension

When the pressure in the blood vessels in the lungs becomes high, the condition is referred to as pulmonary hypertension (PH), also referred to at times as Pulmonary Artery Hypertension (PAH). The distinction between PH and PAH often gets blurred

To pump blood through the lungs with PH, the heart must work harder. The additional effort eventually causes the heart muscle to weaken and fail [1].

Pulmonary arterial pressure is easily measured using echocardiography. A value greater than or equal to 35 mm Hg is considered PAH and classified as follows: mild PAH (35-50 mm Hg), moderate PAH (50-70 mm Hg), and severe pulmonary hypertension (> 70 mm Hg) [2].

Primary pulmonary hypertension is a rare disease with an unknown cause. Pulmonary hypertension is generally caused by chronic obstructive pulmonary disease, left ventricular dysfunction, and hypoxemia-related disorder.

Drug Treatment and its Mechanism of Action:

  1. Anticoagulant – Such as warfarin to help prevent thrombosis
  2. Diuretics – To remove excess fluid from the body cause by heart failure
  3. Oxygen Treatment – This involves inhaling air that contains a higher concentration of oxygen than normal
  4. Digoxin – This can improve your symptoms by strengthening your heart muscle contraction and slowing down your heart rate
  5. Endothelin receptor antagonists (ERA): It will inhibit the binding of endothelin, a vasoconstrictive peptide, to its receptors on smooth muscle cells which results in vasodilation.the drugs are such as bosentan, ambrisentan and macitentan
  6. Phosphodiesterase 5 inhibitors (PDE5I): By stopping PDE5 from working, PDE 5 inhibitors (i.e., sildenafil and tadalafil) cause the blood vessels to relax. This increases blood flow to the lungs and lowers blood pressure [3].
  7. Prostacyclin analogues (PCA): The binding of prostacyclin to the receptor activates the G-protein and increases intracellular cAMP, which activates protein kinase A. This inhibits platelet aggregation, relaxes smooth muscle, and dilates the pulmonary arteries. Currently there are three prostacyclin analogues available – epoprostenol, iloprost and Treprostinil.
  8. Guanylate cyclase stimulator (sGC): Soluble guanylate cyclase stimulators enhance the activity of sGC, an enzyme in the cardiopulmonary system that relaxes vascular smooth muscles, resulting in pulmonary vasodilation, reduced PAH, and improved cardiac output. The drugs are Adempas, vericiguat.
  9. Calcium channel blockers (CCB): Calcium-channel blockers inhibit the calcium influx into vascular cells leading to relaxation of smooth muscle cells and vasodilatation. The drugs are Nifedipine, Diltiazem, Nicardipine and Amlodipine.

The primary pulmonary hypertension is usually progressive and ultimately fatal so the last option is lung transplantation the survival rates were 79% at one year, 63% at three years, 52% at five years, and 29% at 10 years [5].

As per ABIM the guidelines PAH treatment

Initial Treatment Strategies

Patient without cardiopulmonary there are 3 risk factors

  1. Low or Intermediate = Initial ERA + PDE5I therapy (Class I)
  2. High = Initial ERA + PDE5I and IV/SC PCA (Class IIa)

Patient with cardiopulmonary comorbidities All risk categories are followed Initial oral monotherapy with PDE5I or ERA (Class IIa) [8]

Follow-up Treatment Strategies

There are 4 risk factors are there

  1. Low: Continue initial therapy (Class I)
  2. Intermediate-Low: Add PRA (Class IIa) or Switch from PDE5I to sGC (Class IIb)
  3. Intermediate-High or High: Add IV or SC PCA and/or evaluate for lung transplantation (Class IIa) [8]

Pediatric Pulmonary Hypertension Treatment:

There have been numerous medications used and studied in the treatment of pediatric PAH. PDE5 inhibitors, endothelin (ET) receptor antagonists, and prostacyclin agonists have all been thoroughly studied for their efficacy in pediatric PH treatment [11].

Pediatric-Pulmonary-Hypertension-Treatment

Portal Hypertension

Portal hypertension refers to high blood pressure in the portal vein and the smaller veins that branch off from it, also known as portal venous system. Through the portal vein, blood flows from stomach, intestines, pancreas, and spleen into the liver. The blood is filtered by the liver before it is returned to the heart and circulated throughout the body. When something blocks or slows the flow of blood through the portal vein, the pressure in the portal venous system rises. The body attempts to compensate for the increased pressure by diverting blood flow to other veins. The increased blood flow causes these veins to expand and their walls to stretch and weaken. They may leak into the abdomen and cause bleeding [6].

Normally, portal vein pressure ranges between 1-4 mm Hg higher than the hepatic vein free pressure, and not more than 6 mm Hg higher than right atrial pressure. Pressures that exceed these limits define portal hypertension [12].

Etiology

There are several causes of portal hypertension. The causes can be classified as prehepatic, intrahepatic, or post hepatic.

  1. The causes of pre-hepatic etiology are either increased blood flow or obstruction within the portal vein or splenic vein. A blockage in the portal or splenic veins could be caused by thrombosis or tumour invasion or compression of these veins.
  2. Intrahepatic causes are classified as pre-sinusoidal, sinusoidal, or post-sinusoidal. Schistosomiasis, congenital hepatic fibrosis, early primary biliary cholangitis, sarcoidosis, and chronic active hepatitis can all result in pre-sinusoidal intrahepatic causes. Cirrhosis, alcoholic hepatitis, vitamin A deficiency, and cytotoxic drugs are all potential sinusoidal causes. Post-sinusoidal causes are caused by sinusoidal obstruction syndrome or veno-occlusive disease.
  3. Finally, posthepatic causes can be at the level of the heart, hepatic vein, as in Budd-Chiari syndrome, or inferior vena cava [7].

Drug Treatment and its Mechanism of Action

  1. Nonselective beta-blocker (NSBB) therapy: NSBBs, such as propranolol and nadolol, principally act on β1 receptors, resulting in splanchnic vasoconstriction and a reduction of portal inflow. These drugs are used for primary and secondary prevention of variceal hemorrhage
  2. Nitrates: The rationale for using nitrates in portal hypertension is primarily based on the fact that they reduce the hepatic venous pressure gradient and on the knowledge that deficient intrahepatic nitric oxide release could be one of the mechanisms involved in the development of increased portal resistance in early cirrhosis.
  3. Vasopressin Analogues: Vasopressin is the most potent splanchnic vasoconstrictor; it reduces blood flow to all splanchnic organs, decreasing portal venous inflow and portal pressure. The drugs are Terlipressin
  4. Stomatostation Analogues: Through vasoconstriction, somatostatin diminishes blood flow to the portal system, thus decreasing variceal bleeding [9]

Surgical procedures

  1. TIPSS and shunt surgery
  2. Prevention of recurrent bleeding – Sclerotherapy & TIPSS
  3. Portosystemic shunt surgery
  4. Liver Transplant

Reference

Anwardeen-Sirajuddin

Anwardeen Sirajuddin

Clinical Pharmacist-CST

 

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