Dosage - Complexation and Protein Binding
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
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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.)
