Dosage - Complexation and Protein Binding

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montmorillonite clays are inclusion complexes that can trap compounds between their __ __

lattice layers

montmorillonite clays are an example of this type of inclusion complex

layer type

2 ratios used to determine stoichiometry of complexes

ligand-to-metal and donor-to-acceptor

using the method of continuous variation, if no complex is formed, there is a ___ correlation

linear

used for binding and transport of plasma lipids

lipoproteins

when using binding analysis, potential errors are due to drug binding to the __ and volume changes due to __

membrane, osmosis

this analytical method is based on measuring additive properties of a mixture of complexing compounds

method of continuous variation

these inclusion complexes are widely used because they have a hydrophilic surface and hydrophobic cavity

cyclodextrins

these inclusion complexes have complexation through hydrophobic and van der Waals interactions

cyclodextrins

dynamic dialysis measures the rate of ___ of drug from dialysis cell

disappearance

drug interactions with proteins may cause ___ of body hormones or a coadministered agent

displacement

this type of analysis of protein-drug binding is a fast method applicable to studies of competitive inhibition of protein binding

dynamic dialysis

clathrates work by simple ___

entrapment

2 methods of analyzing protein-drug binding

equilibrium dialysis (ED) and ultrafiltration (UF)

when using binding analysis, if binding occurs, drug concentration in the protein compartment will be ____ (greater/less) than concentration of free drug

greater

2 natural chelates

hemoglobin and chlorophyll

EDTA is called a ____ because it has 6 points for attachment

hexadentate

what plays an important role in metal complexes?

hybridization

majority of ligands bind albumin by ___ interactions

hydrophobic

type of complexes that have a drug trapped in open lattice or cage-like crystal structure

inclusion complexes

what is the coordination number of cobalt?

6

Do Practice Problems: 10-9 and 10-11

...

do calculations on slide 27/28

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do calculations on slide 30/31

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what are 2 types of organic complexes?

1) hydrogen bonds (or weak donor-acceptor type interactions) 2) charge transfer complexes

__ absorbs drug on polymer itself and drug precipitates out

PVP

what type of plot can be used to correct for errors from low concentration data points in protein binding analysis

Scatchard

the method of continuous variation can measure: (3)

absorbance, dielectric constants, refractive index

formation of drug complexes can affect drug __ and ___

absorption, bioavailability

caffeine forms complexes with __ and __ drugs

acidic, ester

drug interaction with proteins may form a drug-protein complex that itself is biologically ___

active

used for binding of basic drugs

alpha1-acid glycoprotein

analysis of the interaction between a group/receptor in a protein P with a drug molecule D can be done using __ __

binding equilibria (equation on slide 23)

bile acids, urea and thiourea, and starch-iodine are examples of this type of inclusion complexes

channel lattice type

what is formed from a metal and compounds with 2 or more donor groups?

chelates

these are inclusion complexes that have cage-like lattices with entrapped coordinating compounds

clathrates

one example of complexation of inorganic complexes has __ as an acceptor and ___ as the ligand

cobalt, ammonia

drug interaction with proteins may change the __ of the protein so that it's altered form is capable of binding a ___ agent

configuration, coadministered

these are a type of monomolecular inclusion compounds that cup-shaped cyclic oligomers of D-glucose

cyclodextrins

are there chemical bonds involved in clathrates?

no

do inclusion complexes have dipole dipole interaction or electrostatic interaction?

no

this analytical method is useful when complexation changes pH

pH titration method

charge transfer complexes induce ___

polarization

binding of drugs to polymers may lead to ___, delayed __, and loss of ___

precipitation, absorption, activity (recall that MW of polymers is huge)

__ __ is the most important protein in binding to drugs in the plasma

serum albumin

T/F: after binding with metals, structure is very rigid

true

T/F: analytical methods are used to determine stability constants of complexes

true

T/F: caffeine can form a complex with benzocaine

true

T/F: polymer-drug complexes can have drug interactions with polymer (plastic) containers

true

T/F: proteins may facilitate the distribution of drugs throughout the body

true

T/F: proteins may inactivate the drug by not enabling a sufficient concentration of free drug to develop at receptor site

true

T/F: proteins may retard the excretion of a drug

true

T/F: using the method of continuous variation, if the measured property is proportional only to complex concentration, stability constant can be determined from an equation listed on slide 17

true

T/F: there is a long list of pharmaceutical benefits of cyclodextrins

true (enhanced aqueous solubility, improved stability, enhanced absorption and bioavailability, improved taste and odor, etc.)


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