Absorption Flashcards
Biopharmaceutics
Relationship between the physical and chemical properties of a drug in a dosage form and the pharmacologic response after administration
What 5 factors is biopharmaceutics dependent upon?
1) chemical nature
2) physical state
3) type of dosage form
4) presence/absence of excipients
5) pharmaceutical process
Pharmacokinetics
Study and characterization of the time course of the drug absorption, distribution, metabolism, and excretion (ADME). The relationship of these processes to the intensity and time course of the therapeutic and adverse effects of drugs.
Bioavailability
Rate and extent (amount) to which a drug is absorbed from a drug product into the body or to the site of action
Clinical Pharmacokinetics
The application of pharmacokinetic methods in drug therapy. It involves a multidisciplinary approach to individually optimized dosing strategies based on the patient’s disease start and patient-specific considerations
Pharmcodynamics
Refers to the relationship between drug concentration at the site of action (receptor) and pharmacologic response
Absorption
factors affecting drug absorption (transport processes, pH, lipophilicity, particle size, first-pass effect); factors affecting dissolution rate
Distribution
body fluid compartments, tissue distribution, protein-binding
Metabolism
phase 1 and 2 reactions, Michaelis-Menton (phenytoin), genetics, age, disease states, drug interactions
Excretion
renal clearance (filtration, secretion, reabsorption), enterohepatic circulation, biliary clearance
Bioavailability and Bioequivalence
methodology for measuring (experimental design, statistical considerations), relative and absolute bioavailability
Read chart on page 4
okay
Excretion is done by the _____
kidneys
Metabolism is done by the ______
liver
How do lipophilic drugs get across the membrane?
- use diffusion to cross membrane
- once it passes, it’s in an aqueous environment
How do hydrophilic drugs get across the membrane?
-transport proteins to cross the membrane
______ = plasmid protein that binds a lot of drugs
albumin
Overall rate of absorption is faster in capsule or tablet?
capsule
Relative pH of stomach?
1-3
Relative pH of small intestine?
5-7
Relative pH of large intestine?
7-8
Tablet has _____ dissolution rate.
very limited
Granules have ____ dissolution rate.
limited
Very small particles from a capsule have _____ dissolution rate.
optimal
Why don’t suppositories work if you put them up to far?
You defeat the purpose, it will reach mesenteric vein which feeds into the portal vein and will go through first-pass metabolism (which is what you are trying to avoid by using suppositories).
If you insert it correctly, it goes straight to inferior vena cava and you bypass the first-pass metabolism.
______ drugs are better at crossing membranes
unionized
pH partition theory:
Absorption depends on?
pKa, lipid solubility, pH of solution
What 2 equations do you need to know?
AH A- + H+
Ka = [A-][H+]/[HA]
**Also know henderson hasselbach equation
Liver sinusoids have holes in them called _________
fenestrations
*only plasma proteins and things that are blood-soluble will pass through these holes
Sinusoid has how many zones?
3 zones
If you are putting a big liver into a smaller body, apoptosis happens on Zone __ cells
3
Which Zone gets all the nutrients first?
Zone 1
Liver has ___ blood supply
dual
- portal vein which feeds mesenteric (low in oxygen)
- hepatic artery which is high in oxygen but doesn’t originate from gut
*portal vein and hepatic artery meet
Drug uptake is highest in which zone?
Zone 1
Drug uptake is lowest in which zone?
Zone 3
Describe the fluid-mosaic model of the cell membrane
A) Pericellular aqueous pathway
B) Transcellular lipophilic pathway
-Lipid-soluble agents
C) Transport proteins
-Glucose, amino acids, nucleosides
D) Efflux pump
E) Receptor-mediated transcytosis
-insulin, transferrin
F) Adsorptive transcytosis
-albumin, other plasma proteins
**See slide 10
Exocytosis
Materials are exported outside of the cell
Endocytosis
Is a form of active transport in which a cell transports molecules into the cell by engulfing them in an energy-using process.
Budding
a form of growth? idfk
What do drug transporters control?
- Controls intracellular drug concentrations and access to drug metabolizing enzymes
- Controls systemic drug concentrations - absorption and excretion
- Controls drug concentrations at the site of action
What are the two groups of transporters?
1) SLC Uptake Transporters
2) ABC Efflux Transporters
List some SLC Uptake Transporters
OATPs OATs OCTs PEPTs MATEs
List some ABC Efflux Transporters
P-gp (ABCB1)
BCRP (breast cancer resistant protein)
MRPs (multidrug resistant protein
BSEP (bile salt export protein)
What can “Drug as a Substrate of Transporter” do?
- Determinant of drug disposition (ADME)
- Prediction of potential drug-drug interactions (DDI)
What can “Drug as an Inhibitor of Transporter” do?
- Affects intracellular/systemic concentrations of affected drugs
- DDI potential with other substrate drugs
Describe P-gp
- important efflux transporter
- kicks stuff out of the cell
- P-gp can work against you if you want something in the cell
As a general rule, the SLC transporters are responsible for _____ of molecules into cells
uptake
Most SLC transporters are located in the ____ ______ although there are some members located in mitochondria or other intracellular organelles
cell membrane
SLC transporters are named using the format SLCnXm:
n = ?
family number (1-52)
SLC transporters are named using the format SLCnXm:
X = ?
letter for the subfamily
SLC transporters are named using the format SLCnXm:
m = ?
number representing the individual family member
One exception is SLC family 21 (OATPs) which have what format?
SLCOnXm
As a general rule, the ABC transporters are responsible for _____ of macromolecules from cells
efflux (removal)
ABC transporters are transmembrane proteins that use ___ ________ as an energy source to translocate substrates across membranes.
ATP hydrolysis
ABC transporters are named using the format ABCxN:
X = ?
family (A-G)
ABC transporters are named using the format ABCxN:
N = ?
a number representing the individual family member
ABC transporters can be very _____ proteins
large
Transporters are everywhere! List a few locations
- intestinal epithelia
- hepatocytes
- kidney proximal tubules
- blood brain barrier
Diffusion correlates with ______
temperature (proportional to degrees K)
Will diffusion be stopped by a 30 degree temperature drop?
No - decreasing temp will decrease production of ATP, but since diffusion is a passive process and does not require ATP, it will not be slowed down by this temperature drop
Will transport be stopped by a 30 degree temperature drop?
Yes, because when you lower the temp you decrease production of ATP (which transport depends on) so you will slow transport
Active transport:
Can move a substrate ______ a concentration gradient
against
Active transport:
Requires expenditure of _____
energy
Active transport:
At low [drug] rate is proportional to _____
[drug]
Active transport:
At high [drug] carrier mechanism is _______
saturated
Active transport:
shows ______
specificity
Active transport:
Subject to competitive ______
inhibition
Active transport:
Shows site ______
specificty
Active transport:
Is inhibited non competitively by ??
substances that interfere with the respiration of cells
How do you tell the difference between diffusion or transport?
Transporters require energy
How does volume influence gastric emptying?
The larger the starting the volume the grater the initial rate of emptying. After this initial period the rate slows
How does physical state influence gastric emptying?
Solutions or suspensions empty more rapidly than chunks
How do fatty acids influence gastric emptying?
Reduction in proportion to chain length
How do triglycerides influence gastric emptying?
Reduction in rate of emptying, unsaturated more effected linseed and olive oils most effective
How do carbohydrates influence gastric emptying?
Reduction
How do amino acids influence gastric emptying?
Reduction, proportional to concentration
How does osmotic pressure influence gastric emptying?
increase at lower concentrations, decrease at higher concentrations
How do acid chemicals influence gastric emptying?
reduction
How do alkali chemicals influence gastric emptying?
increase
How do anticholinergic drugs influence gastric emptying?
decrease in emptying
How do narcotic analgesics influence gastric emptying?
decrease
How does metoclopromide influence gastric emptying?
increase
How does ethanol influence gastric emptying?
reduction
How does body position influence gastric emptying?
lying on left side reduces emptying
How does viscosity influence gastric emptying?
increase viscosity reduces emptying
How does emotional state influence gastric emptying?
- aggressiveness increases contractions and emptying
- depression reduces
How do bile salts influence gastric emptying?
reduces
How do disease states influence gastric emptying?
rate is reduced in some hypothyroidism, pyloric lesions
How does exercise influence gastric emptying?
vigorous exercise reduces it
How does gastric surgery influence gastric emptying?
emptying difficulties can be a serious problem
Facts affecting absorption of drugs across the gut?
- age
- blood flow
- pH
- food
- other drugs
Drugs can either _____, ______, or _______ the absorption of other drugs.
reduce, delay, or increase
**or not affect it
Time vs. Plasma Drug Concentration Graph:
higher slope = ?
faster absorption
Time vs. Plasma Drug Concentration Graph:
lower slope = ?
slower absorption
