Luminal fluid volume

The dissolution of a drug in the gut lumen will depend on luminal conditions, e.g., pH of the luminal fluid, volume available, lipids and bile acids and the hydrodynamic conditions produced from the GI peristaltic movements of the luminal content toward the lower bowel. Such physiological factors influence drug dissolution by controlling the different variables in equation 1 that describe the dissolution rate. This is summarised in Table 4.4 adapted from Dress-man et al. (1998). 

Recently, an approach mimicking the GI tract and feasible for pharmaceutical dissolution studies has been published [47], Coming from the area of nutritional research, this approach reflects some promising aspects, such as relevant luminal pH values, peristalsis, luminal bacterial colonization, and relevant fluid volumes. However, permeation is only reflected by diffusion through hollow fiber membranes and thus is not in the scope of this chapter. Nevertheless, it will be interesting to see whether it will be possible to expand such a perfect in vitro device toward a more realistic intestinal epithelium. 

Rectal fluid Volume pH Buffering ability Surface tension Viscosity Composition Luminal pressure from rectal wall... 

The papilla is the smallest anatomical portion of the kidney. Papillary tissue consists primarily of terminal portions of the collecting duct system and the vasa recta. Papillary blood flow is low relative to cortex and medulla less than 1% of total renal blood flow reaches the papilla. However, tubular fluid is maximally concentrated and the volume of luminal fluid is maximally reduced within the papilla. Potential toxicants trapped in tubular lumens may attain extremely high concentrations within the papilla during the process of urinary concentration. High intraluminal concentrations of potential toxicants may result in diffusion of these chemicals into papillary tubular epithelial and/or interstitial cells, leading to cellular injury. 

Finally, the efficacy of a diuretic is also determined ii, the patient s plasma volume and renal function status, cn> currently admini.stered drugs that reduce the GFR. andon currently administered drugs that bind competitively to dr OATS or OCTS and reduce the active tubular secretion ml luminal fluid concentration of the diuretic. 

Ociasionally. a patient may experience hypercalcemia or liypcr-uiicemia after long-term use of a thia/idc or thia/idc-like diuretic. Tliis results from diuretic-induced reduction of the pti-irem s plasma volume and a concomitant compeasulory increase in the proximal tubule reabsorption of luminal fluid and solutes. In such a situation, mote Ca and uric acid than usual will be reabsorbed proximally. The seriousness of these two adverse cffccLs depends in part on the duration and extent of the plasma volume r uction. 

Fig. 2. Osmolarity of the absorbate, relative to Ringer s solution, at various stages in the absorption process. Abscissa, percentage of the initial luminal volume reabsorbed by the end of the experiment ordinate, ratio of the osmolarity of the absorbate to the osmolarity of Ringer s solution. Gallbladders were allowed to absorb varying fractions of the luminal fluid, then the absorbate osmolarity was computed from the amount of water and ions absorbed. (Identical solutions bathed both sides of the gallbladder except in the experiment indicated by. v, in which the outer solution was Ringer s and the luminal solution K-free. The circles denote experiments performed with Ringer s solution the square, that with Na2S04 solution and the +, that with a K-rich solution.) (From (2J.)...

Structurally diverse cannabinoid CB1/CB2 agonists inhibit peristalsis induced in segments of isolated intestine (ileum or colon) by continuous luminal fluid infusion (41) or electrical field stimulation (43). Indeed, these agonists seem to reduce both the preparatory phase of peristalsis (i.e., longitudinal muscle contractions in response to flnid or electrical field stimulation) as well as the subsequent emptying phase in which intestinal circular muscles contract towards the aboral end. Overall, cannabinoids increase the threshold pressure and the volume for triggering peristalsis but decrease comphance and ejection pressure. 

Aldosterone acts on the distal tubule of the nephron to increase sodium reabsorption. The mechanism of action involves an increase in the number of sodium-permeable channels on the luminal surface of the distal tubule and an increase in the activity of the Na+-K+ ATPase pump on the basilar surface of the tubule. Sodium diffuses down its concentration gradient out of the lumen and into the tubular cells. The pump then actively removes the sodium from cells of the distal tubule and into the extracellular fluid so that it may diffuse into the surrounding capillaries and return to the circulation. Due to its osmotic effects, the retention of sodium is accompanied by the retention of water. In other words, wherever sodium goes, water follows. As a result, aldosterone is very important in regulation of blood volume and blood pressure. The retention of sodium and water expands the blood volume and, consequently, increases mean arterial pressure. 

Many physiological aspects affect drug absorption from the rectum (Table 7.1). Influential factors include the pH of the rectal contents, state of the mucus layer, volume and viscosity of rectal fluid, luminal pressure from the rectal wall on the dosage form, enzymatic and microbacterial degradation by rectal epithelium, presence of stools, and venous drainage differences within the rectosigmoid regions. 

In diseases of the small intestine, active secretion caused by cyclic nucleotide stimulation can result in a large volume of water and electrolytes moving into the lumen. Additionally, enteric neuron activation of mast cells can increase intestinal capillary permeability and promote passive fluid secretion. Diseases that increase intestinal permeability can result in passive secretion of protein-rich fluid into the intestinal lumen. Active secretion of electrolytes and water is a feature of many diarrheal disorders and can be stimulated by bacterial enterotoxins. Several bacterial enterotoxins interact with intestinal epithelial cell membrane adenylate cyclase or guanylate cyclase, resulting in increased cAMP or cGMP. These, in turn, activate basolateral chloride channels, resulting in an increase in the luminal secretion of chloride, accompanied by sodium and followed by water (Gemmell 1984). Bacterial enterotoxins that stimulate cAMP include cholera toxin, Escherichia coli... 

OVERVIEW OF GI WATER AND ELECTROLYTE FLUX Huid content is the principal determinant of stool volume and consistency water normally accounts for 70-85% of total stool weight. Net stool fluid content reflects a balance between luminal input (ingestion and secretion of water and electrolytes) and output (absorption) along the length of the GI tract. The daily challenge... 

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