Term
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Definition
-the interaction between two or more compounds to form a complex
-consisting of a central atom(or ion) bound to surrounding molecules/ions |
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Term
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Definition
| the molecules or ions surrounding the central atom in a complex |
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Term
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Definition
| the atom within the ligand which is bound with the central atom |
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Term
| What is another name for the central atom? |
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Definition
substrate
*usually a metal also |
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Term
| Which properties does complexation alter? |
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Definition
-solubility
-stability
-partitioning
-energy absorption/emission
-conductance |
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Term
| What is coordination number? |
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Definition
the maximum number of bonds the central atom can form
in other words the max number of ligands that can bind to the substrate |
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Term
| In what ways does complexation benefit pharmaceuticals? |
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Definition
-Enhance aqueous solubility
-Enhance drug stability
-Aid in optimization of drug delivery systems
-Enhance excretion of hydrophilic compounds
-alter pharmacologic activity |
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Term
| Give an example of complexation enhancing aqueous solubility. |
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Definition
| theophylline complexes with ethylene diamine to form aminophylline which has higher solubility than theophylline |
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Term
| Give an example of complexation enhancing drug stability. |
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Definition
| the formation of inclusion complexes such as cyclodextrin and channel lattices |
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Term
| Give an example of how complexation aids in optimization of drug delivery systems. |
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Definition
-ion-exchange resins
-distribution is altered by complex formation with plasma proteins |
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Term
| How does complexation alter pharmacological activity of drugs? |
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Definition
| by modifying its interaction with receptors at activation site |
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Term
| What are ways in which complexation is NOT beneficial to pharmaceuticals? |
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Definition
-Aqueous solubility of tetracyclines(antibiotics) goes down when complexed with calcium ions.(dont take with milk, yogurt, or other Ca2+ products)
-Co-administration of some drugs with antacids decrease their GI absorption |
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Term
| What are the three general types of complexes? |
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Definition
-Metal Ion Complexes
-Organic Molecular Complexes
-Inclusion Compounds |
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Term
| What are the two types of metal ion complexes? |
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Definition
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Term
| Describe the inorganic metal ion complex. |
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Definition
-Complex where each ligand donates a pair of electrons to form a coordinate covalent link.
-Monodentate ligands
-Considered a Lewis acid-base interaction with the ligands(bases) donating pairs of electrons to the metal ion(acid) |
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Term
| What are examples of the inorganic metal ion complex? |
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Definition
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Term
| Define coordinate covalent bond. |
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Definition
| a covalent bond formed when both electrons in the shared pair come from only one atom |
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Term
| Describe the Chelate Metal Ion Complex. |
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Definition
-complex where two or more donor groups per ligand combine with the central atom
-Polydentate(bidentate or more) |
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Term
| What is an example of a hexadentate? |
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Definition
EDTA
Ethylenediamine tetraacetic acid |
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Term
| What are examples of naturally occurring chelate metal ion complexes? |
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Definition
| Chlorophyll, hemoglobin, myoglobin, and cytochrome c |
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Term
| What is polydentate and monodentate? |
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Definition
Polydentate refers to a ligand that has multiple donor groups combine with the substrate
Monodentate only has one donor group bind with the substrate |
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Term
| Describe Organic Molecular Complexes |
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Definition
Complexes that are held together by weak NONCOVALENT forces such as hydrogen bonds, Van der Waals etc.
Occurs between two small molecules or a small molecule and a large molecule |
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Term
| What is an example of a small/small molecule Organic Molecular Complex? |
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Definition
| ethylene diamine + theophylline to form aminophylline |
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Term
| What is an example of a small/large molecule Organic Molecular Complex? |
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Definition
Iodine + poly(vinylpyrrolidone) to form povidone-iodine
also drug-plasma protein complexes |
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Term
| What are some other examples of Organic Molecular Complexes? |
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Definition
-Quinhydrone complex (1:1 benzoquinone and hydroquinone)
-Picric acid complex (2:1 picric acid and weak base)
-Polymer complex (PEG, polystyrene, carboxymethylcellulose)
polymers and drugs |
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Term
| Describe Inclusion Compounds |
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Definition
complex resulting from the architecture of molecules rather than from their chemical affinity
-one constituent is trapped in the open lattice or cage of the other
-forms a stable arrangement and can help with solubility |
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Term
| What are the two common inclusion compounds? |
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Definition
Cyclodextrin Complex
Channel Lattice Type |
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Term
| Describe Cyclodextrin Complexes |
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Definition
most popular type of inclusion compound
-donut shaped cyclic oligosachharides of D-glucopyranose
the drug is incorporated inside this donut hole to form the complex |
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Term
| What are other names for cyclodextrin and the drug when forming the complex? |
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Definition
cyclodextrin= host
drug= guest |
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Term
| What is the range for the cavity dimension of a cyclodextrin? |
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Definition
5-8 angstroms
1 angstrom= 10^-8 cm or .1 um |
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Term
| What is the structure of glucopyranose? |
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Definition
| 6 membered ring with one oxygen in replace of a carbon. all hydrogens are in the vertical positions |
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Term
| What is the significance of alpha, beta, and gamma in relation with cyclodextrins? |
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Definition
tells number of glucopyranoses
alpha-6
beta-7
gamma-8 |
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Term
| Describe the Channel Lattice type Inclusion Compounds. |
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Definition
Cholic acids (primarily DCA) that can form channels in which the complexing molecules can fit.
Also urea, thiourea, and starch-iodine |
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Term
| What compounds can deoxycholic acid(DCA) form complexes with? |
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Definition
| paraffins, organic acids, and aromatic compounds. |
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Term
| What compounds can urea and thiourea complex with in their channel like structures? |
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Definition
unbranched paraffins
alcohols
ketones |
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Term
| Describe the starch-iodine solution channel-like complex |
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Definition
| iodine molecules entrapped within the spirals of glucose moieties |
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Term
| What are layer type complexes? |
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Definition
stubstances are entrapped within linear layers of the complex
ex- graphite, bentonite |
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Term
| What are Clathrate complexes? |
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Definition
cage like lattice that completely encloses the substance(no bonds just physical entrapment)
ex-warfarin sodium clathrate of water, alcohol, and solid warfarin sodium |
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Term
| Are protein-drug bindings generally reversible or irreversible? |
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Definition
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Term
| How do you measure the affinity between a protein and a ligand? |
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Definition
using ASSOCIATION constant
Ka=[PL]/[P][L]
units of 1/M or liters/mole |
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Term
| What is capacity of binding(v)? |
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Definition
| the number of ligand binding sites in a protein molecule |
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Term
| Do plasma bound drugs pass through capillary walls? |
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Definition
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Term
| Do we measure total drug levels or just free drug levels? |
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Definition
total drug levels
-free levels are proportional to total levels so measuring total drug levels can be used to determine desired effect
we do this because its to time consuming to measure the free amount of drug |
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Term
| If you double the total dose what happens to the free amount of drug? |
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Definition
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Term
| What is the most important plasma protein? |
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Definition
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Term
| Where is Albumin synthesized? |
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Definition
the liver
conditions affecting the liver may affect concentration levels of Albumin |
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Term
| What conditions cause hypoalbuminemia? |
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Definition
| cirrhosis, viral hepatitis, renal failure, surgery, and burns |
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Term
| What conditions cause hyperalbuminemia? |
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Definition
| dehydration, neurological disorders |
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Term
| What is more common, hypoalbuminemia or hyperalbuminemia? |
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Definition
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Term
| Which drugs bind to albumin? |
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Definition
-acidic(anionic)
phenytoin, tolbutamide, warfarin, naproxane, ibuprofen |
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Term
| What drugs are capable of displacing warfarin for albumin? |
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Definition
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Term
| What drugs bind to alpha-acid glycoprotein(AAG)? |
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Definition
-basic (cationic) and neutral
Ex- propranolol, imipramine, and lidocaine |
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Term
| Do drugs that bind to AAG also have the possibility of binding to Albumin? |
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Definition
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Term
| Where is AAG synthesized? |
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Definition
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Term
| Which is more common, conditions leading to higher levels of AAG or lower levels of AAG? |
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Definition
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Term
| What are the concentration levels of Lipoproteins? |
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Definition
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Term
| Where are Lipoproteins synthesized? |
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Definition
| liver and intestinal mucosa |
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Term
| Can drugs change the affinity between all three proteins and other drugs? |
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Definition
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Term
| Besides the three major proteins what other major blood components can bind drugs? |
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Definition
| Immunoglobulins(IgG) and erythrocytes(red blood cells) |
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Term
| Do highly protein bound drugs tend to stay in circulation or bind to tissue? |
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Definition
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Term
| Do highly bound protein drugs have low or high volumes of distribution? |
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Definition
Low because it cannot spread out into tissue
basically equivalent to that of blood's volume of distribution (5L) |
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Term
| What is the requirement for a drug to displace another drug off of a protein? |
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Definition
| Have a larger Ka value, in other words have a higher affinity to bind with the protein then the drug currently attached |
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Term
| What two things can occur when a bound drug in unbound and more is in free form? |
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Definition
increase pharmacological effect
toxicity levels |
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Term
| What four general things can change the protein-ligand binding equilibrium? |
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Definition
| age, disease state, malnutrition, trauma |
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Term
| What two ways can you change the free drug concentration? |
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Definition
Change total concentration (external)
Change binding affinity with other drug(internal) |
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