Splanchnic blood flow

Only non-selective p-blockers reduce bleeding complications in patients with known varices. Blockade of P, receptors reduces cardiac output and splanchnic blood flow. 02-Adrenergic blockade prevents p2-receptor-mediated splanchnic vasodilation while allowing unopposed a-adrenergic effects this enhances vasoconstriction of both the systemic and splanchnic vascular beds. The combination of P, and P2 effects makes the non-selective p-blockers preferable to car-dioselective agents in treating portal hypertension.1,36,41... 

These animal studies should indicate to the pharmacist that blood flow can, under certain circumstances, be an important patient variable that may affect the absorption of drugs. Patients in heart failure would generally be expected to have a decreased cardiac output and, therefore, a decreased splanchnic blood flow. This could lead to a decreased rate of absorption for drugs when the blood flow rates in Eq. (7) become rate-limiting. In addition, redistribution of cardiac output during cardiac failure may lead to splanchnic vasoconstriction in patients [57], Other disease states and physical activity can also decrease blood flow to the GIT [2 4], Thus, the pharmacist must be aware of the possible effect of blood flow rate, especially alterations in the rate, on the availability of drugs. 

The mainstay of primary prophylaxis is the use of nonselective / -adrenergic blocking agents such as propranolol or nadolol. These agents reduce portal pressure by reducing portal venous inflow via two mechanisms decrease in cardiac output, and decrease in splanchnic blood flow. They prevent bleeding, and there is a trend toward reduced mortality. 

Vasoactive drug therapy (somatostatin, octreotide, or terlipressin) to stop or slow bleeding is routinely employed early in patient management to allow stabilization of the patient and to permit endoscopy to proceed under more favorable conditions. These agents decrease splanchnic blood flow and reduce portal and variceal pressures, without significant adverse effects. 

Changes in splanchnic blood flow as a result of food depend on direction and magnitude of the type of food ingested. 

The splanchnic blood flow was found in one study to range from 845 to 5260 ml. per minute in different individuals.27 Such differences should not be surprising in view of anatomical and other differences already mentioned (p. 30). Coronary blood flow and cardiac oxygen consumption have also been found to vary widely in dogs.28... 

Elderly patients may absorb drugs less completely or more slowly because of decreased splanchnic blood flow or delayed gastric emptying. Reduced gastric acidity may decrease the absorption of drugs that require high acidity. 

Absorption Decreased absorptive surface Decreased splanchnic blood flow Increased gastric pH Altered gastrointestinal motility Little change in absorption with age... 

It induces direct contraction of vascular smooth muscle, leading to a reduction of portal and splanchnic blood flow. 

Portal hypertension most commonly occurs as a consequence of chronic liver disease. Portal hypertension Is caused by Increased blood flow within the portal venous system and increased resistance to portal flow within the liver. Splanchnic blood flow is increased in patients with cirrhosis due to low arteriolar resistance that is mediated by increased circulating vasodilators and decreased vascular sensitivity to vasoconstrictors. Intrahepatic vascular resistance is increased in cirrhosis due to fixed fibrosis within the spaces of Disse and hepatic veins as well as reversible vasoconstriction of hepatic sinusoids and venules. Among the consequences of portal hypertension are ascites, hepatic encephalopathy, and the development of portosystemic collaterals—especially gastric or esophageal varices. Varices can rupture, leading to massive upper gastrointestinal bleeding. 

GIT motility has a significant effect on GIT absorption of a toxicant. For example, excessively rapid movement of gut contents can reduce absorption by reducing residence time in the GIT, while the presence of food in the stomach can delay the progress of drugs from the stomach to the small intestine where most of the absorption will occur. Increased splanchnic blood flow after a meal can result in absorption of several drugs (e.g., propranolol), but in hypovolemic states, absorption can be reduced. 

Transjugular intrahepatic portosystemic shunt (TIPS) is a side-to-side non-selective portosystemic shunt that is frequently performed in cirrhosis to manage the complications of portal hypertension, such as variceal bleeding. The observation that the bioavailability of oral midazolam was significantly higher in cirrhotic patients with TIPS than in cirrhotic controls and healthy volunteers [57] may be due to reduced intestinal CYP3A activity or reduced contact with CYP3A in the entero-cyte due to increased splanchnic blood flow [57, 92]. 

Slow and incomplete absorption of procainamide has been reported in patients with acute myocardial infarction and has been attributed to decreased splanchnic blood flow (26). Decreased splanchnic blood flow also may reduce the bioavailability of NAPA, the acetylated metabolite of procainamide. Although an explicit relationship between CLp and... 

Somatostatin and its synthetic analogue octreotide reduce portal pressure by decreasing splanchnic blood flow. Octreotide has the advantage of a longer duration of action so that it can be given as a bolus injection rather than the constant intravenous infusion needed for administration of somatostatin. Its can be used as an alternative to terlipressin, having similar efficacy and indications for use. 

The reason for this appears to lie in the relative flow rates of blood and lymph. The rate of blood flow in the splanchnic circulation is 1.0-1.5 L/min, or 30% of cardiac output. This rate may increase to 2 L/min after a meal. Lymph flow through the same region is only l-2ml/min, but may increase to 5-20ml/min after a meal. Lymph flow in this region is thus 500-700 times slower than blood flow. Relatively fast splanchnic blood flow establishes virtual sink conditions on the serosal side of the GI epithelium and ensures a steep concentration gradient. These conditions promote efficient absorption into the bloodstream rather than into lymph. 

Of more importance in relation to the influence of food on absorption is the rate of blood flow in the capillary system. Food may cause an increase in splanchnic blood flow leading to alterations in drug... 

It has also been suggested that beta-blockade may compromise the splanchnic vasculature. Intravenous propranolol reduces splanchnic blood flow experimentally by 29% while reducing cardiac output by only 6% (81). 

Hannemann, L. Reinhart, K. The effects of low-dose dopamine on splanchnic blood flow and oxygen uptake in patients with septic shock. Intensive Care Med. 1997, 23, 11. 

Several animal studies have demonstrated the beneficial effect of vasopressin on coronary and cerebral blood flow. Although vasopressin improves vital organ perfusion during VF, myocardial oxygen consumption is lower with vasopressin than with epinephrine. Vasopressin also may have a beneficial effect on renal blood flow by stimulating V2 receptors in the kidney, causing vasodilation and increased water reabsorption. With regard to splanchnic blood flow, however, most studies have shown that vasopressin has a detrimental effect compared with epinephrine. ... 

Although splanchnic blood flow and DO2 may increase with dopamine, there is no preferential increase in the splanchnic perfusion as a fraction of cardiac output and systemic increases in D02. One study found an inverse relationship between fractional splanchnic flow at baseline and the change in fractional splanchnic blood flow such that dopamine was effective in increasing the fractional splanchnic blood flow in those in whom it was normal but worsened it in those with high baseline values, such as occurs with redistribution of regional blood flow in septic shock. Clinically, it is difficult to distinguish prospectively either subset of patients. 

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