General Principles of pharmacology.docx.pdf

General Principles of Pharmacology (Dr Abdulameer.K.Leelo) How the drug act in human body‫؟‬ Drug receptor: A drug receptor is a specialized target that binds a drug and mediates its pharmacological action. These receptors are specialized membrane-bound proteins. the drug-receptor complex: The forma...

General Principles of Pharmacology (Dr Abdulameer.K.Leelo) How the drug act in human body‫؟‬ Drug receptor: A drug receptor is a specialized target that binds a drug and mediates its pharmacological action. These receptors are specialized membrane-bound proteins. the drug-receptor complex: The formation drug-receptor complex will leads to a biological response. The degree of the biological response is proportional to the number of drug-receptor complexes. A common way to present the relationship between the drug concentration and the biological response is with a concentration- (or dose-) response curve. the biological effect is more closely related to the plasma concentration, so concentration-response curves are important. What are the Agonist?: Agonist: An agonist can be a drug or the endogenous hormone or enzyme for the receptor. Increasing concentrations of the agonist will increase the biological response until there are no more receptors for the agonist to bind or a maximal response has been reached. Example adrenaline , acetylcholine How the antagonist induce effect in the body? Antagonists: block or reverse the effect of agonists. The antagonist has no effect of their ownm its effect due to inhibition of the agonist effect. 1 | Page  The binding of an antagonist to a receptor does not produce a biological effect. The antagonist can block the effect of an agonist or it can reverse the effect of an agonist. Example: the mechanism of action of β-blockers, which block the effect of epinephrine or norepinephrine. Another method for antagonists is competitive; that is, they compete for the same site on the receptor that the agonist wants. If the agonist wins, a response is produced or if the antagonist wins, no response is produced. As we increase the concentration of the agonist, we increase the probability that an agonist molecule will win the receptor spot and produce an effect. At a high enough agonist concentration, the poor antagonist doesn’t have a chance at the receptor; it is simply outnumbered Therapeutic index: is a measure of drug safety. A drug with a higher therapeutic index is safer than one with a lower therapeutic index The lethal dose (LD50) is the dose that kills 50% of the animals that receive it. Sometimes the Toxic dose (TD50) is used in place of the LD50. Absorption, Distribution, and Clearance Orally administered drugs are absorbed from the gastrointestinal (GI) tract. The blood from the GI tract then travels through the liver, the great chemical plant in the body. Many drugs that undergo liver metabolism will be extensively metabolized during this passage from the GI tract to the body. This effect of liver metabolism is called the first-pass effect. 2 | Page What are the bio-availability of drugs? Bioavailability is the amount of drug that is absorbed after administration by route X compared with the amount of drug that is absorbed after intravenous (IV) which is 100%. Administration route X is any route of drug administration other than IV. Examples: oral, ointment, suppository, drops, & other methods. Suppose you are testing a compound in clinical trials, the new drug is administered orally and plasma levels determine that only 75% of the oral dose reaches the circulation. Compared with intravenous (IV) administration where 100% of the dose reaches the circulation, the bioavailability of the new drug is 0.75 or 75%. They discover that some of the drug is inactivated by the acid in the stomach. So redesign the pill with a coating that is stable in acid but dissolves in the more basic pH of the small intestine. The bioavailability of the drug increases to 95%. The new drug becomes a best-selling product. 3 | Page The plasma concentration designed against the time and the area under the curve is an indication of bioavailability. In this graph, an orally administered drug is compared with the same drug administered intravenously How the drugs clean from the body? TOTAL BODY CLEARANCE: Clearance is a term that indicates the rate at which a drug is cleared from the body. Total body clearance is the sum of the clearances from the various organs involved in drug metabolism and elimination (liver , kidney, GIT, lungs). It is defined as the volume of plasma from which all drug is removed in a given time. STEADY (constant) STATE CONCENTRATION: With multiple dosing, or a continuous infusion, a drug will accumulate until the amount administrated per unit of time is equal to the amount eliminated per unit of time. The plasma concentration at this point is called the steady-state concentration (Css). A continuous IV infusion of a drug was started at the beginning point of the graph. The concentration of the drug in the plasma was followed over time. When the amount delivered in a unit of time is equal to the amount eliminated in the same time unit, the plasma concentration is said to have reached a steady state. 4 | Page Rarely are drugs given as a single dose. Normally repeated doses are given and sometimes drugs are given as a continuous intravenous (IV) infusion like heparin. When a drug is given as a continuous infusion it will increase in concentration in the blood until the rate of elimination is equal to the infusion rate. At this point, the amount going in per unit time is equal to the amount going out. The plasma concentration at this point is called the concentration at steady state 5 | Page