optional module d Flashcards
where is asprin first extracted
bark of willow trees
how is asprin made now
reacting acetic anhydride with saliculic acdid
what forms asprin or acetylsalicilic acid
salicylic acid and acetic anhydride
what is the goal of drug production
to minimise costs and maximise profits
the drug development proces
drug discovery
pre clinical trials
phase I, II and III of clinical trials
review
manufacturing
whats an issue with coutnergeit medicines
drug purity and the containing of the active drug ingredient
what is combinatorial chemistry
a laboratory method that involves using robotics to synthesise thousands of different compounds at a time, usually peptides or small molecules. The compounds can then be tested for effectiveness, and then kept for further testing or modification, or discarded. With this highly automated process, large volumes of molecules can be synthesised and tested in a short period of time, but it is more of a trial-and-error approach, resulting in a large amount of molecules made that have no activity. Although it is difficult for scientists to mimic natural processes, combinatorial chemistry is proving to be making new advancements in drug discovery.
double blind test
Part of the drug development process is to conduct a ‘double blind test’ where a placebo is offered to one group of patients, while the other group receives the drug. A placebo is a pill, lotion or injection that does not contain the active ingredient that the drug has, and is used to see if the drug does have a measurable effect compared to not using the drug. Many times, people taking the placebo report to have improvements in their health, even though they are not taking the actual drug. This “placebo effect” has been noted in numerous studies.
a placebo is
identical to the trial drug, except it is missing the active drug ingredient under study.
Drugs can be administered in a variety of ways including:
Ingestion by mouth (e.g. pills or syrups).
Injection with a syringe under the skin into fat or muscle tissue or bloodstream.
Inhalation by mouth or nose (e.g. as with an inhaler or nebuliser).
Absorption through the skin (e.g. medicated lotions or stick-on patches).
Absorption in the rectum or vagina (e.g. suppositories).
Applied into the ear or eye (e.g. drops of prepared solutions).
why can all drugs not be adminstered orally
Some medicines, however, may irritate the digestive tract or cannot be absorbed by this method and must therefore have another route into the body. Some drugs are best absorbed when applied to the part of the body that is being treated, for example, antibiotic drops for an ear or eye infection.
The speed and ability of the body to absorb and use the medicine, known as
metabolism
what is quicker injectin or oral adminsteration
injection. Some drugs are best employed with a quick absorption of the entire dose, such as with an insulin injection when treating diabetes, while others are more effective when absorbed slowly over time, such as the hormones used in birth control skin patches.
what determines form of administeration
dosage of drug
freq of adminsteration needed
tolerance of drug
potential for addiction
how can drug addiciton be deterred
A slower, time-released method, such as with oral ingestion or a skin patch, can help to keep the levels of medicine in the body lower and more consistent, and avoid dependency.
where is the drug aiming
the target site
how do drus that have an effect on specific types of cells do
The target cells are identified by three-dimensional receptors into which the drug fits like a key in a lock. If the drug passes by cells that do not contain the receptor, it will not bind to the cell and have a medicinal effect.
bioavailability
the fraction of the administered dosage that reaches the target site.
what is the only method of administeration that is 100% bioavailability
intravenous
risks of oral administeration
irritation of digestive tract
drug maybe destroyed by stomach acidity
absorbed by bacteria in small intestine
different types of injection
intramuscular
subcutaneous
intravenous
which layer does intravenous enter
dermis under epidermis`
how can polarity affect bioavailability
Since the drug must eventually reach the blood, which is polar as it has a water solvent, the drug must have some polarity, since “like dissolves like”. For the drug to enter the cell, it must also have some nonpolarity to pass through the cell membrane. Therefore, drugs must have both polar and nonpolar properties.
what functional groups must drugs have to be absorbed
Drugs must have both polar and nonpolar functional groups to be absorbed by the body and at the cellular level.
polar functional groups include
hydroxyl, carboxyl or amino groups
why are some drugs to be taken either with food or on an empty stomach
If the drug is administered orally (usually with a sip of water), then a polar drug will generally dissolve within the polar environment of the contents of the stomach. If the drug is not very polar, it might bind to food particles instead, preventing it from being absorbed.
State factors that can affect the ability of the body to absorb a drug.
Age
Weight
Gender
Method of administration
administration
weight
mass
polarity
Polarity
functional group
functional groups
solubility
stomach contents
how does age affect bioavailability
as the body ages, its chemical processes change, thus possibly increasing or decreasing the rate the body can absorb a medicine.
how does weight affect bioavailability
generally a greater body mass requires a higher dose to keep the concentration at a level that has a medicinal effect.
What is meant by the term ‘drug tolerance’?
A decreased effect of the drug on the body when taken over a long period of time.
Medicines can target specific cells in the body, which are identified by
receptors on the cell membrane.
therapeutic window
where the drug is effective is
the effective dose
where it has a effect in 50% of the population
what is the lethal dose
where it kills half the population
toxic dose
where a serious toxic effect is observed for half the epopulation
ED50 -
the minimal effective dose for 50% of the population (animal and human trials).
LD50 -
the lethal dose for 50% of the population (animal trials).
TD50 -
the toxic dose for 50% of the population (human trials).
theraputic indexes for animal and human studies
therapeutic index=LD50/ED50 (for animal studies)
therapeutic index=TD50/ED50 (for human studies)
A medicine with a low therapeutic index would be considered to be…
not safe, but could be used with careful monitoring.
For drugs that are available without a prescription, the medicine would usually have…
a high therapeutic index.
what reaction takes place to create asprin
an esterification reaction
what is required to create asprin
Like for all esterification reactions, heat and a strong acid (H2SO4) are required to catalyse the reaction and ensure a greater product yield.
what is the product that will be asprin and ho wis it collected
asprin is white crystals that can be collected by filtration (gravimetric or vacuum filtration) when the mixture cools in an ice bath following the reaction.
why shouldnt you use the asprin you make by yourself
it will have low purity and the by-product of acetic acid may be present in your sample, along with salicylic acid and acetic anhydride that may not have reacted if the reaction had not gone to completion. And, of course, a classroom laboratory is hardly a sterile environment!
to improve the purity of the product, the asprin crystals are subjected to a
recrystallisation process
how does recrystallisation of asprin work
by removing impurities by dissolving them in ethanol, which has polar and nonpolar properties. The impurities will dissolve and be rinsed away with the ethanol/water mixture, leaving behind the pure aspirin crystals, which have a melting point of 136°C, meaning it will become a solid when cooled to room temperature.
The process of recrystallisation
Recrystallisation is the process of purifying a solid organic product using the following steps:
Add a small amount of a solvent (generally ethanol is used) and place in a hot water bath to dissolve crystals.
Add cold water and/or use an ice bath to lower temperature to crystallisation point of organic product.
Collect solid organic product using filtration (vacuum or gravimetric). Any impurities will remain dissolved and flow through.
how to test purity of a sample using mp
use melting point
a pure sample of asprin will melt very close to 136 degrees (melting point range)
An impure sample will have a melting point lower than the theoretical temperature, as impurities disrupt the crystalline structure, weakening the attractive forces between particles. The lower the purity, the greater temperature difference from the theoretical melting point, and the broader the melting point range.
how to test for purity using infrared spectroscopy
Infrared spectroscopy (IR) identifies specific types of bonds in a molecule. For aspirin, the types of bonds expected in a pure sample are strong absorption around 1700 cm-1 for the C=O bond in carboxylic acids, and broad absorption around 2800 cm-1 for the O-H bond in carboxylic acids. Using IR is helpful to determine if the sample tested contains the type of bonds (and thus specific functional groups) expected in aspirin, or it might identify the bonds present in the impurities.
The melting point of aspirin is 136°C. The presence of impurities in a sample of aspirin would cause the melting point to…
decrease and have a broad melting point range.
what class of drugs does asprin belong to
analgesics
what are analgesics
medicines that provide relief from pain (analgesia). Some different analgesics include aspirin, acetaminophen/paracetamol and opiates. Some analgesics work at the site of the trauma while others work in the brain to alter the perception of pain.
how is asprin primarily used
a pain reliever, fever reducer and anticoagulant
side effects of asprin
can irritate the stomach and lead to ulcers if overused
blood thinner
found to improve circulation for diabetics
when are prostaglandins produced
When we experience physical trauma, the cells in our body respond with a series of steps that ends with the production of chemical substances called prostaglandins
what are antipyretics
fever reducers
how does asprin stop prostaglandin production
Aspirin works by stopping the enzyme that produces prostaglandins, which is called cyclooxygenase (known as COX). Aspirin does not have a specific target site, but rather acts to inhibit the production of prostaglandins throughout the body, so any and all pain, swelling or fever will be treated.
what is blood made up of
mainly plasma (which has water as a solvent), but also red and white blood cells, antibodies and other substances. Blood is slightly viscous due to the presence of dissolved fats, proteins and other components. Since blood is travelling within a contained system of vessels pumped by the heart, any blockage or leak could have devastating effects.
what happens when a blood vessel is damaged
When a blood vessel is damaged, such as when cutting your finger, small fragments of broken blood cells, called platelets, coagulate, or clump together, to stop the leak of blood out of the circulatory system. This is commonly known as blood clotting. Over time, the walls of the vessel can repair itself and the body returns to normal blood flow and pressure. For people with low levels of platelets, such as those with the condition of haemophilia, the blood does not clot well and this can lead to a severe loss of blood or even death.
what is a myocardial infarction / heart attack
when a blockage means parts of the body don’t receive blood or nutreitns
effect of asprin on coagulation
Aspirin works by slowing down the clumping of platelets, so instead of coagulating, they anti-coagulate. People experiencing symptoms of a heart attack or stroke are sometimes recommended to chew two aspirin tablets while on their way to hospital to reduce the severity of the attack. Aspirin can also be taken as a prophylactic, or preventative measure, to slow or prevent the formation of a blockage in the first place. Generally a low dose of aspirin is used for this purpose, and is often recommended to middle-aged or elderly people with a family history of stroke or heart disease, or even for pregnant women, as pregnancy can increase the risk of blood clots.
how can the solubility of apsrin be chemically modified to increase its solubility in aqueous solutions
Aspirin can be chemically modified to a salt to increase its solubility in aqueous solutions. By dissolving the acetylsalicylic acid in sodium hydroxide, the hydrogen on the carboxyl functional group is replaced by a sodium ion, as shown in the reaction below, to make sodium acetylsalicylate, sometimes called soluble aspirin.
The sodium acetylsalicylate product is more soluble in water than the aspirin molecule, as ions have a stronger attractive force to the dipoles in water molecules than the intermolecular forces of the carboxyl functional group. Having a product with greater aqueous solubility means that orally ingested sodium acetylsalicylate will reach the stomach more quickly. The bioavailability of soluble aspirin, however, is almost the same as the insoluble form because the ionic salt reacts with stomach acid to produce (insoluble) aspirin. One method of increasing the bioavailability of aspirin is to administer the drug intravenously. As discussed in section D.1.2, this method of administration produces the highest possible bioavailability.
asprin and alochol ahev what sort of effect when taken together
a synergistic effect
each drug has a higher medicinal effect when taken in combination than when taken separately
Aspirin works as an anticoagulant by
slowing down the clumping of platelets.
Modifying aspirin into a salt:
increases aqueous solubility and has a limited effect on its bioavailability
how do communicable diseases generally spread
bacteria and viruses
The only course of treatment for a virus is
prevention with an immunisation.
how is penicllin made now
Populations of fungi are fermented in large, stainless steel tanks under controlled conditions in a sterile environment. In order to produce a stressful environment, scientists provide penicillin with lactose sugar, rather than glucose sugar that the fungus prefers as a food source. The temperature, pH and other nutrients added to the batch also ensure that the fungi are under stress.
what is added to tanks of fungi to make penicclin in a stressful environment
lactose not glucose
temp and pH slightly inconvenient
The key feature of any penicillin molecule is the
beta-lactam ring. The beta-lactam ring is important for the action of penicillin in preventing the growth of bacteria.
what parts of penicllin gives rise to different structures an functions
different side chains for the r group
penicllin g
also known as benzyl penicillin, is a very potent antibiotic that has been used successfully to treat syphilis, meningitis and other bacterial infections. Notice that the benzene ring is nonpolar and as a result, penicillin G must be injected to have an effect, as it is not water-soluble enough to be absorbed by oral ingestion.
penicllin v
Penicillin V, by contrast, contains an oxygen before the benzene ring. This provides slightly more solubility in water and therefore penicillin V is prescribed as an oral antibiotic to treat minor infections like tonsillitis.
Different side chains result in different penicillin molecules.
why must penicllin g be injected
Penicillin G is not stable in the acidic environment of the stomach, so it cannot be taken orally and must be injected to have better bioavailability.
how is ampicllin produced
by chemically modifying the R group to include an amino group. The presence of this amino group allows ampicillin to better penetrate the cell walls of bacteria and thus has greater action on stopping the growth of bacteria for respiratory infections. The amino group also allows for greater solubility in water, so ampicillin is often prescribed orally, rather than intravenously.
cell walls are made with layers of
peptiodglycan
what is peptiodglycan
sugars and amino acids known as murein
how are layers of peptidoglycan arranged for cell walls
When the layers of peptidoglycan are made for the cell wall, they are cross-linked, which means there are covalent bonds holding the layers together (this is common in polymers). This cross-linking provides additional structure and rigidity for the cell wall.
how does cross linking occur
by the action of certain enzymes, known as transpeptidase, also known as the penicillin binding protein (PBP).
what happnes if a cell wall is not cross linked
A cell wall that is missing the necessary cross-linking will eventually have too much water entering the cell via osmosis, causing the cell to burst. Since animal cells do not have a cell wall or transpeptidase, penicillins cannot bind, so they have no effect on animal cells.
how does bacteria interfere with cross linking
The beta-lactam ring effectively binds to transpeptidase (the penicillin binding protein) and thus interferes with the action of the enzyme, therefore not allowing the cell wall to be cross-linked.
Some bacterial infections do not respond to a course of antibiotics. This is because some bacteria are capable of producing enzymes that destroy penicillin. These enzymes are known as
penicillinase or beta-lactamase. Penicillinase works to break the beta-lactam ring in the penicillin molecule, thus rendering it ineffective in binding to transpeptidase (also known as the penicillin binding protein).
For example, having a larger, bulkier R-group seems to make penicillin more resistant to ??? so naturally-occurring penicillins can be chemically modified to make penicillin more effective at stopping the growth of bacteria.
penicillinase
causes of antibiotic resistance
oversubscription of antibiotics
not following entire prescribed dose
bacteria that produce penicllinase in large quantities are penicillin resistant
Beta-lactam antibiotics, such as penicillin, kill bacteria by
preventing cross-linking of peptidoglycan layers in the cell wall.
Penicillin binds to transpeptidase, also known as the penicillin binding protein, to prevent cross-linking of peptidoglycan layers in the cell membrane.
Antibiotic resistance is caused by the action of penicillinase, also known as beta-lactamase, which
breaks the beta-lactam ring.
what is the active medicinal ingredient in the latex extracted from the opium seed pod
morphine
The morphine extracted can be used directly or be processed to make two other drugs, ???? , the latter commonly known as heroin.
codeine and diamorphine
codeine, diamorphine and morphine are
analgesics
why must opiates be slightly polar
bloood is polar and opiates must travel to the brain
why must opiates be slightly non polar
to cross the blood brain barrier
functional groups of morphne
two hydroxyl which add polarity and water solubility to the structure
how is morhine prescribed
Morphine is prescribed orally in a tablet or liquid or by intramuscular or intravenous injection. The bioavailability of morphine taken orally is approximately 30%.
codeine functional groups
one hydroxyl group with an bonded to a methyl alkyl functional group which forms an ether and therefore slightly decreasign the polarity and water solubility. As a result codeine can pass into the brain more easily.
which is stronger codeine or morphine
However, codeine is less effective at binding to receptors in the brain and therefore has 1/10 the strength of morphine, so it is only suitable for mild to moderate pain.
diamorphine functional groups
two hydroxyl functional groups substituted with O bonded to an acetyl side chains, which forms 2 ester groups and greatly reduces the polarity and solubility in water compared to morphine and codeine. The bioavailability of diamorphine is less than 35% when taken orally.
how is diamorphine administered
As a result, diamorphine is generally not taken orally, but is injected intravenously. With the decrease in polarity, diamorphine can pass into the brain much more easily than both morphine or codeine. It also binds to the receptors in the brain more effectively than both morphine and codeine, making diamorphine have 4-5 times the strength of morphine. It is rarely used medically and only for severe pain due to its highly addictive nature. Diamorphine is used recreationally, but is regarded as an illegal drug in many countries.
list the opiates in decreasing polarity
morphine
codeine
diamorphine
Synthesis of codeine from morphine by a methylation reaction.
Codeine is sometimes referred to as methylmorphine since one hydroxyl functional group is replaced with a methyl alkyl group via a methylation reaction. In this reaction, the morphine is reacted with CH3I (iodomethane, also known as methyl iodide) in an alkaline solution. This makes an ether linkage. This reaction is actually reversed in the liver when the body is breaking down the codeine for elimination.
what is different about diamorphine to morphine and codeine
Unlike morphine and codeine, diamorphine is not naturally found in the opium latex and it is only made synthetically by reacting morphine with ethanoic acid in an esterification reaction.
describe the synthesis of diamorphine from morphine by an esterification reaction.
The hydroxyl functional groups on the morphine molecule each react by a condensation reaction with the carboxylic functional group on the ethanoic acid. The result is an ester linkage and the elimination of water.
Which of the three opiates (morphine, codeine or diamorphine) is the most polar?
morphine
When the body experiences a trauma, a chemical pathway occurs with the end result being the production of
prostaglandins
what can prostaglandins do
increase body temp
cause a fever
produce the sensation of pain
The sensation of pain is caused by
the direct action of prostaglandins on the nerve endings locally at the site of the trauma or by acting on the perception of pain in the central nervous system in the brain.
what is the difference between asprin and opiates with how they deal with prostaglandins
Some analgesics, such as aspirin, work to interfere with prostaglandin production and treat pain (and the associated trauma) locally. Other analgesics, like opiates, work to interfere with the sensation of pain in the brain (and do not address the trauma).
how does the sensation of pain come about
When the central nervous system receives a pain stimulus from the nerve endings at the site of a trauma, the pain signal is transmitted through the nerve cells, called neurons, to the spinal cord and then the brain. Neurons can communicate to one another using chemicals called neurotransmitters, to transmit the signal faster and across small gaps between neurons, called synapses, where they interact with receptors on the neuron on the other side of the synapse. Specific parts of the brain are then stimulated to give the sensation of pain.
what are the natural pain relievers produced by the body
endorphins
The structures of an endorphin, the body’s natural pain reliever, and morphine, the pain reliever produced by poppies. Note the similarity in structure.
how does the body interpret opiates as endorphins
Endorphins bind to endorphin receptors (also called opioid or opiate receptors) in brain cells to intercept the pain signal. Opiates also bind to the same endorphin receptors, since they share a similar chemical structure. As the endorphin receptors cannot tell the difference between a natural endorphin and an opiate, the pain signal is interrupted centrally for the body.
describe how dopamine makes opiates addictive
For example, dopamine is a neurotransmitter that is produced when the endorphin receptor binds to a natural endorphin or to an opiate. The release of dopamine causes feelings of pleasure, which adds to the addictive nature of opiates.
why is codeine known as a pro drug
About 10% of codeine is metabolised in the liver into morphine, although this can vary between individuals. For this reason, codeine is known as a prodrug; a drug that is converted to a more active form once inside the human body. However, this conversion is quite slow and other products are also made, which have no medicinal effect.
why is diamorphien mroe instant acting
Diamorphine contains more nonpolar functional groups than morphine or codeine, so it is faster at crossing into the lipid layer that surrounds the brain. Diamorphine can only bind to one receptor, so the effect of diamorphine is immediate, but does not last long.
Which of the following explains why codeine, compared to morphine, is less effective at treating pain?
Codeine is first metabolised in the liver back into morphine
most common method of administeration of morphine, codeine and diamorphine
oral oral oral
injection better for morphine and diamorphine
order of strength of opiates
codeine
morphine
diamorphine
disadv of morphine
Moderately addictive.
Withdrawal if taken for extended periods.
adv of morphine
Quickly relieves pain.
Mild side effects.
Option for convenient administration (oral ingestion).
adv of codeine
Suitable for mild pain.
Drug is slowly metabolised, so fewer doses are required.
Convenient administration.
Structures of morphine, diamorphine (heroin) and methadone.
Identify three functional groups that are present on both influenza antiviral medicines.
ether, carboxamide (amide), amino
symptoms of HIV infection
which forms of radiation have the worst and best penetrating power
TAT picture
how to calcualte the conc of radioisotope left in agiven sample use this equation
how is liquid liquid extraction carried out and when
A separatory funnel is a piece of equipment that is often used to extract an organic compound from a mixture. Two solvents, one polar and one nonpolar, will form layers when placed together as they cannot dissolve in each other. The relative densities of the two solvents will determine which layer is on top (lower density) and which is on the bottom (higher density). The mixture is then placed in the funnel with the two solvents and then shaken (and vented to relieve gas pressure), allowing all compounds to mix and interact with the solvents. The funnel and contents are then allowed to settle, where the compounds will separate based on their interaction with either of the two solvents. The funnel stop cock valve can then be opened, separating one solvent from the other, obtaining the desired compound.
