3.12
Distribución de medicamentos: Unión a proteínas plasmáticas
Los medicamentos se adhieren principalmente a las proteínas plasmáticas, quedando solo un pequeño porcentaje sin unir. La porción no unida se puede ca…
La mayoría de los fármacos se unen principalmente a proteínas plasmáticas como la albúmina, y sólo una pequeña fracción permanece sin unir. Esta fracción libre no ligada es igual a uno menos la fracción que está ligada.
Los fármacos ácidos se unen de forma reversible a la albúmina plasmática para formar grandes complejos inactivos que son incapaces de difundirse a través de las barreras biológicas.
Estos complejos fármaco-proteínas sirven como reservorios de fármacos. Cuando la concentración de fármacos libres disminuye, los complejos se disocian rápidamente, liberando el fármaco libre y manteniendo la fracción libre.
La cantidad de fármacos unidos a proteínas está influenciada por la concentración de fármaco y proteína libres, el número de sitios de unión y la afinidad entre el fármaco y los sitios de unión.
Diferentes fármacos o sustancias endógenas pueden unirse competitivamente a las proteínas plasmáticas.
Por ejemplo, la unión competitiva de la sulfonamida reduce la afinidad de la albúmina por la bilirrubina, lo que provoca la liberación de bilirrubina libre. Esto puede aumentar el riesgo de encefalopatía bilirrubínica en los recién nacidos.
Del mismo modo, durante el ejercicio, el metabolismo de las grasas libera altas concentraciones de ácidos grasos libres en el plasma. Estos ácidos grasos desplazan a los fármacos unidos a la albúmina y aumentan la concentración de fármacos libres.
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Q1: What fraction of drugs remains unbound in plasma?
Only a small fraction of drugs remains unbound in plasma, while most bind to plasma proteins like albumin. The unbound free fraction equals one minus the fraction that is bound. This free fraction is pharmacologically active and capable of producing drug effects and crossing biological barriers to reach target tissues.
Q2: How do drug-protein complexes function as drug reservoirs?
Acidic drugs reversibly bind to plasma albumin, forming large inactive complexes that cannot diffuse across biological barriers. When free drug concentration declines, these complexes rapidly dissociate to release free drug, maintaining the unbound fraction. This reservoir mechanism helps sustain drug availability and therapeutic effects throughout the body.
Q3: What factors determine the amount of protein-bound drug?
Protein-bound drug quantity depends on the concentration of free drug and protein, the number of available binding sites, and the affinity between drug and binding sites. These factors work together to establish equilibrium between bound and unbound drug states, influencing overall drug distribution and pharmacological activity.
Q4: How does competitive binding affect drug and bilirubin levels?
Different drugs and endogenous substances compete for plasma protein binding sites. When sulfonamide competitively binds to albumin, it reduces albumin's affinity for bilirubin, causing free bilirubin release. This increases bilirubin encephalopathy risk in newborns by elevating unbound bilirubin concentrations in the bloodstream.
Q5: What happens to drug-protein binding during exercise?
During exercise, fat metabolism releases high concentrations of free fatty acids into plasma. These fatty acids displace drugs bound to albumin through competitive binding, increasing the concentration of free, unbound drugs. This displacement can enhance drug bioavailability and potentially alter therapeutic effects and drug efficacy.
Q6: Why are acidic drugs unable to cross biological barriers when protein-bound?
Acidic drugs form large, inactive complexes when reversibly bound to plasma albumin. These complexes are too large and polar to diffuse across biological membranes, effectively sequestering the drug in the vascular compartment. Only the unbound free fraction can penetrate tissues and exert pharmacological effects at target sites.
Q7: How does the unbound drug fraction relate to drug efficacy?
Only the unbound free fraction of drug is pharmacologically active and capable of producing therapeutic effects. The unbound fraction is calculated as one minus the bound fraction. Changes in protein binding through competitive displacement or altered protein concentrations directly affect drug efficacy, clinical outcomes, and therapeutic success.