Paper 3 Flashcards
What is the definition of a drug?
A substance that has some type of physiological effect when introduced into the body
What do most drugs act with
?
Some kind of receptor molecule in the body
How do drugs work?
Receptors generally large protein molecule
With an active site, which has a specific shape
Only allows a limited number of molecules to fit depending on their shape
Drug Development (Explain the stages)?
Identifying the need
Identifying the possible structure of a new drug
Modification + Testing the drug activity of a range of molecules –>
1.) In Vitro
2.) Then in Vivo
Synthesis of the possible drug or extraction of the drug from a natural source
Animal Studies dose equation?
LD50/ED50
Human Studie dose equation?
TD50/ED50
How do we decide which drug to administer?
- Is it solid, liquid or gas
- How quickly/effectively it can reach a certain part of the body
- How stable is it in bodily environments
Definition of bioavailability?
The fraction of the administered dosage that reaches the target part of the human body
Factors affecting Bioavailability?
Method of administration
The polarity of the drug
What affects the polarity of a drug?
- Dependent on the functional group
Tolerance?
Human body constantly adapts to the chemicals it meets
Repeated use –> Drug Tolerance
- Need larger amounts for the original effects
Why would increasing the dose be a bad thing in regard to Tolerance?
Increasing the dose
- ST –> temporarily overcomes tolerance
- LT –> Greater tolerance
Definition of Side effects?
adverse effects which the drug was not prescribe for
Addiction?
When the patient becomes compulsive about taking the drug regardless of the consequences
- Increased problems of Tol and SE
What is aspirin?
an Ester
Equation of Aspirin
Displayed Formula
Salicylic Acid + Ethanoic acid –> Aspirin
This does not produce a vast yield of Aspirin so Ethanoic Anhydride might be needed.
What is the catalyst in the reaction that results in the formation of Aspirin?
Conc. sulfuric acid
How to prep Aspirin?
- Add Salicylic Acid into a conical flask
- Add excess ethanoic anhydride and mix reagents carefully
-Leave the flask until the reaction is completed
- Add cold deionized H2O –> convert excess ethanoic anhydride into ethanoic acid.
- Filter the mixture by vacuum filtration
- Recrystalise the mixture
How to recrystallize the mixture of aspirin initially made?
Re-dissolve aspirin with hot ethanol
Filter using vacuum filtration
Cool in ice bath
Filter mixture again
does Aspirin have an OH group?
yeah
How soluble is Aspirin in water?
Aspirin is not that soluble in water due to the large non-polar phenyl group
How can aspirin’s aqueous solubility be improved?
Neutralisation with a base to give it ionic sodium salt
Mechanism of Penicillin?
Structure: Beta Lactam ring
Four membered ring is strained
Makes carboxamide group reactive
Ring opens up and reacts with the enzyme that is responsible for the formation of vital cross-links in the new bacterial cell walls
Cell wall is weakened and permeable
Leads to the bacteria taking too much water and dying
How does Aspirin work?
Mild Analgesic
functions by intercepting the pain stimulus at the source, often by interfering with the production of substances that cause pain
How else can aspirin be used?
Can be used as an anticoagulant
–>
Helps to prevent blood clots
Why do people who take aspirin are not advised to drink alcohol?
synergistic effect –> caused by the presence of both drugs that is greater than the sum of their individual effects
can lead to bleeding in the stomach
Names of all functional groups
SEE
What are two reasons for tolerance of drugs?
- More you use –> Greater Metabolism –> More drug excreted and less remains in the body
- Body adapts by desensitizing target molecules which drugs bind to so it is not able to produce the same effect
What is the mutation that is resistant to penicilin
penicilinase
What do strong analgesics do?
- Temporarily bind to opiod receptors in brain whch block transmission of pain signals
Advantages of taking Opiates?
- Relief of severe pain
- Used in cancer patients
Disadvatages of taking opiates?
- Naseau and vomiting
- Constipation
- Respitory Depression
- Physical and pshycological dependence
how do mild analgesics relieve pain?
Intercepts the pain stimulus at the source
Interferes with the production of substances that cause pain.
what is the definition of a synergistic effect?
an effect caused by the presence of both drugs that is greater than the sum of ther individual effects
Why should you not take alcohol with aspirin?
Synergistic effect
Can lead to bleeding in the stomach
Explain the importance of beta-lactam ring in penicilins?
- Interferes with enzyme responsible for bacterial cell wall
- Beta lactam ring is strained
- Has smaller bond angles
Why is the over prescription of penicillin a bad thing?
- Bacteria can become resistant to the antibiotic due to a greater number of bacteria being exposed
- A greater probability of resistance developing
Explain how a strong analgesic relieves pain?
- Crosses the brain blood barrier
- Binds to opiod receptor sites in the brain
- Supresses the transmission of pain receptors in the brain
What are two effects of an excess of stomach acid?
Acid Reflux - A burning sensation when acid flows up into the oesophagus
Peptic Ulcers - a painful open sore in the lining of the stomach or small intestine
What are antacids?
Things that can simply neutralise excess acids in the stomach
What are some examples of antacids?
Calcium Hydroxide
Magnesium Hydroxide
Aluminium Hydroxide
Sodium Carbonate
Sodium Bicarbonate
Which drugs inhibit the production of Acid?
- H2 agonists
- Proton Pump Inhibitors
How do H2 agonists inhbit the production of Acid?
- (rantadine) Zantac block the action of histamine
- Rantidine molecule prevents the secretion of this acid by reversibly binding to the H2 histamine receptors in the cell
- Part of Rantadine molecule has a similar shape to histamine and so fits into the receptor side
- Inhibits the secretion of acid by the cells in the lining of the stomach
How do Proton Pump Inhibitors inhibit the production of acid?
Prilosec and Nexium
- Blocks the enzyme responsible for pumping the Hydrogen ions out of the cells and into the stomach
Can you describe how omeprazole works to reduce the secretion of acid?
- Omeprazole is less polar
- More easily crosses the lipid base cell membrane into the cellls
- Becomes charged to creates and active form
- Active form binds to proton pump
Why are Proton Pump inhibitors more effective than H2 Agonists in prohibiting thr secretion of acid in the stomach?
- Much more effective than H2 agonists because their action is irreversible, so they permanently deactivate the proton pump
What is the point of the buffer solution?
When you add medicine into your body might be acidic or baisc so the pH of the medicine might affect your body.
The buffer solution keeps your pH constant in the body when a drug is administered
A buffer solution is added to the drug formulation
What is the definition of a buffer solution?
A buffer solutiuon is one that resists change in pH when small amounts of acid or alkali are added
Why do you not suddenly stop taking Prilosec or Nexium (PPI)?
You run the risk of a rebound effect (acid reflux)
- You have to decrease the dose gradually
equation of pH?
pH = pKa + log([A-])
[HA}
Are viruses always parasitic?
Yes
Why are viruses more difficult to target than bacteria with drugs?
-Viruses lack a cell structure and only reproduce inside living cells
- Many viruses can mutate rather easily –> leading to changes in the composition of their protein coat –> leading to the resistance to drugs
How do Antiviral drugs work?
- They alter the cell’s genetic material so that the virus cannot use it to multiply
- Preventing the viruses from multiplying by blocking enzyme activity involved with either replication of DNA within the host cell, or the release of the new viruses
What are examples of anti-viral drugs?
Tamiflu and Zanamavir
How do Zanamivir and Tamiflu work?
They inhbit the enzyme neuraminidase
Neuraminidase is produced by the virus as part of the mechanism that allows the new viruses to leave the host cell after replication
Where are synthetic drugs always made?
Labs
What is the definition of Metabolism?
The speed and the ability to absorb and use the medicine
State one factor that can affect the ability of the body to absorb a drug?
- Age
- Weight
- Method of Administration
- Polarity
- Solubility
Therapeutic Effect
A desirable and beneficial effect; it alleviates symptoms or treats a particular disease
Low Level Waste:
- Items contaminated with radioactive material.
- Can be stored on site until it has decayed Landfill sites.
- Some are incinerated to reduced volume and disperse over a wider area
High Level Waste:
- Spent fuel rods and materials from nuclear reactors.
- Stored in concrete casks inside concrete bunkers
- Underground in stable areas/Deep in Ocean
Therapeutic Window
The range of dosages between the minimum amounts of the drug that produce the desired effect and a medically unacceptable adverse effect
Give some examples of mild analgesics?
Ibuprofen and paracetamol
What is the definition of an analgesic?
Any medicine, such as aspirin, that reduces pain without inducing unconsciousness.
Can you explain the structure of morphine and what this means for its solubility?
Morphine has two hydroxyl functional groups
–> Adds Water solubility to the structure
How polar is morphine?
Fairly polar
What is the structure of codeine?
- Has one hydroxyl functional group
- Substituted with an O bonded
- To a methyl alkyl functional group
- Which forms an ether
How polar and soluble is codeine in comparison to morphine??
- Slightly decreased polarity
- Lower water solubility
Why might codeine be more potent than morphine but less than diamorphine?
- It has a lower polarity and solubility in water allowing it to cross into the brain barrier more easily than Morphine
- However, Codeine is less effective at binding to the **receptors which means it has ** 1/10 the potency of Diamorphine
-
What is codeine suitable for?
Mild to moderate pain
Can you talk about the structure of Diamorphine?
- 2 Hydroxyl functional groups
- Substituted with O
- Bonded to an acetyl side chains
- Which forms two ester groups
How polar and soluble is diamorphine?
It is not very polar (in comparison to morphine and codeine) and not very soluble in water either
How bioavailable is diamorphine?
35% (when taken orally)
How is codeine usually made?
- You can create it synthentically by reacting morphine and Iodomethane
- This creates an ether linkage
- However, this product is unfortuanately reversed by the liver .
- Essentially, we get back to morphine and Iodomethane.
How to make codeine from morphine?
Methylation reaction
Morphine + CH3I (in an alkaline solution)
This makes an ether linkage
How to make Diamorphine?
Not found naturally in opium latex
- Only made by reacting morphine with ethanoic acid
- Called an esterification reaction
- Hydroxyl Group from Morphine reacts with Carboxylic Group of Ethanoic Acid
- Forms an ester linkage
- This reaction also results in the production of water
Morphine + Ethanoic Acid?
Diamorphine + Water
Which of the three opiates (morphine, codeine or diamorphine) is the most polar?
Morphine contains two hydroxyl funtional groups, which are more polar than the methyl group on codeine and the acetyl groups on diamorphine.
Can codeine be made naturally?
I mean … kinda.
Opium Latex holds around 3% of Codeine
HOWEVER, the easiest way to make it is through a methylation reaction.
Can codeine be made naturally?
I mean … kinda.
Opium Latex holds around 3% of Codeine
HOWEVER, the easiest way to make it is through a methylation reaction.
What are some side effects of diamorphine on the body?
- Diamorphine (very little amount of non-polar groups)
- Diamorphine can only bind to one receptor –> so the effect of diamorphine is immediate and does not last long
What are some of the side effects of Codeine?
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.
State the name of the opiates that are produced within the human body.
Endorphins
What is the relative order of effectiveness of the three opiates from lowest to highest?
Diamorphine
Morphine
Codeine
Why is Codeine less effective at treating pain than morphine?
Codeine, although less polar and more capable of passing into the brain than morphine, is only about 1/10 the strength of morphine.
This is because morphine has a much greater affinity for the endorphin receptors in the brain compared to codeine.
About 10% of codeine is metabolised in the liver into morphine, although this can vary between individuals.
What is the most common method of administration of morphine?
Injection (100% bioavailability)
Pill (30% bioavailability)
What are some advantages of using Codeine?
- They are suitable for mild pain
- Drug is slowly metabolised so fewer doses are required
- Convenient Administration
How addictive are morphine, codeine and diamorphene relatively?
Morphine - Moderately addictive (Withdrawal if taken for extended doses)
Codeine - Addiction is possible
Diamorphene - Highly Addictive (must be injected) –> Drug metabolises so frequently more dosages are required
What is codeine used for?
Minor pains such as headaches or cough suppression
What is Morphine used for?
- Moderate to severe pain (following surgery, childbirth or after breaking a bone)
What is diamorphine used for?
Alleviates severe pain
What are some common side effects and negative side effects of morphine?
Drowsiness, weight loss
More negative side effects:
- Blurred visions and chest pain
Symptoms of an overdose of morphine?
- Muscle spasms
- Fevers
How does a doctor take his patient off morphine?
When patients have become accustomed to the medication they can experience physiological addiction and withdrawal to the medication if removed suddenly.
How are Morphine, Codeine and Diamorphine taken?
Morphine:
- Oral tablet or liquid
- Intramuscular or intravenous injection (100% bioavailability)
Codeine:
- Oral ingestion
Diamorphine:
- Oral ingestion
- Intravenous ingestion
Why cant an Antancid be a very strong base?
- It could cause damage to the mouth on the journey to the stomach
How much acid does an antacid neutralise and why?
An antacid does not neutralise all of the acid to leave sufficient acid for digestion
Why are other additives used to an antacid?
Contains colouring and anti foaming agents to decrease the bloating from the carbon dioxide gas
Sodium Bicarbonate + Hydrochloric acid equation?
NaHCO3 (s) + HCl (aq) → NaCl (aq) + CO2 (g) + H2O (l)
What type of issues are Antacids useful for?
- Useful for ocassional or mild stomach acid issues
Why is excessive use of Antacids bad for you?
Chronic or excessive use of antacids is not recommended for long-term issues of excess stomach acid because it can worsen the problem.
Buffer Solution equation?
H2CO3 (aq) + H2O (l) ⇌ HCO3- (aq) + H3O+ (aq)
What is usually wasted the most in a chemical reaction?
The solvent (80-90%)
Can you give some examples of Polar and Non-Polar Solvents?
Polar: Water + Alchohols
Non-Polar: Alkanes, Ethers, and Benzene
What is more harmful, Polar or Non-Polar solvents?
Non-Polar Solvents
How do you normally dispose of polar solvents?
- Filtration/Distillation to remove impurities
- Water can then be disposed of normally
- Alcohol would need to be diluted to very low conc
- They can be disposed of as waste water or incinerated with a combustion reaction
Weaknesses of disposing Non-Polar solvents such as Benzene or Hexane
Benzene and its derivatives are often carcinogenic (cancer-causing) to humans and animals and can inhibit photosynthesis in plants.
Hexane is a neurotoxin that can cause numbness and weakness in the arms and legs and stunted growth in plants.
Name 6 Green Chemistry principles?
- Prevention of Waste
- Atom Economy
- Less hazard Chemical designs
- Safe and restricted use for solvents
- Energy Efficiency
- Design for Degradation
Why do we look at Atom Economy when we are making Drugs etc:
- All materials in a reaction should be used up
How can we dispose of Solvent Waste Solution?
- Incinerate it via Combustion
What are some benefits of using Combustion to dispose Solvent Waste Solutions?
- The energy produced from the combustion reaction can be used as a source of energy for other reactions
What are the negatives of using Combution as a means of disposing of Waste Solution?
Combustion produces CO2 (has negative effects on the environmet)
Can you name two examples of Bad solvents?
-Benzene
- Chlorinated Hydrocarbons bad for the stratosphere (Free radicals can destroy the ozone layer molecules blud!)
How can Solvent Waste be recycled?
Fractional Distillation
- Seperates the solvents by heating them up to their corresponding Boiling points
- You can then recycle the good ones
Name some problems with using Fractional Distillation to recycle Solvent WASTE solution? And why would these disadvantages be irrelevant?
High Initial Cost
- However, they save more energy in the LT
Can you give a succesful example of Drug Synthesis?
- Tamiflu is very much needed as a medicine
- Needs shikimic acid for its synthetic production
- Main problem is: Shikimic Acid is made from found naturally only in Star Anise Plant
- BUT, High Demand and Low Service, may cause the population of Star Anise Plant to rapidly decrease
- Plant no no good for the environment
- Scientists succesfully found a way to produce shikimic acid without the use of plants
- We create it using E.Coli in the process of Bio Synthesis
What are the conditions needed for E.Coli to make Oseltamivir (Tamiflu)
- Needs sugar (carbohydrates)
- Controlled Temperature so that we can make lots of it without using too much energy or waste
What is the synthesis of Oseltamivir from Shikimic Acid without plants an example of?
- Green Chemistry at its finest!
- Example of using minimum energy consumption + waste production to produce larger quantities of shikimic acid
How can Benzene be disposed of?
- Incinerated via Combustion
- Has to be diluted with H20
- Biodegradation –> More ‘Green’ as it produces CO2 at a slower rate
What are nuclear medicines used for and how are they useful?
They use radioactive substances to dignose and treat diseases wie krebs
Uses of Radioactive Isotopes?
X-rays
How do we produce Nuclear Waste?
When we do not use radioactive isotopes
and
Materials/Equipments have come into contact with radioactive isotopes
Why might Nuclear Waste be harmful?
They could still be producing Gamma Rays
- Can cause damage at the cellular level
What does the risk of serious health effects from gamma radiation depend upon?
- The amount of dosage/The amount of time
What happens when you have high exposure to Gamma Radiation?
‘Radiation Sickness’
Salicylic Acid + Ethanoic Anhydride
–> Aspirin vs Acetic Acid
SHOW THE STRUCTURAL FORMULA FOR THE FORMATION OF ASPIRIN
SEE IN TEXTBOOK
SHOW THE STRUCTURAL FORMULA FOR THE FORMATION OF ASPIRIN
SEE IN TEXTBOOK
What catalyst is used in the aspirin reaction?
Acid: H2SO4
Also needs heat to drive the reaction forward
One way to increase the purity of aspirin?
To improve the purity: Recrystallisation
- Dissolve aspirin in ethanol + add water and then cool it down with ice
- When we cool it the aspirin starts to form again
- Then we filtrate it
Ehtanol has non-polar + polar properties –> The impurities will be dissolved and rinsed away with the ethanol
One way to measure the purity of aspirin?
Infrared spectroscopy
- The Bond asborption should be around 1700 cm for the CO double bonds
- The Bond absorption should be around 2800 for O-H bonds
The Infrared Spectroscopy tells you what functional groups are expected in aspirin
Opiates
strong analgesics
work on opiod receptors in the brain
How to convert morphine to codeine
METHYLATION
How to draw ionic form of aspirin
see
salicylic acid + ethanoic anhydride
Aspirin + CH3COOH
THE HIGHER THE THERAPEUTIC I THE…
LOWER THE CHANCE OF DYING
X TIMES THE DOSE
State how penicillins may be modified to increase their effectiveness.
Modify the side chain
What is the difference between bioavailability and solubility?
SEE
Describe how penicillin combats bacterial infections.
ring is «sterically» strained
inhibits enzyme/transpeptidase «in bacteria» that produces cell walls
prevents cross-linking of bacterial cell walls
cells absorb water AND burst
cells cannot reproduce
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).
In animal testing, the therapeutic index is calculated using the lethal dose and the minimum effective dose. Explain for kids why the minimum effective dose is used instead of the maximum?
If they used the maximum effective dose, they might see really good results, but they could also see more side effects and risks
A medicine with a low therapeutic index would be considered to be…
not safe, but could be used with careful monitoring.
Explain why diamorphine crosses the brain blood barrier more easily
blood-brain barrier is hydrophobic/non-polar/made of lipids ✔
morphine has hydroxyl/OH «groups»/is more polar AND diamorphine hasester/ethanoate/OCOCH3/acetate «groups»/is less polar/is lipid soluble ✔
State one advantage of using morphine as an analgesic
effective against strong pain
Explain, with reference to the action of penicillin, why new penicillins with different side-chains need to be produced.
bacterial resistance «to older penicillins/antibiotics» ✔
prevent penicillinase/beta-lactamase/enzyme in bacterium to deactivate/open penicillin/beta-lactam ring ✔
State and explain the relative solubility of codeine in water compared to morphine and diamorphine
codeine less soluble «in water» than morphine AND more soluble than diamorphine
OR
morphine > codeine > diamorphine «in terms of solubility in water» ✔
more/stronger/greater hydrogen/H bonding «due to more hydroxyl groups leads to greater solubility» ✔
State the natural source from which codeine, morphine and diamorphine are obtained.
opium poppy/plants/seeds ✔
