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Therapeutic strategies in pulmonary hypertension.

Fuso L, Baldi F, Di Perna A - Front Pharmacol (2011)

Bottom Line: The management of patients with PH has advanced rapidly over the last decade and the introduction of specific treatments especially for PAH has lead to an improved outcome.These drugs act in several pathogenetic mechanisms of the PH and are specific for PAH although they might be used also in the other groups of PH.It is also possible to adopt a goal-oriented therapy in which the timing of treatment escalation is determined by inadequate response to known prognostic indicators.

View Article: PubMed Central - PubMed

Affiliation: Respiratory Disease Unit, Catholic University Rome, Italy.

ABSTRACT
Pulmonary hypertension (PH) is a life-threatening condition characterized by elevated pulmonary arterial pressure. It is clinically classified into five groups: patients in the first group are considered to have pulmonary arterial hypertension (PAH) whereas patients of the other groups have PH that is due to cardiopulmonary or other systemic diseases. The management of patients with PH has advanced rapidly over the last decade and the introduction of specific treatments especially for PAH has lead to an improved outcome. However, despite the progress in the treatment, the functional limitation and the survival of these patients remain unsatisfactory and there is no cure for PAH. Therefore the search for an "ideal" therapy still goes on. At present, two levels of treatment can be identified: primary and specific therapy. Primary therapy is directed at the underlying cause of the PH. It also includes a supportive therapy consisting in oxygen supplementation, diuretics, and anticoagulation which should be considered in all patients with PH. Specific therapy is directed at the PH itself and includes treatment with vasodilatators such as calcium channel blockers and with vasodilatator and pathogenetic drugs such as prostanoids, endothelin receptor antagonists and phosphodiesterase type-5 inhibitors. These drugs act in several pathogenetic mechanisms of the PH and are specific for PAH although they might be used also in the other groups of PH. Finally, atrial septostomy and lung transplantation are reserved for patients refractory to medical therapy. Different therapeutic approaches can be considered in the management of patients with PH. Therapy can be established on the basis of both the clinical classification and the functional class. It is also possible to adopt a goal-oriented therapy in which the timing of treatment escalation is determined by inadequate response to known prognostic indicators.

No MeSH data available.


Related in: MedlinePlus

Soluble guanylate cyclase (sGC) as a target in pulmonary arterial hypertension (PAH). The sGC stimulator Bay41-2272 and the activator Bay58-2667 increase cGMP production, thereby regulating smooth muscle function. Bay41-2272 is an NO-dependent stimulator acting preferentially on the physiological form of sGC containing the iron II heme [Fe(II) heme] (left). In contrast, Bay58-2667 is a NO-independent activator preferably addressing the oxidized (and therefore NO-insensitive) iron III heme form [Fe(III) heme] of sGC (right). Increased levels of cGMP then result acutely in vasodilatation and antiaggregation and result chronically in antiremodeling of the vascular wall as well as unloading of the right ventricle. cGMP, cyclic guanosine monophosphate; GTP, guanosine triphosphate; NO, nitric oxide; Ox. stress, oxidative stress; RV, right ventricle. Reproduced with permission from Dumitrascu et al. (2006).
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Figure 5: Soluble guanylate cyclase (sGC) as a target in pulmonary arterial hypertension (PAH). The sGC stimulator Bay41-2272 and the activator Bay58-2667 increase cGMP production, thereby regulating smooth muscle function. Bay41-2272 is an NO-dependent stimulator acting preferentially on the physiological form of sGC containing the iron II heme [Fe(II) heme] (left). In contrast, Bay58-2667 is a NO-independent activator preferably addressing the oxidized (and therefore NO-insensitive) iron III heme form [Fe(III) heme] of sGC (right). Increased levels of cGMP then result acutely in vasodilatation and antiaggregation and result chronically in antiremodeling of the vascular wall as well as unloading of the right ventricle. cGMP, cyclic guanosine monophosphate; GTP, guanosine triphosphate; NO, nitric oxide; Ox. stress, oxidative stress; RV, right ventricle. Reproduced with permission from Dumitrascu et al. (2006).

Mentions: An animal model study conducted on mice with PAH induced by chronic hypoxia and rats with PAH induced by MCT, showed that both the sGC stimulator “Bay 41-2272” and sGC activator “Bay 58-2667” could reverse PH and pulmonary vascular remodeling (Figure 5; Dumitrascu et al., 2006).


Therapeutic strategies in pulmonary hypertension.

Fuso L, Baldi F, Di Perna A - Front Pharmacol (2011)

Soluble guanylate cyclase (sGC) as a target in pulmonary arterial hypertension (PAH). The sGC stimulator Bay41-2272 and the activator Bay58-2667 increase cGMP production, thereby regulating smooth muscle function. Bay41-2272 is an NO-dependent stimulator acting preferentially on the physiological form of sGC containing the iron II heme [Fe(II) heme] (left). In contrast, Bay58-2667 is a NO-independent activator preferably addressing the oxidized (and therefore NO-insensitive) iron III heme form [Fe(III) heme] of sGC (right). Increased levels of cGMP then result acutely in vasodilatation and antiaggregation and result chronically in antiremodeling of the vascular wall as well as unloading of the right ventricle. cGMP, cyclic guanosine monophosphate; GTP, guanosine triphosphate; NO, nitric oxide; Ox. stress, oxidative stress; RV, right ventricle. Reproduced with permission from Dumitrascu et al. (2006).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3108478&req=5

Figure 5: Soluble guanylate cyclase (sGC) as a target in pulmonary arterial hypertension (PAH). The sGC stimulator Bay41-2272 and the activator Bay58-2667 increase cGMP production, thereby regulating smooth muscle function. Bay41-2272 is an NO-dependent stimulator acting preferentially on the physiological form of sGC containing the iron II heme [Fe(II) heme] (left). In contrast, Bay58-2667 is a NO-independent activator preferably addressing the oxidized (and therefore NO-insensitive) iron III heme form [Fe(III) heme] of sGC (right). Increased levels of cGMP then result acutely in vasodilatation and antiaggregation and result chronically in antiremodeling of the vascular wall as well as unloading of the right ventricle. cGMP, cyclic guanosine monophosphate; GTP, guanosine triphosphate; NO, nitric oxide; Ox. stress, oxidative stress; RV, right ventricle. Reproduced with permission from Dumitrascu et al. (2006).
Mentions: An animal model study conducted on mice with PAH induced by chronic hypoxia and rats with PAH induced by MCT, showed that both the sGC stimulator “Bay 41-2272” and sGC activator “Bay 58-2667” could reverse PH and pulmonary vascular remodeling (Figure 5; Dumitrascu et al., 2006).

Bottom Line: The management of patients with PH has advanced rapidly over the last decade and the introduction of specific treatments especially for PAH has lead to an improved outcome.These drugs act in several pathogenetic mechanisms of the PH and are specific for PAH although they might be used also in the other groups of PH.It is also possible to adopt a goal-oriented therapy in which the timing of treatment escalation is determined by inadequate response to known prognostic indicators.

View Article: PubMed Central - PubMed

Affiliation: Respiratory Disease Unit, Catholic University Rome, Italy.

ABSTRACT
Pulmonary hypertension (PH) is a life-threatening condition characterized by elevated pulmonary arterial pressure. It is clinically classified into five groups: patients in the first group are considered to have pulmonary arterial hypertension (PAH) whereas patients of the other groups have PH that is due to cardiopulmonary or other systemic diseases. The management of patients with PH has advanced rapidly over the last decade and the introduction of specific treatments especially for PAH has lead to an improved outcome. However, despite the progress in the treatment, the functional limitation and the survival of these patients remain unsatisfactory and there is no cure for PAH. Therefore the search for an "ideal" therapy still goes on. At present, two levels of treatment can be identified: primary and specific therapy. Primary therapy is directed at the underlying cause of the PH. It also includes a supportive therapy consisting in oxygen supplementation, diuretics, and anticoagulation which should be considered in all patients with PH. Specific therapy is directed at the PH itself and includes treatment with vasodilatators such as calcium channel blockers and with vasodilatator and pathogenetic drugs such as prostanoids, endothelin receptor antagonists and phosphodiesterase type-5 inhibitors. These drugs act in several pathogenetic mechanisms of the PH and are specific for PAH although they might be used also in the other groups of PH. Finally, atrial septostomy and lung transplantation are reserved for patients refractory to medical therapy. Different therapeutic approaches can be considered in the management of patients with PH. Therapy can be established on the basis of both the clinical classification and the functional class. It is also possible to adopt a goal-oriented therapy in which the timing of treatment escalation is determined by inadequate response to known prognostic indicators.

No MeSH data available.


Related in: MedlinePlus