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The three ways by which substances, including drugs, can cross cell membranes are simple diffusion, facilitated diffusion and active transport. Diffusion is the mechanism by which the vast majority of drugs pass across cell membranes. Both simple diffusion and facilitated diffusion are passive processes in that no energy is required other than the kinetic energy of the molecules themselves.
Several factors are known to influence the diffusion of substances across the cell membrane: в the membrane must be permeable to the substance in question; в there must be a concentration gradient; в the molecular sizeweight of the substance must be small enough; в a large surface area is necessary for efficient diffusion; в a short distance is necessary for efficient diffusion. In practice, there is a concentration gradient because the drug is given in sufficient dose, most drug molecules are small enough to be absorbed (otherwise, they would be of no use) and the surface area and distance of the absorbing membrane are favourable.
Simple diffusion is depicted in Figure Simple diffusion of drug molecules depends mostly on lipid solubility.
Simple diffusion is depicted in Figure Simple diffusion of drug molecules depends mostly on lipid solubility. The structure of the cell membrane can be a barrier to diffusion of drugs because it is essentially a lipid bilayer with proteins embedded in the inner and outer surfaces. Lipid-soluble substances diffuse easily through the lipid bilayer and include oxygen, carbon dioxide, fatty acids, steroids and fat-soluble vitamins. The lipid solubility of a drug depends on its state of ionization.
Certain small ions, for example sodium, potassium, calcium and chloride can pass through ion channels in the cell membrane.