Disposition of Drugs Flashcards
Define disposition of drugs
The study of the movement of drugs in the body across biological membranes from the time of absorption until elimination.
Disposition of drugs = _____
Pharmacokinetics
What are the 4 stages of drug disposition?
1: Absorption
2: Distribution
3: Biotransformation
4: Excretion
What are the factors affecting disposition of drugs?
1: Biological cell membranes
2: Concentration gradients
3: Pump mechanisms
4: Site of administration
5: Total body water
6: Plasma protein binding
7: Disease
What are the properties of the biological cell membrane?
1: Phospholipid bilayer
2: Membrane proteins and carbohydrates
3: Cell junctions
4: Aqueous pores
What are the 4 mechanisms of drug transport across the cell membrane.
1: Passive diffusion
2: Facilitated diffusion
3: Active transport
4: Pinocytosis
Describe passive diffusion
1: No energy (ATP) is required for this process
2: Movement down the concentration gradient
3: Hydrostatic pressure differences across membranes
4: Bulk flow of water can carry with it small water soluble substances
What are mechanism types of passive diffusion?
1: Transmembrane
2: Paracellular
3: Simple diffusion
Define transmembrane.
Movement by passive diffusion through aqueous protein channels in the cell membrane.
Define paracellular.
Movement via filtration through intracellular aqueous pores.
Define simple diffusion.
Movement through lipid membrane
How do the majority of drugs move through the body?
Simple diffusion
Describe facilitated diffusion.
1: No energy is required
2: Carrier-mediated transport
3: Movement down the concentration gradient
4: Faster because of the carrier
Describe active transport.
1: Needs carrier and energy
2: Carrier mediated transport
3: Movement up the concentration gradient
4: Primary vs. secondary
What is the most abundant active transport pump in the body?
Na+/K+ ATPase transport pump
Describe Pinocytosis.
1: Cell drinking
2: Specific type of endocytosis where cells engulf the drug molecules dissolved in water.
3: Can interfere with lysosomal function and cause lysosome rupture
What are the properties of passive diffusion?
1: Moves down the concentration gradient
2: Requires no energy
3: Substances can be move in or out of cells
4: Most common form of transport
What are the properties of facilitated diffusion?
1: Moves down concentration gradient
2: Requires a carrier
3: Requires no energy
4: Saturable
5: Substances can be moved in or out of cell
6: May protect cell from harmful substances
What are the properties of active transport?
1: Moves up the concentration gradient
2: Requires energy
3: Symporters or antiporters
4: Satiability
5: Selectivity
6: Competitive inhibition by co-transported compounds
7: Classified into primary or secondary
What are the properties of pinocytosis?
1: Special type of endocytosis or cell drinking
2: Drug dissolved in water
3: Can be toxic
What are the factors affecting simple diffusion?
1: Concentration gradient
2: Lipid solubility
3: Degree of drug ionization
Higher lipid solubility of the drug = _____
Faster crossing cell membranes
Non-lipid soluble drugs are more dependent on _____.
Molecular size
Non-lipid soluble drugs move via _____.
Membrane pores
Membranes are more permeable to _____ forms of drugs.
Non-ionized
Drugs cross biological membranes in the _____ form.
Non-ionized
What does the rate of diffusion depend on?
Degree of ionization
What does the degree of ionization depends on?
1: pH of the drug
2: pKa of the drug
3: pH of environment in vivo
Define pH.
Any solution is determined by the number of protons present
What does the pH of a drug depend on?
Whether it acts as an acid or base in solution
True or False: Most drugs act as strong acids or bases.
False
Weakly acidic drugs are more ionized in _____.
Alkaline solutions
Weakly basic drugs are more ionized in _____.
Acidic solutions
Define pKa?
Equal to the pH of the medium at which the dissolved drug is 50% ionized and 50% non-ionized.
Higher pKa of a weak acid = _____
Higher N/I
Higher pKa of a weak base = _____
Higher I/N
Acidic drugs ionize in _____.
Basic environment
Basic drugs ionize in _____.
Acidic environment
What can the henderson and hasselbach equation be used for?
To determine the degree of ionization
pKa of an acid = _____
pH of the medium + Log N/I
pKa of a base = _____
pH of the medium + Log I/N
