Mkcg medical college and hospital, pharmacology department

1. TRANSLOCATION OF
DRUGS
DR Suvendu Kumar Panda
Pharmacology Department
Mkcg Medical College & Hospital

2.  . The movement or translocation of drug from a side of
biological barrier to the other is called Biotransport.
 The major transport mechanism are: 1- Passive Diffusion,
2-Filtration,
3- Carrier Mediated Transport
A- Facilitated Diffusion
B- Active Transport
4- Pinocytosis
INTRODUCTION

3.  Passive diffusion is a process in which drug diffuses across
the membrane in the direction of its concentration
gradient without requiring any expenditure of energy.
 Lipid soluble drugs diffuse by dissolving in the lipoidal
matrix of the membrane, the rate of transport being
proportional to the lipid:water partition cofficent of the
drug.
 For a weak electrolyte diffusion depands up on the degree
of ionisation of the drug , the pH of the surrounding
environment and lipid:water partition coefficent.
Passive Diffusion

4.  Many drugs are acidic or basic compounds,which are
ionized to a certain degree in aqueous medium. Their
degree of ionization depands on their dissocation
constant (pKa) and pH of the environment and
extentionn of ionisation.
 Henderson –Hasselbach equation-
 For acidic drug
pka=pH+log conc . Of nonionised acid/conc of ionised
acid
For Basic drug-
pka=pH+ conc. Of ionised base/ conc. Of nonionised
base

6. FILRTATION:
* Filtration is defined as a process of passage of drugs
throgh aqueous pores in the membrane or through the
paracellular space.
* Rate of transport in filtration is depand on rate of
blood flow and the size of the aqoueous pore.

7. CARRIER MEDIATED TRANSPORT:
 * All cell membranes express a host of
transmembrane proteins which serve as carriers or
transporters for physiologically important
ions,nutrients ,metabolities,transmitters ,drugs and
xenobiotics etc across the membrane.
* Carrier molecules combined transiently with their
substrate and undergoes a confirmational change .
• After the confirmational change the carrier transport
the substrate to the other side of the membrane
whher the substrate dissosiates and the transporter
return back to its original state.

8.  * Depending on the requirement of energy
,carrier transport is of two type:
1- Facilitated diffusion ,
2-Active transport.

9. FACILITATED DIFFUSION:
• Facilitated diffusion is a carrier mediated transport
process in which the driving force is the
electrochemical gradient of the transported solute.
• This process operates passively without requirement
of energy.
• In facilitated diffusion transporters are mainly
belonging to the Super family of solute carrier(SLC).
• e.g. entry of glucose in to the muscles and fat by
GLUT 4.
• OCT 1 facilitate the movement of thiamine and and
metformin.

11. ACTIVE TRANSPORT:
 Active transport is characterised by a direct
requirement for energy, capacity to move solute
against an electrochemical gradient ,saturabilty and
competative inhibition by cotransported compound.
 Depending on the driving force , the active transport
can be subdivided in to
 Primary active transport,
 Secondary active transport.

12. PRIMARY ACTIVE TRANSPORT:
Primary active transport characterised by membrane
transport that directly couples with ATP hydrolysis.
Na+ K+- ATPase is an example of active transport
mechanism.
Transporter belonging to thr superfamily of ATP
binding cassettee.

13. SECONDARY ACTIVE TRANSPORT:
 Secondary active transport ,the energy to pump one
solute is derived from the downhill movement of
another solute.
 Depending up on the transport direction od the
solute secondary active transporter classified as
either
1-Sympoters or Cotransporter,
2- Antiporters or exchange transporter.
*Example of sympoter: Glucose transfer in to the body
lumen of the small intestine by Na+ glucose transporter
SGLT1.
*Example of antiporters: Na+/Ca++ exchanger.

15. Transporter are broadly classified in to:
1. Solute Carrier Transporter,
2. ATP Binding Cassettee.
SOLUTE CARRIER TRANSPORT :
o Solute carrier superfamily icludes 52 families and represent about 395 genes
in human geneome.
o Transporters in SLC1,SLC3,SLC6,SLC7,SLC 25 and SLC 36 families are
expressed in kidney and intestine.
o Transporter in SLC 2,SLC 5 and SLC 50 families for absorption,execretion
and cellular distribution of glucose and other sugar.
o SLC 11,SLC 30,SLC 39 and SLC 40 families transport zinc ,iron and other
metals.
o SLC 19,SLC 46 and SLC 52 TRANSPORT water soluble vitamins.
o SLC 6 and SLC 18 moves neurotransmitter across the plasma membrane and
storage vesicle respectively.
o OCT translocate dopamine,choline,vecuronium,quinine,procianamide.
o OAT responsible for renal secretion of urate,prostaglandin,p-amino
hippurate,probenecid.
TRANSPORTER

16. • ABC superfamily includes 49
genes .
• 7 groups of ABC
transporter are essential
for many cellualar
processes.
• In eukaryotes most ABC
transporter moves
compound from cytoplasm
to the cell exterior or in to
an intracellular
compartment.
• ABC transports are involve
in diverse cellular
processes:
1. maintenance of
osmotic homeostasis,
2. Nutrient uptake,
3. Cell division,
4. Bacterial immunity ,
antigen processing.
ATP BINDING CASSETTEE

17. IMPORTANT ABC TRANSPORTER AND ITS
TISSUE DISTRIBUTION
NAME TISSUE DISTRIBUTION
MDR1 Liver,Kidney,Intestine,BBB,BTB,B
PB
MRP1 UBIQUITOUS
MRP2 Liver,Kidney,Intestine,BPB.
MRP 3 Liver,Kidney,Intestine
MRP 4 UBIQUITOUS
MRP 5 UBIQUITOUS
MRP 6 Liver,Kidney
BCRP Liver,Intestine,BBB
MDR 3 liver
BSEP liver

18.  P glycoprotein or P-gp which belongs to ABC transporter
superfamily.
 It was first discovered by Chinese hamster ovary cell mutant by
Juliano R.L and Ling V in 1976.
 Present in renal tubular brush boarder membrane, bile
canaliculi,astrocyte foot process in brain microvessel and in G.I.T.
 Responsible for multidrug resistance in cancer cell.
 Plays important part of absorption,distribution and elimination of
many drugs.
 P-gp transports various substate across the cell membrane
a. Drugs such as tacrolimus and quinidine,
b. Chemotherapeuttic agents such as etoposide and vinblastin,
c. Cardiac glcosides like digoxin;
d. Dexamethasone.
 P –gp inhibited by many drugs:
o Azithromycin, captopril,clarithromcin,cyclosporin.
o Quindinine,quinine,reserpine,ritonavir,verapamil.
P –GLYCOPROTEIN

19. It is the process of transport across the cell in
particulatr from by formation of vessicles.
 It helps in transport of protein and big molecules.
 Barring vitamin B12.
PINOCYOTOSIS

20. Thanks
You