Pharmacokinetics Flashcards
pharmacokinetics
what happens to a drug when you put it in your body (effect of body on drug)
What does the drugs concentration in the body depend on
drug regimen (dose, route, formulation, frequency)
how the drug moves through the body over time (ADME)
What does pharmacokinetics describe
ADME
What is on the X axis of a PK curve
Time
what is on the Y axis of a PK curve
Blood level or “plasma concentration”
Pharmacodynamics = __________ = what the drug does to the body
concentration-effect relationship
Pharmacokinetics = ____________ = What the body does to the drug
Dose-Time-Concentration relationship
codeine getting metabolized (broken down) by hte body into a few different compounds, including morphine.
Pharmacokinetics
Opioids, such as codeine and morphine, work by agonizing (activating) mu-opioid receptors in the central nervous system causing analgesia.
pharmacodynamics
a central goal of drug therapy is to _____
achieve a desired effect while inflicting the minimum possible adverse effects
Understanding PK allows us to find the drug dosing regimen necessary to achieve the least possible adverse effects. This is achieved by __________
getting a drugs blood level in the Theraputic window
what is the theraputic window
the window between the minimum theraputic dose and the dose where the drug becomes toxic
what does Enteral mean
goes through the intestine (digestive tract)
what does parenteral mean
Stays outside digestive tract
why does a 150mcg tablet taken orally and 75mcg given IV have the same effectiveness
IV is absorbed better than oral
Bioavailability (F)
the Fraction of intact drug that reaches the systemic circulation
F= _____ for IV drugs
100%
if you take 100mg of a drug and only 80% of the drug reaches the systemic circulation (bloodstream) what is F? (what is bioavailability)
F=80%
What is used to measure bioavailability
Area Under the Curve (AUC)
What does AUC represent
bioavailability, the total systemic exposure to a drug.
What is the blue line, what is he green line
blue line = IV
green line = oral
Which of the PK curves below shows the BEST (highest) bioavailability
the one with the red
What are two things that reduce bioavailability
incomplete amount of absorption
the First pass effect
what is the first pass effect
when the concentration of a drug is greatly reduced before reaching circulation
Paracellular transport
it can go around cells (through the junctions between cells)
facilitated diffusion
it can get trasnported along a concentration gradient
diffusion
it can diffuse through the cells (ie throught the lipid bilayer cell membranes)
In general, drugs that are good at diffusing through lipid bilayers are:
small molecules
lipophilic
uncharged
Which molecule would be better at crossing through cell layers
Fentanyl (left) because its smaller than vncomyocin (right)
This tissue cares alot about size, charge, and lipophilicity of drugs that pass through it
continuous capillaries such as CNS (blood brain barrier), skin and lungs.
This tissue cares a little bit about size, charge, and lipophilicity of drugs that pass through it
fenestrated capillaries such as (kidneys and small intestine)
this tissue cares the least about size, charge, and lipophilicity of drugs that pass through.
sinusoidal capillaries (liver, lymph nodes)
influx transporters
active transport proteins that move drugs into cells
efflux transporters
active transport proteins that move drugs out of cells
active transport
transport requiring energy
What is a significant active trasnporter in PK and what is its job
efflux transporters
job is to keep xenobiotics (drugs) out of certain places.
example: p-gp is an important efflux transporter that keeps many drugs in the intestine and out of the brain
What is an example of p-gp
benadryl and allegra
benadryl is 1st generation antihistamine (drowsy)
Allegra is 2nd generation antihistamines (non drowsy)
this works because allegra has gp-gp transporters that keep the allergy medicine in the systemic circulation but out of the CNS
blocking histamine receptors peripherally helps_______ but blocking histamine receptors in the CNS causes ______
blocking histamine receptors peripherally helps allergies but blocking histamine receptors in the CNS causes drowsiness
What are the additional considerations when considering the absoprtion of tablets/capsules
dissolution of the drug from tablet or capsule form
stability of drug
rate of gastric emptying
intestinal motility and drug interactions
dissolution of the drug from tablet or capsule form includes
that the drug must be in solution to be absorbed and different formulations dissolve at different rates
What does rate of gastric emptying entail
absorption is much faster in the small intestine (more surface area, more permeability, more blood flow)
the speed of getting to small iintestine limits the sped of the drug getting absorbed
food slows gastric emptying
what does inestinal motility and drug interactions entail
pH, surface area, permeability, and efflux transporter density
drugs may bind to other contents of the intestine which can prevent absorption
What are the 2 possible pathways that drugs given by IM/SQ/ID can enter the systemic circulation
diffusion through capillary membranes
getting carried through the lymph system
the pathway consisting of diffusion through capillary membrane is forgiving of ____ and not forgiving of ____
very forgiving of polarity and charge
less forgiving of size
the pathway of getting carried through the lymph system, name 4 facts about this pathway
- lymph system is the body’s “garbage collector”
- large molecules and proteins tend to go this route
- lymph system moves very slowly - which makes absorption slow
- enzymatic breakdown of drugs can occur in lymph nodes
Speed of absorption when given IM/SQ/ID is affected by
slow moving systems
site of injection
local bloodflow
temperature
rubbing at injection site
Vancomyocin ( a large hydrophilic molecule) would be be absorbed which route and why
IV because the large molecule = hard to absorb and hydrophillic = good diffusion through capillary walls
Once any drug reaches the systemic circulation, it gets carried through the _____________, a major site of metabolism
liver
What is the key difference between enteral and parenteral that has to do with passing through the liver
enteral drugs go through the liver before they reach the systemic circulation via the hepatic portal vein
Aside from first pass (getting metabolized by the liver first) what are three other hazards along the way for enteric drugs
- not getting absorbed into the gut wall (exretion into feces)
- breakdown (metabolism) by the gut wall
- excretion into bile by liver
Once a drug gets to the systemic circulation, it starts (reversibly)____________________
Once a drug gets to the systemic circulation, it starts (reversibly) distributing itself to different body tissues (extravascular space)
Where the drug distributes to in the body depends on:
- how well it diffuses through different membranes (size lipophilicity, charge)
- what it likes to bind to (proteins in the plasma or other tissues)
protein bound drugs
drugs that bind heavily to plasma proteins and cannot diffuse through membranes
unbound or free drugs
the only type of drug that can leave the bloodstream (or be active)
some drugs have a particular affinity for certain _________. give an example
tissues
bisphosphonates (osteoporosis drugs) have high affinity for bone minerals
What is the formula for volume of distribution and what does it represent
represents how the drug gets distributed by finding whether the drug stays mostly in the bloodstream or if it enters other tissues
Volume of distribution = total amount of drug in body(mg)/plasma concentration of drug (mg/L)
If the drug stays in the bloodstream what will the volume distribution be
close to the volume of the blood
If the drug diistributes widely around the body, what will the Volume of distribution (Vd) be
very large.
The Vd is an “_________”
imaginary volume
go back and listen to slide 33
Go back and do checkpoints 7,8,9
metabolism is also known as
biotransformation
what happens during metabolism/biotransformation
a parent drug is converted to a metabolite, which is a different chemical form that is more readily excreted from the body
metabolites can be
active or inactive
for example, morphine has both active and inactive metabolites
prodrugs
druugs that have inactive parent forms and active metabolites
such as plavix (clopidogrel)
Metabolism is performed by ________ which are present in tissues all over the body, but the ______ is the most important site of metabolism
enzymes, liver
Phase one metabolism includes
oxidation, reduction, or hydrolysis
phase two metabolism includes
conjugation, acetylation and methylation
some drugs such as hydrophobic drugs go through ________ while others such as hydrophillic drugs _______
some drugs such as hydrophobic drugs go through the phases sequentially (some just do one, or two, some do both) while others such as hydrophillic drugs leave the body before gettting metabolized at all
loves lipids—> _________
loves water —-> _________
loves lipids—> liver
loves water —-> urine
stopped at slide 40
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