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Explain how the relationship between the dose of drug given to an individual and the concentration of drug molecules - Essay Example

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A drug, once administered, has to make a long journey and interact with various body tissues to reach its target receptor site…
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Explain how the relationship between the dose of drug given to an individual and the concentration of drug molecules
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"Explain how the relationship between the dose of drug given to an individual and the concentration of drug molecules"

Download file to see previous pages These factors are discussed in more detail below, based on the description of Goodman, et al. (2011, ch. 2). The characteristics of the drug molecule itself that affect the drug’s concentration at the receptor site include its molecular size, degree of ionization, lipid solubility, and its affinity for serum and tissue proteins. The plasma membrane (of skin or intestinal cells, for example) is a common barrier to drug distribution; drugs that are not lipid soluble will not be able to permeate the membrane and not reach the target site. A drug of small molecular size will travel more easily through the membranes than a larger molecule, reaching the target in higher concentrations. Ionized molecules, and those that bind to proteins, also have difficulties in passing through the membrane. If the drug has a tendency to ionize at the pH of the intestinal lumen or the blood, the ionized form will have difficulty passing through lipid plasma membranes. If the drug interacts with transporter proteins on the cell membrane, its uptake into the cell may be increased or decreased, depending on the direction in which the transporter moves the drug. For example, the P-glycoprotein in enterocytes limits the oral absorption of some cancer chemotherapeutic agents by exporting them back into the lumen of the GI tract. Similarly, it has been found that multidrug transporters such as P-glycoprotein (PGP) and members of the multidrug resistance-associated protein (MRP) family are over-expressed in capillary endothelial cells in epileptogenic brain tissue, and, by transporting anti-epileptic drugs out, these proteins may be responsible for the pharmacoresistance of the epileptic brain to anti-epileptic drugs (Löscher and Potschka, 2002).
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transporters such as P-glycoprotein (PGP) and members of the multidrug resistance-associated protein (MRP) family are over-expressed in capillary endothelial cells in epileptogenic brain tissue, and, by transporting anti-epileptic drugs out, these proteins may be responsible for the pharmacoresistance of the epileptic brain to anti-epileptic drugs (Loscher and Potschka, 2002). If a drug is capable of binding to plasma proteins such as albumin, then some of the drug molecules in the bloodstream bind to the proteins, while the remaining unbound drug molecules are available to reach equilibrium across all membranes and reach the target receptor. Thus, plasma protein binding limits the concentration of the drug at its site of action. When the site of action of concern is the brain, the capability of the drug to cross the blood-brain barrier determines the concentration of administered drug that can reach the target. The more lipophilic the drug in its unbound, non-ionized form, the greater will be its ability to pass through the endothelial cells forming the blood-brain barrier, and thus the higher will be its bioavailability in the brain. How the route of administration affects the fraction of the drug dose that reaches the target is also important. The most common route of administration is oral, however, this route has several implications on bioavailability, and the dose swallowed will not entirely reach the target site. Only a fraction of the ingested drug is absorbed from the intestine, depending on the factors discussed in the previous paragraph. As more absorption takes place in the intestine than the stomach, any factor that increases stomach emptying (such as such as lying down on the right side and level of physical activity) increases drug absorption as the ...Download file to see next pagesRead More
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