Various Physiological barriers as a protective of drug , & their related Bio pharmaceutical action pharmacokinetic action the list of drugs and other relevant details

1. A Project By
Abhishek Roy (Roll 03)
&
Debanjan Chatterjee( Roll 18)
B.Pharm , 4th year 7th sem

2. • 1. Physiological Barriers
• 2.Types of Physiological Barrier
• 3.Simple Capillary Endothelial Barrier
• 4.Simple Cell Membrane Barrier
• 5.Blood-Brain Barrier
• 6.Blood CSF Barrier
• 7.Blood Placental Barrier
• 8.Blood Testis Barrier
• 9.Conclusion
• 10. Reference

3. PHYSIOLOGICAL BARRIER
• A membrane (or a barrier) with special structural feature can be a permeability
restriction to distribution of drugs to some tissue .
Physiological Barrier

4. TYPES OF PHYSIOLOGICAL
BARRIER
• The Important simple & specialized physiological barriers are--
• a. Simple Capillary endothelial Barrier
• b. Simple cell membrane Barrier
• c. Blood -Brain Barrier
• d.Blood- CSF Barrier
• e.Blood-Placental Barrier
• f.Blood-Testis Barrier

5. • The membrane of capillaries that supply blood to most tissues is not a barrier to
moieties , or drugs ..thus all drugs ionised or unionised , with a molecular size(MW)
less than 600 Dalton , diffuse through the capillary endothelium and into the
interstitial fluid .

6. Simple cell Membrane Barrier
• once a drug diffuses from the capillary wall into the extracellular fluid , its further entry into cells of
most tissues is limited by its permeability through the membrane that lines such cells , such a
simple cell membrane is similar to the lipoiidal barrier in the GI absorption of drugs .

7. • The capillaries in the brain are highly specialized & much less permeable to water
soluble drugs . The brain capillaries consist of endothelial cells which are joined to
one another by continuous tight intercellular junctions comprising what is called as
the blood brain barrier. Moreover the presence of special cells called astrocytes &
pericytes .

8. • A solute may thus gain access to brain via only of the two pathway ,.
• Passive diffusion through the lipoidal barrier : which is restricted to small molecules (with a MW less
that a threshold of approx 700 Da ) having high o/w partition coefficient
• Active transport of essential nutrients such as sugars and amino acids . Thus structurally similar
foreign molecules can also penetrate the BBB by the same mechanism .
• List of drugs that can cross BBB-
Name of the Drug Solubility Used as
Levodopa Water (66mg/ml) Anti Parkinsons disease
Carbidopa Water (3.8 mg/ml) Anti Parkinsons disease
Sulphadiazine Ethanol , Methanol
acetone
Meningitis
Carmustine Alcohol, poorly soluble
in water
Brain Tumour
Lomustine Polar solvents Brain Circinoma

9. BLOOD BRAIN BARRIER AS A DRUG PROTECTIVE
• The 3 different approaches are …
• 1) Use of permeation enhancers such as dimethyl sulphoxide (DMSO)
• 2.)Osmotic disruption of the BBB by infusion internal carotid artery with mannitol
• 3.)Use of dihydropyridine Redox system as durg carriers to the brain
• In the latter case , the lipid soluble dihydropyridine is linked as a carrier to the polar drug to
form a prodrug that readily crosses the BBB.

10. • The cerebrospinal fluid(CSF) is formed mainly by the choroid plexus of the lateral
third & fourth ventricles & is similar in composition to the ECF of brain The capillary
endothelium that lines the choroid plexus have open junctions or gaps and drugs
can flow freely into the extracellular space between the capillary wall and the
choroidal cells.

11. BLOOD –CSF BARRIER AS A
DRUG PROTECTIVE
• As in the case of BBB only highly lipid soluble drugs can cross the blood CSF barrier with relative case whereas
moderately lipid soluble and partially ionised drugs permeate slowly. A drug that enters the CSF slowly can’t achieve
a high concentration as the bulk flow of CSF continuously removes the drug .for any given drug its concentration in
the brain will always be higher than in the CSF .
• List of drugs that are permeable through the Blood –CSF Barrier are-
Name of the Drug Solubility Used as
Sulphamethoxazole Dimethyl sulphoxide
(51mg/ml)
Sulphonamide Antibiotic
Trimethoprim Water (0.4mg/ml),
ethanol(2.6mg/ml at 20°
C)
Di hydro folate reductase
inhibitor
Ofloxacin Water 28.3 mg/ml Eye Infection
Timolol water (15mg/ml) Glucoma
Esmolol Water & very soluble in
HCL
PSVT(Paroxymal supra
ventricular tachycardia)
Labetolol Water (117 mg/ml ) Anti Hypertensive

12. BLOOD PLACENTAL BARRIER
• The maternal and the fetal blood vessels are separated by a number of tissue
layers made of fetal trophoblast basement membrane and the endothelium which
together constitute the placental barrier the flow of blood in the maternal and the
fetal blood vessels is shown in the figure

13. PLACENTAL BARRIER AS A
DRUG PROTECTIVE
• The human placental barrier has a mean thickness of 25 microns in early pregnancy that reduces to 2 micron at full
term which however does not reduce its effectiveness. Many drugs having molecular weight less than 1000 Da &
moderated to high lipid solubility that is Ethanol Sulphonamides Barbiturates gaseous anaesthetics steroids
narcotic analgesics anti convulsants and some antibiotics
• An agent that cause toxic effects on fetus is called as TERATOGEN.
• TERATOGENECITY is defined as fetal abnormalities caused by administration of drugs during pregnancy
• Drugs can affect the fetus at 3 stages as shown in the underneath table
Period Significance Harazdous Effects
First 2 weeks Fertilization and implantation stage Miscarriage
2-8 weeks Period of organogenesis Cleft palate, optic atrophy, mental
retardation ,neural tube defects etc
8weeks onwards Growth and development Development and functional
abnormalities

14. • This barrier is located not at the capillary endothelium level but at sertoli-sertoli cell
junction . It is the tight junction between the neighbouring sertoli cells that act as the
blood-testis barrier . This barrier restricts the passage of drugs to spermatocytes
and spermatids …

15. Name Solubility Related Physiological Barrier Used as
Levodopa Water (66mg/ml) Blood Brain Barrier Anti Parkinsons disease
Fluconazole Water (8-10 mg/ml) Simple cell membrane barrier Anti Fungal
Silver Sulphadiazine Ethanol , Methanol acetone Simple capillary endothelium
barrier
Burn Therapy
Carmustine Alcohol, poorly soluble in water Blood Brain Barrier Brain Tumour
Sulphamethoxazole Dimethyl sulphoxide (51mg/ml) Blood CSF barrier Sulphonamide Antibiotic
Doxorubicin Water (10mg/ml) Blood Testis Barrier Prostate cancer
Ofloxacin Water 28.3 mg/ml Blood CSF Barrier Eye Infection
Cisplatin dissolve 250mg inside a sigma flask in
41,655ml of PBS to make a solution of
20mM
Blood Placental Barrier Ovarian Carcinoma

16. References
• D.M Brahmankar & Sunil B Jaiswal; Biopharmaceutics and
Pharmacokinetics –A Treatise; 3rd Edn ,111-114.
• Anil Baran Singha Mahapatra ; Essential of Medical Physiology ; Current
Books International , Kolkata : 4th Edn , 2014; 256 , 392,370,383.
• Dickerson & Vascan ; Physiological Barriers ; University Of Chicago,
United States Of America ; The Journal of physiology; 31990; 429: 10-46.

17. Thank you