Receptors are cellular molecules that drugs bind to in order to produce a physiological effect. The affinity and intrinsic activity of a drug determine its effect. Affinity refers to how tightly a drug binds to a receptor, while intrinsic activity refers to the drug's ability to activate the receptor. Agonists have both high affinity and intrinsic activity, causing a physiological response by activating the receptor. Antagonists have affinity but no intrinsic activity - they bind receptors but don't activate them, instead blocking agonists from binding. A drug's strength depends on its binding affinity for receptors and the balance between therapeutic and toxic effects.
Receptors are cellular molecules that drugs bind to in order to produce a physiological effect. The affinity and intrinsic activity of a drug determine its effect. Affinity refers to how tightly a drug binds to a receptor, while intrinsic activity refers to the drug's ability to activate the receptor. Agonists have both high affinity and intrinsic activity, causing a physiological response by activating the receptor. Antagonists have affinity but no intrinsic activity - they bind receptors but don't activate them, instead blocking agonists from binding. A drug's strength depends on its binding affinity for receptors and the balance between therapeutic and toxic effects.
Receptors are cellular molecules that drugs bind to in order to produce a physiological effect. The affinity and intrinsic activity of a drug determine its effect. Affinity refers to how tightly a drug binds to a receptor, while intrinsic activity refers to the drug's ability to activate the receptor. Agonists have both high affinity and intrinsic activity, causing a physiological response by activating the receptor. Antagonists have affinity but no intrinsic activity - they bind receptors but don't activate them, instead blocking agonists from binding. A drug's strength depends on its binding affinity for receptors and the balance between therapeutic and toxic effects.
Receptor: Any cellular macromolecule that a drug binds to
initiate its effects. The natural function of a receptor is to
participate in neuotransmission or physiologic regulation.
Drug: A chemical substance that interacts with a biological system to produce a physiologic effect.
Factors Governing Drug Action
Two factors that determine the effect of a drug on physiologic processes are affinity and intrinsic activity.
Affinity is a measure of the tightness that a drug binds to the receptor.
Intrinsic activity is a measure of the ability of a drug once bound to the receptor to generate an effect activating stimulus and producing a change in cellular activity.
Affinity and intrinsic activity are independent properties of drugs. AGONISTS have both affinity, that is, the ability to bind to the receptor, as well as intrinsic activity, the ability to produce a measurable effect. ANTAGONISTS, on the other hand, only have affinity for the receptor. This property allows antagonists to bind to the receptor. However, because antagonists do not have intrinsic activity at the receptor no effect is produced. Because they are bound to the receptor, they can prevent binding of agonists. The Concept of Affinity The binding of a drug to a receptor is determined by the following forces: Hydrogen bonds Ionic bonds Van der Waals forces Covalent bonds To bind to a receptor the functional group on a drug must interact with complementary surfaces on the receptor. The binding of a drug, illustrated here as D, to the receptor, illustrated as R, can be described by this expression.
This is a reversible reaction and when at equilibrium, the rate of drug- receptor complex formation [DR] is equal to the rate of drug-receptor complex dissociation. In other words,
[D] [R] k 1 = [DR] k -1
The rate of formation of the drug-receptor complex is described by k 1 . In simpler terms k 1 describes the associate of a drug to its receptor. Similarly, k -1 is a term that describes the ease at which a drug dissociates from its receptor.
Affinity is a term that describes the strength of drug binding to its receptor and is the ratio of k 1 /k -1 .
Affinity = k 1 /k -1
Kd = k -1 /k 1
A drug which binds with great avidity to the receptor is said to have high affinity. That is k 1 (drug association) is much greater than k -1 (drug dissociation). Kd is the equilibrium dissociation constant. There is an inverse relationship between the Kd and affinity. The smaller the Kd, the greater the affinity. The equilibrium dissociation constant is an important term in pharmacology. This is a unique value for each drug. The units of the dissociation constant are some measure of concentration such as molar, millimolar, micromolar, nanomolar and so forth. Dissociation constants are usually small numbers, significantly less than 1, such as 1 x 10 -8 or 10 nanomolar. A drug that has a dissociation constant of 1 nanomolar is said to have a higher affinity than a drug that has a dissociation constant of 1 micromolar. This is because 1 nanomolar is much smaller than 1 micromolar. By appropriate manipulation we can write the equation:
Where [D] is the concentration of drug, [DR] is the concentration of receptor bound with drug, [RT] is the total number of receptors and Kd is the equilibrium dissociation constant. This equation describes the binding of drugs to pharmacologic receptors and states that the amount of drug bound to the receptor is dependent on the DRUG CONCENTRATION AND KD. To illustrate, assume that a drug has an equilibrium dissociation of 1nM. How many receptors would be occupied by a drug if it is given at a concentration of 0.5 nM? When a drug is given at a concentration equal to its Kd, 50% of the total receptor population will be occupied by the drug. To illustrate, assume a drug with a Kd of 1 nM is given at 1 nM.
Lowering blood pressure The Therapeutic Index The Therapeutic Index is the ratio of the ED50 of a drug to produce a lethal effect to the ED50 to produce a therapeutic effect. The dose required to produce death in 50 % of a population is referred to as the LD50. For the drug example above, the ED50 for the beneficial effect of blood pressure lowering is 0.4 nM while the LD50 is 40 nM. Therefore, the therapeutic index will be:
The Therapeutic Index is a measure of the safety of a drug. All other factors being equal, the larger the difference between the LD50 and ED50 the safer the drug.
Drugs that stimulate are called agonists and those that block are called antagonists. Narcotics are classic agonist drugs. These pain medications go to specific receptors in the body and cause the receptors to shut down the pain response. Non-steroidal medications (including aspirin) are classic antagonist drugs. Cyclo-oxygenase is an enzyme which is blocked by the anti-inflammatory medicines. Blocking this enzyme (antagonist) reduces inflammation and therefore decreases pain. About half of the drugs we use are agonists and the other half are antagonists. The strength of the drug is determined by how well they bind the receptor sites or how well they block those sites.