Chapter 2 Part I Flashcards
What are the different mechanisms of drug transport
passive : simple and facilitated
active: carried mediated
ion pair
pinocytosis
convection
the passage of molecules through a membrane that does not actively participate in the process
passive diffusion
the rate of diffusion or transport across a membrane is proportional to the difference in drug concentrations on both sides of the membrane
this is known as
ficks first law
ficks first law is
dc/dt = -DA (change in c/ change in x)
D= diffusion coefficient
A = surface area
change in c = concentration gradient
change in x = diffusion distance/thickness
the process of absorption is driven by ___ of a drug across a membrane
concentration gradient
concentration gradient of a drug is dependent on its
aqueous solubility and formulation
carrier mediated transport is mainly for
hydrophilic molecules
carrier proteins are ______
integral membrane proteins
_____ undergo a conformational change after binding to the substrate
carrier proteins
molecules to be transported bind to and take a ride using a membrane protein known as ___ or ____
carriers
transporters
_____ is when carrier mediated process occurs only in the presence of a concentration gradient
facilitated diffusion
in facilitated diffusion, transporter proteins create a __________ through which ions and small hydrophilic molecules pass
water filled pore
T or F each carrier protein is specific to just one type of ion or molecule in active transport
T
T or F solutes cannot be transported against their concentration gradient in active transport
F, they can be
the requirement of active transport is
ATP, source of energy
the rate of active transport is determined by
michelis menten equation
what is the michaelis menten equation
rate of drug absorption =
(C) x Vmax / Km + (C)
what does Km stand for
affinity constant of the drug for the carrier
the concentration of drug that produces 1/2 of Vmax
Vmax is equivalent to
the maximal rate of absorption
pore transport is
the transport of drug through aqueous pores of the biological membrane
what is a another name for pore transport
convective transport
what is the diameter of aq pores
7-10 angstrom
what type of molecules can pass through the aq pores
only low molecular weight molecules can pass - 150 for spherical and 400 for chain like
what are the rate determining steps in absorption of orally administered drugs
rate of dissolution
rate of drug permeation through the biomembrane
T or F absorption can still take place if there is no dissolution
F, no dissolution = no absoprtion
drug in particle form to drug in solution form is
dissolution
drug in solution form to drug in blood is
permeation
what form of a drug has very limited dissolution
tablet form
what form of a drug has the best dissolution
once it has been disintegrated to small particles
what is lipinskis rule of 5
a guideline that predicts if a chemical compound can be an orally active drug
What is lipinskis rule of 5
1 - Molecular weight
drug MW is inversely proportional to drug permeability (<500dA)
2 - lipophilicity LogP
drug liphophilicity is directly proportional to drug permeability (does ` exceed 5)
3,4 - number of hydrogen bond donors and acceptors is inversely proportional to drug permeability (no more than 10 H bond acceptors all N or O, no more than 5 H bond donors N-H or O-H)
poor permeation and poor absorption happens when
MW > 500 daltpns
Lop P is greater than 5
more than 5 h bond donors
more than 10 H bond acceptors
POLAR SURFACE AREA IS GREATER THAN 140 A2
according to lipinskis rule of 5, there may not be more than ___ violation to be an orally active drug
one
T or F lipinksis rule of 5 is not applicable for substrates of transporters and natural products
T
rates of dissolution and absorption of a variety of drugs are related to their ____
ionization constants
particle size affects dissolution rate, ___ and F
absorption
which kind of drug can get through the lipid membrane? ionized or non ionized
non ionized
why does a non ionized drug get through the membrane more easily
higher lipid solubility
a drug dissolves more rapidly when the surface area is increased or decreased?
increased
reducing or increasing particle size increases surface area
reducing
increased surface area leads to faster
dissolution
how can you reduce particle size
miling
pulverizing
grinding
what are the exceptions to decreasing particle size and decreasing solubility
tetracycline - enough solubility
erythromycin - destroyed in the gut, small particle size is disadvantage
extended release tablets
particle size has significant influence on which six drugs
griseofulvin
nitroflurantoin
spironolactone
tolbutamide
procaine
penicillin
the ability of a substance to crystallize into two or more different crystal forms is known as
polymorphism
In polymorphism, each of of the crystal forms have the same _____ but different _____ in the crystal lattice
chemical structure
conformations
T or F physical properties, solubility, and rate of dissolution can be different for different polymorphs
T
The energy required for a molecule of drug to escape from a crystal is ______ than it is required to escape from an amorphous powder
much greater
the amorphous form of a compound is always ___ soluble than a corresponding crystal form
more
the thermodynamically most stable form of a pharmaceutical solid is more or less soluble
less soluble
a ______ polymorph is more soluble but less stable
metastable
do dissolution rates vary with different salt forms
yes
which salt form has the highest solubility
sodium, NAa
the measure of a drug’s lipophilicity and an indication of its ability to cross cell membranes is
partition coefficient
is partition coefficient oil/water or water/oil
oil/water
Partition (P) is also known as
distribution coefficient (D)
distribution coefficient is
the ratio of concentration of a compound in the two phases of a mixture of two immiscible solvents at equilibrium
Po/w =
(Coil/Cwater)equilibrium
the partition co efficent is the ratio of concentrations of a _____ compound between an aqueous and organic solvent
unionized
how is partition coefficient measured
measured by adjusting the pH so that compound remains predominantly in the unionized form in the solvent
lopP is
the log of the ratio of concentrations of the unionized solute in the solvents
a drug is lipophilic when P is
greater than 1
when P is less than 1 the drug is
hydrophillic
membrane permeability is the rate of
drug transport across a biological membrane
what information does membrane permeability provide
absorption characteristics of the drug
if ionization increases what happens to polarity, partition coefficient, and permeation
increases, decreases, decreases
if ionization decreases, what happens to polarity, partition coefficient and permeation
decreases, increases, increases
according to FDA, a drug is considered ______ when its highest clinical dose strength is soluble in 250 mL of aq media over a pH range 1-7.5 at 37.5 C
highly soluble
according to FDA, a drug is considered _______ if the absorption or an orally administered dose in humans is greater than 90% when determined usng mass balance or in comparison to an IV reference dose
highly permeable
Class I drugs are
highly soluble and permeable
Class II drugs are
low solubility and highly permeable
Class III drugs are
high solubility
low permeability
Class IV drugs are
low solubility
low permeability
what is the dosage form approach for Class I drugs
simple solid oral dosage form
what is the oral dosage form approach for class II drugs
techniques to increase surface area like particle size reduction, solid solution, solid dispersion
or solutions using solvents and surfactants
what is the oral dosage form approach for class III drugs
incorporate permeability enhancers to maximize local lumenal concentration
what is the oral dosage form approach for class IV drugs
class II and III approach combned
from class I to IV, what are the chances of non oral dose being required
increasing chances
what are some class I drugs
chloroquine
diltiazem
metoprolol
paracetamol
propranolol
theophylline
verapamil
what are some class II drugs
carbamazepine
danazol
gilbenclamide
ketoconazole
nifedipine
phenytoin
troglitazone
what are some class III drugs
acyclovir
atenolol
catopril
cimetidine
metofrmin
neomycin B
ranitidine
What are some class IV drugs
coenzyme Q
cyclosporin A
ellagic acid
furosemide
ritonavir
saquinavir
taxol
what is the list of slowest to fastest absorption in terms of formulation
tablets
capsules
powders
suspensions
emulsion
liquids
tablets are disintegrated from ____ to ____
granules, fine particles, dissolution, drug in solution to drug in blood
what are the formulation factors?
dosage form
excipients
phosphate
tablet hardness vs disintegration
table coating
product age and storage conditions
T or F product aging and imporper storage have no effect on bioavailibility
F it does adversely
what are some physiologic factors
area of absorptive surface
vascularity
pH
presence of other substances
GI motility
functional integrity of absorptive surface
diseases
in case of shock, what route is preferred?
IV
vasoconstrictors restrict the
absorption of local anesthesias
increase in vascularity increases the
rate and extent of absorption
T or F aid pH favors acidic drug absorption, basic pH favors basic drugs
T
Do pathophysiologic conditions such as burns increase or decrease the permeability of drugs across the skin
increase
