General and Systematic Veterinary Pharmacology

BARRIERS TO DRUG DISTRIBUTION

Blood brain barrier: (BBB)

• A physical / functional barrier which does not permit ionized and non lipid soluble drugs to pass through into the Central Nervous System
• It is mainly formed by the endothelial cells of the CNS blood vessels. Its purpose is to protect the brain from the chemical environment of the rest of the body due to the delicate balance between excitation and inhibition maintained within the CNS.
• The brain capillaries do not contain fenestrations (holes). There are more tight junctions in brain capillaries decreasing the rate of diffusion through interstitial spaces. Glial cells ensheath the brain capillaries providing a second set of cell membranes which must be traversed as well as a second intracellular compartment where cellular metabolic processes can transform entering substances
• Chemical or enzymatic barrier - MonoAmineOxidase, cholinesterase - This barrier prevents 5 HT, catecholamines, ACh from entry into CNS
• Carrier mediated transport – to facilitate exit of drugs
• Highly lipophilic drugs enter easily because they cross membranes. (Fig. 18) Unionized forms of drugs enter more easily than ionized forms. Penicillin, streptomycin, gentamicin – do not cross the BBB
• Chloramphenicol - can cross the BBB

Placenta

• Virtually not a barrier
• Any drug taken by mother is likely to affect the fetus
• Hence care must be taken while administering drugs to pregnant animals. Only highly ionised drugs and drugs with low lipid solubility are excluded from passing through the placenta.
• It is important from the point of view of teratogenicity of drugs

Milk

• Governed by rules of passage across membranes.
• The mammary gland epithelium, like the other biological membranes act as a lipid barrier and many drugs readily diffuse from the plasma into the milk.
• The pH of milk varies somewhat; but in goats and cows it is generally 6.5 – 6.8 if mastitis is not present. Weak bases tend to accumulate in milk because the fraction of ionized, nondiffusible drug is higher. Agents delivered by intramammary infusion can diffuse into the plasma to a greater or lesser degree based on pH differences and the pKa of the drug.
• In cows Maximum Residue Levels (MRL) in milk has been  recommended for many drugs to minimise human exposure risk.
• In case of drug admnistration, milk to be discarded upto withdrawal time.