Time course of absorption, distribution, metabolism & excretion
Pharmacokinetics
Pharmacokinetics can be simplified by asking
"What does the body do to the drug?"
Time course of effect, relationship between drug concentration and site of action
Pharmacodynamics
Pharmacodynamics can be simplified by asking
"What does the drug do to the body?"
Drug dose absorption is
Systemic
Drug dose distribution is related to
tissues
End result of pharmacodynamics when its all fucked
toxicity
End result of pharmacodynamics when its all chill
efficacy
LADME
L
Liberation
LADME
A
Absorption
LADME
D
Distribution
LADME
M
Metabolism
LADME
E
Excretion
Dumb example(s) of Liberation
-Jailbreaking chemicals
-Enteric coating to prevent drug exposure before small intestine - protecting the drug from the stomach (acid) and/or protecting the stomach (lining) from the drug
-Delayed/extended release stimulants-- cardiac damage mitigation
Dumb example(s) of Absorption
carrying an unmetabolized drug to its destination
Dumb example(s) of Metabolism
CYP 450 enzymes impact on 90% of oral drugs
Breaking a drug down so it can do its job and stop being a fancy bitch
too much Tylenol wrecking the liver because it does everything around here
Dumb example(s) of Excretion
Drinking a gallon of lidocaine and getting nothing after the liver gets its hands on it
water soluble drugs being dumped by the kidneys
CMAX is the point of
Peak serum concentration in body
AUC (area under the curve) is
the exposure number
AUC often drives what component of drug development?
Dosing
CL is
Clearance
Vd is
Volume of distribution
t1/2 is
half-life
F is
bioavailability
When is drug clearance accomplished?
Blood volume is completely cleared
How is drug clearance measured?
volume/time
Volume is ____________ from clearance
Independent
Dependent
Independent
Half-life is ________________ on clearance
Independent
Dependent
Dependent
What route does not require bioavailability consideration?
IV
Primary parameters of pharmacokinetics are
Clearance
Volume of distribution
Secondary parameters of pharmacokinetics are
Half life
Bioavailability
CYP 450 is an enzyme family commonly involved in
breaking down oral medications
The gut wall is made up of
simple columnar epithelium
What is the the first step in determining onset of action, rate of absorption, availability, etc.
Liberation
What can drugs be excreted through?
urine, bile, sweat, saliva, tears, milk, and/or stool
What can oral medication absorption be physiologically influenced by?
-First-pass
-Anything that makes you bad at food:
delayed gastric emptying
garbage intestinal blood flow
slow bitch bowels
gastric pH
lazy millennial enterocytes
How would you use the Henderson-Hasselbalch equation to predict concentrations of a base instead of a weak acid?
Turn the ratio upside down
(un-ionized/ionized)
If the pH is lower than the pka: In an acid
the compound has a proton and is unionized
pKa
the acid-base dissociation constant
If the pH is lower than the pka: In a base
the compound has a proton and is ionized
pKa is the pH at which
a compound is equally ionized and unionized
What can pass through the lipid bilayer?
Free, unionized drug molecules
What typically uses passive diffusion?
Nutrients
Passive diffusion is common for pharmaceuticals
T or F
F
The measure of a drug moving across a membrane
permeability
what molecules go across membranes the fastest?
small, lipophilic, unionized molecules
What must be added for facilitated diffusion?
A carrier protein in the membrane
Passive and facilitated diffusion are both dependent on:
concentration gradient
Molecules only move which direction on a concentration gradient
High to low
Facilitated diffusion
Wants to make it through the cell wall but needs help
Active transport
Forces drugs into places it doesnt want to go
Large and hydrophilic molecules will need
active transport
large, scared of fat
needs help
bulk transport
needs endocytosis through cell wall into cell plasma
Passive Diffusion
lipophilic, small
active transport
hydrophilic, low to high
across GI tract, across cell membrane, anything except for IV admin
requires active, passive, transport
Drugs usually exist in two froms
weak acid, weak base
acids dissociate into
proton, acid
charged molecules dont ____ well
absorb
not charged, nonpolar
easily absorbed
weak acids need to be in an acidic environment to be
absorbed
best area of GI tract for absorbing weak acids are
duodenum
Weak bases need to be in a basic environment to be
absorbed
alkaline environments decrease the number of
protons in the environment
factors affecting absorption
pH, decreased blood flow, decreased gi motility