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what the body does to the drug
pharmacokinetics
what the drug does to the body
pharmacodynamics
What is this the definition of?
Chemical substances found within an organism that are not naturally produced or recognized within the organism.
xenobiotics
Why does the human body restrict access to xenobiotics?
body doesn’t know if drugs are good or bad for us
Cmax is the max ________ in the blood
concentration
Tmax is the time it takes to reach _______.
Cmax
During which of the ADME processes can drug interactions occur?
ALL
How do
solubility
sterics
electronics
pertain to biological barriers?
solubility- “goldilocks” not to hydrophobic/phillic
sterics- size can’t be too big
electronics- nonpolar molecules cross membranes easier
What does the following equation represent?
F= amount of drug that reaches circulation/ amount of drug that is administered
bioavailability
If a drug passes all of Lipinski’s rules, would it likely be inactive or active drug?
active
True or False: Lipinski’s rule states that a drug-like molecule cannot have more than 10 hydrogen bond acceptors
True
What are the four parameters for Lipinski’s rule?
how many H-bond donors?
how many H-bond acceptors?
What molecular weight?
What Log P?
≤5 H-bond donors
≤ 10 H-bond acceptors
< 500 molecular weight
≤ 5 Log P
a semipermeable membrane in the brain that is characterized by tight junctions and astrocytes.
(a lot less permeable compared to a normal capillary)
Blood-Brain Barrier (BBB)
_____________ are pharmacologically inactive compounds that are converted to their active forms by metabolism.
Prodrug
What is the correlation between the amount of substance administered and amount of substance in systemic circulation?
Volume of distribution
creatinine definition
A waste product produced by muscles from the breakdown of creatine phosphate. It is filtered by the kidneys and excreted in urine. Elevated levels indicate kidney dysfunction.
p-glycoprotein definition
A protein found in cell membranes that acts as a pump to remove foreign substances, like drugs, from cells. It plays a role in drug resistance and limiting the absorption of certain medications in the body.
Isozyme definition
enzymes that differ in amino acid sequence but catalyze the same chemical reaction
ligand definition
molecule that binds to the receptor
Therapeutic Window definition
reflects a concentration range that provides efficacy without unacceptable toxicity
therapeutic index defintion
a measure of a drug's safety and effectiveness. It is the ratio between the dose that produces therapeutic effects and the dose that causes toxic effects.
A (higher/lower) therapeutic index indicates a safer drug.
Higher
Area under the curve Abbreviation
AUC
Clearance (abbr and definition)
Cl
a measure of the body’s efficiency in eliminating drug from the systemic circulation
bioavailability (abbr and definition)
F
the fraction of drug absorbed into the systemic circulation
What are the 3 ways drugs can be eliminated using the renal system?
filtration
secretion
reabsorption
CYPs (abbr and defintion)
cytochrome P450 enzymes
responsible for 75% of drug metabolism
first pass metabolism
Vd abbreviation
volume of distribution
GCPR
G protein-coupled receptor
What is the kidney blood flow per minute?
1.2-1.5 L
NF-kB
nuclear factor-κB
Transcription factor involved in immune response and inflammation.
MAPK abbr
mitogen-activated protein kinase
Kd
acid dissociation constant
ED50
half-maximally effective dose
TD50
half-maximally toxic dose
LD 50
half-maximal lethal dose
The larger the volume of distribution indicates what about the drug molecule?
More hydrophobic
Calculate the volume of distribution for the following drug:
Dose= 400 mg
Cmax= 0.06 mg/L
Vd=
6667
(increased/decreased) clearance indicates that more was removed from the body.
increased
What is based upon the max response to the ligand?
efficacy
____________ has positive efficacy
____________ has zero efficacy
____________ has negative efficacy
agonist, antagonist, inverse
The greater the potency, the smaller the dose at which ______ occurs.
a. EC50
b. TC50
c. LC50
a (EC50)
According to the graph, which drug is the most potent? which drug is the more effective?
Most potent- 1
More effective- 2&3 are equal
What kind of agonist is able to produce the maximum response?
full agonist
What kind of agonist is able to produce a sub-maximal response?
partial agonist
What kind of agonist binds to the same site on the receptor as the endogenous ligand?
orthosteric
What kind of agonist binds to a different site on the receptor as the endogenous ligand?
allosteric
Drugs that occupy receptors and activate them are ___________.
While drugs that occupy receptors but do not activate them are __________.
agonists, antagonists
What is the measure of strength of drug-receptor binding and how do we measure that strength?
affinity, Kd
If a drug has an affinity of 80%, if we wanted to find the ED50, what percent would we be looking at?
40%
More affinity = ______ potent
more
What term is used to describe your baseline? This is what the body attempts to restore after the effects of drugs.
Status Quo
___________ is the reduced effects/ reaction to drug following repeated use.
a. dependence
b. tolerance
c. tachyphylaxis
d. attenuation
tolerance
How can tolerance be overcome?
a. increasing # of receptors
b. increasing dose
c. decreasing dose
d. stopping drug use immediately
b
____________ can be physiological and/or psychological. It is when your baseline functionality needs a drug.
Alternative defintion:
Physiological effect: need drug in order to achieve baseline state Psychological effect: fear of not having the drug due to withdrawal/subtherapeutic situation
Dependence
Can you be addicted to redbull?
Can you be dependent on redbull?
addicted- no
dependent- yes
What is the main difference between addiction and dependence?
the psychocomponent. in addiction you seek drug in order to achieve pleasure associated with taking drug
What term describes the following?
Short-term tolerance to a drug or treatment. Repeated exposure leads to diminished response.
a. fade
b. resistance
c. tachyphylaxis
d. attenuation
c
True or False: Tachyphylaxis is non-reversible
FALSE
______________: drug binds, decreased response
______________: # of receptors decreases
desensitization, downregulation
True of False: Feedback Regulation may occur at cellular or system level, and be delayed or immediate.
TRUE
Attenuation is the decrease of response at the __________ level.
receptor
An increased response to a drug with prolonged use is:
a. sensitization
b. desensitization
c. reverse tolerance
d. tolerance
SATA
a,c
Abrupt removal of what causes supersensitivity?
antagonist
How does supersensitivity differ from sensitization?
sensitization- increase response to a drug with prolonged use
supersensitivity- abrupt antagonist removal results in increased receptor activity.
Monica is a 62-year-old woman with diabetes. She takes Lantus, and over the next couple months her cells express fewer insulin receptors. This is an example of:
a. upregulation
b. tachyphylaxis
c. dependence
d. downregulation
d
What is a type A (ADR)?
a. based on the mechanism of action
b. idiopathic, causes something else
c. based on the physiochemical properties
d. idiopathic, causes it’s intended action
a
What is a type B (ADR)?
a. based on the mechanism of action
b. idiopathic, causes something else
c. based on the physiochemical properties
d. idiopathic, causes it’s intended action
b
What do the following abbreviations stand for:
FDA
ISMP
WHO
And which ones, are ADRs reported to?
food and drug administration
Institute for Safe Medication Practices
World Health Organization
ADRS reported to all 3 organizations
Why do ADRs happen? We are changing ____________.
homeostasis
___________ __________ range of efficacy without toxicity/lethality
___________ __________ ratio of toxicity/lethality to efficacy
therapeutic window
therapeutic index
What is the Therapeutic Index when 400 mg of Drug A causes LD50 and 50mg of Drug A causes ED50?
8
What type of receptor is a protein that binds endogenous ligands?
physiological receptor
A receptor is acting without a ligand binding to it and producing activity.
What does this describe?
constitutive activity
What/ Who makes endogenous ligands?
your body
Drugs that mimic the effects of endogenous ligands are ____________.
agonists
__________-receptor binding will create/enhance biological effect
agonist
Does the concentration of agonist have anything to do with efficacy?
Yes
Where do primary agonists bind?
Where do allosteric agonists bind?
same site as endogenous ligand (orthosteric site)
different site as endogenous ligand
A ______________ enhances the effect of a drug by binding to another substance.
potentiator
What do antagonists do to the actions of agonists?
SATA
a. reduce
b. induce
c. block
d. release
a, c
When an agonist and antagonist compete for the same binding site.
a. competitive
b. allosteric
c. chemical
d. physiological
a
Binds to a different site on the receptor
a. competitive
b. allosteric
c. chemical
d. physiological
b
Binds to the agonist and prevents agonist from binding
a. competitive
b. allosteric
c. chemical
d. physiological
c
A drug that counters the effects of another by binding to a different receptor and causing opposing effects
a. competitive
b. allosteric
c. chemical
d. physiological
d
A graph of increasing response to increasing drug concentration or dose is a
__________-_______ response curve
graded-dose response curve
A graph of the fraction of a population that shows a specified response at progressively increasing doses is a __________-_______ response curve.
quantal dose
A competitive antagonist binds to the ___________ site.
orthosteric
With an uncompetitive antagonist, the antagonist binds to the ____________ site. Additionally, inhibition requires binding of the ___________.
allosteric, agonist
With inverse agonists, what is the key consideration?
constitutive activity
What binds to the allosteric site and enhances agonist activity?
allosteric potentiator
What can antagonists effect?
a. potency
b. efficacy
c. both
c
Why might chemical antagonists decrease affinity of agonists?
Chemical antagonists bind to agonist, so less binding/affinity to form the drug-receptor complex
competitive antagonists _______________ the potency of agonists
a. increase
b. decrease
b
Allosteric and Pseudoirreversible antagonists do what to potency?
decrease
Allosteric and irreversible antagonists do what to efficacy?
decrease
Allosteric potentiators impact the dose-response curve how?
increase potency
occupancy in terms of pharmacology is defined as
when a drug binds to the receptor, the receptor is occupied
What term is used to describe the % of receptors that are occupied by a drug
fractional occupancy
If a receptor has no constitutive activity, what will be the effect of an inverse agonist on that receptor?
decrease potency
Note
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