Drug Influence on Body and What the Body Does to the Drug Essay

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Drug Action

Pharmacokinetics explains the process by which a drug is absorbed, distributed, metabolized, and eliminated from the body. These processes are dependent on the amount of the drug administered, the method of administration (which affects the rate of absorption, biotransformation, and even excretion), and how the drug binds in the tissues. In essence, a drug's ability to transverse the cellular membranes depends on its solubility and molecular size and shape. The passive diffusion of the drug across cellular membranes depends on its lipid solubility as well as concentration gradients outside and inside the cellular membrane and the pH differences across the membrane. Active transport of the drug occurs when the drug is actually moved by components of the membrane. This can allow a drug move against concentration and electrochemical gradients but it requires energy, can be selective, and can be inhibited by similar molecules. The absorption rate is influenced by the drug concentration (with high concentrations being absorbed quicker than lower concentrations), the drug solubility, the circulation at the site of action, and the area of the absorbing surface. Absorption is also affected by the type of administration. For instance oral administration is affected by most of these aforementioned factors, whereas intravenous administration can bypass many factors involved in absorption and desired concentrations can be obtained immediately. However, with intravenous administration there are dangers of rapid and adverse concentrations being administered, there is little ability to reverse the action of the drug, and some drugs cannot be administered intravenously. Intravenous administrations can be subcutaneous or intramuscular, intro -- arteriole, etc. Other routes of administration such as pulmonary (sniffing), topical, etc. can also affect absorption rates.

Once absorbed into the body the blood flow typically determines the distribution of the drug and well-perfused organs are affected first followed by other areas. For example non- lipid soluble drugs are restricted in the distribution because they cannot pass the cell membranes as easily as soluble drugs.

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There are also other limitations of absorption such as the blood brain barrier limits entry of certain drugs into the CNS. In general, biotransformation reactions alter lipid soluble drugs into more hydrophilic metabolites. This occurs in two phases: Phase I biotransformation provides a functional group to increase the polarity of the metabolite (either oxidation, reduction, or hydrolysis), whereas phase II biotransformation increases water solubility and excretion of the metabolite from the body. The most important factor affecting biotransformation is genetic differences in people; however, environmental and physiological factors such as pollutants and age and gender can also affect biotransformation.

The elimination or excretion of drugs most commonly occurs as metabolites; however, sometimes excretion of the drug directly occurs. Metabolites are more easily excreted than lipid soluble compounds. The most important organ of excretion is the kidney (via urine). Other excretion mechanisms include the intestines via metabolites not reabsorbed from the intestinal tract (bile) and unabsorbed orally ingested drugs (feces), the lungs, and less commonly through breast milk and through the skin.

The pharmacokinetics of aspirin are as follows: Aspirin (salicylic acid) has a pKa of approximately 3.4 making it a weak acid. It is not soluble in the acidic environment of the stomach. The higher pH and larger surface area of the small intestine allows aspirin to be absorbed there, which allows it to be transferred to salicylate and to dissolve. Anywhere between 50 and 80% of salicylate in the bloodstream is protein bound and the remainder remains in an active ionized state. The pH of the blood stream is around 7.4, thus aspirin is the ionized avoiding diffusion back to the stomach. If binding sites are saturated this can lead to increased toxicity.

The volume of distribution is approximately 10% of body weight, but acidosis leads to increased volume of distribution due to enhanced tissue penetration. At smaller doses all pathways function via first order kinetics. Higher doses can saturate the pathways.....

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