Lecture 9 Flashcards
Upper and lower rectum have what type of tissue
Upper - Simple Columnar
Lower - strat. squamous non-keratinized->keratinized near sphincter = HIGHLY FOLDED
Which areas of rectum show high drug absorption?
Strat. Squamous and non-keratinized
Problem with rectal drugs
Low residence time (stimulates bowel movement)
Oral absorption first step
Disintegration/ deaggregation of particle
Dissolution action
Getting drug out of particles and into solution
What can cross GI barrier for absorption?
Free Active Pharmaceutical Ingredient (API)
Dissolution
The rate at which the drug releases (has to release at certain time)
Biorelevant dissolution times are…
Variable from person to person
T/F: There can be variation with dissolution within same patient
True
T/F: Greater GI residence leads to lower absorption
False (higher absorption)
T/F: Gastric pH and residence changes can happen if formulation is taken before meals
True (fed state may be a little less predictable, but still possible)
Factors influencing solubility
Buffer capacity
Bile salts
Regional Fluids
Other Drugs
Potential issues from endogenous substrates
Strong Buffer Capacity…
Resists changes, holds pH well
Buffer capacity/pH-
solubility relationship
Higher the buffer capacity and pH, higher solubility
Higher solubility of drug means what for absorption?
More of the drug is able to be absorbed
T/F: Transporters and enzymes vary along GI tract
True
T/F: Diet and Chemical Exposure varies in GI
True
Two big challenges for GI Physiology Clinical Considerations
Pharmacogenetics
Genomics
T/F: Drug-nutrient and drug-drug interactions are common in GI tract
True
Drug distribution is different between…
Different compounds based on their physiochemical properties
Where do lipophilic compounds partition vs hydrophilic?
Lipo- Fatty tissues
Hydro- Tissues where endothelium is permissive (spleen/liver)
Nature of pharmacokinetic processes
Described by concentration time profiles (blood/plasma vs. time)
Compartments represent kinetically similar tissues/spaces
Processes can be reversible/irreversible
Can be linear/non linear
Fast and slow processes tend to “disappear”
What two main factors dictate distriubtion?
Perfusion and Permeability rates
Drug distribution restricted to one tissues vs at diff rates trend (linear/non-linear?)
Restricted - Linear
Different rates - non linear
Bioavailability Definition
The rate and extent of drug absorption
Absolute Bioavailability definition
is the AUC of a given dosage form compared with the AUC of the same dose injected intravenously
Relative bioavailability
Refers to the AUC of a given dosage form compared to an arbitrary reference standard
T/F: Bioequivalent means the therapeutic effect of two dosage forms are equivalent
False
