Medicinal Chemistry Flashcards
What are the different ways to administer a drug?
Orally, through eye/ear drops, suppository, parenteral (injection), skin patches, and inhalation
Define bioavailability
The fraction of an administered drug that reaches the blood supply.
What factors affect the bioavailability of drugs?
How they are administered, their solubility, and their functional groups
What phenomenon accounts for the low bioavailability of orally administered drugs?
The first-pass effect; this means that after drugs are swallowed, enzymes in the digestive tract alter them chemically and then they are further broken down in the liver.
What are the three types of side-effects?
Beneficial, benign, and adverse
What is the difference between tolerance and addiction?
Tolerance is when the physiological effect of a drug is diminished because of repeated doses (which means more is needed to have the desired effect). Addiction occurs when an individual becomes dependent on a drug to feel normal and withdrawal symptoms occur when the drug is withheld.
What is therapeutic window?
The concentration of a drug that must be present in the blood supply for it to have the therapeutic effect but not produce adverse effects.
How is the therapeutic index calculated?
the ratio of the minimum dosage required to produce the therapeutic effect to the maximum dosage that causes adverse effects in 50% of the population (for this second measurement, toxicity is used for humans and the lethal amount is used in animal studies)
The effectiveness of a drug depends on on its ability to bind to receptor sites in the body. What type of bonding usually occurs between the drug and the receptor sites?
Non-covalent forms of bonding such as ionic and hydrogen bonds, van der Waal’s forces, or hydrophobic interactions.
What is another name for pain killers?
Analgesics
What is the name for the chemicals that activate pain receptors around the body?
Prostaglandins
How are prostaglandins produced?
They are released by cells damaged by chemical, thermal, or mechanical energy
Other than signaling pain receptors, what effect do prostaglandins have?
They cause the inflammatory response (by widening blood cells near the site of injury) and they raise the body’s temperature (fever)
There is a type of pain killer that prevent the stimulation of local pain receptors and inhibit the function of prostaglandins. There are two names for this type of pain killer. What are they?
Mild analgesics or Non-narcotics
The bark of the (1)________ tree contains (2)_______, which allows it to alleviate pain; however, it (3)_______
(1) willow
(2) salicylic acid
(3) tastes like crap
The Bayer company made a (1)______ of salicylic acid, which makes it taste better. It is called (2)_____, and it reduces pain as well as fever, making it both an analgesic and an (3)_________.
(1) ester-derivative
(2) aspirin
(3) antipyretic
What is salicylic acid reacted with to produce aspirin, what is this reaction called, and what is a byproduct of the reaction?
ethanoic anhydride
esterification
ethanoic acid
How is the ethanoic acid byproduct removed from the aspirin?
The product is cooled, which causes crystals to form then washed with water. The ethanoic acid dissolves in the water and gets washed away, but the aspirin isn’t soluble in water to it remains separate.
How is the aspirin purified after having been washed?
In a process called recrystallization, the crystals are dissolved in hot ethanol and then slowly cooled. This separates the aspirin because it is less soluble than the impurities and unreacted salicylic acid. Then filtration is used to remove the salicylic acid crystals.
How can the identity of aspirin be confirmed?
melting point determination (it has a higher and better-defined melting point than the mixture of salicylic acid and alcohol) and infrared spectroscopy
What are the main differences in the IR spectra of salicylic acid and aspirin?
salicylic acid has a peak for its hydroxyl group and acetylsalicylic acid has a peak for its ester group
What is another side effect of aspirin?
it works as an anticoagulent, which is good for people at risk of heart attacks and strokes.
What are adverse side effects of aspirin?
they cause ulcers and people can be allergic to them
How can aspirins bioavailability be increased?
It can be reacted with NaOH to make it more polar and therefore more soluble in the blood (which is polar)
penicillin is an…
antibiotic
What aspect of penecillin’s structure makes it reactive?
the beta-lactam ring has 90 degree bond angles but wants 120 or 109.5 degree bond angles. This makes the bonds in the beta-lactam extremely reactive.
What enzyme does penecillin react with that makes it useful?
it reacts with transpeptidase, the enzyme responsible for building the cell wall for bacterias. This means that water can get inside the bacteria and it bursts.
what are two limitations of penicillin?
it is easily broken down by stomach acid so has to be injected (although a pill form was developed by modifying one of its side chains) and a lot of people are allergic to it
What do some bacteria produce that allow them to be immune to penicillin?
penicillinase or beta-lactamase
How does penicillinase work?
it opens the beta-lactam ring, rendering it useless
What to penicillin derivatives were created to withstand penicillinase and how do they work?
methicillin and oxacillin; they have modified side chains, which prevent the penicillinase from breaking open the beta-lactam ring before it can react with the transpeptidase
What type of analgesic are opiates and what does that mean?
they are strong analgesics or narcotics, meaning they cut off the transmission of pain in the brain, that is, they prevent the perception of pain
To which receptors do opiates bind?
the opioid receptors in the brain
Why is it hard for opiates to enter the brain?
the blood-brain barrier is made mostly of lipids to prevent polar molecules from entering via the blood
What are the three opiates you need to know?
codeine, morphine, and diamorphine
What limits morphine’s bioavailability?
It has two O-H functional groups, which make it extremely polar, thus making it harder for it to cross the blood-brain barrier
What makes codeine a semi-synthetic drug?
It is most commonly derived from morphine, but it can also be found in small quantities in opium.
How does codeine differ from morphine?
It replaces one of the hydroxyl groups with a methyl ether group. This makes it less polar and easier to cross the blood-brain barrier.
What is the name of the process used to turn morphine into codeine? And what effects does this have on its effectiveness?
Methylation (it gains a methyl ether) and it makes it less polar so it can pass more easily through the blood-brain barrier, but it makes it less able to bind to the opioid receptor site in the brain
What is the name of the process used to turn morphine into diamorphine? And what effect does this process have on the effectiveness of the drug?
esterification (both hydroxyl groups are replaced by ester groups) this makes it much less polar, so it can pass through the blood brain barrier most effectively of the three opiates
What also increases as the narcotic and analgesic effects of opiates increase?
the side effects and its potential to cause addiction and tolerance
What must happen to diamorphine inside the brain before it can bind to the opium receptors?
Its ester links are broken by enzymes called esterases and it turns back into morphine so that it can bind to the opium receptor sites
What is 6-acetylmorphine?
Another derivative of morphine that is produced in the body and only has one ester group, making it better at binding to receptor sites and therefore even more dangerous than heroin
What are some side effects of strong analgesics?
Constipation, suppression of the cough reflex, and constriction of the pupil
What drug is used to combat addiction to heroine?
Methadone, it has a longer effect so it helps reduce drug craving and withdrawal symptoms
How does the stomach release HCl
the parietal cells in the lining of the stomach release HCl
What is another word for HCl in the stomach?
gastric juice
What are the two functions of HCl?
kill bacteria that entered the body with the food and aid in digestion
What are some problems that arise from the production of excess gastric juice?
acid indigestion, ulcers, and heartburn
What term refers to feelings of discomfort in the upper abdomen?
dyspepsia
What are the two methods for treating excess acid secretion in the stomach?
H2-receptor antagonist and proton pump inhibitor
What is the role of histamine that is relevant to this course?
It stimulates the secretion of stomach acid by reacting with H2 receptors in the parietal cells
What is the name for drugs that target the histamine- H2 receptor interaction to treat excess stomach acid?
H2-receptor antagonists
What is an example of an H2-receptor antagonist?
Ranitidine (aka Zantac)
Explain how the proton pump works
The parietal cells pump an H+ ion into the stomach in exchange for one K+ ion (to balance the charge). However, this requires energy, which is provided by the H+/K+ ATPase or gastric proton pump.
How to proton pump inhibitors work?
They inhibit the release of H+ ions into the stomach
How do antacids work?
They relieve the symptoms of excess stomach acid by neutralizing the HCl
Why can’t strong bases be used as antacids?
They are very caustic and can harm the stomach
In what ways do Mg and Al antacids complement each other?
Magnesium works faster but Aluminum provides longer lasting effects, and magnesium acts as a laxative while aluminum causes constipation
What is a side effect of antacids that contain carbonate and hydrogen carbonate and how is this side effect accounted for?
they cause the release of carbon dioxide, which means bloating and farting
Whats a fancy word for fart?
Flatulence
What are the two main components of a virus?
Protein and nucleic acid
How are bacteria and viruses different?
bacteria have a cell structure and viruses don’t . Bacteria can reproduce on their own while viruses can’t (they need to do so inside another living cell)
What does the body do in response to a viral infection?
produce antibodies to provide the body with immunity against the viruse
What are two viruses that can be dormant inside of cells and reemerge years after the original infection?
herpes and chicken pox
What does prophylactic mean?
preventative treatment
What are three things that make viruses particularly hard to combat?
They don’t have normal cell structures, rendering penicillin and other antibiotics useless, they spread rapidly within the body by hijacking cells (and are already in abundance once symptoms appear), and they mutate very quickly
Other than prophylactic methods, how can viral infections be treated?
Antivirals work to interfere with the life cycle of viruses and prevent the release of new viruses from host cells
What was the first proton pump inhibitor to be created?
omeprazole (prilosec) which was followed by esomeprazole (Nexium)
How does Amantadine work?
it functions as a prophylactic treatment by altering the cell membranes in the body to prevent entry by a virus
What are the two proteins on the surface of the flu virus that allow it to function?
Hemagglutinin and Neuraminidase
What is the role of Hemagglutinin?
It allow the virus to dock on the host cell
What is the role of Neuraminidase?
It starts the cleavage reaction which allows the new viruses to escape the host cell and spread
What is the name of the place on the host cell where the neuraminidase enzyme binds?
the substrate (also called sialic acid)
How do neuraminidase inhibitors work?
They bind to the active site on the neruaminidase and prevent the neuraminidase from binding to the substrate
What was the first neuraminidase inhibitors to be produced?
Zanamivir (it was then followed by oseltamivir
How do the structures of oseltamivir and zanamivir differ?
Zanamivir has a corboxylic acid and three hydroxyls while oseltamivir has an ester
Which cells does HIV target?
CD4+ T cells (white blood cells)
What does retrovirus mean and give an example
Its genetic information is in the form of RNA and it releases its RNA into the host cell and the reverse transcriptase enzyme then makes viral DNA out of the RNA. This DNA then integrates itself into the host cell’s DNA and replicates as the cell divides. Example: HIV
What are three things that make HIV particularly hard to treat?
It lies dormant for a long time, so there is nothing to respond to
It mutates very quickly
It destroys helper T cells, which are the very ones responsible for fighting viral infections
What effect do antiretroviral drugs produce?
They don’t completely sure the patient, they suppress the HIV infection making it less life-threatening
What steps in the HIV virus’ life cycle do ARV drugs interrupt?
the binding of the virus to the CD4+ t cell’s membrane, the reverse transcriptase of viral RNA to DNA, the integration of viral DNA into the host cell’s chromosome, and the release of new viral particles from the host cell
What are the most effective ARV drugs?
Reverse transcriptase inhibitors
What three standards are used to determine whether solvents are preferred or undesirable?
Their toxicity to the workers, the safety of the process (flammability and explosiveness), and whether they harm the environment
List some preferred solvents
water, ethanol, 2-propanol, propanone, and ethyl ethanoate
List some undesirable solvents
CH2Cl2, HCHO, CCl4, C6H6
________, __________, and _________ are generally hazardous and should be replaced by _________, ________, and ________
Chlorinated compounds, ethers, and benzes (should be replaced by) water, alcohols, and esters
Other than making the waste safer, how can the environment be protected? Give a case study for this
Reducing the amount of waste released in general. Solvent recycling was attempted with the arthritis drug Celebrex
Explain how the half-life of radioactive waste determines how it should be disposed of
The half-life of of high-level waste is long, meaning its impact on the environment is prolonged (this is the opposite for low-level waste). This must be accounted for in how the waste is disposed of
Give some examples of low-level waste
clothing, shoe covers, and paper towels
How is low level waste disposed of?
It is stored in sealed containers for a few hours or days until the radioactivity decays and then they can be disposed of normally (landfills, compression, sewage, etc.)
How is high-level waste disposed of?
The high-level waste is stored under water in cooling ponds for 5 to 10 years and then it is transferred to dry, underground storage
What makes the disposal of high-level waste more complicated than that of low-level waste?
Sometimes the byproducts of the decay process are themselves radioactive, and the decay process releases a lot of heat
What is an alternative to using certain radioactive materials?
Using fluorescent dyes
What are superbugs?
Bacteria that are methicillin-resistant and have genes that make them immune to antibiotics
The use (or abuse) of what type of antibiotics has led to the evolution of infections such as Clostridium difficile (which are very hard to treat)
broad-spectrum antibiotics
What are other uses for antibiotics that have contributed to the amount of antibiotics released into the environment?
growth promotion/prophylactic uses for livestock
sanitizers/cleaning products
pest control
What are two ways that antibiotics reach the environment?
Through animal waste (after being administered to livestock) and through improper drug disposal at the individual or professional level
What are negative outcomes of the improper disposal of antibiotics?
Bacteria develop resistance to the antibiotics
water sources become contaminated
plants can be contaminated by the antibiotics
How can individuals minimize the development of antibiotic-resistant bacteria?
avoiding overuse, completing their prescription, and disposing of them properly
Where does oseltamivir come from?
shikimic acid (from the star anise)
Why have there been efforts to find alternate sources of shikimate?
The process of extracting shikimate from the star anise plant has low yields
What alternate sources of shikimate have been discovered?
extracting it from pine tree needles
extracting it from genetically engineered bacteria
extracting it from the Indian sweetgum tree
What is the success story behind the production of Viagra?
An alternate reaction route was used and it produced one fourth of the waste and reduced the amount of toxic reagents
What is the success story behind the anti-inflammatory, ibuprofen?
An alternate preparation method was used, and the atom economy increased from 40% to 77%
What reagent is used to prepare diamorphine from morphine?
ethanoic anhydride
