3. Disposition of Drugs Flashcards
What is Drug Disposition?
the study of the movement of drugs in the body across biological membranes from the
time of absorption until elimination
What are the stages of drug disposition?
Absorption
Distribution
Biotransformation
Excretion
Describe what the biological cell membrane is composed of
Composed of a lipid bilayer
Membranes also contain membrane proteins and carbohydrates
There are aqueous pores or junctions between cells
List the ways drugs can be transported across the cell membrane
Passive diffusion
Facilitated diffusion
Active transport
Pinocytosis
What movements are included in passive diffusion?
Transmembrane and paracellular movement
Simple diffusion
What is Transmembrane Movement?
movement of water is either
by passive diffusion through aqueous protein
channels or by flow resulting from osmotic or hydrostatic difference across the membrane
What is paracellular transport?
transport of water is through intercellular aqueous pores
Tissues that have a barrier mechanism have?
“tight” intercellular junctions
What can bulk flow of water carry with it?
small water-soluble substances
What are factors that affect simple diffusion?
Concentration gradient
Lipid solubility
Degree of ionization
Describe Concentration Gradient
Drugs move across membranes from high concentration to low concentration
Describe Lipid Solubility
Is measured by lipid partition coefficient (the ratio between solubility of drug in
lipid to its solubility in water).
The higher the lipid solubility of the drug the faster the drug crosses cell
membranes
Describe Degree of ionization
Drugs cross biological membranes in the non
ionized form (lipid soluble and do not
carry electric charges).
The rate of diffusion depends on the ratio between the non ionized form of the drug
to the ionized form (N/I)
Ionization of the drug depends on:
The pH of the drug
The pka of the drug
The pH of the medium (environment)
What is the pka of a drug?
the pH at which a weak electrolyte is 50% ionized and 50%
nonionized
Most drugs are?
weak electrolytes (weak acids or weak bases)
Acidic drugs ionize in?
alkaline medium
Basic drugs ionize in?
acidic medium
Henderson and Hasselbalch equation
pka of an acid = pH of the medium + Log N/I
pka of a base = pH of the medium + Log I/N
N = Non ionized
I = Ionized
What happens to the N/I value when the Pka of a weak acid is higher?
its higher
What happens to the N/I value when the Pka of a weak base is lower?
Its higher
Quaternary ammonium compounds such as d-tubocurarine are?
mostly ionized
Phenylbutazone, a weak acidic drug (pka 4.4) is?
mostly non ionized in the stomach
Then it is absorbed from the stomach because it is lipid soluble.
When it reaches the plasma (pH 7.4) it is mostly ionized and is trapped in plasma
(pH 1.4)
What is facilitated diffusion?
A carrier-mediated transport that does not need energy.
A drug moves across the membrane from high concentration to low concentration at a faster rate (downhill movement)
Transporters can move drugs from?
from outside the cell into the cell or from inside the cell
outside the cell
Transporters may act as a what?
a barrier system to protect cell from toxic substances by moving them from inside the cell outside the cell
What is an example of facilitated diffusion?
Movement of glucose across a muscle cell membrane by insulin-sensitive glucose transporter
What is active transport?
A drug moves across the membrane from low concentration to high concentration (uphill movement).
A carrier-mediated transport that requires energy
Primary active transport uses energy that comes directly from what?
ATP such as Na+-K+ ATPase
Secondary active transport uses stored energy in the?
in the Na+ electrochemical gradient that
was created using ATP in primary active transport
Secondary active transporters are classified into what?
symporters (cotransporters) such as
the Na+ -depended glucose transporters in the GI epithelium and renal tubules or antiporters (exchangers) such as Na+-Ca+2 exchanger protein
Active transport is characterized by?
saturablility
selectivity
competitive inhibition by cotransported compounds
What is Pinocytosis?
Is a specific type of endocytosis where the cell engulfs the drug molecules dissolved in water
An example of pinocytosis
Sequestration of aminoglycoside antibiotics by renal tubular cells
