Drug action

The action of drugs on the human body is called pharmacodynamics, and what the body does with the drug is called pharmacokinetics. The drugs that enter the human tend to stimulate certain receptors, ion channels, act on enzymes or transporter proteins. As a result, they cause the human body to react in a specific way.

There are two different types of drugs:

• Agonists - they stimulate and activate the receptors
• Antagonists - they stop the agonists from stimulating the receptors

Once the receptors are activated, they either trigger a particular response directly on the body, or they trigger the release of hormones and/or other endogenous drugs in the body to stimulate a particular response.

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Short Note on Receptors

The drugs interact at receptors by bonding at specific binding sites. Most receptors are made up of proteins, the drugs can therefore interact with the amino acids to change the conformation of the receptor proteins.

These interactions are very basic, just like that of other chemical bondings:

Ionic Bonds

Mainly occur through attractions between opposite charges. For example, between protonated amino (on salbutamol) or quaternary ammonium (eg acetylcholine), and the dissociated carboxylic acid group. Similarly, the dissociated carboxylic acid group on the drug can bind with amino groups on the receptor.

This type of bonds are very strong, and varies with so it could act over large distances.

Cation-π interactions can also be classified as ionic bonding. This occurs when a cation, eg acetylcholine, interacts with the negative π bonds on an aromatic group of the receptor.

Ion-diple and dipole-dipole bonds have similar interactions, but are more complicated and are weaker than ionic bonds.

Hydrogen bonds

Only act over short distances, and are dependent on the correct alignment between functional groups.

• Van der Waals' forces
• Induced dipole
• Covalent bonds

Of course, drugs not only just act on receptors. They also act on ion channels, enzymes and cell transporter proteins.

Receptors are located on all cells in the body. The same receptor can be located on different organ, and even on different types of tissues.

How shape of Drug Molecules affect drug action

When talking about the shape of molecules, the scientists are mainly concerned with the 3D conformation of drug molecules. There are many isomers of a particular drug, and each one will have their own effects. This effect is not only what the drug activates, but also changes the potency of each drug.

Potency

Potency is a measure of how much a drug is required in order to produce a particular effect. Therefore, only a small dosage of a high potency drug is required to induce a large response. The other terms used to measure the ability of a drug to trigger a response are:

• Intrinsic Activity which defines:
  • Agonists as having Intrinsic Activity = 1
  • Antagonists as having Intrinsic Activity = 0
  • and, Partial Agonist as having Intrinsic Activity between 0 and 1

• Intrinsic Efficacy also measures the different activated state of receptors, and the ability for a drug to cause maximum response without having to bind to all the receptors.

The specificity of drugs

Drug companies are obsessed with trying to make a drug that is specific only to the receptors they desire. This is because a drug could act on different receptors. Since receptors are located everywhere in the body, a non-specific drug will cause many more side effects than a more specific drug.

The actual conformation and shapes of the drugs will affect the specificity of the drugs. A good example is Acetylecholine (ACh). This drug is used by our body's parasympathetic nervous system to activate the muscarinic and nicotinic cholinergic receptors. However, research has discovered a drug which is more specific to each of these two receptors. In another words, the discovered drugs, namely Muscarine and Nicotine are more potent to their own receptors than ACh.

Image of Drugs Acetylecholine, Muscarine, Nicotine and Atropine

Affinity

The specificity of drugs cannot be talked about with mentioning the affinity of the drugs. The affinity is a measure of how tightly a drug binds to the receptor. If the drug does not bind well, then the action of the drug will be shorter and the chance of binding will also be less. This can be measured numerically by using the dissociation constant K_D. The value of K_D is the same as the concentration of drug when 50% of receptors are occupied.

The equation can be expressed as K_D =

But the value of K_D is also affected by the conformation, bonding and size of the drug and the receptor. The higher the K_D the lower the affinity of the drug.

References