Mucosal membrane

Oral mucosal membranes provide a port for systemic therapy as weU. Nitroglycerin sublingual tablets (Nitrostat) abort acute mgina attacks methyl-testosterone [58-18-4] buccal tablets (Android 5) are indicated for testosterone [58-22-0] replacement therapy (39) md nicotine [54-11-5] gum (Nicorette) aids in smoking cessation. 

The food, now in a liquid form known as chyme, passes through the pyloric sphincter into the duodenum, where stomach acid is neutralized. There is wide variation in lengths of the components of the small intestine (i.e., duodenum, jejunum, and ileum) between individuals (Table 98-1). Most absorption of digested carbohydrate and protein occurs within the jejunum. Most fat absorption occurs within the jejunum and ileum. In the small bowel, breakdown of macronutrients (i.e., carbohydrate, protein, and fat) occurs both within the lumen of the gut and at the intestinal mucosal membrane surface. The absorptive units on the intestinal mucosal membrane are infoldings known as... 

The absorption of drugs from the rectal [32] cavity has been studied in some detail. Muranishi et al. [34] have shown that a significant increase in the absorption and lymphatic uptake of soluble and colloidal macromolecules can be achieved by pretreating the rectal mucosal membrane with lipid-nonionic surfactant mixed micelles. They found no evidence of serious damage of the mucosal membrane. Davis [30] suggested that the vaginal cavity could be an effective delivery site for certain pharmaceuticals, such as calcitonin, used for the treatment of postmenopausal osteoporosis. 

In practice, estimation of Laq requires information on the rate of solute removal at the membrane since aqueous resistance is calculated from experimental data defining the solute concentration profile across this barrier [7], Mean /.aq values calculated from the product of aqueous diffusivity (at body temperature) and aqueous resistance obtained from human and animal intestinal perfusion experiments in situ are in the range of 100-900 pm, compared to lumenal radii of 0.2 cm (rat) and 1 cm (human). These estimates will necessarily be a function of perfusion flow rate and choice of solute. The lower Laq estimated in vivo is rationalized by better mixing within the lumen in the vicinity of the mucosal membrane [6],... 

Precellular solute ionization dictates membrane permeability dependence on mucosal pH. Therefore, lumenal or cellular events that affect mucosal microclimate pH may alter the membrane transport of ionizable solutes. The mucosal microclimate pH is defined by a region in the neighborhood of the mucosal membrane in which pH is lower than in the lumenal fluid. This is the result of proton secretion by the enterocytes, for which outward diffusion is slowed by intestinal mucus. (In fact, mucosal secretion of any ion coupled with mucus-restricted diffusion will provide an ionic microclimate.) Important differences in solute transport between experimental systems may be due to differences in intestinal ions and mucus secretion. It might be anticipated that microclimate pH effects would be less pronounced in epithelial cell culture (devoid of goblet cells) transport studies than in whole intestinal tissue. 

Figure 11 Schematic of mucosal membrane sodium-proton exchanger and chloride-bicarbonate exchanger responsible for pH homeostasis in enterocyte cytosol. Microclimate pH is maintained by mucosal slowing of proton diffusion away from the lumenal membrane.

Figure 12 Schematic of generation of mucosal microclimate pH as a transmucosal proton-gradient driving force for di- and tripeptide carrier-mediated translocation across the mucosal membrane into the enterocyte.

Em - Pc defines the electrical potential gradient across the mucosal membrane where potential inside the enterocyte is negative. 

The coupling of solute transport in the GI lumen with solute lumenal metabolism (homogeneous reaction) and membrane metabolism (heterogeneous reaction) has been discussed by Sinko et al. [54] and is more generally treated in Cussler s text [55], At the cellular level, solute metabolism can occur at the mucosal membrane, in the enterocyte cytosol, and in the endoplasmic reticulum (or microsomal compartment). For peptide drugs, the extent of hydrolysis by lumenal and membrane-bound peptidases reduces drug availability for intestinal absorption [56], Preferential hydrolysis (metabolic specificity) has been targeted for reconversion... 

Sublingual (SL) In the mouth under the tongue this allows the tablet or gum to slowly dissolve, so that the released drug can be gradually absorbed across the buccal mucosal membrane. Nicotine gum is administered by this route. 

Initial symptoms of COPD include chronic cough and sputum production patients may have these symptoms for several years before dyspnea develops. The physical examination is normal in most patients who present in the milder stages of COPD. When airflow limitation becomes severe, patients may have cyanosis of mucosal membranes, development of a barrel chest due to hyperinflation of the lungs, an increased resting respiratory rate, shallow breathing, pursing of the lips during expiration, and use of accessory respiratory muscles. 

Figure 1. Solute transfer across an idealised eukaryote epithelium. The solute must move from the bulk solution (e.g. the external environment, or a body fluid) into an unstirred layer comprising water/mucus secretions, prior to binding to membrane-spanning carrier proteins (and the glycocalyx) which enable solute import. Solutes may then move across the cell by diffusion, or via specific cytosolic carriers, prior to export from the cell. Thus the overall process involves 1. Adsorption 2. Import 3. Solute transfer 4. Export. Some electrolytes may move between the cells (paracellular) by diffusion. The driving force for transport is often an energy-requiring pump (primary transport) located on the basolateral or serosal membrane (blood side), such as an ATPase. Outward electrochemical gradients for other solutes (X+) may drive import of the required solute (M+, metal ion) at the mucosal membrane by an antiporter (AP). Alternatively, the movement of X+ down its electrochemical gradient could enable M+ transport in the same direction across the membrane on a symporter (SP). A, diffusive anion such as chloride. Kl-6 refers to the equilibrium constants for each step in the metal transfer process, Kn indicates that there may be more than one intracellular compartment involved in storage. See the text for details...

The methods of solute transfer across the serosal/basolateral membrane can include ion channels and antiporters similar to those described earlier. In the case of serosally located cation channels, these primarily work because the intracellular electrolyte concentration is high enough to overcome the electrical gradient (e.g. some K+ channels). For anion channels, the negative charge inside the cell compared with the blood will help drive (repel) anions from the cell (e.g. CL efflux on voltage-sensitive channels in the intestine [58]). In the case of antiporters, the operation is fundamentally the same as that used in the mucosal membrane, except that the driving force is derived from an ion... 

Mucosal membrane the external environmental surface of an epithelium such as the gut. 

Both food and drinks can worsen the symptoms of UI by diverse mechanisms overfilling of the bladder, irritation of the mucosal membrane of the bladder, promote infections, stimulating the production of urine or interfering with the brain s signals to the bladder (Box 5.7). 

Human exposure to bromomethane is most likely to occur by inhalation or dermal contact (see Chapter 5). Inhalation exposure may cause neurological, respiratory and renal damage. Dermal contact may cause skin lesions while oral exposure leads to digestive tract mucosal membrane irritation (see Section 2.2). 

Calcium play vital role in excitation - contraction coupling in myocardium. Calcium mediates contraction in vascular and other smooth muscles. Calcium is required for exocytosis and also involved in neurotransmitters release. Calcium also help in maintaining integrity of mucosal membranes and mediating cell adhesions. Hypercalcemia may occur in hyperthyroidism, vitamin D intoxication and renal insufficiency, which can be treated by administration of calcitonin, edetate sodium, oral phosphate etc. Hypocalcemia may occur in hypothyroidism, malabsorption, osteomalacia secondary to leak of vitamin D or vitamin D resistance, pancreatitis and renal failure. Hypocalcemia can be treated by chloride, gluconate, gluceptate, lactate and carbonate salts of calcium. 

Cocaine hydrochloride is a water-soluble salt that can be injected or absorbed by any mucosal membrane (eg, nasal snorting). When heated in an alkaline solution, it is transformed into the free base, "crack cocaine," which can then be smoked. Inhaled crack cocaine is rapidly absorbed in the lungs and penetrates swiftly into the brain, producing an almost instantaneous "rush."... 

For oral delivery, complexes will also dissociate rapidly on dilution in the stomach and intestinal contents and it is generally believed that only the drug, and not the complex, is absorbed (Thompson, 1997). Therefore, the primary function of complexes is to increase the dissolution rate and extent of drug dissolution. Other reported effects of CDs on oral absorption of drugs include enhancement of mucosal membrane permeation by CD as mentioned earlier in this chapter. 

When ketoprofen was loaded with chitosan-coated ethylcellulose microparticles and the plain ethylcellulose microparticles, similar findings were obtained. Although ketoprofen is well absorbed from the GI tract, chitosan appears to influence the absorption profile. Chitosan allowed the particles to make contact with the mucosal membrane and be retained at adhesive sites, which means that the drug remains in the small intestine longer. This facilitated the absorption of ketoprofen in chitosan-coated microparticles loaded with ketoprofen. Chitosan is considered to improve the absorption properties of plain microparticles [33]. 

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