Question

How do bulk, active, and passive transport move drugs through the body and into the brain

Answer 1

Many drugs need to pass through one or more cell membranes to reach their site of action. A common feature of all cell membranes is a phospholipid bilayer, about 10 nm thick. Spanning this bilayer or attached to the outer or inner leaflets are glycoproteins, which may act as ion channels, receptors, intermediate messengers (G-proteins) or enzymes. Cells obtain molecules and ions from the extracellular fluid, creating a constant in and out flow. The interesting thing about cell membranes is that relative concentrations and phospholipid bilayers prevent essential ions from entering the cell. Therefore in order for drugs to move across the membrane these problems must be addressed. In general, this is completed by facilitated diffusion or active transport. In facilitated diffusion, relative concentrations are used to transport in and out. Active transports uses energy (ATP) to transfer molecules and ions in and out of the cell.

Concept of drug cross the cell membrane

Cellular signals cross the membrane through a process called signal transduction. This three-step process proceeds when a specific message encounters the outside surface of the cell and makes direct contact with a receptor. A receptor is a specialized molecule that takes information from the environment and passes it throughout various parts of the cell. Next, a connecting switch molecule, transducer, passes the message inward, closer to the cell. Finally, the signal gets amplified, therefore causing the cell to perform a specific function. These functions can include moving, producing more proteins, or even sending out more signals.

Methods of Drug cross the cell membrane

Passive Transport

The most common method for drugs to cross the cell membrane is by Passive Diffusion. Drug molecules will diffuse down its concentration gradient without expenditure of energy by the cell. However, the membranes are selectively permeable, so it has different effects on the rate of diffusion on different drug molecules. The rate of diffusion also can be enhancing by transport proteins in the membrane by Facilitated Diffusion. There are two types of transport proteins that carry out the facilitated diffusion, Channel protein and Carrier Protein.

Active transport

Active transport is an energy-requiring process. The drug molecule, transport against the a concentration gradient, and most of the protein used are carrier proteins, rather than channel proteins. There are also two type of active transport

Primary active transport which directly uses energy to transport molecules across a membrane.Sometime the carrier protein can be an electrogenic pump.

In secondary active transport or Co-transport also uses energy to transport molecules across a membrane. However, It differs from primary transport is that there is no direct coupling of Adenosine triphosphate|ATP; instead, the electrochemical potential|electrochemical potential difference created by pumping ions out of the cell is used.

Into the brain drugs acts by passing blood brain barrier

The blood–brain barrier (BBB) prevents the brain uptake of most pharmaceuticals. This property arises from the epithelial-like tight junctions within the brain capillary endothelium. The BBB is anatomically and functionally distinct from the blood–cerebrospinal fluid barrier at the choroid plexus. Certain small molecule drugs may cross the BBB via lipid-mediated free diffusion, providing the drug has a molecular weight <400 Da and forms <8 hydrogen bonds. These chemical properties are lacking in the majority of small molecule drugs, and all large molecule drugs. Nevertheless, drugs can be reengineered for BBB transport, based on the knowledge of the endogenous transport systems within the BBB. Small molecule drugs can be synthesized that access carrier-mediated transport (CMT) systems within the BBB. Large molecule drugs can be reengineered with molecular Trojan horse delivery systems to access receptor-mediated transport (RMT) systems within the BBB. Peptide and antisense radiopharmaceuticals are made brain-penetrating with the combined use of RMT-based delivery systems and avidin–biotin technology. Knowledge on the endogenous CMT and RMT systems expressed at the BBB enable new solutions to the problem of BBB drug transport.