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PHARMACOLOGY • icmr notes
Drug-Receptor Interactions: • • Drugs are primary targets for receptors, which are tiny protein locks in cell membranes. • • Drug specificity is crucial for targeted action. • • Drugs can interact with receptors in two ways: as angonists (mimic natural molecules) or as antagonists (bind to receptor but don't activate it). • Pharmacokinetics: • • Explores the stages of drug absorption, distribution, metabolism, and elimination. • • Understanding these processes helps predict drug action, dosage requirements, and potential drug interactions.
Pharmacodynamics: • • Focuses on the mechanism of action, dose-response relationship, therapeutic effect, and side effects. • • Additional factors influencing drug action include age, genetics, physiological state, and drug interactions. • • Understanding these principles helps develop safer and more effective medications.
• Study of how the body absorbs, distributes, metabolizes, and excretes drugs. • • Absorption: Drugs enter the bloodstream via various routes, influenced by factors like chemical properties, administration route, and stomach presence. • • Distribution: Drugs are distributed throughout the body, influenced by blood flow, tissue binding, and cell membrane cross-linking. • • Metabolism (biotransformation): Drugs are metabolized in the liver to inactive or active metabolites, affecting effectiveness, toxicity, and action duration. • • Excretion: Drugs and their metabolites are excreted from the body, affecting concentration and action duration.
• Half-life: The half-life of a drug determines dosing frequency and steady-state concentration. • • Crucial in drug development and clinical practice, aiding in dosage regimens, drug interactions, and individual drug responses.
• Study of drug's biochemical and physiological effects on the body. • • Understanding how a drug interacts with its target molecule to produce its effects. Receptor Binding • • Drugs exert their effects by binding to specific receptors on cells. • • Types of Receptor Interactions: • • Drugs can inhibit or activate enzymes, altering biochemical pathways and cellular functions. • • Enzyme inhibitors block enzyme activity, while activators enhance enzyme activity. Ion Channel Interactions • • Drugs can modulate ion channels, affecting cell excitability and communication.
Second Messenger Systems • • Drugs can modulate receptors linked to second messenger systems, leading to changes in cellular function and gene expression. Quantitative Aspects • • Potency: The concentration of a drug required to produce a specific effect. • • Efficiency: The maximum effect a drug can produce, regardless of dose. • Affinity: The strength of binding between a drug and its receptor. • Dose-Response Relationships • • The relationship between the dose of a drug and its effect.
Drug metabolism and • elimination
Drug Metabolism: • • The liver plays a crucial role in drug metabolism, transforming the drug molecule into metabolites for easier elimination. • • Phases of drug metabolism include Phase I Reactions and Phase II Reactions. • • Factors influencing drug metabolism include enzyme activity, liver function, and the ionization state of drugs. Drug Elimination: The Final Farewell • • The kidneys are the primary route for excretion of water-soluble drugs and their conjugates. • • Factors affecting renal excretion include Glomerular Filtration Rate (GFR) and Urine pH. • • Other routes include Biliary Excretion and Pulmonary Excretion.
• Metabolism and elimination work together to remove drugs from the body. • • A well-metabolized and efficiently eliminated drug has a predictable duration of action and minimizes the risk of accumulation and potential toxicity. • Clinical Significance • • Understanding drug metabolism and elimination helps determine appropriate dosing frequency, understand drug interactions, and tailor drug therapy.
Types of Drug Receptors: • • Cell Surface Receptors: Located on the cell membrane, transmit signals from outside to the inside. • • Ion Channel Receptors: Control the flow of ions across the cell membrane. • • G Protein-Coupled Receptors (GPCRs): Activate intracellular signaling pathways through G proteins. • • Enzyme-Linked Receptors: Have enzymatic activity or are associated with enzymes activated upon ligand binding. • • Intracellular Receptors: Located inside the cell, activated by lipophilic ligands. Signaling Pathways: • • G Protein-Coupled Receptors (GPCRs): Activation leads to G proteins, regulating enzyme activity and cellular responses.
• Enzyme-Linked Receptors: Activation leads to the activation of intracellular kinase domains, regulating gene expression, cell growth, and differentiation. • • Ion Channel Receptors: Ligand binding causes conformational changes regulating ion flow across the cell membrane. • Downstream Effects: • • Gene Expression: Activation of certain receptors can lead to changes in gene expression. • • Cellular Responses: Receptor activation can lead to changes in cell membrane potential, secretion of neurotransmitters or hormones, and modulation of enzyme activity.
• Cell Signaling: • Receptors play a crucial role in cell communication and response to environmental changes. Drug-Receptor Interactions: • • Agonists: Bind to and activate receptors, mimicking the action of endogenous ligands. • • Antagonists: Bind to receptors but do not activate them, blocking the action of endogenous ligands or other agonists. • • Partial Agonists: Bind to receptors and produce a partial response, acting as both agonists and antagonists.
Drug Interactions: • • Drug interactions occur when two or more substances alter each other's effects within the body. • • Examples include increased drug levels, inhibition of metabolism, decreased protein binding, decreased drug levels, induction of metabolism, and decreased absorption. • • Pharmacodynamic interactions involve how drugs affect the body at a cellular or tissue level. • • Adverse drug effects (ADEs) are any unwanted or harmful effects of a medication beyond its intended therapeutic action. • Types of ADEs • • Type A Reactions (Augmented): Dose-related and predictable extensions of the drug's known pharmacological effects.
• Type B Reactions (Bizarre): Unpredictable and unrelated to the drug's mechanism of action. • • Type C Reactions (Continued Therapy): Arise due to prolonged use of a medication. Minimizing Drug Interactions and Adverse Effects • • Strategies include providing a complete medication history, clear communication, medication adherence, and genetic testing. • • Understanding these mechanisms can promote safer and more effective medication use and improve patient care.
• Uses detailed knowledge of a biological target to design a drug molecule that interacts with the target in a specific way. • • Contrasts with traditional methods of drug discovery, which often involve screening large libraries of compounds. Target Identification and Validation • • Identifies a specific biological target involved in a disease process. • • Validates the target to ensure modulating its activity will lead to a therapeutic benefit. Structure-Based Drug Design • • Determines the target's protein structure using techniques like X-ray crystallography or NMR spectroscopy.
• Identifies the binding site on the target where the drug molecule will interact. • • Uses computer-aided drug design (CADD) tools to design drug molecules to interact with the target in a specific way. Structure-Activity Relationship (SAR) Studies • • Optimizes lead compounds to improve their potency, selectivity, and pharmacokinetic properties. Pharmacokinetic and Toxicity Studies • • Tests lead compounds to determine their absorption, distribution, metabolism, and excretion (ADME) properties. • • Evaluates the safety profile of lead compounds to prevent harmful side effects.
Preclinical and Clinical Testing • • Tests lead compounds in animal models to evaluate their efficacy and safety. • • Moves to clinical trials to determine their safety and effectiveness. • FDA Approval • • Submits a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for approval to market the drug. • • Monitors the drug's safety and effectiveness through post-marketing surveillance studies.
• Drug development involves four phases: • Preclinical Research, Phase I Clinical Trials, Phase II Clinical Trials, Phase III Clinical Trials, and Phase IV Clinical Trials. • • Preclinical Research: Involves exploring a drug candidate's potential therapeutic effect, mechanism of action, and basic safety profile. • • Phase I Clinical Trials: First-in-human studies involving a small group of healthy volunteers. • • Phase II Clinical Trials: Expand the investigation to a larger group of patients with the specific disease or condition the drug targets. • • Phase III Clinical Trials: Large-scale, controlled trials involving hundreds or thousands of patients.
• Phase IV Clinical Trials (Post-Marketing Surveillance): Monitor the drug's long-term safety and effectiveness in a broader real-world setting. • Intricacies of Clinical Trials: • • Clinical Trial Design: Can be designed in various ways, with different control groups, blinding, and randomization. • • Ethical Considerations: Adhere to strict guidelines to protect participant safety and well-being. • • Data Analysis and Regulatory Approval: • Data from each trial phase is meticulously analyzed to assess the drug's safety and efficacy.
The Challenges and Importance of Clinical Trials: • • Clinical trials are complex, expensive, and time-consuming, but essential for ensuring the safety and effectiveness of new drugs. • • The future of drug development is constantly evolving, with new technologies like personalized medicine and gene therapy emerging.
