Farmacos via nasal

Medicamentos Vía Nasal

Elementos importantes de la vía nasal
Fossas - región olfactoria y región respiratoria Mucosa nasi Cilia - columnas de células epiteliales 3 meatos - superior, media e inferior Ducto nasolagrimal - meato inferoir + ductos lagrimales y senos - transferencia de drogas hasta el esófago

Elementos importantes de la vía nasal
Conexión a oído por la nasofaringe oespacio postnasal y el canal auditivo Única conexión entre el medio ambiente y el SNC Viaje por la placa cibriforme - neuronas oflactorias, células de soporte del lecho capilar, fluido cerebroespinal Absorción por difusión pasiva - lipófilas y no-ionizadas

Elementos importantes de la vía nasal
Mucus = 95-97% agua, 2.3-3% sales, 1-2% mucina - capa de 5 a 20 µm Escleroproteína - movimiento ciliar yretención de sólidos Movimiento ondulatorio Dirección de la faringe de 4 a 6 mm/min

Mecanismos en la vía nasal
Estornudo - irritación de filetes nerviosos Exudación - permeabilidad capilar aumentada Hipersecreción Obsrucción nasal por inflamación Prurito, hidrorrea - histamina

Usos de la vía nasal
Local Uso sistémico de proteinas y péptidos Alta vascularidad 200 cm2 para absorción de drogaspotentes V acunas - moléculas polares y grandes

able, pharmacological effects much later. As an example, the cytokine intraleukin-2 (IL-2) (in its PEG-ylated form) is rapidly cleared from the blood compartment and a pharmacological effect (increase

other options have a low bioavailability. Some bioavailability data on the intratracheal administration of proteins in rats are shown in Table35.5. The extent of absorption depends strongly on the nature

Table 35.4 Alternative routes of administration to the oral route for biopharmaceuticals (adapted from Crommelin and Sindelar 1998)
Route Nasal Relative advantage Easily accessible, fast uptake, proven track record with a number of 'conventional' drugs, probably lower proteolytic activity than in the Gl tract, avoidance of first-passeffect, spatial containment of absorption enhancers is possible Relatively easy to access, fast uptake, proven track record with 'conventional' drugs, substantial fractions of insulin are absorbed, lower proteolytic activity than in the Gl tract, avoidance of hepatic first-pass effect, spatial containment of absorption enhancers (?) Easily accessible, partial avoidance of hepatic first-pass effect,probably lower proteolytic activity than in the upper parts of the Gl tract, spatial containment of absorption enhancers is possible, proven track record with a number of 'conventional' drugs Easily accessible, avoidance of hepatic first-pass effect, probably lower proteolytic activity than in the lower parts of the Gl tract, spatial containment of absorption enhancers is possible, option toremove formulation if necessary Easily accessible, avoidance of hepatic first-pass effect, removal of formulation is possible if necessary, spatial containment of absorption enhancers is possible, proven track record with 'conventional' drugs, sustain/controlled release possible Relative disadvantage Reproducibility (in particular under pathological conditions), safety (e.g. ciliary movement), lowbioavailability for proteins Reproducibility (in particular under pathological conditions, smokers/ non-smokers), safety (e.g. immunogenicity), presence of macrophages in the lung with high affinity for particulates Low bioavailability for proteins

Pulmonary

Rectal

Buccal

Low bioavailability of proteins, no proven track record yet (?)

Transdermal

Low bioavailability of proteins551

Acción local
Objetivo: repermeabilizar, disminuir la secreción e inflamación Antimicrobianos, vasoconstrictores, antialérgicos, humectantes, corticoides y mucolíticos AB: eficacia relativa por periodos que permiten creación de resistencia Simpaticomiméticos - vasoconstrictores -efecto de rebote

Beneficios de la vía nasal
Perfiles plasmáticos sostenidos o pulsátiles Rápida absorción...