Receptor regulation in pharmacology.pptx

Pharmacy

1. Receptor Regulation Dr. Usman Ali, Ph.D. Pharmacology

2. Revision

3. Therapeutic Index Is the ratio of the LD50 to ED50 Represent an estimate of the safety of a drug .

4. Efficacy describes ability of drug-bound receptor to produce a response. Potency is the amount of drug needed to produce a certain response. Affinity describes strength of drug binding with receptor. Intrinsic activity – capacity to induce a functional change in the receptor.

5. Command Center Reception

6. Receptors A receptor is that  component  (macromolecule) of a cell (on or inside the cell) that interacts with the drug, and this interaction leads to a chain of events that alter the activity of the cell. Important: Drug binds to the receptors to illicit a biological response (toxic/therapeutic). Effectors Effectors are  molecules that act in response to the drug  (or more precisely, the  drug-receptor complex ) and participate in the aforementioned chain of intracellular events leading to the drug’s effects .

7. Command Center Reception Reception Reception Reception

8. Command Center Reception Reception Reception Reception Reception Reception Reception Reception Reception Reception

9. Command Center Reception Reception

10. Upregulation Upregulation (i.e ., increase in the number) of receptors occurs when the  activity of the receptor is lower than usual  (e.g., due to long-term administration of an antagonist). For example, administration of beta-blockers upregulates β adrenoreceptors . Thus, if  β-blockers  are abruptly stopped, it can cause rebound hypertension because of the sudden stimulation of a large number of β adrenoreceptors .

11. Chronic decrease in the concentration of hormone and in response the target cell increase the no of receptor to and normalize/regularize the normal physiological activities. Hypersensitivity Why? To cause effective stimulation Two method 1 activate inactivated receptor 2. Over production of receptors via message to nucleus

12. Downregulation Downregulation (i.e., decrease in number) is the inverse of upregulation. It  occurs due to repeated or long-term administration  of an agonist. Along with downregulation, desensitization of the receptor to the drug may also occur. This is a physicochemical alteration in the receptor which makes it unresponsive to the drug; this is also called tachyphylaxis and is seen in chronic drug use, for example. Important:  The process is useful in the prevention of cell damage due to the high concentration of an agonist.

13. Chronic increase in the concentration of hormone and the target cell decrease the receptors to and normalize/regularize the physiological activities. Hyposensitivity ( sensitivity to ligand is decreased) Why? To stop over stimulation

14. Agonists Drugs that bind to physiological receptors and mimic the regulatory effects of the endogenous signaling compounds are termed agonists . If the drug binds to the same recognition site as the endogenous agonist (the primary or orthosteric site on the receptor) the drug is said to be a primary agonist . Allosteric agonists bind to a different region on the receptor referred to as an allosteric site.

15. Antagonist Drugs that block or reduce the action of an agonist are termed antagonists . Antagonism most commonly results from competition with an agonist for the same or overlapping site on the receptor (a syntopic interaction) Physical antagonist binds to the drug and prevents its absorption like charcoal binds to alkaloids and prevents their absorption. Chemical antagonist combines with a substance chemically like chelating agents binds with the metals. Physiological antagonist produces an action opposite to a substance but by binding to the different receptors e.g. adrenaline is a physiological antagonist of histamine because adrenaline causes bronchodilatation by binding to β 2 receptors, which is opposite to bronchoconstriction caused by histamine through H1 receptors. Pharmacological antagonists produce no effect , shows no intrinsic activity.

16. Partial agonists - Agents that are only partly as effective as agonists regardless of the concentration employed. Inverse agonists - Many receptors exhibit some constitutive activity in the absence of a regulatory ligand ; drugs that stabilize such receptors in an inactive conformation are termed inverse agonists (produce effect opposite to that of agonist).

17. POTENCY The amount of the drug needed to produce a given effect. potency is determined by the affinity of the receptor for the drug. The dose causing 50% from the maximal effect (EC50) can be obtained from graded dose-response curve. In quantal dose response curve, ED50, TD50 and LD50 are potency variables.

18. Repeated administration of a drug results in diminished effect “ Tolerance ”. Tachyphylaxis : is a type of tolerance which occurs very rapidly . Desensitization: decreased response to the agonist after its repeated injection in small doses. May be due to 1- Masking or internalization of the receptors. 2- Loss of receptors (down regulation)- decreased synthesis or increased destruction. 3- Exhaustion of mediators (depletion of catecholamine).