carriers used in body to move hydrophilic drugs

1. Carrier mediated drug transport
Seminar created by:kumar samudra gupta kaushik
Roll no.-20

2. Basic concept of carrier mediated
• The carriers appear to present either an import or an export site to the
transported molecule and undergo substrate-induced conformational
change.
•“simple carrier”
(Widdas, 1952; Lieb
and Stein, 1968),
the
“alternating
conformer model”
(Jardetzky, 1966) or
the “iso uni uni
carrier model”

3. Active transport
• It requires a carrier that binds the drug to form a carrier–drug complex
that shuttles the drug across the membrane and then dissociates the drug
on the other side of the membrane.
• when a drug is absorbed by a carrier-mediated process, the rate of drug
absorption increases with drug concentration until the carrier molecules
are completely saturated. At higher drug concentrations, the rate of drug
absorption remains constant, or zero order.
• A few lipid-insoluble drugs that resemble natural physiologic metabolites
(such as 5-fluorouracil) are absorbed from the gastrointestinal tract by this
process

4. Types of active transport
• Primary-energy obtained- hydrolysis of ATP.
• The transporters belong to the superfamily of ATP binding cassette(ABC)
transporters whose intra cellular loops have ATPase activity.
• ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP,
MRP, ALD, OABP, GCN20, White). The P-type ATPases are:
Na,K ATPase (plasma membrane)
Ca ATPase (sarcoplasmic reticulum, plasma membrane)
H,K ATPase (gastric mucosa)
These are called P-type ATPases because a phosphorylated intermediate is
formed during the transport catalytic cycle.

5. SODIUM POTASSIUM PUMP
• To maintain inside the cell a low concentration of sodium and a high
concentration of potassium. It is an electrogenic pump which
creates a potential difference between both sides of the
cytoplasmic membrane.
To ensure the polarization of excitable and contractile tissues:
depolarization and repolarization correspond respectively to a
sodium influx and a potassium exit. Na+/K+-ATPase restores the
equilibrium.
Eg:Multidrug resistance associated protein 2
Substrates include anticancer drugs such as vinblastine

6. SECONDARY: In this type of active transport effected by another set of
solute carrier transporters,the energy to pump 1 solute is derived from
the downhill movement of another solute.These are of 2 types:
1.symport:when the concentration gradient are such that both the
solutes move in same direction.
Eg.- (e.g. Na/Glc, Na/Amino acid, H+/Glc,
Na+/neurotransmitter co-transporters)
2.antiport:when the concentration gradient are such that both the
solute move in opposite direction
Eg:- Cl-/HCO3-, Na,Ca exchangers
eg:The absorption of glucose in intestines and the renal tubules is by
sodium glucose transporters(SGLT1).

7. VESICULAR TRANSPORT
• Vesicular transport is the process of engulfing particles or dissolved
materials by the cell. Pinocytosis refers to the engulfment of small solutes
or fluid, whereas phagocytosis refers to the engulfment of larger particles
or macromolecules, generally by macrophages.
• eg : insulin from insulin-producing cells of the pancreas into the
extracellular space. The insulin molecules are first packaged into
intracellular vesicles, which then fuse with the plasma membrane to
release the insulin outside the cell.

8. Ion transport
• Strong electrolyte drugs are highly ionized or charged molecules, such as
quaternary nitrogen compounds with extreme pKa values. Strong
electrolyte drugs maintain their charge at all physiologic pH values and
penetrate membranes poorly. When the ionized drug is linked up with an
oppositely charged ion, an ion pair is formed in which the overall charge of
the pair is neutral.
• Eg: the formation of ion pairs to facilitate drug absorption has been
demonstrated for propranolol, a basic drug that forms an ion pair with
oleic acid, and quinine, which forms ion pair with hexylsalicylate .

9. Intestinal
1. Amino acid transporter
2. Oligopeptide transporter
3. Phosphate transporter fostomycin
4. Bile acid transporter s3744
5. Glucose transporter p-Nitrophenyl--D-glucopyranoside
6. P-glycoprotein efflux vinablastin
7. Monocarboxylic acid salicylic acid
transporter
Gabapentin
Cefixime

11. REFERENCE
• http://www.pharmacorama.com/en/Sections/NAK-ATPase-
Digoxin.php.TIME-6.45PM DATE:20-04-2016
• Applied biopharmaceutics and pharmacokinetics,5th edition
by Leon Shargel,, Susanna Wu Pong, Andrew B.C.
YU,PUBLISHER:MC GRAW HILL’S.TIME-7AM,DATE:19-04-
2016
• Essentials of medical pharmacology ,6th edition k.d
tripathi.page no.13-15
•
https://www.boundless.com/biology/textbooks/boundless-
biology-textbook/structure-and-function-of-plasma-
membranes-5/active-transport-66/primary-active-
transport-337-11474/ TIME-6.45PM DATE:20-04-2016