Drug Disposition I Flashcards
Processes by which drugs cross biological membrane: (3)
Passive diffusion lipid aqueous
Passive transport
Active Transport
The most common and important mechanism of drug movement is active lipid diffusion, in which the drug dissolves in the lipid membrane and diffuses across driven by a concentration gradient. True or false?
false, passive diffusion
Rate of passive lipid diffusion depends on (3)
concentration gradient (affected by blood flow)
surface area
lipophilicity
2 major classes of drug transporters: Most drugs transported by which one?
Uptake& Efflux
Efflux
SLC transporters co-transport solutes like sodium. What type of transporter is this?
uptake
ABC transporters use ATP is an example of what transporter?
efflux
pump things out of the cell
Most drugs are ____ electrolytes.
weak
Ionized forms of chemicals do penetrate lipid membranes. True or false?
false
do not
Degree of drug ionization: (2)
pKa–intrinisic property of drug
pH of surrounding medium
weak acids: mainly ionized at pH __ pKa. weak bases: mainly ionized at pH __ pKa
>
The nonionized form is free to be absorbed across the gastric epithelial cell layer. Once it reaches the plasma, it encounters a pH that is now above its pKa. Therefore, aspirin will now be mostly in the ionized form. The rapid ionization of aspirin in the plasma maintains the concentration gradient of the diffusible (nonionized) form of aspirin, and diffusion will continue until equilibrium is reached. Thus, the total amount of aspirin at equilibrium (which never occurs in reality, this is only a conceptual example) will be 8000-fold higher in the high pH compartment. This is known as ___ ____.
ion trapping
What type of tissue contains : tight junctions lipid diffusion only
gastrointestinal epithelium
Molecules cross ______ endothelial cell layer by: Transcellular diffusion Aqueous diffusion Receptor-mediated endocytosis/pinocytosis Bold = most common
capillaries
Most capillaries are ______: (porous regions within and between cells) admit water-soluble molecules up to 60 kDa via ______ transport.
fenestrated
paracellular
________ capillaries are very leaky and allow RBCs and WBCs to pass
Discontinuous
_______ capillaries have tight junctions (but differ in the degree of pinocytosis)
Continuous
______ is the main drug barrier in the brain.
BBB
In the placenta, the human trophoblast basement membrane is quite porous. Admits most drugs < ____ MW
600
Factors affecting oral absorption: (7)
solubility stomach acid pH range tight junctions, lipid solubility surface area transport to liver via portal vein and first pass metabolism Intestinal motility, gastric emptying, blood flow
Enteral routes of drug administration: (3)
oral
sublingual (to avoid first pass metabolism and liver)
rectal
Parental routes of drug administration: (7)
IV IM subcutaneous inhalation nasal transdermal topical
Pulmonary administration of drugs: (4)
Gaseous anesthetics
Smoking
Aerosols for topical effects on lungs e.g. albuterol for asthma Aerosols for delivery to systemic circulation droplet or particle size is critical
Gaseous diffusion of anesthetics depends on: (3)
solubility in blood
drug concentration
ventilation
____ _____, not concentration, in blood determines delivery to CNS.
Partial pressure
