Unit 1- Distribution

Question 1

Central Compartment

Answer 1

Blood

Question 2

Drug Distribution

Answer 2

Drugs must be distributed from central compartment to peripheral tissues and may be released back into systemic circulation

Question 3

Factors Determining Distribution

Answer 3

Lipid solubility and penetration of membranes, regional blood flow, concentration gradient, protein binding, transport proteins

Question 4

Tissues with high blood flow/mass ratio

Answer 4

Brain, heart, liver, KIDNEY, endocrine glands

Question 5

Tissues with intermediate blood flow/mass ratio

Answer 5

Muscle, skin

Question 6

Tissue with low blood flow/mass ratio

Answer 6

Adipose tissue, bone

Question 7

Kidney Perfusion

Answer 7

Cortex receives 25% of cardiac output, medulla receives a small amount

Question 8

Drug Transport

Answer 8

Majority by plasma proteins, seldom by RBC, less importantly lymph

Question 9

Acidic drug binding

Answer 9

Albumin

Question 10

Basic drug binding

Answer 10

α1-glycoprotein

Question 11

Plasma Protein Binding

Answer 11

Reversible noncovalent binding with plasma proteins to move through circulation until dissociating when it reaches the tissue with a higher binding affinity

Question 12

Protein binding and distribution

Answer 12

Only free drug can cross cell membranes, binding can slow down reaching site of action and effect drug response

Question 13

Binding and glomerular filtration

Answer 13

Limits filtration and slows metabolism and secretion

Question 14

Protein-binding percentage

Answer 14

Expressed in % of drug bound, may fall when amount of drug is greater than binding capacity of the protein

Question 15

Displacement

Answer 15

Competition for the same site on plasma proteins, one ligan may habe a higher affinity

Question 16

Distribution Equilibrium

Answer 16

Steady state, amount of drug leaving plasma for tissues is equal to amount of drug leaving tissues for plasma

Question 17

Psuedoequilibirium

Answer 17

True equilibrium may not ever be reached because drug is continually being eliminated

Question 18

Half-Life and Equilibrium

Answer 18

Less likely with drugs with short half life, especially at a long dosing interval

Question 19

Blood-Brain Barrier

Answer 19

Glial cell layer between capillary endothelium and nervous tissue, only nonionized lipid-soluble compounds can penetrate

Question 20

Transporters barring distribution

Answer 20

Tissues may possess transporters that accumulate chemicals against concentration gradients, BBB has efflux transport mechanisms to remove drugs from specific sites

Question 21

Ivermectin Sensitive Collies

Answer 21

Defective MDR1 protein allows drugs to enter the CNS

Question 22

MDR1 Defect

Answer 22

Premature stop codon causes truncation and defective protein

Question 23

Volume of Distribution

Answer 23

Amount of tissue to which a drug is distributed, volume to which a drug would have to be distributed if it were distributed at plasma concentration after IV adminsitration

Question 24

PDC and Vd relationship

Answer 24

PCD and response to a drug varies inversely with Vd