Physiological Barriers To Drug Distribution

Blood-Brain Barrier

The capillary membrane between the plasma and brain cells is much less permeable to water-soluble drugs than is the membrane between plasma and other tissues. Thus, the transfer of drugs into the brain is regulated by the blood-brain barrier. To gain access to the brain from the capillary circulation, drugs must pass through cells rather than between them. Only drugs that have a high lipid-water partition coefficient can penetrate the tightly apposed capillary endothelial cells.

Drugs that are partially ionized and only moderately lipid soluble will penetrate at considerably slower rates. Lipid-insoluble or highly ionized drugs will fail to enter the brain in significant amounts. Because the pH of the cerebrospinal fluid is about 7.35, there is some tendency for weak organic bases to concentrate in the cere-brospinal fluid and for weak organic acids to be excluded. In addition, because only the unbound form of a drug is available for diffusion, extensive plasma protein binding also can have dramatic effects on the extent of drug transfer into the brain.

Inflammation, such as occurs in bacterial meningitis or encephalitis, may increase the permeability of the blood-brain barrier, permitting the passage of ionized lipid-insoluble compounds (e.g., penicillin and ampi-cillin) that would otherwise be restricted from penetrating into the brain extracellular fluid.

The flow of cerebrospinal fluid is essentially unidirectional; that is, it flows from its site of formation in the choroid plexus through the ventricles to its site of exit at the arachnoid villi. Drugs in this fluid can either enter the brain tissue or be returned to the venous circulation in the bulk flow of cerebrospinal fluid carried through the arachnoid villi. Some drugs, such as penicillin, will not leave the cerebrospinal fluid compartment by bulk flow but will be actively transported by the choroid plexus out of the fluid and back into the blood. Finally, drugs may diffuse from brain tissue directly into blood capillaries.

Though drugs appear to cross the blood-brain barrier by passive diffusion, transporter systems in the blood-brain barrier pump drugs back out into the systemic circulation. As in the gut, the Pgp transporter system is the primary active transporter in the blood-brain barrier identified to date. This ATP-dependent transporter system picks up substrates that have crossed the capillary endothelial cells and transports them back to the systemic circulation, limiting their penetration into the CNS. Thus, not only are the physicochemical properties of the drug a determinant for penetration into the CNS but penetration also depends on whether the drug is a substrate for the Pgp transporter system.

An important consequence of the existence of a variety of routes of drug removal from the brain is that drugs that slowly penetrate the CNS may never achieve adequate therapeutic brain concentrations. Penicillin, for example, is a less effective antibiotic centrally than it is peripherally.

Placental Barrier

The blood vessels of the fetus and mother are separated by a number of tissue layers that collectively constitute the placental barrier. Drugs that traverse this barrier will reach the fetal circulation. The placental barrier, like the blood-brain barrier, does not prevent transport of all drugs but is selective, and factors that regulate passage of drugs through any membrane (e.g.,pKa, lipid solubility, protein binding) are applicable here.

In general, substances that are lipid soluble cross the placenta with relative ease in accordance with their lipid-water partition coefficient and degree of ioniza-tion. Highly polar or ionized drugs do not cross the placenta readily. However, most drugs used in labor and delivery are not highly ionized and will cross. They are generally weak bases with pKa values of about 8 and tend to be more ionized in the fetal bloodstream, since the pH of fetal blood is around 7.3 as compared with the maternal blood pH of 7.44. Differences in maternal and fetal blood pH can give rise to unequal concentrations of ionizable drugs in the mother and the fetus.

Active efflux transporters also exist in the placenta, analogous to the gut and blood-brain barrier. These are Pgp, multidrug resistance-associated protein (MRP), and breast cancer resistance protein (BCRP). These transport proteins are located in many tissues but also appear to be expressed in the placenta. Though the substrate specificities of these proteins have not been completely described, they appear to function as efflux transporters, moving endogenous and exogenous chemicals from the placental cells back to the systemic circulation. In this way, they serve as a mechanism to protect the fetus from exposure to unintended chemicals.

Blood-Testis Barrier

The existence of a barrier between the blood and testes is indicated by the absence of staining in testicular tissue after the intravascular injection of dyes. Morphological studies indicate that the barrier lies beyond the capillary endothelial cells and is most likely to be found at the specialized Sertoli-Sertoli cell junction. It appears that Pgp, the efflux transporter protein, also plays a role in forming this blood-testis barrier. This protein probably plays a role in preventing certain chemotherapeutic agents from reaching specific areas of the testis and thus hinders treatment of the neoplasm.

^Study Questions

1. Following oral administration, a drug is absorbed into the body, wherein it can exert its action. For a drug given orally, the primary site of drug absorption is:

(A) The esophagus

(B) The stomach

(C) The upper portion of the small intestine

(D) The large intestine

2. Patients can exhibit alterations in the rate and extent of drug absorption because of various factors. All of the following factors might affect the rate and/or extent of drug absorption EXCEPT:

(A) Gastric emptying time

(B) Intestinal motility

(C) The presence of food

(D) The formulation of the drug

(E) A generic form of the drug

3. The body has developed defense mechanisms that reduce the amount of foreign chemicals, such as drugs, that enter the body. One of the more prominent of these mechanisms is an efflux transport system that pumps some drugs back into the intestinal lumen following absorption into the enterocytes and that is responsible for the lack of complete absorption of some drugs. This efflux transport system is:

(A) Facilitated diffusion

(B) P glycoprotein

(c) Cytochrome P450 3A (D) Pinocytosis

4. All of the following statements concerning the blood-brain barrier and the passage of drugs from the systemic circulation into the cerebrospinal fluid are TRUE EXCEPT:

(A) Ionized drugs are more likely to cross into the CSF than un-ionized drugs.

(B) The higher the lipid solubility of a drug, the more likely it will cross into the CSF.

(C) Inflammation of the meninges improves the likelihood that drugs will cross the blood-brain barrier as compared to the uninflamed state (i.e., normal condition).

(D) P glycoprotein serves to pump drugs back into the systemic circulation from endothelial cells lining the blood-brain barrier.

5. Which of the following organs or tissues is a potential site for drug accumulation of lead that has been ingested?

Was this article helpful?

+6 -1
10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook


  • Ulrich
    Is the placental barrier impermeable to water soluble drugs?
    7 years ago
  • Pontus
    What is a physiological barrier of drug distribution?
    7 years ago
  • Rahel
    What are d physiological barriers that affects drug distribution?
    6 years ago
  • haris
    What are physiological barriers to distribution of drugs?
    5 years ago
    Why penicillin cross placental barrier?
    5 years ago
  • Jonathan
    Can CNS drugs cross the placental barrier?
    5 years ago
  • Yohannes
    How does the placenta barrier acts as a barrier for drug distribution?
    5 years ago
  • taziano
    What are the barriers of drug in body?
    5 years ago
  • Maria Angelo
    Does ionisation of a drug can change blood brain barrier permeability?
    4 years ago
  • asmara
    What are the barriers to drug distribution in the body?
    4 years ago
  • Winta
    What are barriers of administration in pharmacology?
    4 years ago
    What features makes the brain, placenta and testis barriers to drugs?
    4 years ago
  • Kaija
    What are physical barriers of drug distribution?
    4 years ago
  • asmeret
    What is the physical barrier to drug absorption of urethral route?
    4 years ago
  • delma
    Why placental brrier is not affective as blood brain barreir?
    4 years ago
  • patrizio
    Which medicine will not go through placental barriers?
    4 years ago
  • markus
    How does blood brain barrier effect drug distribution?
    4 years ago
  • medhanie
    What are the natural barrier that prevent drug distribution?
    4 years ago
  • kevin
    How does placental barrier affect drug distribution?
    4 years ago
    Is amniotic sac a physical barrier to drug distribution?
    4 years ago
  • kidane
    How is placenta a barrier to absorption?
    4 years ago
  • Daniel
    How drugs crosses plasma membranes and barriers?
    4 years ago
  • Joyce
    What are the limitation of placenta as a barrier s?
    4 years ago
  • roderick watt
    How do drugs affect biological barrier in the body?
    3 years ago
    How drugs are distributed thru various barriers apart from blood brain barrier and placenta?
    3 years ago
  • Angelica Gammidge
    Why placental barrier is not effective as blood brain barrier?
    3 years ago
  • marisa iadanza
    What type of drugs cross placental barrier?
    3 years ago
  • yonas
    Why is placenta an effective barrier?
    3 years ago
    How drug pass through barriers in body?
    3 years ago
  • senja
    What are the substances can cross the placental barrier?
    3 years ago
  • yonatan
    Why most highly ionised drug br adninistered in the brain?
    3 years ago
  • Carola
    How can an ionised drug be administered in the brain?
    3 years ago
  • john handy
    How to administer a highly ionised drug to cure neuronal diseases?
    3 years ago
    How must a highly ionised drug be administered to treat a neuronal disorder?
    3 years ago
  • Tess
    How is a highly ionised drugly administered to treat a neuronal disorder?
    3 years ago
  • uta
    What are physiologic barriers to distribution of drugs?
    3 years ago
  • claudia
    How must a highly ionised drug administered in order to treat neuronal disorder?
    3 years ago
  • torsten
    Can pennicillins enter the CNS from the blood?
    3 years ago
  • birikti girmay
    How does drug ionisation affect distribution?
    3 years ago
  • sarah
    How do we cross physiological barrier?
    3 years ago
  • Tesfay
    How blood barrier affect distribution of drugs?
    3 years ago
  • mimosa
    What are the natural barriers of drug distribution in the target area?
    3 years ago
  • howard
    Is blood testes barrier a physiological barrier to drug absorption?
    2 years ago
  • steven
    Does penicillin cross the placenta?
    2 years ago
  • antti
    Why only some drug penetrates through placental barrier?
    2 years ago
  • ralph
    Why ois the placental barrier not aseffective as bbb?
    2 years ago
  • finley
    What is not a barrier to distribution of medications?
    2 years ago
  • sini
    How blood brain barrier affect drug distributiin?
    2 years ago
  • paul
    How does tissue ph affect drug distribution?
    2 years ago
  • Veikko
    Why is placebtal barrier not effective as BBB?
    2 years ago
  • senay
    What are roles of barriers and how do these barriers affect drug penetration?
    2 years ago
  • kedija haylom
    What are the roles of barriers in drug administration?
    2 years ago
  • petra
    Is placenta a physiological barrier?
    2 years ago
  • marmaduke
    Why are drugs that are partially ionized penetratable through brain blood barrier at slower rate?
    2 years ago
  • matthew
    What are physiological barriersof distribution?
    2 years ago
    What are brain barries for drug distribution?
    2 years ago
  • kathryn lee
    Is penicillin lipid soluble?
    2 years ago
  • becky
    How placental membrane barrier permeable to substances?
    2 years ago
  • anne
    How meningitis and inflammation affect permeability of drug?
    2 years ago
  • louis
    How is drug distributed to the brain?
    2 years ago
  • massimo trevisano
    How is drug distributed to the placenta?
    2 years ago
  • sarama
    How drug is distributed to the placenta and the brain?
    2 years ago
  • brigitte gerber
    What are the role drug barriers?
    2 years ago
  • JOHN
    What are the roles of barrier and how do these barriers affect drug penetration?
    2 years ago
  • anu
    What is the role of barriers and how do barriers affect drug penetration?
    2 years ago
  • timoteo fiorentini
    What are the roles of barriers and how do thes barriers affect drug peneteration?
    2 years ago
  • Yonas
    What are the roles of thevbarries and how do these barriers affect drug penatration?
    2 years ago
  • gimja
    What is drug pharmacological treatment for blood brain barries?
    2 years ago
    What are special barriers to drug distribution?
    2 years ago
  • henry
    Is the placenta chemo drug barrier?
    2 years ago
  • Blanco
    Does the placenta barrier affect drug distribution?
    2 years ago
  • dieter
    Which of the following does not influence the absorption of a drug quizlet?
    2 years ago
  • Damian
    How do water soluble drugs affect the distribution of medicine?
    2 years ago
  • frank
    Is the placenta an effective drug barrier?
    2 years ago
  • katherine
    What medications does the blood brain barrier stops?
    2 years ago
  • Miniya
    What drug is permeable to blood brain barrier?
    2 years ago
  • Thelma
    What tissue barrier in pharmacology?
    1 year ago
  • Lea
    Is the placental barrier permeable to water soluble drugs?
    1 year ago
  • fearne reid
    How does the ability to cross a membrane affect the distribution of a drug?
    1 year ago
  • seppo
    What is the purpose of the blood brain barrier and the fetal placental barrier?
    1 year ago
  • anna
    Why is the blood brain barrier a key factor in cns pharmacology?
    1 year ago
  • mira
    What is physiological barrier pharmacology?
    1 year ago
  • violanda
    Which of the following will most likely cross the bloodbrain barrier quizlet?
    1 year ago
  • walter tran
    What are biological barriers in pharmacology?
    1 year ago
  • abrha michael
    How drugs pass the placenta barrier?
    12 months ago
  • michael
    What are physiological barriers in pharmacology?
    26 days ago

Post a comment