Pharmacodynamics Lecture 2024 PDF

PHARMACODYNAMICS Seini Vi Class of 2024 Semester 2 Learning Objectives Compare and contrast the terms potency and efficacy. Distinguish among an agonist, a partial agonist, and an antagonist. Explain the relationship between receptors and drug action. THE GRADED...

PHARMACODYNAMICS Seini Vi Class of 2024 Semester 2 Learning Objectives Compare and contrast the terms potency and efficacy. Distinguish among an agonist, a partial agonist, and an antagonist. Explain the relationship between receptors and drug action. THE GRADED DOSE RESPONSERELATIONSHIP AND THERAPEUTIC RESPONSE As discussesd, frequency distribution curves were used to visualize patients differences in responses to medications in a population It is also useful to visualize the variability in responses observed within a single patient. Grade – Dose Response relationship is a fundamentaal concept in pharmacology. By observing and measuring the patient’s response obtained at different doses of the drug, one can explain several important clinical relationships. POTENCY AND EFFICACY POTENCY -A drug that is more potent will produce a therapeutic effect at a lower dose, compared with another drug in the same class. For example, consider two agents, drug X and drug Y, that both produce a 20-mm drop in blood pressure. If drug X produces this effect at a dose of 10 mg and drug Y produces it at 60 mg, then drug X is said to be more potent. Thus, potency is one way to compare the doses of two independently administered drugs in terms of how much is needed to produce a particular response. EFFICACY The second method used to compare drugs is called efficacy, which is the magnitude of maximal response that can be produced from a particular drug.  Which is more important to the success of pharmacotherapy, potency or efficacy? drug A is more potent because it requires a lower dose to produce the same effect. drug A is more efficacious because it pro- duces a higher maximal response. Examples for Potency and Efficacy Specific example of headache pain. Two common over-the-counter (OTC) analgesics are ibuprofen (200 mg) and aspirin (650 mg). The fact that ibuprofen relieves pain at a lower dose indicates that this agent is more potent than aspirin. At recommended doses, however, both are equally effective at relieving headache pain; thus, they have the same efficacy. If the patient is experiencing severe pain, however, neither aspirin nor ibuprofen has sufficient efficacy to bring relief. Narcotic analgesics such as morphine have a greater efficacy than aspirin or ibuprofen and can effectively treat this type of pain. From a pharmacotherapeutic perspective, efficacy is almost always more important than potency. In the previous example, the average dose is unimportant to the patient, but headache relief is essential. As another comparison, the patient with cancer is much more concerned about how many cancer cells have been killed (efficacy) than what dose the nurse administered (potency). Although the nurse will often hear claims that one drug is more potent than CELLULAR RECEPTORS AND DRUG ACTION Drugs act by modulating or changing existing physiological and biochemical processes. To exert such changes requires that drugs interact with specific molecules and chemicals normally found in the body. A cellular macromolecule to which a medication binds in order to initiate its effects is called a receptor. Receptor theory explains the mechanisms by which most drugs produce their effects. It is important to understand, however, that these receptors do not exist in the body solely to bind drugs. Their normal function is to bind endogenous molecules such as hormones, neurotransmitters, and growth factors. Although a drug receptor can be any type of macromolecule, the vast majority are proteins.  a receptor is depicted as a three- dimensional protein associated with the cellular plasma membrane. The extracellular structural component of the receptor usually consists of several protein subunits arranged around a central canal or channel. Other protein segments as a part of the receptor macromolecule are inserted into the plasma membrane. Channels may be opened by changes in voltage across the membrane as when voltage-gated calcium channels are opened when electrical signals arrive at nerve endings. In this instance, an electrical signal will open channels and calcium will rush into the nerve terminal to release vescles containing endogenous neurotransmitters. Chemical gated channels, a second type of receptor, will be activated by neurotransmitters after they are released into the synapse. How Drugs Attaches to it’s Receptor A drug attaches to its receptor in a specific manner, in much the way that a thumb drive docks to a USB port in a computer. Small changes to the structure of a drug, or its receptor, may weaken or even eliminate binding (docking) between the two molecules. Once bound, drugs may trigger a series of second messenger events within the cell, such as the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cyclic AMP), the release of in- tracellular calcium, or the activation of specific G proteins and associated enzymes. This is very much like the internal actions that go on within a computer. Biochemical cascades initiate the drug’s action by either stimulating or inhibiting normal activity of the cell. NOT ALL RECEPTORS BOUND TO PLASMA MEMBRANE Not all receptors are bound to plasma membranes; some are intracellular molecules such as DNA or enzymes in the cytoplasm. By interacting with these types of receptors, medications are able to inhibit protein synthesis or regulate cellular events such as replication and metabolism. Examples of agents that bind intracellular components include steroid medications, vitamins, and hormones.  RECEPTORS AND THEIR ASSOCIATED DRUG MECHANISMS Receptors and their associated drug mechanisms are extremely important in therapeutics. Receptor subtypes are being discovered and new medications are being developed at a faster rate than at any other time in history. These subtypes permit the “fine-tuning” of pharmacology. For example, the first medications affecting the autonomic nervous system affected all autonomic receptors. It was discovered that two basic receptor types existed in the body, alpha and beta, and drugs were then developed that affected only one type. The result was more specific drug action, with fewer adverse effects. Still later, several subtypes of alpha and beta receptors, including alpha1, alpha2, beta1, and beta2, were discovered that allowed even more specificity in pharmacotherapy. SOME DRUGS ACT INDEPENDENTLY OF CELLULAR RECEPTORS Some drugs act independently of cellular receptors. These agents are associated with other mechanisms, such as changing the permeability of cellular membranes, depresing membrane excitability, or altering the activity of cellular pumps. Actions such as these are described as nonspecific cellular responses. Ethyl alcohol, general anesthetics, and osmotic diuretics are examples of agents that act by non- TYPES OF DRUG RECEPTOR INTERCATIONS When a drug binds to a receptor, several therapeutic consequences can result. In simplest terms, a specific activity of the cell is either enhanced or inhibited. The actual biochemical mechanism underlying the therapeutic effect, however, may be extremely complex. In some cases, the mechanism of action is not known. When a drug binds to its receptor, it may produce a response that mimics the effect of the endogenous regulatory molecule. For example, when the drug bethanechol (Ure- choline) is administered, it binds to acetylcholine receptors in the autonomic nervous system and produces the same ac- tions as acetylcholine. AGONIST, PARTIAL AGONIST,ANTAGONIST A drug that produces the same type of response as the endogenous substance is called an agonist. Agonists sometimes produce a greater maximal response than the endogenous chemical. The term partial agonist or agonist-antagonist drug describes a medication that produces a weaker, or less efficacious, response than an agonist. A second possibility is that a drug will occupy a receptor and prevent the endogenous chemical from acting. This drug is called an antagonist. ANTAGONISTS COMPETES WITH AGONISTS Antagonists often compete with agonists for the receptor binding sites. For example, the drug atropine competes with acetylcholine for specific receptors associated with the autonomic nervous system. If the dose is high enough, atropine will inhibit the effects of acetylcholine, because acetylcholine cannot bind to its receptors. FUNCTIONAL ANTAGONISTS INHIBITS AGONIST EFFECTS Not all antagonism is associated with receptors. Functional antagonists inhibit the effects of an agonist not by competing for a receptor but by changing pharmacokinetic factors. For example, antagonists may slow the absorption of a drug. By speeding up metabolism or excretion, an antagonist may en hance the removal of a drug from the body. The relationships that occur between agonists and antagonists explain many of the drug–drug and drug– food interactions that occur in the body.  ACTIVITY A nursing student reads in a pharmacology textbook that 10 mg of morphine is considered to provide the same pain relief as 200 mg of codeine. This indicates that the morphine would be considered more ______________ than codeine. (Fill in the blank.) 3.What is the term used to describe the magnitude of maxi- mal response that can be produced from a particular drug? 1. Efficacy 2. Toxicity 3. Potency 4. Comparability 3. The nurse looks up butorphanol (Stadol) in a drug reference guide prior to administering the drug and notes that it is a partial agonist. What does this term tell the nurse about the drug? 1. It is a drug that produces the same type of response as the endogenous substance. 3. It is a drug that will occupy a receptor and prevent the endogenous chemical from acting. 4. It Is a drug that causes unpredictable and unexplained drug reactions. 5. It is adrug that produces a weaker,or less efficacious, response than an agonist drug. The nurse reads that the drug to be given to the patient, has a “narrow therapeutic index.” The nurse knows that this means that the drug has what properties? 1. It has a narrow range of effectiveness and may notgive this patient the desired therapeutic results. 2. It has a narrow safety margin and even a small increase in dose may produce adverse or toxic effects. 3. It has a narrow range of conditions or diseases that the drug will be expected to treat successfully. 4. It has a narrow segment of the population for whom the drug will work as desired. CRITICAL THINKING If the ED50 is the dose required to produce an effective response in 50% of a group of patients, what happens in the other 50% of the patients after a dose has been administered?