Pharmacologic Therapy of Portal Hypertension

Portal Hypertension: Pathophysiology, Diagnosis, and Treatment

“…Thus, these compounds are not used as sole treatment for PH. Chronic oral treatment with isosorbide 5‐mononitrate, however, is frequently used in combination with nonselective β blockade as first‐line treatment to treat PH in humans 97,179,180 . Although pharmacokinetic data are available for the oral administration of isosorbide 5‐mononitrate in dogs, its use in PH has not been described 171 …”

Octreotide decreases portal pressure: Hepatic stellate cells may play a pivotal role

“…This may be the pharmacologic basis of the lower re-bleeding rates in patients receiving 50 µg/h of octreotide after drug withdrawal (Association 2005). Nevertheless, the mechanism of SST/octreotide in reducing portal venous pressure is not clear (Minor and Grace, 2006;Yang et al, 2005). Initial studies suggest that the inhibitory effect of SST/octreotide on the release of glucagon is the principal mechanism by which SST reduces portal venous pressure (Yang et al, 2005).…”

“…Over the last 20 years, marked progress in the understanding of the pathophysiology of portal hypertension has opened doors to pharmacologic treatments. It is assumed that sustained reduction in portal pressure by long-term drug administration may prevent and treat the complications of portal hypertension (Garcia-Tsao et al, 2008;Minor and Grace, 2006). Therefore, a major focus of management of patients with portal hypertension is to reduce functional portal venous flow and portal pressure.…”

Vapreotide: a somatostatin analog for the treatment of acute variceal bleeding

“…Portal hypertension rat models showed significant decrease in portal pressure and collateral flow after administration of vapreotide, providing a potential mechanism for its effect on variceal pressure [20]. Vapreotide binds with high affinity to somatostatin-receptor subtypes 2 and 5 and, unlike octreotide, also has intermediate affinity for subtype 4 [25,26]. Vapreotide is rapidly metabolized to its main metabolite, des-[Trp8-NH2]-vapreotide, which does not bind to somatostatin receptors and is eliminated predominantly in bile (76%), with the remainder eliminated through the kidney.…”