What are the players in drug delivery?
- Dosage form
- Absorption organ
- Target Organ
- Target Cell
What is the ophthalmic route of administration?
What is the site of auricular/otic drug delivery?
What phase is the lipid bilayer?
What are the types of Carrier mediated movement across membranes?
- Facilitated diffusion
- Active transport
What is another term for vesicular mediated transport?
What are the types of Passive transport?
- Around cells
- Diffusion though membranes
What would you expect from a Vmax/Concentration plot of an actively transported molecule?
What would you expect from a Vmax/Concentration plot of an passively transported molecule?
What is the long term for ABC transporters?
ATP binding cassette transporters
What do ABC transporters do?
- Aid in movement across the membrane
- RNA translation
- DNA repair
Describe the composition and location of ABC transporters:
What health related activities are ABC transporters involved in?
- Cystic fibrosis and other diseases
- Tumor resistance
What are the drug substrates for Amino acid transporters?
What are the drug substrates for Peptide transporters?
- b-lactam antibiotics
- ACE inhibitors
What two transporters are peptide transporters?
hPEPT1 and HPT1
What two transporters are nucleoside transporters?
CNT1 and 2
What three transporters are organic anion transporters?
OATP1, 3, and 8
What three transporters are Organic cation transporters?
OCT1 and OCT2
What two transporters are Bile acid transporters?
What are the drug substrates for Nuscleoside transporters?
What are the drug substrates for Organic anion transporters?
- Benzoic Acid
What are the drug substrates for Organic cation transporters?
What are the drug substrates for Bile acid transporters?
What law describes passive movement across a membrane?
What is diffusion?
Process of mass molecular transfer due to random molecular motion and a concentration gradient
What is the driving force for diffusion?
What pharmaceutical examples were given for diffusion?
- Transport of drugs through a polymeric membrane
- Percutaneous absorption
- GI absorption of a drug
What is a Barrier in terms of diffusion?
An area of resistance to diffusion
What is a Membrane?
A solid or semisolid sheet that separates and regulates phases or materials passing through it.
What is Flux (J)?
The amount of material moving through a cross-sectional area over time.
What is Fick's Law used to measure?
What is proportional to?
The concentration gradient
Is the diffusion coefficient a constant?
Does the diffusion coefficient stay the same for a given product?
- No, changes with:
- Solvent properties
- Chemical nature of the diffusant
Summarize Fick's first law:
The Flux is proportional to the Concentration gradient
Summarize Fick's second Law:
The rate of change in a concentration gradient within the diffusional field is proportional to the rate of change in the conc. gradient at the point in the field
What law would you use to describe diffusion through anisotropic membrane?
Fick's first law
What is isotropic?
Not varying in magnitude
What are the assumptions of Diffusion through isotropic membranes?
- Quasi steady state
- No aqueous boundary layer exists
Describe graph of release vs Time of a drug diffusing through an isotropic membrane:
Non-linear at first
Later becomes constantly linear
What is the Lag time in terms of the graph:
The point of interaction for the extrapolated steady state portion of the curve
What is the lag time in terms of the movement of the diffusant?
The time for the penetrant to establish a uniform concentration gradient
What is a transporter that moves substances out of the cell?
What type of transporter moves substances into the cell?
What are the critical factors in influencing whether a transporter is creating efflux or uptake?
The orientation and location in the cell
Describe the rate of drug uptake of a carrier mediated drug:
Fastest at the beginning, slows and eventually plateaus
Describe the rate of transport of a drug that moves by passive diffusion:
Steady state of flux (linear)
Are there more transporters on the Apical (lumen side) of the epithelial GI cells or the basolateral side?
The Lumen side
Where is P-gp located within the cell?
Where is P-gp located within the body?
GI, Liver, Kidneys, Blood Brain Barrier
The action (efflux or uptake) of PGP is what?
Depends on the location in the membrane and cell
What is P-gp?
Transporter called P-Glycoprotein
What Drug properties are important when considering transportation (7)?
- Facilitated diffusion
- Administration (IV vs Oral)
- Competitive binding
What transporter factors contribute to drug movements?
Location on apical or basolateral surface (Uptake vs. Efflux)
What family of transporters does P-Glycoprotein belong to?
- ABC transporters
- Encoded for by MDR1
- Efflux pump
- Apical epithelial cell expression
What therapies does P-gp effect?
Chemotherapies and others
Why is P-gp so important?
It expels drugs
What is a P-gp substrate?
A drug that is expelled by P-gp
What considerations are applicable to P-gp substrates?
Need to consider the route of administration (GI especially tough)
Describe the basic characteristics of a P-gp substrate:
- MW = 250-1200
- Usually lipophilic
- Usually basic or uncharged
Describe the significance of Loperamide and P-gp:
- Loperamide is an m-opioid receptor antagonist which could have analgesia, sedation, etc. (systemic effects)
- Does not have any systemic effects, only GI
- Is a P-gp substrate that is expelled in the GI
If Loperamide is administered PO, what effects does it have?
What drug can elevate the effects and allow Loperamide to enter the CNS?
What would a patient experience if quinidine were administered with loperamide?
Increased anti-diarrheal effects and increased CNS effects
What is quinidine?
Potent P-gp inhibitor
The majority of drug movement happens through what process?
What are the critical parameters of drug movement?
- Concentration gradient
- Rate constants
What is pharmacodynamics?
What the drug does to the body
What is Pharmacokinetics?
What the body does to the drug