Farmacocinética: DISTRIBUIÇÃO | Aula 5 | Farmacologia rápida e fácil | Flavonoide

Pharmacokinetics: Understanding Drug Distribution

Introduction to Drug Distribution

• The video begins with an introduction to pharmacology, focusing on the distribution of drugs within the body after absorption.

• It highlights how drugs travel through the bloodstream, reaching various tissues and compartments in the body.

Mechanisms of Drug Distribution

• The discussion includes a diagram from a previous lesson on pharmacokinetics, illustrating how drugs enter different compartments and interact with binding molecules, primarily proteins.

• Key proteins involved in drug binding are identified: Albumin (attracts acidic drugs) and Alpha-1 acid glycoprotein (binds basic drugs).

Impact of Protein Binding

• When a drug binds to these proteins, it forms a large complex that cannot easily pass into other compartments, thus limiting its action.

• Only free (unbound) drugs can exert therapeutic effects by interacting with receptors; bound drugs remain inactive until released.

Factors Influencing Drug Equilibrium

• As metabolism and excretion occur, the balance between bound and free drug shifts. Proteins release bound drugs back into circulation as they become metabolized.

• Drugs with high protein affinity tend to have prolonged action due to slower dissociation from their protein complexes.

Redistribution of Drugs

• The concept of redistribution is introduced; once a drug has acted on its target, it may return to plasma before being excreted or redistributed elsewhere.

Additional Factors Affecting Distribution

Blood Perfusion

• Blood flow to tissues significantly affects drug distribution; organs like the heart and liver receive more blood compared to adipose or bone tissue.

Lipophilicity

• Lipid solubility plays a crucial role in crossing cell membranes; lipophilic drugs penetrate barriers more effectively than hydrophilic ones.

Age and Body Composition

• Age impacts body composition—children have higher water content while elderly individuals may have altered fat distribution affecting drug behavior.

Pathological Conditions

• Health conditions such as liver disease can reduce plasma protein levels, leading to increased free drug concentrations which may enhance effects or toxicity.

Complications in Drug Interactions

Displacement Phenomenon

• Co-administration of multiple drugs can lead to competition for binding sites on proteins, resulting in increased free concentrations of some medications which could cause adverse effects.

Non-Specific Binding Issues

Understanding Drug Distribution in the Body

The Attraction of Drugs to Biological Structures

• Drugs can be attracted to chemically appealing structures within the body, leading to non-specific binding rather than targeting intended sites.

• Lipophilic drugs may target adipose tissue despite not being designed for it, due to their ability to cross barriers and affinity for fat.

• Tetracycline antibiotics preferentially bind to calcium, resulting in accumulation in bone tissue, which leads to various contraindications.

Concept of Volume of Distribution

• The body is theoretically divided into compartments; understanding these helps explain drug distribution.

• Concentration of a drug in a compartment can be calculated by dividing the dose by the volume of that compartment.

• Different compartments have varying volumes: 0.6 L/kg for water, 0.2 L/kg for extracellular fluid, and only 0.04 L/kg for plasma.

Practical Implications of Drug Distribution

• Plasma does not equally distribute drugs throughout the body; some factors cause drugs to remain more concentrated in plasma than others.

• Volume of distribution (Vd) indicates how much drug is distributed outside the plasma compared to its concentration there.

Calculating Volume of Distribution

• Vd is calculated as total amount of drug in the body divided by its concentration in plasma; this provides insight into how extensively a drug disperses.

• For example, administering 50 mg with a plasma concentration of 0.1 mg/L results in a Vd calculation yielding an abstract value (500 liters), indicating extensive distribution beyond physical volume.

Conclusion on Drug Behavior

• A high Vd suggests that a drug is widely distributed throughout the body rather than remaining confined within blood plasma.

• Understanding these concepts aids comprehension in pharmacology and highlights important considerations regarding medication effects and interactions.