Transporting systems, factors effecting adsorption

Question 1

ABC

Answer 1

-ATPase binding casette - cellular efflux - uses energy expelled from the hydrolysis of ATP to actively exclude compounds from cells i.e. PGP cationic; MRP 1-8 cationic; BCRP cationic and anionic

Question 2

SLC

Answer 2

• solute linked carrier protein - uptake and efflux - ATP independent - functions either in a facilitated diffusion or secondary active transport process

Question 3

Answer 3

Question 4

Lipinskis rule of 5

Answer 4

MW < 500

LogP < 5

HBD < 5

HBA < 10

Rules can be circumvented in the instance where a transporter system exists

Question 5

Carrier mediated transport

Answer 5

Either fascilitated diffusion or active transport

Saturation and competition

Drugs with a moiety simmilart to nutrients are likely to undergo transport i.e. valine

Question 6

Gastric emptying rate

Answer 6

As the major site of absorption is the upper small intestine, delaying the gastric emptying rate will delay time for onset

Decreasing factors: Cold water, Alcohol lying on your side

Factors that increase: Metaclopramide, stressfull emotional states, hyperthyroidism

Question 7

Impact of food

Answer 7

Soluble drugs may precipitate if complexed with agents in the GIT

or form large chelate complexes which cannot be absorbed

i. e. Ca2+ and tetracyclines
- in the presence of food gastric pH is lowered causing issues for drugs wit acid sensitivity

Question 8

Main route of elimination of biologics

Answer 8

renal

Question 9

requirements for biosimmilarity

Answer 9

as it can not be assumed that molecules are identical (post translational modification) activity must be shown

side effects

plasma concentrations

immunogenicity (temperature inflamatory markers)

Question 10

Transporters in the kidney

Answer 10

Question 11

Factors for equivalence

Answer 11

Cmax, Tmax, AUC

curves must be superimposable

Question 12

Methods to bypass the BBB

Answer 12

• Lipidization
• inhibit the actions of pGP i.e. cyclosporin
• Disruption of the BBB- hyperosmotic infusion of 25% mannitol solution, leads to shrinking of the endothelial cells
• utilization of transporters systems i.e. levdopa IF protein is large (peptide or protein) use receptor mediated transporter i.e. monoclonal antibody

Question 13

Effect of digoxin and verapamil

Answer 13

Digoxin is cleared by p-GP and verapamil is a pGP inhibitor therefore increasing exposure of digoxin as p-GP is a primaru efflux transporter. Verapamil increases digoxin exposure by inhibiting active tubular secretion into the urine

Question 14

Statin drugs

Answer 14

Excretion relies on OATP, polymorphims in OATP will therefore reduce clearance and increase exposure,

Tt,Tc,

Question 15

Metabolism based DDI’s

Answer 15

CYP inhibition i.e. erythromyocin