Distribution Part I

Question 1

Hydrostatic Pressure

Answer 1

• The pressure gradient between:
• 1- Arterial end of capillaries entering tissues
• 2- Venous capillaries leaving tissues
• Responsible for penetration of water soluble drugs between endothelial cells
• Small drug molecules filtration into glomerulus.

Question 2

The factors that determine the distribution

constant (kd) into an organ are related to:

Answer 2

1. Blood flow (Q) to the organ.
2. The volume of the organ (VT) (tissue size).
3. The partitioning of the drug into organ

tissues (tissue storage). (R)

Question 3

Processes of Drug Accumulation in Tissues

Answer 3

1. Partitioning- affects affinity to tissues, high affinity vs low affinity.
2. Protein binding.
3. Enzyme transport system.

Question 4

Albumin

Answer 4

• Reversible
• Has specific binding sites

I-Warfarin site: phenylbutazone, sulfonamides and

Phenytoin

II- Benzodiazepine site: probencid, Penicillin

Question 5

Protein Binding

Answer 5

Binding of drugs to blood components

• Plasma Proteins
• Blood Cells (RBC’s are 45% of the volume of blood)

Binding of drugs to tissue proteins

• Fats
• Bones

Question 6

Significance of Protein Binding

Answer 6

• Protein bound drugs are pharmacologically inactive.
• reduction in the volume of distribution.
• increasing drug concentration.
• long duration of action.
• longer half life and reduced rate of elimination.
• Drug displacement in drugs with narrow therapeutic

windows is critical. can increase toxic plasma levels

Question 7

Displacement of drugs from plasma proteins can affect the pharmacokinetics of a drug in several ways

Answer 7

• (1) directly increase the free (unbound) drug concentration as a result of reduced binding in the blood;
• (2) increase the free drug concentration that reaches the receptor sites directly, causing a more intense pharmacodynamic (or toxic) response;
• (3) increase the free drug concentration, causing a transient increase in VD and decreasing partly some of the increase in free plasma drug concentration;
• (4) increase the free drug concentration, resulting in more drug diffusion into tissues of eliminating organs, particularly the liver and kidney, resulting in a transient increase in drug elimination

Question 8

Electrolyte Balance

Answer 8

• The kidney is the main regulator of electrolyte balance.
• Albumin is synthesized in the liver and is the main component of plasma proteins; contributes to osmotic pressure in the blood
• Changes in plasma protein concentration and in plasma drug–protein binding may occur to various degree, thus affecting drug disposition.
• Disease conditions may cause changes in protein concentration and drug–protein binding

→ altering the protein distribution in the body ⇒ more non-protein-bound drug ⇒ more intense pharmacodynamic effect and a change in the rate of drug elimination.

Question 9

On the other hand, a drug that is both extensively bound and actively secreted by the kidneys, such as penicillin, has a short elimination half-life, because active secretion takes preference __________ the drug from the proteins as the blood flows through the kidney

Answer 9

in removing or stripping

Question 10

Albumin Warfarin site ( site I )

Answer 10

• Phenylbutazone
• Sulfonamides
• phenytoin
  *

Question 11

Albumin Bezoodiazepine binding site ( II )

Answer 11

• Probenecid
• Penicillin