FARMACOLOGÍA METABOLISMO Y ELIMINACIÓN DE FÁRMACOS | GuiaMed
Introduction to Pharmacokinetics
Overview of the Class
- The speaker, Christian Poos, introduces the topic of pharmacokinetics and sets the stage for today's class.
- Previous videos covered definitions, steps in pharmacokinetics, importance of administration routes, and detailed discussions on drug release, absorption, and distribution.
Key Concepts in Pharmacokinetics
- Pharmacokinetics is defined as what the body does to drugs; it consists of five key steps: Administration (A), Absorption (A), Distribution (D), Metabolism (M), and Elimination (E).
- Today's focus will be on metabolism and elimination processes.
Understanding Metabolism
Definition and Importance
- Metabolism involves enzymatic processes that transform drugs into active or inactive metabolites with increased solubility for easier elimination from the body.
Types of Metabolic Changes
- Two main changes occur during metabolism: activation (prodrugs converted to active forms) and inactivation (active drugs converted to metabolites).
Sites of Metabolism
Organs Involved
- While metabolism primarily occurs in the liver, it can also take place in kidneys, digestive system, skin, lungs, plasma, and even brain tissue.
Phases of Hepatic Metabolism
Phase 1 Reactions
- Phase 1 includes non-synthetic reactions leading to drug activation or inactivation. Key enzymes involved are part of the cytochrome P450 family.
Enzymatic Activity
- Cytochrome P450 enzymes play a crucial role; particularly CYP3A4 is responsible for about 50% of therapeutic drug metabolism.
Chemical Reactions in Phase 1
- Three main types of reactions occur:
- Oxidation: Addition of oxygen or loss of hydrogen; mainly involves alcohols and aldehydes.
- Reduction: Loss of oxygen or addition of hydrogen; typically involves aldehydes and ketones.
- Hydrolysis: Breakdown using water; commonly affects esters and glycosides.
Phase 2 Reactions
Conjugation Processes
- Phase 2 consists mainly of conjugation reactions where drugs combine with other substances formed within the body. Examples include glucuronidation and acetylation.
Location Within Liver Cells
Metabolism and Factors Influencing Biotransformation
Enzymatic Processes in Metabolism
- The process of metabolism involves various enzymes, including reductases that reduce nitrosative stress compounds and hydrolases that facilitate hydrolysis.
- Metabolism encompasses activation and inactivation of drugs, influenced by several factors affecting biotransformation.
Factors Affecting Biotransformation
Induction and Inhibition of Enzymes
- Induction refers to prolonged exposure to therapeutic drugs, leading to increased enzyme activity and consequently higher rates of drug metabolism.
- Conversely, inhibition occurs with prolonged drug exposure resulting in decreased enzymatic activity, which can elevate drug levels due to reduced metabolism.
Age as a Factor
- Both newborns and the elderly exhibit diminished hepatic enzyme levels, potentially prolonging the half-life of certain medications.
Gender Differences
- Males generally show higher enzymatic activity than females due to testosterone's role in enhancing this activity, while estradiol tends to decrease it.
Genetic Influences
- Genetic variations among individuals can lead to differing enzymatic activities; studies on mice have shown significant differences based on genetic strains.
Pharmacological Elimination Process
Definition and Mechanism
- Elimination is defined as the process through which drugs and their metabolites are expelled from the body. The renal system plays a crucial role in this elimination process.
Renal Function: The Nephron
- The nephron is the functional unit of kidneys responsible for drug elimination through three key processes:
- Filtration Glomerular: Passive filtration at the glomerulus allows low molecular weight substances (including free drugs not bound to proteins) to pass through.
- Reabsorption Tubular: Occurs primarily in the proximal tubule where lipophilic substances diffuse passively back into circulation.
Pharmacokinetics: Drug Elimination Mechanisms
Active Transport and Selectivity in Drug Elimination
- Ionized drugs undergo active transport, which is crucial for selective passage of lipophilic drugs over ionized ones.
- In the distal tubule, only active transport occurs, requiring energy; drug elimination speed increases with higher plasma drug levels.
- The pharmacological elimination process involves glomerular filtration, tubular reabsorption in the proximal tubule, and tubular secretion.
Various Routes of Drug Elimination
- Drugs can be eliminated through multiple organs beyond renal pathways, including pulmonary, gastrointestinal (GI), salivary, hepatic/biliary routes, and even through other bodily fluids.
Pulmonary and Gastrointestinal Elimination
- Pulmonary elimination occurs via diffusion of gases like oxygen and carbon dioxide; drugs are expelled with exhaled air.
- GI elimination typically involves enterally administered drugs being excreted in feces; absorption failures can lead to unintended drug elimination.
Salivary and Hepatic/Biliary Elimination
- Salivary elimination allows for the expulsion of various drugs such as antihypertensives or metals like mercury through saliva diffusion.
- Hepatic or biliary elimination is significant in pharmacokinetics; it involves drug processing by the liver before excretion into bile.
Colon and Other Liquid Eliminations
- Colon-based elimination differs from general GI processes as it relies on blood circulation to transfer drugs into the colon via diffusion or active transport.
- Other forms of elimination include secretions through tears, sweat, or breast milk; maternal drug consumption during breastfeeding poses risks to infants due to potential toxicity.
Conclusion and Engagement
- The discussion wraps up with a reminder about the importance of understanding these mechanisms for safe medication practices during lactation.
- Viewers are encouraged to engage with content by liking videos and suggesting topics for future discussions.