Pharmacokinetics Lecture 1 Lecture Notes PDF

**Subject** **Pharmacology** **Lecture 1** **Pharmacokinetics** **Name: Anas Suleiman** **Number: 0790028580** **Pharmacokinetics:** **Pharmacokinetics (PK)** involves the movement of drugs within the body and is described by four primary processes: absorption, distribution, metabolism, and e...

**Subject** **Pharmacology** **Lecture 1** **Pharmacokinetics** **Name: Anas Suleiman** **Number: 0790028580** **Pharmacokinetics:** **Pharmacokinetics (PK)** involves the movement of drugs within the body and is described by four primary processes: absorption, distribution, metabolism, and elimination (ADME). Understanding these processes is crucial for determining appropriate drug dosages and routes of administration. **1. Absorption** - **Overview**: Absorption is the process by which a drug enters the bloodstream from its site of administration (e.g., oral, intravenous). Key factors influencing absorption include drug formulation, route of administration, and physicochemical properties such as solubility, ionization, and molecular size. - **Mechanisms**: - **Passive Diffusion**: The most common process, where drugs move from a high concentration (e.g., GI tract) to a lower concentration (e.g., bloodstream) without energy use. Lipid-soluble and non-ionized drugs favor passive diffusion. - **Facilitated Diffusion**: Drugs move along a concentration gradient but require carrier proteins. For example, glucose transport via GLUT transporters. - **Active Transport**: Energy-dependent transport that moves drugs against their concentration gradient, using carriers like P-glycoprotein (important in the gut and brain). - **Endocytosis**: Larger molecules (e.g., proteins or antibodies) are engulfed by cell membranes in vesicles for cellular uptake. An example is vitamin B12 absorption in the intestines. - **Example**: Aspirin (a weak acid) is absorbed primarily in the stomach due to the acidic environment, favoring its non-ionized form for passive diffusion. **2. Distribution** - **Overview**: Distribution describes how drugs move from the bloodstream into tissues and organs. It is largely influenced by blood flow, tissue permeability, drug binding to plasma proteins (like albumin), and the drug\'s lipid solubility. - **Volume of Distribution (Vd)**: A theoretical volume that represents how extensively a drug distributes into body tissues relative to the blood. It helps in determining the loading dose. - **Low Vd**: Drugs that stay in the bloodstream, such as heparin. - **High Vd**: Drugs that distribute widely into tissues, such as lipophilic drugs like chloroquine. - **Example**: Warfarin, an anticoagulant, binds extensively to albumin, meaning only the free (unbound) fraction of the drug exerts its effect, leading to a low Vd. **3. Metabolism** - **Overview**: Metabolism primarily occurs in the liver and converts lipophilic drugs into more water-soluble metabolites for excretion. It is divided into two phases: - **Phase I (Functionalization Reactions)**: Introduces or exposes functional groups on the drug molecule through oxidation (often via cytochrome P450 enzymes), reduction, or hydrolysis. These reactions usually increase the drug\'s polarity. - **Example**: The metabolism of diazepam (Valium) through oxidation by CYP3A4. - **Phase II (Conjugation Reactions)**: The drug or its Phase I metabolite is conjugated with a larger polar molecule (e.g., glucuronide, sulfate) to increase solubility and facilitate renal excretion. - **Example**: Glucuronidation of morphine increases its solubility for excretion. - **Cytochrome P450 (CYP) Enzymes**: CYP enzymes are responsible for many Phase I reactions. Inducers (e.g., rifampin) can increase enzyme activity, leading to faster drug clearance, while inhibitors (e.g., ketoconazole) slow down metabolism, increasing drug levels. **4. Elimination** - **Overview**: Drugs are eliminated from the body through metabolism and excretion (primarily renal and biliary routes). Elimination kinetics determine how drug levels decline over time. - **First-Order Kinetics**: The majority of drugs follow first-order kinetics, where a constant fraction of the drug is eliminated per unit time. The rate of elimination is proportional to the drug concentration. - **Example**: Most antibiotics follow first-order elimination, where higher concentrations lead to faster clearance. - **Zero-Order Kinetics**: In zero-order kinetics, a constant amount of the drug is eliminated per unit time, regardless of concentration. This occurs when elimination pathways are saturated. - **Example**: Ethanol exhibits zero-order kinetics, where a constant amount is cleared per hour, regardless of how much is in the system. - **Half-life (t½)**: The time required for the drug concentration to decrease by half in the body. It is key to determining dosing intervals. **5. Steady State** - **Overview**: Steady-state concentration (Css) occurs when the rate of drug administration equals the rate of drug elimination. For most drugs, steady state is achieved after approximately 4-5 half-lives. - **Loading Dose**: Given to rapidly achieve therapeutic concentration, especially in drugs with a long half-life. For instance, digoxin requires a loading dose due to its long half-life. - **Example**: A patient receiving a continuous IV infusion of a drug like vancomycin will reach a steady state after several half-lives, and dosing can be adjusted based on therapeutic levels.