Anesthetics Agents and Pharmacokinetics PDF

Anesthetics Agents Dr. Abbas AlZubaidi- College of Healthcare TEchnologies- AUIB and Pharmacokinetics...

Anesthetics Agents Dr. Abbas AlZubaidi- College of Healthcare TEchnologies- AUIB and Pharmacokinetics Dr. Abbas AlZubaidi- College of Healthcare Technologies- AUIB 1  Anesthetic Agents and Medications Objective: Dr. Abbas AlZubaidi- College of Healthcare TEchnologies- AUIB Classify and describe different types of anesthetic agents. Understand properties and administration of inhalation anesthetics. Explore pharmacokinetics and pharmacodynamics of intravenous anesthetics. Discuss patient safety and dosage calculations. 2  Lecture 1: Classification of Anesthetic Agents Dr. Abbas AlZubaidi- College of Healthcare TEchnologies- AUIB Overview: inhalation, intravenous, and local anesthetics. Classification: mechanism of action, chemical structure, and clinical applications. Differences: volatile vs gaseous inhalation anesthetics. Importance: selecting appropriate agents based on patient and surgical procedures.  Lecture 2: Inhalation Anesthetics Properties: potency, solubility, and MAC. Techniques: vaporization, anesthesia machine, and Dr. Abbas AlZubaidi- College of Healthcare TEchnologies- AUIB breathing systems. Monitoring: control of depth during inhalation anesthesia. Common agents: desflurane, sevoflurane, isoflurane, and nitrous oxide.  Lecture 3: Intravenous Anesthetics Overview: rapid onset, duration, and elimination. Pharmacokinetics and pharmacodynamics. Dr. Abbas AlZubaidi- College of Healthcare TEchnologies- AUIB Techniques: bolus injections, continuous infusions, and target-controlled infusions. Common agents: propofol, etomidate, barbiturates, and opioids.  Lecture 4: Sedatives and Adjunct Medications Role of sedatives and adjunct medications. Common sedatives: benzodiazepines, Dr. Abbas AlZubaidi- College of Healthcare TEchnologies- AUIB dexmedetomidine, and ketamine. Adjunct medications: muscle relaxants, antiemetics, analgesics, and anticholinergics. Considerations: based on patient characteristics and surgical procedures.  Lecture 5: Pharmacokinetics and Pharmacodynamics Introduction to pharmacokinetics. Concept of drug half-life and clearance. Dr. Abbas AlZubaidi- College of Healthcare TEchnologies- AUIB Pharmacodynamics: interaction with receptors and effect on neurotransmission. Factors influencing pharmacokinetics and pharmacodynamics.  Lecture 6: Patient Safety and Dosage Calculations Importance of patient safety. Dosage calculations: drug concentration, dilution, and dosing regimens. Dr. Abbas AlZubaidi- College of Healthcare TEchnologies- AUIB Special populations: pediatric, geriatric, and patients with comorbidities. Prevention and management of medication errors.  ADMINISTRATION OF ANESTHETIC AGENTS Dr. Abbas AlZubaidi- College of Healthcare Technologies-AUIB ANT101- Lecture 1 Dr. Abbas AlZubaidi College of Healthcare Technologies - AUIB 9  ADMINISTRATION OF ANESTHETIC AGENTS Page 594 The process of introducing anesthetic agents into the body. Methods vary based on the type of anesthetic and surgical procedure. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB 10  UPTAKE OF INHALED ANAESTHETIC AGENTS Page 594 Inhalation is a common method of administering anesthetics. The process involves several phases, each influencing the drug's effect. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB ❑ Uptake of inhaled anesthetic agents refers to the process by which these volatile agents move from the lungs into the bloodstream after inhalation. Once the patient inhales the anesthetic, it diffuses from the alveoli in the lungs into the pulmonary blood based on its concentration gradient. ❑ The speed and efficiency of this uptake are influenced by several factors, including the solubility of the anesthetic in blood, the alveolar ventilation rate, and the pulmonary blood flow. ❑ Highly soluble agents tend to equilibrate slowly, leading to a gradual onset of anesthesia, while agents with low solubility exhibit a faster onset. Once in the bloodstream, the inhaled anesthetic is transported to various tissues and organs, with the brain being the primary target to achieve the desired anesthetic effect. 11  Delivery phase Page 594 The initial phase where the anesthetic is introduced to the patient. Ensures a controlled and consistent delivery of the drug. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB Definition: The delivery phase for an anesthesia agent marks a crucial step in the administration of anesthesia during medical procedures. During this phase, the chosen anesthetic agent is introduced to the patient's system, often through inhalation or intravenous routes. Precise equipment, such as vaporizers and infusion pumps, ensures a controlled and accurate delivery. The anesthesiologist or anesthesia provider closely monitors the concentration and volume of the agent being delivered, adjusting as necessary to achieve the desired depth of anesthesia. Throughout this phase, patient safety and comfort are of paramount importance, with continuous monitoring of vital signs and responses to ensure an optimal surgical environment. 12  Pulmonary phase Page 595 The anesthetic is absorbed into the lungs. Factors like lung ventilation and blood flow can Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB influence uptake. Definition The pulmonary phase refers to the stage in which an inhaled anesthetic agent interacts with the respiratory system, specifically the lungs, before entering the bloodstream. Upon inhalation, the anesthetic agent traverses the alveoli in the lungs, where it undergoes passive diffusion based on its concentration gradient. The solubility of the agent in the blood and its partial pressure determine the speed at which equilibrium is reached between the alveolar air and the blood. The pulmonary phase is of particular importance because it dictates the rate of onset and offset of the inhaled anesthetic. Factors like alveolar ventilation, cardiac output, and blood-gas solubility can influence the efficiency of this phase, and thus, the overall effectiveness of the anesthesia. 13  Circulatory phase Page 596 The anesthetic is distributed throughout the body via the bloodstream. Reaches target sites to produce the desired effect. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB Definition The circulatory phase pertains to the transportation of an inhaled anesthetic agent through the bloodstream after its absorption from the lungs. Once the anesthetic has crossed the alveolar membrane and entered the pulmonary blood, it is carried by the circulatory system to the heart and then distributed to various tissues and organs, including the brain where it exerts its primary anesthetic effects. The speed and efficiency with which the anesthetic is delivered to its target sites depend on factors such as cardiac output, blood flow to specific organs, and the solubility of the anesthetic in the blood. This phase plays a crucial role in determining the onset, depth, and duration of anesthesia, as well as the recovery process. 14  MINIMUM ALVEOLAR CONCENTRATION (MAC) Page 596 A measure of anesthetic potency. Represents the concentration needed to Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB prevent movement in 50% of patients exposed to a painful stimulus. A visualization showcasing a set of lungs with highlighted alveoli and a meter indicating the MAC value. Annotations emphasize its significance as a measure of anesthesia potency. 15  THE IDEAL VOLATILE AGENT Page 597 Criteria for the perfect inhaled anesthetic agent. Includes rapid onset, minimal side effects, and easy Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB administration. 16  SPECIFIC PHARMACOLOGY Page 597 Detailed study of various anesthetic agents. Each agent has unique properties and Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB applications. Anesthetic agents are essential for pain-free medical procedures. Each agent has distinct properties determining its use. Rapid-acting agents are ideal for short procedures. Prolonged-effect agents suit lengthier surgeries. Inhalation anesthetics (e.g., sevoflurane, nitrous oxide) are for general anesthesia. Local anesthetics (e.g., lidocaine) numb specific areas. Some agents offer muscle relaxation in addition to pain relief. Anesthesiologists must understand each agent's properties for safe and effective use. 17  Desflurane Page 600 A volatile anesthetic with rapid onset and recovery. Used for maintenance of general anesthesia. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB Desflurane: Desflurane is a highly fluorinated methyl ethyl ether used for induction and maintenance of general anesthesia. It has a rapid onset and offset, making it suitable for surgeries where quick changes in the depth of anesthesia are required. Desflurane is characterized by its low blood-gas solubility, leading to faster recovery times compared to other inhalational anesthetics. However, it can irritate the airways, making it less ideal for induction in patients with reactive airway diseases. Additionally, its environmental impact is of concern as it is a potent greenhouse gas. In clinical settings, desflurane is administered using a vaporizer specifically designed for its use due to its low boiling point. 18  Halothane Page 600 A widely used inhalation anesthetic. Known for its safety profile but can cause liver toxicity in rare cases. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB Halothane is a volatile inhalation anesthetic that was introduced in the 1950s and quickly became a preferred agent for general anesthesia due to its favorable properties, including rapid induction and relaxation of skeletal muscles. It is a colorless to straw-colored liquid with a sweet odor. While Halothane revolutionized anesthetic practice due to its safety profile compared to its predecessors, its use has declined in recent years because of concerns about its potential to cause liver toxicity in some patients and its association with malignant hyperthermia, a rare but severe reaction to certain anesthetics. Modern anesthetic agents with fewer side effects have largely replaced Halothane in many countries. 19  Isoflurane Page 601 A potent inhalation anesthetic. Preferred for its stable cardiovascular effects. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB Isoflurane is a halogenated ether used primarily as an inhalational anesthetic agent in surgical procedures. It is known for its rapid onset and offset, making it a preferred choice for maintaining anesthesia during surgeries. Isoflurane has a sweet, pungent odor and works by depressing the central nervous system, leading to a loss of sensation and consciousness. In addition to its anesthetic properties, it also has a muscle-relaxing effect. Isoflurane is considered safe and effective, but like all anesthetics, its administration requires careful monitoring to ensure the patient's safety. Over the years, it has largely replaced older inhalational anesthetics due to its favorable pharmacokinetic profile and fewer side effects. 20  Sevoflurane Page 602 An inhalation anesthetic with rapid onset and clinical manifestation offset. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB Suitable for outpatient surgeries due to quick patient recovery. A comprehensive diagram showcasing a bottle labeled 'Isoflurane' connected to an anesthesia machine, with a patient inhaling the vaporized Isoflurane through a face mask. Annotations detail its swift action, rapid onset, quick offset, and its efficiency & effectiveness. 21  Introduction to Pharmacodynamics ANT101- Lecture 2 Dr. Abbas AlZubaidi College of Healthcare Technologies - AUIB Dr. Abbas AlZubaidi- College of Healthcare Technologies - AUIB 22  Introduction to Pharmacodynamics Study of drug concentration effects on activity & response Described as 'what the drug does to the body' Focuses on the relationship between drug concentration and the Dr. Abbas AlZubaidi- College of Healthcare Technologies - AUIB resulting effect 23  Concentration–Effect Relationships Essential pharmacodynamic interaction Drug binds reversibly to a receptor Formation of a drug–receptor complex Dr. Abbas AlZubaidi- College of Healthcare Technologies - AUIB Effectiveness determined by drug concentration at the receptor site 24  Efficacy and Drug–Receptor Interactions Agonists: Bind to receptor & produce a maximal response Partial Agonists: Bind to receptor & produce less than maximal response Dr. Abbas AlZubaidi- College of Healthcare Technologies - AUIB Antagonism: Prevent binding by the agonist or interfere with the response outcome 25  Agonists Drugs that activate receptors to produce a response Mimic the body's natural regulatory molecules Can be endogenous (produced within the body) or exogenous (from Dr. Abbas AlZubaidi- College of Healthcare Technologies - AUIB outside the body) 26  Partial Agonists Bind to and activate a given receptor Have only a partial efficacy at the receptor relative to a full agonist Can act as both an agonist and antagonist Dr. Abbas AlZubaidi- College of Healthcare Technologies - AUIB 27  Antagonism Drugs that block the action of agonists Do not have an effect of their own on receptor activity Used to counteract the effects of agonists Dr. Abbas AlZubaidi- College of Healthcare Technologies - AUIB 28  Variations from Predictions Occupancy–Response Inconsistencies: Discrepancies between drug occupancy and resulting response Hysteresis: Delayed effects of drugs Dr. Abbas AlZubaidi- College of Healthcare Technologies - AUIB Pharmacogenetics: Study of how genetics influence drug responses 29  Enzymes in Pharmacodynamics Enzymes play a crucial role in drug metabolism & action Understanding enzyme interactions is vital for effective drug therapy Enzyme inhibitors can increase the effects of certain drugs Dr. Abbas AlZubaidi- College of Healthcare Technologies - AUIB 30  Key Mathematical Model Mathematical models help explain pharmacodynamic principles Models represent interactions of agonists & antagonists Graphical representation aids in understanding drug interactions Dr. Abbas AlZubaidi- College of Healthcare Technologies - AUIB 31  Conclusion Pharmacodynamics is crucial in understanding drug effects Helps in predicting drug responses and interactions Vital for safe and effective drug administration Dr. Abbas AlZubaidi- College of Healthcare Technologies - AUIB 32 Mechanisms of Drug Action ANT101- Lecture 3 Dr. Abbas AlZubaidi College of Healthcare Technologies -AUIB  Mechanisms of Drug Action Introduction to the various ways drugs interact with the body. Overview of the topics to be covered in the presentation. Importance of understanding these mechanisms for healthcare professionals. Dr. Abbas AlZubaidi- College of Healthcare Technologies- AUIB 34  Physicochemical Mechanisms Explanation of how drugs interact based on their physical and chemical properties. Charge Neutralization: Neutralizing charge of cells or molecules. Osmotic Effects: Influencing osmotic balance. Dr. Abbas AlZubaidi- College of Healthcare Technologies- AUIB Adsorption: Drugs adhering to surfaces. Chelation and Inclusion Complexes: Drugs forming complex structures. 35  Pharmacodynamic Mechanisms Overview of drug interactions with specific biological targets. Drug–Cell Membrane Receptors: Proteins on cell membranes initiating responses. Dr. Abbas AlZubaidi- College of Healthcare Technologies- AUIB Intracellular Receptors: Receptors inside the cell modulating function. 36  Pharmacokinetic Actions Discussion on drug movement within the body. Drug Interactions with Enzymes: Affecting metabolic processes. Dr. Abbas AlZubaidi- College of Healthcare Technologies- AUIB Drug Interactions with Transport Proteins: Interacting with transport proteins. 37  Mechanisms of General Anesthetic Action Overview of general anesthetics' effects. Anatomical Sites of Action: Specific regions in the body. Molecular Theories: Interaction at the molecular level. Membrane Lipids: Interaction with lipid layers. Protein Site(s) of Action: Binding to proteins. Dr. Abbas AlZubaidi- College of Healthcare Technologies- AUIB 38  Adverse Effects Discussion on harmful drug reactions. Physicochemical Effects: Reactions from drug properties. Pharmacodynamic Effects: Reactions from drug's action. Pharmacokinetic Effects: Reactions from drug's movement. Dr. Abbas AlZubaidi- College of Healthcare Technologies- AUIB Idiopathic Adverse Effects: Unexplained reactions. Hypersensitivity Reactions: Allergic reactions. Pharmacogenetic Influences: Genetic response factors. 39  Mechanisms of Drug Interactions Overview of drug influence on other drugs. Physicochemical: Interactions based on drug properties. Pharmacokinetic: Interactions affecting drug movement. Pharmacodynamic: Interactions affecting drug's action. Dr. Abbas AlZubaidi- College of Healthcare Technologies- AUIB 40 Pharmacokinetics ANT101- Lecture 4 Dr. Abbas AlZubaidi College of Healthcare Technologies- AUIB 41  Pharmacokinetics The study of how drugs move within the body. Covers absorption, distribution, metabolism, and excretion. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB Essential for determining dosage, route of administration, and potential interactions.  DRUG ADMINISTRATION Refers to the method by which a drug is introduced into the body. Ensures that the drug reaches its intended target in the body. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB Choice of administration can influence drug efficacy and patient compliance.  Absorption The process by which a drug moves from its site of administration into the bloodstream. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB Factors affecting absorption include drug formulation, pH, and blood flow. Critical for determining onset and intensity of drug action.  Enteral administration Drug administration via the gastrointestinal tract, e.g., oral, rectal. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB Most common method due to ease of administration. Affected by factors like gastric pH, food presence, and intestinal motility.  Parenteral administration Drug administration outside the digestive tract, e.g., intravenous, intramuscular. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB Used when rapid drug action is required or when oral administration is not feasible. Bypasses the first-pass metabolism, leading to faster and more complete absorption.  DISTRIBUTION How drugs are transported throughout the body. Influenced by blood flow, tissue permeability, and protein binding. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB Determines how quickly and effectively a drug reaches its target tissues.  Blood flow to tissues Determines the rate at which a drug reaches its target site. Organs with higher blood flow receive drugs more rapidly. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB Vital for drugs targeting specific organs or tissues.  Drug uptake by tissues How drugs are absorbed and used by various tissues. Depends on tissue permeability and drug solubility. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB Can influence drug duration and intensity of action. Drug Uptake by Tissues: When a drug is administered into the body, it doesn't remain confined to the bloodstream. Instead, it undergoes a process known as distribution, where it moves from the bloodstream into various body tissues. The rate and extent of drug uptake by tissues depend on several factors, including the drug's solubility, protein binding affinity, and the blood flow to specific organs. Highly perfused organs like the liver, kidneys, and heart tend to receive the drug more rapidly than less perfused tissues like muscle or fat. Additionally, the physicochemical properties of the drug, such as its size, charge, and lipid solubility, play a crucial role in determining which tissues or cells the drug can enter. Over time, the drug may accumulate in certain tissues, potentially leading to enhanced therapeutic effects or side effects. Understanding drug uptake by tissues is essential for predicting the drug's distribution pattern, duration of action, and potential interactions within the body.  Active transport The movement of drugs against a concentration gradient, requiring energy. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB Ensures efficient uptake of essential drugs by cells. Can be targeted or inhibited by other drugs, leading to interactions.  Protein binding Drugs can bind to proteins in the blood, affecting their distribution. Only unbound drugs can exert therapeutic effects. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB High protein binding can lead to drug interactions and reduced efficacy.  Placental transfer How drugs cross the placenta and affect the fetus. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB ○ Some drugs can harm the fetus, so careful consideration is needed during pregnancy. ○ Understanding this transfer is crucial for safe drug prescription in pregnant patients.  ELIMINATION The process by which drugs are removed from the body. Involves metabolism and excretion. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB Determines drug half-life and informs dosing intervals.  Enterohepatic circulation Circulation of drugs between the intestine and liver. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB Can prolong the action of certain drugs. Influences drug metabolism and can be a factor in drug-drug interactions.  Biotransformation Chemical changes that occur to a drug within the body. Mostly occurs in the liver and can render drugs more or less active. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB Affects drug safety and efficacy and can lead to metabolite-related side effects.  Extraction ratio The proportion of a drug that is removed from the blood during one circulation. Dr. Abbas AlZubaidi- College of Healthcare Technologies -AUIB High extraction drugs are rapidly cleared from the bloodstream. Influences dosing frequency and potential for drug accumulation.