All body functions are mediated by control systems which depend on enzymes, receptors on cell surfaces, carrier molecules, and specific macromolecules eg. DNA. Most drugs act by interfering with these control systems at a molecular level. In order to have their effect, drugs must reach cells via the processes of absorption and distribution already described. Once at their site of action, drugs may work in a very specific manner or non-specifically. Specific mechanisms will be considered first of all.

Interaction with receptors on the cell membrane. A receptor is usually a protein molecule found on the surface of the cell or located intracellularly in the cytoplasm. Drugs frequently interact with receptors to form a drug-receptor complex. In order for a drug to interact with a receptor, it has to have a complementary structure in the same way that a key has a structure complementary to the lock in which it fits (Figure 2). Very few drugs are truly specific to a particular receptor and some drugs wi ll combine with more than one type of receptor. However, many drugs show selective activity on one particular receptor type.

Figure 2 - A drug receptor complex

A drug that has an affinity for a receptor, and that once bound to the receptor can cause a specific response, is called an agonist. Morphine is an opioid agonist that binds to mu receptors in the central nervous system to depress the appreciation of pain. Drugs that bind to receptors and do not cause a response are called antagonists or receptor blockers. These will reduce the likelihood of another drug or chemical binding and hence will reduce or block further drug activity. Antagonists may be competitive, in which case they compete with an agonist for receptor sites and inhibit the action of the agonist. The action of the drug depends on whether it is the agonist or antagonist which occupies the most receptors. For example, naloxone is a competitive antagonist for mu receptors and is may be used to treat opioid overdose. It will compete with morphine for mu receptors and reverse the effects of an excessive dose of morphine. A non-competitive antagonist will inactivate a receptor so that an agonist cannot have an effect.

Drug-receptor binding is reversible and the response to the drug is gradually reduced once the drug leaves the receptor site.

Interference with ion passage through the cell membrane

Ion channels are selective pores in the cell membrane that allow the movement of ions in and out of the cell. Some drugs will block these channels, which ultimately interferes with ion transport and causes an altered physiological response. Drugs working in this way include nifedipine, verapamil, and lignocaine.

Enzyme inhibition or stimulation

Enzymes are proteins and biological catalysts which speed up the rate of chemical reactions. Some drugs interact with enzymes in a manner similar to the drug-receptor complex mechanism already described. Drugs often resemble a natural substrate and compete with the natural substrate for the enzyme. Drugs interacting with enzymes include aspirin, methotrexate and angiotensin-converting enzyme (ACE) inhibitors such as enalapril.

Incorporation into macromolecules

Some drugs may be taken up by a larger molecule and will interfere with the normal function of that molecule. For example, when the anticancer drug 5-fluorouracil is incorporated into messenger RNA, taking the place of the molecule uracil, transcription is affected.

Interference with metabolic processes of microorganisms

Some drugs interfere with metabolic processes that are very specific or unique to microorganisms and thus kill or inhibit activity of the microorganism. Penicillin disrupts bacterial cell wall formation whilst trimethroprim inhibits bacterial folic acid synthesis.

Non-specific mechanisms involve:

• Chemical alteration of the cellular environment. Drugs may not alter specific cell function, but because they alter the chemical environment around the cell, cellular responses or changes occur. Drugs which have this effect include osmotic diuretics eg. mannitol, osmotic laxatives eg. lactulose, and antacids eg. magnesium hydroxide.

• Physical alteration of the cellular environment. Drugs may not alter specific cell function, but because they alter the physical as opposed to the chemical environment around the cell, cellular responses or changes occur. Drugs which have this effect would include docusate sodium which lowers faecal surface tension and many of the barrier preparations available, which protect the skin.

Undesirable responses to drug therapy

Most drugs are not entirely free of unwanted effects. However, drugs which are frequently prescribed, highly potent, or that have a narrow therapeutic index, are likely to increase the risk of unwanted effects.

Terms used to describe undesirable responses to drugs include:

• Adverse reaction. This refers to any undesirable drug effect.
• Side effect. This is used interchangeably with the term adverse reaction. It refers to unwanted but predictable responses to a drug.
• Toxic effect. This usually occurs when too much drug has accumulated in the client. It may be due to an acute high dose of a drug, chronic buildup over time or increased sensitivity to the standard dose of a drug.
• Drug allergy (hypersensitivity). The body sees the drug as an antigen and an immune response is established against the drug. This may be an immediate response or delayed.