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Drugs (2) (Purpose (Permeate physical barrier, Navigate blood &…

- - - - Cellular Sink
- - - - Proteins
      - Peptides
      - GF
      - Antibodies
      - Heparin
      - Glucagon
- - - - Step 1: Intracellular communication => Bind of immune & endothelial cell glycoprotein receptors
      - Step 2: Immune cells cross BBB through paracellular route => Dissolution of brain endothelial cell tight junctions
      - Step 3: Neuroinflammation
  - - - Step 1: Insulin across BBB influencing sympathetic nervous system outflow => Control liver glucose output
      - Step 2: High glucose level in Central Nervous System (CNS) => More ATP & Reactive Oxygen Species (ROS)
      - Step 3: Pericytes sensitive to oxidative stress => Loss => BBB Disruption
- - - - Many drugs possible to be administered
      - Requires Craniotomy
    - - By Cerebrospinal Fluids
      - Epidural Injection
- - - - Skin
        
        Highly Specialized
        
        Controls Permeability
        
        Protects against external attacks
        
        UV
        
        Pathogens
        
        Toxic chemicals
        
        Regulates temp & hydration
        
        Preserves & Maintains internal steady state
      - Mucus
        
        Lines all internal organs
      - Blood-Brain Barrier (Fig 16)
        
        Allows selective molecules to enter
        
        Tightly regulated endothelial layers
        
        Regulates permeation
        
        Gap Junction Proteins
        
        Tight-junction Proteins
      - Mucin
    - - Extracellular
        
        Epithelial
        
        Biological
        
        RES
        
        Phagocytic Cells
        
        Neutrophil
        
        Eosinophil
        
        Basophil
        
        Monocyte
        
        T Cell
        
        B Cell
        
        Natural Killer
        
        Macrophages
      - Intracellular
        
        Cell Membrane
        
        Endosomal Barrier
        
        Proteolytic Enzymes
        
        Nuclear Membrane
- - - - Hydrophobic drugs cross intestinal mucosa through transcellular pathway
    - - Hydrophilic drugs cannot penetrate cellular membrane so use paracellular pathway
    - - Receptor-mediated uptake of drug
    - - Efflux Pumps
        
        Example
        
        P-glycoprotein (Fig 17)
        
        ATP Powered Drug Efflux Pump
        
        Protects from intake of harmful substances
        
        Transportation hydrophobic molecules
        
        Organs