Mechanisms of Drug Action

           ➤A fundamental concept of pharmacology is that to initiate an effect in a cell, most drugs combine with some molecular structure on the surface of or within the cell. This molecular structure is called a receptor.The combination of the drug and the receptor results in a molecular change in the receptor,such as an altered configuration or charge distribution,and thereby triggers a chain of events leading to a response.
           ➞ This concept applies not only to the action of drugs but also to the action of naturally occurring substances,such as hormones and neurotransmitters.Indeed,many drugs mimic the effects of hormones or transmitters because they combine with the same receptors as do these endogenous substances.
           ➞It is generally assumed that all receptors with which drugs combine are receptors for neurotransmitters,hormones, or other physiological substances.

           ➞ Thus, the discovery of a specific receptor for a group of drugs can lead to a search for previously unknown endogenous substances that combine with those same receptors.For example, evidence was found for the existence of endogenous peptides with morphinelike activity.A series of these peptides have since been identified and are collectively termed endorphins and enkephalins .

 ☆DRUG RECEPTORS AND BIOLOGICAL RESPONSES∶➞ 

         ➞ Although the term receptor is convenient, one should never lose sight of the fact that receptors are in actuality.

➞molecular substances or macromolecules in tissues that combine chemically with the drug. Since most drugs have a considerable degree of selectivity in their actions, it follows that the receptors with which they interact must be equally unique.

➞Thus,receptors will interact with only a limited number of structurally related or complementary compounds. The drug–receptor interaction can be better appreciated through a specific example.

➞The end-plate region of a skeletal muscle fiber contains large numbers of receptors having a high affinity for the transmitter acetylcholine. 

➞Each of these receptors, known as nicotinic receptors, is an integral part of a channel in the postsynaptic membrane that controls the inward movement of sodium ions.

➞.The acetylcholine combines with the receptors and changes them so that channels are opened and sodium flows inward. 

➞The more acetylcholine the end-plate region contains, the more receptors are occupied and the more channels are open.When the number of open channels reaches a critical value, sodium enters rapidly enough to disturb the ionic balance of the membrane,resulting in local depolarization. 

➞The local depolarization (end-plate potential) triggers the activation of large numbers of voltage-dependent sodium channels, causing the conducted depolarization known as an action potential.

➞The action potential leads to the release of calcium from intracellular binding sites.