How do drugs get into cells?

Published on 23/06/2015 by admin

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Last modified 23/06/2015

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Chapter 16 How do drugs get into cells?

Chapter contents

Absorption at the cellular level 123
Distribution of the drug 125

Absorption at the Cellular Level

• Cell membranes are effectively selective biological barriers that inhibit the passage of certain molecules.
• Cell membranes are largely made up of two layers of phospholipids.
• Globular proteins – of varying size and make-up – are embedded within the membrane. These tend to be for transport and regulatory functions.

Drugs or remedies cross cell membranes by the following methods:

• passive diffusion
• facilitated passive diffusion
• active transport
• pinocytosis.

Passive Diffusion (Absorption)

• Accounts for the greatest amount of chemical transport across the cell membrane.
• Uses no energy.
• Transfer occurs down a chemical gradient; in other words, chemicals move from an area of high concentration to an area of low concentration (osmosis) (Figure 16.1); This can be from the gastrointestinal tract to the bloodstream, where the concentration of the substance is lower.
• Chemicals absorbed this way tend to be fat soluble and non-polar, features that allow them to pass across the phospholipid membrane. Some polar molecules can pass through but they must be very small.
• Small molecules will penetrate the membrane more easily, and therefore more rapidly, than a large molecule.
• Because there is rapid removal of substrates due to the circulation flowing rapidly past the site, absorbed chemicals become distributed over a wide area of the body.
image

Figure 16.1 Passive diffusion into a cell.

As the pH varies through the digestive tract, so do the characteristic of many compounds (see Chapter 8 ‘Acids and bases’, p. 55). This leads to certain compounds being more non-polar than others. This then affects how easily they can pass through the membrane. The condition of the digestive tract is therefore an important factor in chemical absorption.

Facilitated Passive Diffusion

• Does not work against a concentration gradient but is a type of enhanced osmosis.
• There is possibly some type of carrier that combines reversibly with the molecules on one side of the membrane and transfers them over to the other side. Such carriers are specific for certain molecules.
• The whole process is limited by the number of carriers present, so it is possible for the system to reach saturation, at which point it will be unable to work any faster.
• The process seems to require no energy.

• Passive Diffusion Through Protein Channels and how these Channels are ‘Gated’

Sodium, potassium and calcium salts, which are vital to the function of cells, need to be able to pass through cell membranes down a concentration gradient. Such a mechanism is provided by proteins, which can be seen by electron microscopy across the cell membranes. These channels can be placed in an open position or closed because they are ‘gated’. In other words, a barrier can go across the channel when required to prevent the flow of the ions.

Various medications can affect the patency (openness) of these sodium, potassium and calcium channels, e.g. calcium-channel blockers (which, as the name suggests block the calcium channels and prevent the flow of calcium) and potassium channel activators (which keep the potassium channels open to allow the flow of potassium out) in heart medication.

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