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Pharmacokinetics is the study of drug absorption, distribution, metabolism and excretion. The absorption of a drug molecule depends on its physiochemical properties. To gain access to the site of action, drug molecule must cross one or more barriers- the gastrointestinal mucosa, and the membranes that separate the various aqueous compartments of the body, i.
In general, there are four main ways by which small drug molecules cross cell membranes: Many drugs are highly soluble in lipids and therefore penetrate cell membranes freely, by diffusion. Lipid solubility is one of the most important pharmacokinetic characteristic of a drug, which determines its site of action.
Diffusion through Aqueous Channels: In most parts of the body there are gaps between the endothelial cells of the capillaries, which are large enough to permit small drug molecules to cross by aqueous diffusion, but too small to allow protein molecules to pass through.
In central nervous system vascular beds, the capillary endothelium is continuous.
In fact, there are tight junctions between adjacent capillary endothelial cells which, together with their basement membrane and a thin covering from the processes of astrocytes separate the blood from the brain tissue.
This blood-brain barrier restricts the passage of lipid insoluble substances from the blood to the brain and cerebrospinal fluid. Lipid insoluble polar drugs such as penicillin, methotrexate gain little access to the brain.
Many cell membranes possess highly specific transport mechanism, i. The carrier-mediated drug transport plays an important role in the transfer of drugs at the renal tubule, biliary tract, gastrointestinal tract and blood brain barrier sites.
It involves the transport of a drug molecule across the cell by formation of vesicles. This is applicable to protein and other macromolecules and rarely to drugs.
Drugs absorbed from the gastrointestinal tract are carried by portal vein to the liver before reaching the systemic circulation. Thus, the bioavailability of orally administered drugs is much less as compared to other routes of drug administration. This removal of drug as it passes through liver is called the first pass effect or pre-systemic elimination.
After absorption a drug passes into the circulation.
Many drugs are poorly soluble in plasma and are bound to plasma proteins. It is important to know that the free unbound fraction of the drug is pharmacologically active and it is the free fraction of the drug that passes from the circulation into body water, e.
The protein bound fraction of the drug acts as a store from where the free drug is released to maintain steady levels of pharmacologically active drug.
The distribution of the drug is an important factor in determining its therapeutic usefulness.
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The drugs initially enter the circulation and highly vascular organs, from where, depending on lipid solubility, diffuse out of the circulation into the tissue spaces and some enter the cells and are bound within the tissues.
The drugs pass in between these compartments, but the entry and elimination is only through the central compartment. The average volume of the distribution space for an adult is — plasma 3 litres, extracellular space 15 litres and total body water 36 litres.
When the volume of distribution exceeds the total volume of body water e. After distribution has proceeded to the point where the concentration of drug in plasma is in dynamic equilibrium with that in body tissues, the drug levels in plasma and tissue fall in parallel as the drug is eliminated from the body.
This is equilibrium phase or elimination phase. Measurement of drug concentration in plasma provides the best reflection of drug levels in tissues during this phase. The elimination half-life of a drug is the time taken for the circulating concentration of the drug to fall by half.Respiratory System-Short Essay Questions (SEQs) 1.
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