Option D Flashcards
What do medicines and drugs do?
Alter incoming sensory sensations
Alter a person’s mood or emotions
Alter the physiological state of the body including COORDINATION and CONSCIOUSNESS
Define a drug and describe the difference between a pharmaceutical drug and recreational drugs
A substance that causes a physiological change in the body. A pharmaceutical drug is taken for medical reasons whereas recreational drugs are taken for leisure purposes e.g: cannabis, ecstasy, alcohol
What is a therapeutic effect
The beneficial effect of a medicine
Describe the oral way of taking medication
Medicines are taken by mouth e.g: tablets, capsules, pills
Describe inhalation
Vapour breathed in by smoking, e.g: asthma medication, neubilisers
Skin patches
Absorbed through the skin into the blood e.g: hormone patches
Suppositories
Rectum, e.g: laxatives for constipation
Eye or eye drops
treatment for eye or ear infections
Injection (parenteral)
Injected into the muscle, blood or under the skin
Describe intramuscular injection
Drug is injected directly into the muscle
Intravenous?
Drug injected into bloodstream - 100% bioavailability as directly in bloodstream
Subcutaneous?
Drug is injected directly under the skin
Describe the layers of the skin
Every Doctor Sells Medicine
Epidermis
Dermis
Subcutaneous tissue
Muscle
Which drug administration method has the fastest effect?
Intravenous
What is bioavailability?
The fraction of the administered dosage of a drug that enters the bloodstream, thereby accessing the site of action
What factors affecting bioavailability:
Method of admin
Polarity (solubility) of the drug
Types of functional groups present in the drug
Describe the bioavailability of an oral drug
They are often broken down during administration during digestion before reaching the bloodstream. An oral dose of a drug must be 4 times higher than dosage that is given intravenously
How does the polarity of a drug affect its solubility?
Very hydrophillic drugs are soluble in aqueous body but are poorly absorbed due to their inability to cross cell membranes which are composed of lipids.
Very hydrophobic drugs are not soluble in body fluids
For a drug to be readily absorbed, it must be mostly HYDROPHOBIC but also have some solubility in aqueous solutions.
What are the 2 major properties that contribute towards water solubility of a functional group?
Ability to ionize
Ability to form hydrogen bonds
E.g: COOH, NH2
Examples of non-polar functional groups
Phenyl group
Hydrocarbon chain (alkyl group)
Describe aspirin solubility
Largely non-polar molecule and so has low solubility in WATER due to presence of phenyl group
How to increase aspirin solubility
React it with aqueous NaoH, forming an ionic salt
How can drugs be chemically modified to increase their bioavailability?
Drugs containing an ACIDIC or BASIC functional group can be chemically modified to form an ionic salt
What is the therapeutic window
Measure of the relative margin of the safety of a drug. The wider the therapeutic window, the safer the drug.
A wide therapeutic window means that there is a wide margin between doses that are effective and doses that are toxic
A narrow therapeutic window means only a small increase in the effective doses may produce toxic effects
What is the therapeutic index
Ratio between lethal dose and effective dose
Formula for Therapeutic index in humans
TI = median toxic dose/ median effective dose
Main stages of drug development
Drug is synthesized in the laboratory
tested on animals
tested on humans - half given real drug, other half given placebo
Placebo effect
When the body is fooled into healing itself naturally
What are the factors that must be determined during drug testing
Risk: benefit ration - balance between risks and benefits
Unwanted side effects
Drug tolerance - when patient needs to take larger doses to gain original effect
BRIEF:
How is aspirin produced? (acetylsalicylic acid) and state the 2 catalysts that can be used
Ethanoic acid is excess and sali is LIMITING
Reacting salicylic acid with ethanoic anhydride to produce ASPIRIN and ETHANOIC ACID
Catalyst: CONCENTRATED sulfuric acid or H3Po4
Salicylic acid turns into aspirin via ESTERIFICATION - a condensation reaction
Mr of Aspirin
C9 H8 O4
Detailed steps of aspirin production
- Concentrated sulfuric acid is added to the reaction mixture of salicyclic acid and ethanoic anhydride which is warmed gently. This is the catalyst.
- The product is cooled to form crystals which are then suction filtered and washed with cold water
- Aspirin has very low solubility in cold water so this removes the soluble acids but not the aspirin
- Aspirin purified in a process called re-crystallisation
- This involves dissolving the impure crystals in a small volume of hot ethanol
Water is then added and the solution is then cooled, then chilled
acetylsalicylic acid then crystallises and the unreacted acetylsalicylic acid remains dissolved in solution
How can the purity of aspirin be determined
Infrared spectrum - 2 peaks: OH group and C=O in ester and carboxylic
Melting point - pure aspirin has a melting point between 128 and 140 degrees. Impurities lower the melting point and cause it to melt over a much wider temperature range
Describe the difference between the IR spectrum of acetylsalicylic acid and salicylic acid
Prescence of a peak corresponds to PHENOL in salicyclic which is absent in aspirin
Abscence of a C=O group corresponding to esters in salicyclic acid. Instead there is only one bond which corresponds to C=O group in carboxylic acids
Describe the 3 functional groups in aspirin
Phenol group
Carboxyl group
Ester
Although it has a polar carboxylic group, sol is limited due to non-polar phenol group.
Sodium acetylsalicylate
When water added to ^, dissociates to form Na+ ions and acetylsalicylate ions
Ionic salts are more soluble in water as they form stronger ion-dipole interactions with water
How does converting aspirin to an ionic salt change its bioavailability
Increases SOLUBILITY but does NOT increase bioavailability.
This is because the acetylsalicylate ion is converted back to the unionised form in the acidic environment of the stomach
So COO- functional group changed back to COOH
Bioavailability can be increased by injecting it intravenuously
Describe uses of aspirin
Aspirin is a mild-analgesic (painkiller) - blocks sensation of pain at source
Aspirin works by blocking the action of enzymes that produce prostaglandins which are involved in transmitting impulses to the brain as well as causing fever and swelling. Aspirin prevents prostaglandins to be produced, eliminating pain
Aspirin is also used as an anti-coagulant. Prevent blood from clotting. Prevents heart attack and strokes. Aspirin also has anti-inflammatory properties, taken for arthritis and rheumatism.
Side effects of aspirin
Bleeding of the lining of the stomach. This is increased by drinking alcohol at the same time as taking aspirin which is known as the synergistic effect.
What is a synergistic effect
When 2 drugs increase each others effectiveness when taken together
What is penicillin
A group of antibiotics used to treat a range of bacterial infections. Derived from Penicillium Fungi and can be taken ORALLY or via INJECTION
How was penicillin discovered
Flemming was working with bacteria cultures. He noticed that a fungus had contaminated some of his cultures and left a clear region where no bacterial colonies were growing.
He concluded that something in the fungus was inhibiting the growth of the bacteria.
Describe the structure of penicillin
Beta-lactam ring - partly responsible for anti-biotic properties
3 carbon atoms, 1 nitrogen atom - nitrogen and 2 carbons are sp3 hybridised - 109.5
Carbon in carbonyl group is sp2 hybridised
The bond angles are usually reduced to 90 degrees which strains the bonds
Due to the strain, the beta-lactam ring breaks easily
How do beta-lactam antibiotics work
BLA work by interfering with cell wall formation in bacteria by inhibiting the enzymes responsible for creating cross-links in the cell wall.
When the beta-lactam ring comes into contact with the bacteria, the ring opens and binds irreversibly to the enzyme responsible for catalysing cross-links in the bacterial cell walls.
Water enters cell, increasing the osmotic pressure inside the cell, causing the cell to burst
How to make penicillin more resistance to penicillinase enzyme
Modify side chains in penicillin to make them more resistant to the P enzyme, which could deactivate the original form of penicillin (penicillin G).
Side chains can also be modified to increase resistance to break down by stomach acid
What are morphine and codeine
Opiates - strong analgesics
Opiates are natural analgesics that are derived from opium which is found in Poppy seeds.
Opiate analgesis work by temporarily bonding to receptor sites in the brain, preventing the transmission of pain impulses without depressing the CNS
When are strong analgesics used?
Relieve pain caused by injury, heart attack or cancer. They have side effects
Discuss the advantages of strong analgesis
- provide relief for acute or temporary pain
- Wide therapeutic window
- relieve anxiety
- faster distribution of drug due to intravenous admin
Discuss the disadvantages of strong analgesis
- euphoria
- lack of self-control
- indulge in dangerous behaviour
- Regular usage can lead to addiction
- build up tolerance - overdose chances
What is the blood-brain barrier?
A layer of tightly packed cells that protect brain by restricting passage of substances from B.strwam to brain
BBB - composed of Lipids - non-polar + hydrophobic
BBB is not easily crossed by polar molecules
For a drug to penetrate BBB, it must be non-polar and lipid soluble.
What do the analgesic properties of opiates depend on?
Their ability to move from the blood, where aqueous solubility is important, to the brain where lipid solubility is important to cross the blood-brain barrier
What are opiate receptors
Once in the brain, opiates attach to opioid receptors which reduce the perception of pain. Opiates produce nausea, drowsiness and can also depress respiration
Compare the structures of morphine, coedine and diamorphine (heroin)
C=C present in all - alkenyl
Phenol in all
Tertiary amine group
Ether group
Coedine - 1 OH group
Morphine - 2 OH
Coedine - 2 ether groups
Morph and DI - 1 ether group
Dia - 2 ester
Morph + coedine = 0 ester
Describe why morphine is a polar molecule
2 OH groups make it a polar molecule. But it is less soluble in lipids
Describe synthesis of diamorphine from morphine
Esterification
Both OH groups are converted into ester groups
Morphine is reacted with either ethanoic acid or ethanoic anhydride to produce diamorphine and WATER
2 hydroxyl groups replaced by 2 ester groups, making DIA less polar and more lipid soluble
This can now cross BBB more rapidly and in higher concentrations than morphine
so diamorphine is more potent but effects do not last as long as diamorphine
Describe synthesis of codeine
Codeine produced from morphine in a methylation reaction
An OH group is converted to methoxy ( OHCH3 ) group
Codeine becomes less polar than morphine and cross BBB
But reaction also reduces codeine’s ability to bond to opioid receptors, making it a weaker analgesic than morphine
Describe use of antacids
Antacids reduce excess stomach acid. Stomach contains HCL to kill pathogens.
Antacids work by neutralising excess HCL - they are weak bases
Strong bases cannot be used as antacids
Equation for sodium bicarbonate and HCL?
NAHCO3 + HCL -> NaCl + CO2 + H2O
What are alginates
Alginates produce a neutralising layer which prevents acid in the stomach rising into the oesophagus (heart-burn)
If asked to compare effectiveness of different bases on HCL:
Write out BALANCED chemical equation
Work out moles of base from masses given
Calculate with moles of HCL using the ratio
Whichever base reacts with the greatest number of moles of HCL, that is the most effective base
What do stomach acid inhibitors do?
Stomach acid inhibitors inhibit the production of stomach acid
PPIs and H2 receptor antagonists are both stomach acid inhibitors
PPIs inhibit proton pumps in stomach
H2 blockers block the histamine receptors in acid-producing cells in the stomach, reducing the amount of acid produced by the cells in the lining of the stomach
How does histamine work
Histamine stimulates stomach acid secretions by interacting at H2 receptors in the stomach lining.
H2 blockers compete with histamine for binding with H2 receptors
They block the interaction of histamine with H2 receptors, preventing the release of stomach acid
Describe an example of a PPI
Omeprazole
Describe an example of a H2 blocker
Ranitidine
How to calculate the pH of a buffer solution
pH = PKa + LOG (A-/HA)
HA = initial concentration of weak acid A- = initial concentration of the salt
What are the 2 assumptions of the Henderson Hasselbalch equator for pH of buffer
A weak acid partially dissociates - equilibrium lies to the left. Initial concentration of weak acid is equal to the equilibrium concentration of the weak acid because dissociation is so small.
Salt we use completely dissociates in solution. Initial conc = equilbirum conc of anion
difference between bacteria and viruses
Viruses = protein coat and nucleic acids
Not considered living organisms as they do not carry out metabolic processes and derive their energy from host cell
UNLIKE viruses, bacteria are self-reproducing units
many organelles
carry out metabolic processes
Bacteria are much larger than viruses
Why are viruses harder to cure
Viruses lack a structure whereas bacteria have a cell wall and so antibiotics can cure bacterial infections by disruption of cell wall production
Viruses mutate quickly so adapt to drugs
Bacteria are more complex and can be targeted in more ways whereas viruses lack sub-units that can be targeted by anti-bacterials.
Viruses must be targeted on a genetic level whereas bacteria can be killed by simple chemical agents.
How do anti-virals work?
Alter the cell’s genetic material so the virus cannot use it to multiply
Prevent viruses from multiplying by blocking enzyme activity within the host cell
How do anti-virals work?
Alter the cell’s genetic material so the virus cannot use it to multiply
Prevent viruses from multiplying by blocking enzyme activity within the host cell
Bind to cellular receptors targeted by viruses
Prevent or hinder the release of viruses from cells
Describe Oseltamivir and Zanamivir
Both used as antivirals to prevent the spread of the flu virus
Zanamivir is taken in by inhalation due to its low bioavailability when taken orally.
Oseltamivir can be taken orally as its bioav not changed by inhalation
Compare structures of oseltamivir
O:
Alkenyl Carboxamide amine ester ether
Z:
Alkenyl carboxamide amine ether carboxyl hydroxyl - 3
Zanamivir is more soluble in polar solvents than O
What happens to the ester group in oseltamivir in human body
Ester group is hydrolysed to a carboxyl group. Both Oseltamivir and Zanamivir work by inhibiting the enzyme, neuraminidase by binding to its active site
What is neuraminidase
An enzyme found on the surface of the influenza virus that enables the virus to be released from the host cell
By inhibiting this enzyme, virus does not leave host and infect other cells
What the difficulties of treating HIV:
HIV destroys T-cells, cells that protect body from infection
HIV mutates rapidly
HIV uses host cells to replicate
Drugs used to treat HIV may also harm the host cell
What is radioactive waste
Can be classified as low level, intermediate, or high level waste
High level waste gives off large amounts of ionizing radiation for a long time - long half life
Examples of low level waste and disposal method
Shoes
Protective clothing
gowns
Stored in shielded containers until the isotopes have decayed and then disposed as non-radioactive waste
Examples of intermediate waste and disposal method
Co-60, Cs-137
Stored in shielded containers in underground repositories
What are the 3 ways in which antibiotics are released
Antibiotics given to animals to prevent livestock diseases
Improper disposal of antibiotic medicines by hospitals and households
Antibiotics excreted by humans in urine
Dangers of antibiotic waste
AB in agricultural waste like manure and water run off can end up in soil and groundwater
Antibiotics in urine and pharmaceutical waste enter the sewage system at low concentrations
Sewage treatment plants are rarely equipped to remove antibiotics to remove antibiotics from waste water and can ultimately end up in the drinking water supply
Preferred solvents for reaction media?
Water Propan-1-ol Ethyl ethanoate methanol ethanol
Useable solvents for reaction media
Cyclohexane octane ethanoic acid Ethane nitrile Methyl benzene
Undesirable solvents?
Pentane Dichloromethane Dichloroethane Carbon tetrachloride Trichloromethane
Discussion of environmental issues related to left-over solvents.
Many undesirable solvents are volatile organic compounds
VOCs can cause nose and throat discomfort, nausea and fatigue
Form low level ozone and smog
What is green chemistry
- Prevent waste
- Maximise atom economy
- Design less hazardous chemical syntheses
- Design safer chemicals and products
- Increase energy efficiency
- Use safer solvents and reaction conditions
Explain how green chemistry was used to develop the precursor for Tamiflu (oseltamivir)
Synthesis of oseltamivir requires shikimic acid, extracted from the pods of star anise
Problems with synthesis of oseltamivir:
- complex, ten step process
- 6-8 months needed
- 30kg of star anise produces only 1kg of shikimic acid
Using the principles of green chemistry:
- production of shiki from fermentation of genetically engineered bacteria
- Extraction of shikimic acid from pine needles
What is taxol and where is it obtained from
Taxol is an anti-cancer drug used in chemotherapy.
Obtained from the bark of a yew tree
Bark contains very small amount of taxol, so initially supply was limited and the process was non-renewable
A semi-synthetic route was developed in which the precursor of taxol was isolated from the leaves of the European Yew Tree.
This route gives a yield 0.2% higher
But conversion from 10-DAB to taxol is complex and requires a range of solvents and organometallic reagents
Is taxol soluble?
Low solublility in water
Only 3 hydroxyl groups
To increase its water solubility, taxol is dissolved in alcohol with the addition of polyoxyethylated castor oil
What is a chiral auxilliary
A chiral auxiliary is an optically active substance that is temporarily incorporated into an organic synthesis so that it can be carried out asymmetrically with the selective formation of a single enantiomer.
