Lecture 5 (Cut off Exam 1) Flashcards
Passive Diffusion
How do small polar molecules transport?
Passive diffusion via pores.
How do large polar molecules transport?
Specialized transport via active transport or facilitated diffusion.
How do lipid molecules transport?
Passive diffusion through lipid bilayer membranes.
How do monosaccharides transport?
Translocation through things like intestinal walls from high concentrations to low.
Types of Membrane Proteins (2)
- Intrinsic - hydrophobic forces
- Extrinsic - electrostatic & hydrogen bonding. Amphiphilic
Can do things like receptors, channels, or pores.
Passive Diffusion Aspects (6)
- Random Movements
- No external energy
- Major process
- Moves things from high concentration to low
- Fick’s Law of Diffusion
- 1st order = percentage / unit time
Fick’s Law of Diffusion Coefficient Meanings (9)
- -dM/dt = reducing of initial mass over times
- S = Surface area of membrane layer
- D = Diffusion coefficient
- K = Permeability Coefficient
- h = thickness of membrane
- f(UD) - (subscript), fraction unionized in donor compartment
- C(TD) - (subscript), total concentration in donor compartment
- f(UR) - (subscript), fraction unionized in receptor compartment
- C(TR) - (subscript), total concentration in receptor compartment
Brodie’s pH Partition Ratio Things to Remember (4)
- pH first for weak acids
- pKa first for weak bases (A before B)
- weak acids are unionized (absorbed) in acidic environments and ionized (non-absorbed) in basic
- weak bases are unionized (absorbed) in basic environments and ionized (non-absorbed) in acidic
- *Snapshot of time, instantaneous equilibrium based on pHs**
Transport Overviews (3)
- Lipophilic - trancellular or paracellular
- Low molecular weight - lipid cell membrane or drug diffusion & absorption (latter has several methods)
- Intestine - Diffusion or carrier-mediated mechanism
Carrier-Mediated Intestinal Absorption Aspects (3)
- Transporter location is either brush border or basolateral membrane
- Specific ions or essential nutrients utilize this method
- Utilize directional flux transporters
Types of Flux Transporters (2)
- Influx transporters - increase drug absorption
2. Efflux transporters - decrease drug absorption
What occurs under sink conditions for Fick’s Diffusion Law?
C(TR) goes to zero since saturation isn’t possible
Which aspects of Fick’s equation are critical for absorption determination?
f(U) & C(TD)
Carrier Molecules
- very selective
- must be structurally similar with same mechanism between different carriers carrying same substrate
- competition sites for absorption
- *Saturation of system can occur at high drug concentrations**
- zero-order - certain amount of drug / unit time
Types of Carrier-Mediated Transport (2)
- Facilitated Diffusion
2. Active Transport
Facilitated Diffusion
- follows concentration gradients (high ==> low)
- NO energy input
- saturable due to its competitive kinetics and selective structure
- only minor role in drug absorption
- two types of proteins
2 Types of Facilitated Diffusion Proteins
- Channel Proteins - move water and ions
2. Uniporters - move sugars or amino acids
Active Transport
- involved in gastrointestinal absorption and renal/bilipid secretion
- some lipid-insoluble drugs and physiologic metabolites utilize this pathway
- moves AGAINST concentration gradient (low ==> high); therefore requiring energy
- creates a carrier-drug complex in a cell that moves the drug from the intestine (for example) to the blood
Transporter Types (7)
- Amino Acid Transporter
- Oligopeptide Transporter
- Phosphate Transporter
- Bile acid Transporter
- Glucose Transporter
- Monocarboxylic acid Transporter
- P-Glycoprotein Efflux - nonselective
* *7 = ONLY EFFLUX, ALL OTHERS ARE INFLUX AND SELECTIVE**
P-gp effects on Bioavailability
- drastically effects bioavailability of drugs and, by extension their efficacy.
- increases their Tmax and decreases their Cmax and AUC
Vesicular Transport Terminology (5)
(ALL via vesicles)
- Pinocytosis - intake of small solutes or fluids
- Phagocytosis - intake of large particles or macromolecules
- Endocytosis - bringing into a cell
- Exocytosis - taking out of a cell
- Transcytosis - taking across a cell (used for large proteins or the sabin polio vaccine)
Pore (Convective) Transport
- *Faster than passive diffusion alone**
- utilized by small molecules like water and sugar
- use aqueous channels or pores
- transports proteins form the open pores
- this phenomena explains the rapid renal excretion of drugs and uptake of drugs into the liver
Ion-Pair Formation
- occurs with strong electrolyte drugs that are highly ionized, charged, and have extreme pKa values (example - quaternary nitrogen containing compound)
- these are ALWAYS ionized at physiological pH and therefore have poor membrane permeability
- neutralized with opposite charged ions to make them lipophilic
Examples of Drugs that go through Ion-Pair Formation
- Propranolol + oleic acid
- Quinine + hxylsalicylate
- Amphotericin B + DSPG
