FARMACOCINÉTICA ABSORCIÓN DISTRIBUCIÓN METABOLISMO ELIMINACIÓN | GuiaMed

Introduction to Pharmacokinetics and Asthma

Overview of the Session

• The speaker, Christian Poos Alico Halcón, introduces the topic of pharmacokinetics and asthma.

• The session will cover detailed steps in pharmacokinetics including release, absorption, distribution, metabolism, and elimination.

Definition and Importance of Pharmacokinetics

• Pharmacokinetics is defined as what the body does to drugs; it encompasses all processes affecting drug action.

• A mnemonic for remembering pharmacokinetic steps is "LADME," which stands for Liberation, Absorption, Distribution, Metabolism, and Elimination.

Understanding Drug Release

Defining Drug Release

• Drug release refers to the processes that allow the active ingredient to exit its pharmaceutical form (e.g., capsule or tablet).

• This process typically occurs when a drug reaches the duodenum or intestine after administration.

Key Concepts in Drug Release

• Active Ingredient: The substance responsible for producing a pharmacological effect (e.g., naproxen or ibuprofen).

• Excipients: Inactive substances used to deliver the active ingredient without having any therapeutic effect (e.g., flavorings or colorants).

• Pharmaceutical Form: The combination of active ingredients and excipients that forms a medication (e.g., capsules or solutions).

Types of Pharmaceutical Forms

Categories of Pharmaceutical Forms

• Solid forms include powders, capsules, tablets, and suppositories.

• Semi-solid forms consist of ointments and creams.

• Liquid forms encompass syrups, solutions, suspensions, and injectable medications.

Summary of Key Terms

• Active ingredients produce effects; excipients are inactive carriers. Together they create pharmaceutical forms leading to effective medications.

The Process of Absorption

Defining Absorption

Understanding Drug Absorption Mechanisms

Overview of Blood Circulation and Drug Absorption

• The process of drug absorption involves the transition from the site of administration to the bloodstream, requiring various mechanisms for effective penetration through cellular membranes.

Composition of Cellular Membranes

• All organisms consist of cells with cellular membranes, which are crucial for drug penetration. Understanding membrane composition is essential for grasping how drugs enter the body.

Structure of Cell Membranes

• Cell membranes primarily comprise cholesterol, proteins, and phospholipids. These components create a lipophilic environment that facilitates drug entry.

Mechanisms of Transport Across Membranes

• Drugs penetrate cell membranes via two main transport mechanisms: passive transport and specialized transport.

• Passive transport includes simple diffusion and filtration.

• Specialized transport encompasses facilitated active transport and pinocytosis.

Classification of Transport Mechanisms

• Transport mechanisms are generally classified into passive (simple diffusion, facilitated diffusion) and active (primary and secondary active transport), based on ATP usage.

• Active transport utilizes ATP to move substances against concentration gradients, while passive methods do not require energy.

Factors Influencing Drug Absorption

Solubility as a Key Factor

• Solubility affects how easily a drug can pass through cell membranes. Drugs can be categorized as:

• Lipophilic (fat-soluble), which pass through membranes more readily.

• Hydrophilic (water-soluble), which may struggle unless they are low molecular weight compounds.

Formulation Impact on Absorption

• The pharmaceutical formulation influences absorption efficiency:

• Solid forms like tablets require dissolution before absorption occurs, making them less efficient compared to liquid formulations such as syrups or suspensions.

Concentration Effects on Drug Types

• The type of drug also plays a role in absorption rates:

• Weak acids/bases dissociate partially in solution, while strong acids/bases fully dissociate. Stronger dissociation typically leads to faster absorption rates.

Additional Factors Affecting Absorption

• Other factors influencing drug absorption include:

• pH levels in gastric juices,

• blood circulation,

• surface area available for absorption,

Understanding Drug Absorption and Distribution

Factors Influencing Drug Absorption

• The absorption of a drug is directly related to blood circulation; higher blood flow leads to greater absorption, while lower flow results in reduced absorption.

• Surface area plays a crucial role in absorption; larger surface areas enhance drug uptake, with the intestinal mucosa and pulmonary alveolar epithelium being key sites for this process.

• Molecular size affects absorption; smaller molecules are absorbed more easily than larger ones due to their ability to pass through biological membranes more readily.

Understanding Drug Distribution

• Drug distribution refers to the movement of a drug from the bloodstream into body tissues where it exerts its effects.

• Once in circulation, drugs travel through the bloodstream to reach various tissues, which is essential for their therapeutic action.

Mechanisms of Drug Distribution

• The initial step in distribution involves the binding of drugs to plasma proteins within the bloodstream.

• Common plasma proteins include albumin, alpha-1 acid glycoprotein, lipoproteins, and steroid-binding globulin. Each protein has an affinity for different types of drugs.

Protein Binding Dynamics

• Albumin primarily binds acidic drugs, while alpha-1 acid glycoprotein and lipoproteins are more associated with basic drugs. Steroid-binding globulin has a strong affinity for cortisol and steroids.

• When bound to proteins, drugs are inactive and do not exert therapeutic effects. Only unbound (free) drugs are pharmacologically active.

Implications of Protein Binding on Efficacy

• The percentage of a drug that binds to plasma proteins determines its activity level; for instance, penicillin binds 60% while ibuprofen binds 90%, meaning only 40% and 10% respectively remain active.

Distribution of Drugs in the Body

Overview of Drug Distribution

• Various drugs can pass through active tissues, targeting organs such as the heart, lungs, liver, brain, stomach, and kidneys.

• The second step in pharmacokinetics is drug distribution to different body organs.

Blood-Brain Barrier

• The central nervous system has a unique barrier known as the blood-brain barrier (BBB), which regulates tissue permeability.

• The BBB restricts large molecules from entering the brain while allowing non-ionized small molecules to penetrate.

• Capillary endothelial junctions are narrower in the BBB, making it difficult for larger drugs to access cerebral tissues.

Drug Binding and Release

• Drugs can bind to plasma proteins for extended periods (from hours to years), acting as reservoirs that gradually release medication into circulation.

• Plasma proteins serve as storage sites for drugs but may not provide immediate therapeutic effects compared to free drug forms.

Tissue Affinity of Drugs

• Some drugs have specific affinities for certain tissues beyond just binding with plasma proteins.

• Examples include heavy metals like mercury and bismuth accumulating in kidneys and liver; digoxin primarily deposits in the heart; tetracyclines tend to accumulate in bones and teeth.

Mechanisms of Redistribution

• Redistribution occurs via active transport rather than simple diffusion or filtration processes.

• Understanding where different drugs deposit within organs is crucial for effective treatment strategies.

Factors Influencing Drug Distribution

Key Factors Affecting Distribution

• Similar to absorption, various factors influence drug distribution including organ size, blood flow rate, protein binding affinity, solubility of the drug, and volume of distribution.

Organ Size

• Larger organs have a greater capacity for drug distribution; significant examples include intestinal mucosa and skeletal muscle.

Blood Flow Rate

Understanding Drug Distribution and Protein Binding

The Role of Plasma Proteins in Drug Activity

• A drug bound to plasma proteins is considered inactive, while free drugs are active. This highlights the importance of understanding protein binding in pharmacology.

• If a drug binds excessively to proteins (over 80%), it can lead to a lack of free, active drug available for therapeutic effects, complicating distribution.

• Knowledge of specific binding percentages for each medication is crucial; for example, ibuprofen and penicillin have different binding characteristics.

Solubility and Its Impact on Drug Distribution

• Drugs can be lipophilic (fat-soluble) or hydrophilic (water-soluble). Lipophilic drugs generally distribute more effectively than hydrophilic ones.

• Molecular weight also affects distribution; low molecular weight compounds tend to distribute more readily compared to high molecular weight ones.

Volume of Distribution Explained

• Volume of distribution (Vd) refers to the apparent space in the body that a drug occupies. It is calculated using the formula: Vd = amount of drug in the body / plasma concentration.

• Understanding Vd helps determine how widely a drug will be distributed throughout the body.

Clinical Examples Illustrating Volume of Distribution

• In dehydrated patients, reduced water compartments lead to decreased volume of distribution and increased plasma concentration of medications.

• Conversely, in patients with fluid overload, an increased volume of distribution results in lower plasma concentrations for the same dosage.

Conclusion and Engagement

• The concept of volume of distribution is essential for determining appropriate dosages based on individual patient conditions.

• Viewers are encouraged to engage with content by liking videos and suggesting topics for future discussions.