Pharm Test 1 Flashcards
What dictates the duration of drug action?
- only as long as the drug binds to the receptor (because of constituent activity)
- long term downstream effects last until downstream effectors go away (when downstream is used up)
- Covalent bonds (receptor is desensitized or degraded. (think g protein))
Good receptor properties:
- selective- drug binds to a single receptor or receptor type
- alteration- a drug binds and the receptor changes to create a downstream effect
Bad receptor properties:
Drug carriers. They bind to the drug and carry them places, but when it’s done, it won’t have any effect on the body
The part of the drug that is not bound to a carrier is said to be in it’s
free form
What is the most important drug carrier?
albumin
When a plasma protein is bound to a drug, that drug (can or cannot) cross ______.
Why?
cannot cross barriers
the protein is too large
What partially dictates whether a drug is bound or not?
It’s charge and how it interacts with a particular carrier protein
When can a drug cross barriers?
when it is in it’s free form
What can a drug bind to that will effect how much of a drug we have to give?
plasma protein binding.
The more bound to protein the less that’s usable to bind to receptors.
Giving phenytoin to a malnourished patient will have what effect?
A higher effect. Because they don’t have as much albumin for the drug to bind to.
What are inert binding sites?
A carrier in the blood- it doesn’t elicit a response.
What are the 3 types of carrier receptors?
Albumin
alpha 1 acid glycoprotein
lipoproteins
What type of drug does albumin bind to?
acidic drugs
What type of drugs does alpha 1 acid glycoproteins bind to?
basic drugs
what type of drugs to lipoproteins bind to?
neutral drugs
Define potency
concentration or dose of a drug required to produce 50% of that drugs maximal effect.
what is the maximal efficacy?
Greatest possible response a dose can deliver
Describe the Potency of drug A, B, C, and D.
Drug B is very potent because it’s 50% response only takes a small drug dose.
Drug A, C, and D each have less and less potency, because it takes more and more the drug to reach it’s 50% response.
Which drug(s) has the highest efficacy?
A,C,D
The larger the therapeutic index, the ______
safer the drug
What is the therapeutic index?
a margin of safety between the effectiveness of a dose vs the toxic dose for 50% of the population (studied).
What is the therapeutic index ratio?
What type of drugs have a wide therapeutic index?
OTC drugs
What is the ED50?
median effective dose on 50% of a population studied.
What is an idiosyncratic response?
A unusual drug response (we don’t know the reason behind it)
What causes idiosyncratic responses?
Genetic factors
What is tolerance?
When a person changes their response to a drug over time.
Need more and more morphine
What is tachyphylaxis?
quick tolerance
What are the 4 causes of variation in drug responsiveness?
- Alteration in concentration of drug that actually reaches the receptor.
i.e. age, weight, sex, disease state - variation in concentration of endogenous receptor ligand (not every person has the same amount of receptors. Disease can change this)
- alteration in number of function of receptors (native ligand binding to receptors and using them all up so none are left for the drug)
- Changes in components of response distal to receptor. (the downstream effect)
What is the largest and most important cause of variation in drug response?
Changes in components of response distal to receptor. (downstream effect)
Can a drug cause desired and toxic effects at the same receptor?
yes. i.e. racemic mixtures
In order to cross barriers effectively, drugs should be_______
uncharged
What effects the charge of a drug?
The disassociation constant and the pH of the environment that it is in.
It tells us at which pH you’re going to have equal amouts of both the charged and the uncharged form.
How can you predict if a drug is going to be charged?
If pH<pKa; favors the protonated form
Weak acids: protonated=uncharged
Weak bases: protonated= charged
What is the protonated form?
When the Hydrogen ion is attached
What is the unprotonated form?
when the hydrogen ion is not attached
How can you predict if a drug is going to be uncharged?
if the pH>pKa; favors the unprotonated form
Weak acid: protonated=uncharged
Weak base: protonated=charged
Are weak bases charged or uncharged when it’s protonated?
charged
Are weak acids charged or uncharged when it’s protonated?
uncharged
Aspirin (weak acid); pKa=3.5
in stomach pH=1.5
protonated/unprotonated?
charged/uncharged?
protonated
uncharged
morphine (weak base) pKa= 7.9
in stomach pH=1.5
protonated/unprotonated?
charged/uncharged?
protonated
charged
Aspirin (weak acid); pKa=3.5
in intestine pH=6.5
protonated/unprotonated?
charged/uncharged?
Unprotonated
charged
morphine (weak base) pKa= 7.9
in blood pH=7.4
protonated/unprotonated?
charged/uncharged?
technically protonated & charged
near equilibrium because there is a minor difference in 7.4 and 7.9
What are biologic drugs?
created by living organisms or extracted from living systems and changed in the lab
what is recombinant DNA technology?
take a protein that’s normally produced in a human,
put it in an animal (living thing, can be bacteria)
animal produces protein for us
what are fusion proteins?
monoclonal antibodies that are produced from recombinant DNA
What is a monoclonal antibody?
an antibody produced from a single clone of a plasma cell that produces antibodies.
Why do monoclonal antibody dugs have less adverse effects?
They have an area called the antigen binding site which only binds to a particular antigen. Very specific.
-mab tells us the drug is a
monoclonal antibody
Describe how a monoclonal antibody is made.
Target an antigen in the body i.e. cancer cell
inject the antigen into a mouse
mouse makes antibodies
kill mouse
use spleen cells (where antibodies are made)
merge it with myeloma cell to make it immortal
-isolate culture
-propagate
-harvest
What is an antigen?
a substance that causes the immune response to make antibodies against it
In order for a drug to be on the market approved by the FDA, the drug has to be both
safe and effective
pure botanicals like Multivitamins, to be approved by the FDA, have to be
safe, but not necessarily effective
Who was instrumental in blocking Thalidomide from being approved in this country?
Dr. Olden-Kelsey
Describe the process from discovering a drug till it gets on the market.
A. In vitro studies-done on the cell to find a lead compound
B. apply for a patent
C. animal testing
D. investigational new drug has to be approved
E. clinical testing in 3 phases
1. is it safe pharmacokinetics 20-100 broke college students healthy
2. does it work on patients? double blind sick people100-200
3. does it work on pts. with the disease? 1000-6000
F. Marketing
4. post marketing surveillance
receptors are what type of molecule?
protein
What is an orphan receptor?
a receptor that has no known native ligand. about half
what is the most important category of receptors called?
seven-transmembrane (7TM) receptors
GPCR
What is the first step in cell signaling?
a ligand binds to a receptor
what are second messengers?
compounds within the cell that have an effect on the cell
What are effector proteins?
proteins that effect the cell in some way and make it change. (the downstream response)
What is a lag period?
When the effector proteins effect is to change transcription and translation of DNA
What is persistence?
When a drug is given once and its effects remain for hours or days.
d/t protein pathway degradation (it may take a while for the downstream effect to finally stop)
What is a kinase?
an enzyme that attaches a phosphate group to another protein
What attaches a phosphate group to a protein and actives the protein in a signal transduction cascade?
a kinase
Are there intracellular receptors?
Yes
What is a catalytic receptor?
A receptor that activates an enzyme on the inside
What are the two types of catalytic receptors?
- the receptor itself becomes an enzyme and activates
- the receptor activates a protein which activates a number of additional enzymes
What is a G protein coupling receptor?
GPCR
a receptor that has a g protein attached to it. When activated, the g protein is released and finds an enzyme to activate.
What is a G protein?
a trimeric protein which means it is made of 3 different amino acids. alpha, beta and gama. these are all strung together. The beta and gama help the binding to the receptor. The Alpha subunit binds to either GDP or GTP.
It is a Guanine nucleotide bonding protein.
What does the alpha subunit of a G protein bind to?
guanine diphosphate (inactive form)
or guanine triphosphate (active form)
Describe what is going on in this picture.
- drug binds to the receptor
- the receptor changes the confirmation. This activates the the alpha subunit.
3-4. The alpha subunit can now bind to GTP instead of GDP. - The alpha with GTP goes away and activates the effector in the cell.
- With the empty space left from where the alpha subunit left, another inactive subunit sneaks in and takes it’s place.
Can a drug bind more than once to a single receptor?
It is possible, when the alpha subunit leaves, the drug also leaves. The drug can then rebind, or another ligand can bind to that receptor.
If a GDP is bound to a receptor, is the protein active or inactive?
Inactive. It takes 3 phosphates for the protein to become active.
What is the activation response in a g-protein receptor cascade?
When an alpha subunit can bind to GTP instead of GDP which allows the alpha GDP combination to go away and activate the effector cell.
A downstream effect can happen quickly when a ________ is opened by the GPCR.
ion channel
A downstream effect happens more slowly when _______ happens.
The effector goes into the nucleus to change transcription and translation.
What are examples of secondary messengers?
cAMP
IMP3
Secondary messengers are activated by _______
the effector protein
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