Pharmacological treatment of pulmonary hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension ( PH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance) (characterized by an elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)) includes various classes of drugs. These medications fall into the following drug categories: phosphodiesterase type-5 (PDE-5) inhibitors, soluble guanylate cyclase Guanylate cyclase An enzyme that catalyzes the conversion of GTP to 3. Diarrheagenic E. coli (sGC) stimulants Stimulants Stimulants are used by the general public to increase alertness and energy, decrease fatigue, and promote mental focus. Stimulants have medical uses for individuals with ADHD and sleep disorders, and are also used in combination with analgesics in pain management. Stimulants, prostacyclin Prostacyclin A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from prostaglandin endoperoxides in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension. Eicosanoids receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors agonists, endothelin receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors antagonists, and calcium channel blockers Calcium Channel Blockers Calcium channel blockers (CCBs) are a class of medications that inhibit voltage-dependent L-type calcium channels of cardiac and vascular smooth muscle cells. The inhibition of these channels produces vasodilation and myocardial depression. There are 2 major classes of CCBs: dihydropyridines and non-dihydropyridines. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers) ( CCBs CCBs Calcium channel blockers (CCBS) are a class of medications that inhibit voltage-dependent L-type calcium channels of cardiac and vascular smooth muscle cells. The inhibition of these channels produces vasodilation and myocardial depression. There are 2 major classes of CCBS: dihydropyridines and non-dihydropyridines. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers)). Via differing pathways, the overall effect of the medications is vascular smooth muscle relaxation and vasodilation resulting in a fall in pulmonary arterial pressure. Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation, adverse events, and drug interactions are dependent on the class of drugs.
Last updated: 31 Mar, 2022
Pulmonary hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension ( PH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance) is defined as an elevated pulmonary arterial pressure.
Chemical structure of sildenafil Sildenafil A phosphodiesterase type-5 inhibitor; vasodilator agent and urological agent that is used in the treatment of erectile dysfunction and primary pulmonary hypertension. Phosphodiesterase Inhibitors
Image: “ Sildenafil Sildenafil A phosphodiesterase type-5 inhibitor; vasodilator agent and urological agent that is used in the treatment of erectile dysfunction and primary pulmonary hypertension. Phosphodiesterase Inhibitors” by Yikrazuul. License: Public DomainNitric oxide (NO)–soluble
guanylate cyclase
Guanylate cyclase
An enzyme that catalyzes the conversion of GTP to 3.
Diarrheagenic E. coli (sGC)–
cGMP
cGMP
Guanosine cyclic 3.
Phosphodiesterase Inhibitors pathway:
Nitric oxide is synthesized in the blood vessels from L-
arginine
Arginine
An essential amino acid that is physiologically active in the l-form.
Urea Cycle, catalyzed by endothelial NO synthase. Nitric oxide goes to the smooth muscle layer of the vessel and activates sGC by binding its heme group. Soluble
guanylate cyclase
Guanylate cyclase
An enzyme that catalyzes the conversion of GTP to 3.
Diarrheagenic E. coli then converts GTP to
cGMP
cGMP
Guanosine cyclic 3.
Phosphodiesterase Inhibitors. The downstream effects include vasodilation, inhibition of
fibrosis
Fibrosis
Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.
Bronchiolitis Obliterans, platelet
aggregation
Aggregation
The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin; collagen) and is part of the mechanism leading to the formation of a thrombus.
Coagulation Studies, and smooth muscle proliferation. The image indicates areas in the pathway where the medications (PDE-5 inhibitors, sGC stimulators, and nitric oxide) exert their therapeutic mechanisms.
CNGC: cyclic nucleoside gated-ion channel
GMP:
guanosine monophosphate
Guanosine monophosphate
A guanine nucleotide containing one phosphate group esterified to the sugar moiety and found widely in nature.
Purine and Pyrimidine Metabolism
GTP: guanosine triphosphate
NOS:
nitric oxide synthase
Nitric oxide synthase
An NADPH-dependent enzyme that catalyzes the conversion of L-arginine and oxygen to produce citrulline and nitric oxide.
Megacolon
PDE: phosphodiesterase
PKG:
protein kinase
Protein kinase
A family of enzymes that catalyze the conversion of ATP and a protein to adp and a phosphoprotein.
Interferons G
Chemical structure of riociguat
Image: “Riociguat” by Vaccinationist. License: Public DomainChemical structure of prostacyclin Prostacyclin A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from prostaglandin endoperoxides in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension. Eicosanoids
Image by Lecturio.Chemical structure of treprostinil
Image: “Treprostinil” by Fvasconcellos. License: Public DomainChemical structure of iloprost
Image: “Iloprost” by Vaccinationist. License: Public DomainChemical structure of selexipag
Image: “Selexipag” by Vaccinationist. License: Public DomainMedications | Pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics | Indications | Adverse drug effects |
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Epoprostenol Epoprostenol A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from prostaglandin endoperoxides in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension. Hemostasis |
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Chemical structure of bosentan
Image: “Bosentan” by Fvasconcellos. License: Public DomainChemical structure of macitentan
Image: “Macitentan” by Anypodetos. License: Public DomainChemical structure of ambrisentan
Image: “Ambrisentan” by Fvasconcellos. License: Public DomainMedications | Pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics | Indications | Adverse drug effects |
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Chemical structure of diltiazem Diltiazem A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of calcium ion on membrane functions. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers)
Image: “2D structure of diltiazem Diltiazem A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of calcium ion on membrane functions. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers)” by Vaccinationist. License: Public DomainChemical structure of verapamil
Image: “Skeletal formula of verapamil” by Vaccinationist. License: Public DomainCardiovascular effects of
calcium channel blockers
Calcium Channel Blockers
Calcium channel blockers (CCBs) are a class of medications that inhibit voltage-dependent L-type calcium channels of cardiac and vascular smooth muscle cells. The inhibition of these channels produces vasodilation and myocardial depression. There are 2 major classes of CCBs: dihydropyridines and non-dihydropyridines.
Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers) (
CCBs
CCBs
Calcium channel blockers (CCBS) are a class of medications that inhibit voltage-dependent L-type calcium channels of cardiac and vascular smooth muscle cells. The inhibition of these channels produces vasodilation and myocardial depression. There are 2 major classes of CCBS: dihydropyridines and non-dihydropyridines.
Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers)):
Calcium channel blockers
Calcium Channel Blockers
Calcium channel blockers (CCBs) are a class of medications that inhibit voltage-dependent L-type calcium channels of cardiac and vascular smooth muscle cells. The inhibition of these channels produces vasodilation and myocardial depression. There are 2 major classes of CCBs: dihydropyridines and non-dihydropyridines.
Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers) slow down the sinoatrial (SA) node, causing a lowered
heart rate
Heart rate
The number of times the heart ventricles contract per unit of time, usually per minute.
Cardiac Physiology.
Calcium
Calcium
A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Electrolytes channel blocker intake leads to vascular smooth muscle relaxation, causing vasodilation.