Pharmacodynamics PDF

Pharmacodynamics Kirk Cyrus Nada, BSN, RN Learning Objectives At the end of this lecture, students will be able to: 1. Define the meaning of pharmacodynamics. 2. Determine the therapeutic index and drug safety. 3. Familiarize with graded dose response relationship and therapeutic Responses 4. Di...

Pharmacodynamics Kirk Cyrus Nada, BSN, RN Learning Objectives At the end of this lecture, students will be able to: 1. Define the meaning of pharmacodynamics. 2. Determine the therapeutic index and drug safety. 3. Familiarize with graded dose response relationship and therapeutic Responses 4. Differentiate potency and efficacy. 5. Understand the cellular receptions and drug action as well the types of drug receptor Interactions. 6. Discuss the pharmacodynamics of specific drugs. Pharmacodynamics The study of the interactions between the chemical components of living systems and the foreign chemicals, including drugs, that enter those systems. how medications exert their effects on the body and how the body responds to these medications. Mechanisms of Action Drug Interactions Therapeutic Effects Individual Variation Dose-Response Relationship Monitoring and Evaluation Onset, Peak, and Duration Patient Education Side Effects and Adverse Reactions *Drugs usually work in one of four ways* To replace or act as substitutes for missing chemicals To increase or stimulate certain cellular activities To depress or slow cellular activities To interfere with the functioning of foreign cells, such as Invading microorganisms or neoplasms leading to cell death Therapeutic Index & Drug Safety The therapeutic index of a drug is a key parameter in pharmacology that quantifies the relative safety of a drug by calculating the ratio between the dose that causes toxicity in half the population (50%) to the dose that proves to be effective for half the population (50%). Therapeutic Index & Drug Safety The larger the therapeutic index (TI), the safer the drug is. If the TI is small (the difference between the two concentrations is very small), the drug must be dosed carefully and the person receiving the drug should be monitored closely for any signs of drug toxicity. Importance of Therapeutic Index of a Drug The therapeutic index (TI) is the range of doses at which a medication is effective without unacceptable adverse events. Therapeutic Window The dose range of a drug that provides safe and effective therapy with minimal adverse effects. Generally, at low concentrations, a drug runs the risk of being ineffective; at high concentrations, the risk of adverse effects is increased. Graded Dose-Response Relationship As the concentration of a drug increases, the magnitude of its pharmacologic effect also increases. The graph of the response versus the drug concentration or dose is called a graded dose- response curve. The response is a graded effect, meaning that the response is continuous and gradual. This contrasts with a quantal response, which describes an all-or-nothing response. Plotting the same data on a semilogarithmic concentration axis usually results in a sigmoid curve. These plots are often employed because the range of doses (or concentrations) may span several orders of magnitude. Graded Dose-Response Relationship As the concentration of a drug increases, the magnitude of its pharmacologic effect also increases. The graph of the response versus the drug concentration or dose is called a graded dose- response curve. The response is a graded effect, meaning that the response is continuous and gradual. This contrasts with a quantal response, which describes an all-or-nothing response. Plotting the same data on a semilogarithmic concentration axis usually results in a sigmoid curve. These plots are often employed because the range of doses (or concentrations) may span several orders of magnitude. Therapeutic Index Measurement of drug safety Refers to the relationship between toxic and therapeutic dosing Therapeutic Index a safer drug has a higher therapeutic index (very large lethal dose, very small effective dose) a more dangerous drug has a lower therapeutic index (may require regular monitoring of drug levels) A drug's effect can be evaluated in terms of potency and efficacy. POTENCY (strength) refers to the amount of drug needed to produce an effect q (e.g., relief of pain or reduction of blood pressure). EFFICACY is a drug's capacity to produce an effect q (such as lowering blood pressure).  "[Potency is] an expression of the activity of a drug, in terms of the concentration or amount needed to produce a defined effect.” - Neubig et al. (2003) "Different drugs may have varying capacities to initiate a response and consequently occupy different proportions of the receptors when producing equal responses. This property will be referred to as the efficacy of the drug". - Stephenson (1956) Two drugs can be equiefficacious (i.e., produce the same maximal response) but vary in potency (dose required to produce the response). Cellular Receptors and Drug Response Many drugs interact with specific cellular proteins known as receptors. As a result of this interaction, activation or inhibition of a sequence of biochemical events is usually initiated. Cellular Receptors These are specialized proteins located on or within cells that recognize and bind to specific molecules, known as ligands. These ligands can be hormones, neurotransmitters, drugs, or other signaling molecules. The binding of a ligand to its receptor triggers a series of events that ultimately lead to a cellular response. Types of Cellular Receptors G-protein-coupled receptors (GPCRs) These are the most common type of receptor in the human body. They are embedded in the cell membrane and are linked to intracellular G-proteins. When a ligand binds to a GPCR, it activates the G-protein, which in turn can initiate a variety of cellular responses, such as changes in gene expression or activation of enzymes. Types of Cellular Receptors Enzyme-linked receptors These receptors are also embedded in the cell membrane and are linked to enzymes. When a ligand binds to an enzyme-linked receptor, it activates the enzyme, leading to a cellular response. Types of Cellular Receptors Ion channel-linked receptors These receptors are ion channels that open or close in response to ligand binding. This can alter the flow of ions into and out of the cell, affecting the cell's electrical properties and signaling pathways. Types of Cellular Receptors Intracellular receptors These receptors are located inside the cell, in the cytoplasm or nucleus. They bind to lipid-soluble ligands that can pass through the cell membrane. When a ligand binds to an intracellular receptor, it forms a complex that can enter the nucleus and regulate gene expression. Cellular-Receptor Interactions Drugs often act by binding to specific cellular receptors. This binding can lead to a variety of effects, including: Agonists: Drugs that bind to and activate a receptor, mimicking the effects of the natural ligand. Antagonists: Drugs that bind to a receptor but do not activate it, blocking the effects of the natural ligand. Inverse agonists: Drugs that bind to a receptor and produce an effect opposite to that of the natural ligand. Factors Affecting Cellular-Response The response to a drug can be influenced by several factors, including: Affinity: The strength of the interaction between a drug and its receptor. Efficacy: The ability of a drug to produce a maximum response. Potency: The concentration of a drug required to produce a given effect. Selectivity: The ability of a drug to bind to a specific receptor subtype. Pharmacokinetics: The absorption, distribution, metabolism, and excretion of a drug. Pharmacodynamics: The study of how drugs interact with the body to produce their effects.