Carrier mediated drug transport

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 pK a 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 Amino acid transporter   Oligopeptide transporter   Phosphate transporter fostomycin Bile acid transporter s3744 Glucose transporter p - Nitrophenyl --D- glucopyranoside   P-glycoprotein efflux vinablastin   Monocarboxylic acid salicylic acid transporter Gabapentin Cefixime

10. THANKS FOR YOUR ATTENTION

11. REFERENCE http://www.pharmacorama.com/en/Sections/NAK-ATPase-Digoxin.php.TIME-6.45PM DATE:20-04-2016 Applied biopharmaceutics and pharmacokinetics,5 th 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 ,6 th 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