Molecules Exam 1a Flashcards
Pharmacology
The study of drug action on biological systems. What can we target?
Medicinal Chemistry
Design and optimization of drug molecules
Pharmaceutics
The science of drug delivery systems
What is a Drug?
Any chemical agent (other than food) that causes a physical or emotional change in an individual
Most drugs are less than how many daltons?
500
Serendipitous Drug Discovery
When your research is looking for something but you end up discovering something else
Why would enhancing a side effect be a good thing?
You can alter a drug with a certain side effect, such as increasing urinary output, and alter that drug to be made to increase urinary output (diuretic)
Why is selectivity important?
If there is a certain receptor that produces a certain side effect that you want to inhibit, you design the drug to be an antagonist to that receptor.
2 main reasons that drugs fail in clinical phase
Safety and efficacy
What is the importance of Gleevec?
It is a cancer therapy drug that kills cancer cells but leaves healthy cells intact. Gleevec’s mechanism focuses on a specific protein that does not exist anywhere else in the body.
Gene cloning is done with what kind of proteins?
Recombinant
Pharmacokinetic concept
When a drug is working to change the amount/concentration of another drug
Pharmacodynamic concept
When a drug changes the effect of another drug without changing the amount of drug
Pharmacokinetic definition
What the body does to the drug
Pharmacodynamic definition
What the drug does to the body
What route of administration is the only route that does not go through the venous side?
Inhalation
Absorption
When the drug has to go through a barrier before it can enter the bloodstream
When would it be desirable for an oral drug to have minimal absorption?
If the drug is treating something in the intestines, then it would be beneficial for the drug to stay there to treat it
Bioavailability
The rate and extent to which a drug is absorbed and becomes available at the site of action
Fenestrae
Windows(opening/pore) in capillaries that drugs can pass through endothelial cells
What organ does not have fenestrae?`
Brain capillaries
3 properties that allow molecules to freely diffuse through cell membranes
Low molecular weight, high lipid solubility, and uncharged
Does increased lipid solubility increase or decrease absorption?
Increase
What do you do to polar functional side groups in order to increase membrane permeability?
Remove them. The less polar functional groups, the more lipophilic the drug is and more easily absorbed.
What are prodrugs and why are they important?
They are drugs with added esters where polar or ionizable groups are masked with hydrophobic residues. After uptake of the drug, the hydrophobic groups are cleaved enzymatically which leaves the original drug in the bloodstream.
Is an acidic drug better absorbed in an acidic environment or basic environment? Why?
Acidic because it will be protonated and made neutral, which will allow it to be absorbed.
Where will amphetamine (pka 10) be best absorbed? Stomach (pH 1) or intestine (pH 8.5)?
Intestine because its more basic and deprotonates the drug making it neutral and able to be absorbed.
Why is it beneficial for a drug to not cross a membrane? Think of inhalers.
You inhale the drug into your lungs, so you want the drug to be charged so that it stays in the lungs instead of being absorbed.
Ion Trapping
Drug molecules tend to accumulate where the pH most favors ionization. They get stuck on one side.
How would you change the urine pH to increase excretion of acidic drugs like aspirin?
You would increase pH to make more basic to make them charged so they are excreted instead of reabsorbed.
What is partition coefficient?
Can be used to determine where a drug will go in the body
Drugs with partition coefficient greater than 1
Diffuses through cell membranes easily and is likely to be found in all 3 fluid compartments
Drugs with partition coefficient less than 1
Fairly water-soluble so they are often unable to cross and require more time to distribute throughout the rest of the body
Atenolol is hydrophilic, and propranolol is lipophilic. If a patient is experiencing CNS side effects such as nightmares, which drug is better to use?
Atenolol because it is hydrophilic so it is polar so it has a harder time going across the blood-brain barrier to affect the CNS
What is an inducer?
A drug that increases the rate of another drug’s metabolism which makes the drug excreted more, which lessens its effectiveness
What is an inhibitor?
A drug that that decreases the rate of another drug’s metabolism which makes it accumulate more, which can lead to toxic levels in the body
If clearance is high, is the half-life high or low?
Low
Zero order kinetics
Constant amount per unit time is metabolized
First order kinetics
Constant faction per unit time is metabolized
Why can men metabolize alcohol more than women?
Women have almost no alcohol dehydrogenase enzyme which is what breaks down alcohol
How does hepatitis affect drug metabolism?
Decreases metabolism
How does nephritis affect drug excretion?
Decreases excretion
What does it mean that enzymes are polymorphic?
Everyone has different enzymes to break down drugs, no two people are the same
Pharmacogenomics
Study of how genes affect a person’s response to drugs
ADRs
Adverse drug responses
How can SNPs affect proteins?
They can be silent and keep it normal, or they can affect it so that is is low or nonfunctioning
What is a normal protein called?
Wild type
What mutation is a STOP?
Nonsense
Intermediate metabolizer
Slower metabolism than normal, will require a lower dose because it is being broken down slower
Poor metabolizer
Very low metabolic activity. Even small dose can be toxic because so little drug is being broken down
Ultrarapid metabolizer
Very fast metabolism, will require higher dose because so much drug is being broken down very quickly
When does a prodrug become active
After metabolism
How does warfarin work?
Inhibits VKORC1 which leads to reduced amount of vitamin K available to serve as a cofactor for clotting proteins
True or False? Most diseases are polygenic, perhaps requiring more than one target to be addresses.
True
Biotechnology
The manipulation of natural biological processes to benefit society
Plasmid
Small, circular piece of DNA that not only is separate from the chromosome, but can also replicate independently
How can plasmids help us?
It is a way to easily get genes into bacteria by inserting gene into plasmid
How do we copy and read DNA in biotech?
Transformation; insert recombinant plasmid into bacteria to create a transformed protein that does the function you need it to
Why is the DNA code universal?
All living organisms use the same DNA and read their genes the same way. This is how we are able to use animals to help us
How do we cut DNA?
Restriction enzymes: They cut DNA at specific places called recognition sites and form sticky ends
What is the molecular paste that puts sticky ends back together?
DNA ligase: Forms bonds between the sugar and phosphate backbone of the DNA molecule
How do you find the gene of interest?
Use nucleic acid hybridization
Polymerase Chain Reaction (PCR)
DNA often needs to be amplified in order to have a large enough amount to study in detail. Uses primers to do this
How do we measure DNA size?
Agarose gel electrophoresis
When working with expression, what material do we use?
RNA
Gene Therapy
Treatment of genetic disease by alteration of the affected person’s genotype, or the genotype of the affected cells
What do iPS cells do?
Take skin cells and change them into stem cells which are then changed to neurons
Transgenic Animal
Way to achieve large scale production of therapeutic proteins from animals for use in humans (milk)
Gene Knockout
Disrupt a gene in the animal and then look at what functions are affected as a result of the loss of the gene
