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Chapter: Pharmaceutical Drugs and Dosage: Complexation and protein binding

Pharmaceutical Drugs and Dosage: Complexation and protein binding - Review questions answers


Review questions

6.1 Name the following coordination compounds?

A.      [CoBr(NH3)5]SO4

B.      [Fe(NH3)6][Cr(CN)6]

C.      [Co(NH3)5Cl]SO4

D.      [Fe(OH)(H2O)5]2+

E.       (C5H5)Fe(CO)2CH3

6.2 Write the molecular formulas of the following coordination compounds?

A.      Hexaammineiron(III) nitrate

B.      Ammonium tetrachlorocuprate(II)

C.      Sodium monochloropentacyanoferrate(III)

D.      Potassium hexafluorocobaltate(III)

6.3 Identify the most prominent human plasma protein?

A.      α1-acid glycoprotein (AAG)

B.      Human serum albumin (HSA)

C.      Globulin

D.      Insulin

6.4 Which of the following forces are involved in molecular complexes?

A.      Hydrogen bonding

B.      Hydrophobic interactions

C.      Van der Waals forces

D.      Covalent bonding

E.       Ionic bonding

6.5 Which of the following forces are involved in coordination complexes?

A.      Hydrogen bonding

B.      Hydrophobic interactions

C.      Van der Waals forces

D.      Covalent bonding

E.       Ionic bonding

6.6 What are the important parameters for characterizing drug–plasma protein binding?

A.      Protein concentration

B.      Drug concentration

C.      Binding affinity

D.      Binding capacity

E.       Rate of binding

6.7 Explain the factors affecting plasma protein binding of drugs.

6.8 What is the effect of plasma protein binding on the dosing regimen of a drug?


Answer:

6.1 A. Pentaamminebromocobalt(III) sulfate

B. Hexaammineiron(III) hexacyanochromate (III)

C. Pentaamine cholorocobalt (III) sulfate

D. pentaaquahydroxoiron (III) ion

E. Cyclopentadienyliron dicarbonyl dimmer

6.2 A. [Fe(NH3)6](NO3)3

B. (NH4)2[CuCl4]

C. Na3[FeCl(CN)5]

D. K3[CoF6]

6.3 B.

6.4 A, B, C.

6.5 E.

6.6 A, B, C.

6.7 The factors affecting plasma protein binding of drugs are as follows:

• The extent of protein binding of many drugs is a linear function of partition coefficient P.

• Plasma protein binding may determine the characteristics of drug action or transport.

• Protein binding changes with drug concentration and protein concentration.

• On increasing the drug/protein ratios, saturation of some sites can occur and there may be a decrease in binding.

6.8 Only a free drug is able to cross the capillary endothelium. When protein binding occurs with high affinity and the total amount of drug in the body is low, the drug will be present almost exclu-sively in the plasma. As plasma proteins are large molecules, drugs that are bound to proteins cannot pass out of vascular space. Thus, plasma protein binding will control the distribution of drugs. As plasma protein binding increases, the extent of distribution decreases. However, some drugs may exhibit both a high degree of plasma protein binding and a large volume of distribution. Binding of drugs to plasma proteins is a dynamic equilibrium. If the unbound (or free) drug is able to cross biological membranes, the drug may exhibit an extensive volume of distribution, despite a high degree of protein binding. As a free drug moves across the membranes and out of vascular space, the equilibrium will shift, in essence drawing the drug off the plasma protein to replenish the free drug lost from vas-cular space. This free drug is now also able to traverse membranes and leave vascular space. In this way, a drug with a very low free fraction (i.e., a high degree of plasma protein binding) can exhibit a large volume of distribution. Disease states that alter plasma protein concentration may alter the protein binding of drugs. If the concen-tration of protein in plasma is reduced, there may be an increase in the free fraction of drugs bound to that protein. Similarly, if pathological changes in binding proteins reduce the affinity of the drug for the protein, there will be an increase in the free fraction of the drug.

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