Medicinal Chem Flashcards
1
Q
Define effective dose (ED50)
A
Dosage required to produce a therapeutic effect for 50% of tested population
2
Q
Define toxic dose (TD50)
A
Dosage required to produce a toxic effect for 50% of tested population
3
Q
Define lethal dose (LD50)
A
Dosage required to kill 50% of tested ANIMAL population
4
Q
Define therapeutic index
A
Ratio measuring the relative safety of a drug
5
Q
Formula for therapeutic index, differentiating between therapeutic index for animal studies and human studies
A
Animal studies = Lethal Dose/Effective Dose
Human studies = Toxic Dose/Effective Dose
6
Q
Define therapeutic window
A
Range of concentration of drug in the blood for it to produce the therapeutic effect without causing toxic effects
7
Q
Why is a narrow therapeutic window problematic?
A
Toxic levels are easily reached
8
Q
Define side effects
A
Adverse effects of drugs
9
Q
Define tolerance
A
When the body becomes less responsive to the drugs and a larger dosage is required to produce the same effect
10
Q
Why is a high dosage dangerous
A
Can increase the risk of dependence and increase the possibility of reaching the lethal dose
11
Q
Define addiction
A
Psychological or physical dependence on drugs
12
Q
Give several withdrawal symptoms
A
- Depression
- Anxiety
- Fever
- Cold sweats
- Nausea
- Insomnia
13
Q
Define bioavailability
A
Fraction of administered dosage that reaches target part of human body
14
Q
Why does oral administration of drugs give low bioavailability?
A
Drugs can be broken down by the digestive system before they are absorbed
15
Q
Ethical considerations faced by medical researchers
when developing medications
A
- Risk to benefit ratio
- Animal testing
- Effects on environment
16
Q
Administration of drugs that gives the highest bioavailability is ___
A
Intravenous injection
17
Q
Outline how pulmonary administration works
A
Rapid absorption into blood through the lungs which have a large surface area
18
Q
Give the equation for the conversion of salicylic acid into aspirin
A
Salicylic acid + Ethanoic anhydride –> Aspirin + Ethanoic acid
19
Q
Reagent, catalyst and conditions for conversion of salicylic acid into aspirin
A
Reagent: Ethanoic anhydride, (CH3CO)2O
Catalyst: Concentrated sulfuric acid or phosphoric acid
Condition: Water bath
20
Q
The conversion of salicylic acid into aspirin is a ___ reaction
A
Nucleophilic substitution/Condensation
21
Q
How does aspirin relieve pain?
A
Relieves pain by preventing the production of prostaglandins at site of pain
22
Q
Other than relieving pain, what therapeutic effects does aspirin have?
A
- Anti-inflammatory (Prevents swelling)
- Anti-pyretic (Reduces fever)
- Anti-coagulant (Decreases blood’s ability to clot)
- Reduces risk of strokes and heart attacks
23
Q
Side effects of aspirin
A
- Excessive bleeding and ulceration of stomach (Synergistic effect when taken with alcohol)
- Acidosis (Decrease in blood pH)
- Reye’s syndrome in young children
24
Q
Define synergistic effect
A
Effect of 2 or more drugs on the body that is greater than their individual effect
25
Outline a method to separate aspirin from a non-acidic mixture
- Add NaOH to convert aspirin to its water-soluble salt
- Separate immiscible layers
26
Outline a method to purify aspirin
Recrystallisation using ethanol as a solvent
27
Why does isolation of the aspirin involve the addition of ice-cold water?
Aspirin has low solubility in water at low temperatures
28
Why is aspirin not stored in hot, humid locations?
Water causes hydrolysis
29
Methods to confirm the identity of aspirin
- Melting point
- 1H NMR
- Mass spectrometry
- X-ray crystallography
30
Methods to confirm the identity of PURE aspirin
- Melting point is higher
- Melting point is closer to literature value
- Smaller range of melting point values
31
Why is aspirin SLIGHTLY soluble in water?
- Polar hydroxyl group
- Non-polar large benzene ring
32
Method to increase the solubility of aspirin in water
- React aspirin with NaOH to turn it into an ionic salt
- Ionic compounds are more soluble than covalent compounds
33
Give the equation for the conversion of aspirin, C6H4(OCOCH3)COOH, into its water-soluble ionic salt
C6H4(OCOCH3)COOH (s) + NaOH (aq) --> C6H4(OCOCH3)COONa (aq)
+ H2O
34
Why is aspirin a better alternative than paracetamol?
Paracetamol has a narrow therapeutic window and smaller therapeutic index
35
Why is aspirin a better alternative than ibuprofen?
Ibuprofen can increase the risk of stomach bleeding
36
How does penicillin combat bacterial infection?
- Highly strained beta-lactam ring opens up
- Irreversibly inhibits enzyme responsible for the cross-linking of bacterial cell wall
- Results in a weakened cell wall
- Causes bacterial cell to burst due to the high osmotic pressure caused by water from the surroundings entering the cell
37
How can we mitigate the resistance of bacteria to penicillin?
- Modify side chain
- Prevents enzyme in bacteria from deactivating penicillin
38
How do opiates relieve pain?
Block transmission of pain by binding to opioid receptors in the brain
39
Other than relieving pain, what therapeutic effects do opiates have?
Cough suppression effects
40
Why are opiates addictive?
- Releases dopamine
- Gives a feeling of euphoria
- Interacts with opioid receptors in the brain
41
Functional groups present in morphine, codeine and diamorphine are ___
- Benzene
- Amino
- Ether
42
Solubility of opiate derivatives:
Morphine > Codeine > Diamorphine
Explain why
- Morphine has 2 hydroxyl groups
- 1 of the hydroxyl groups in morphine is replaced with an ether group in codeine
- Both hydroxyl groups in morphine are replaced with ester groups in diamorphine
- Non-polar compounds cross the hydrophobic blood-brain barrier more easily
43
Method to synthesise codeine from morphine
React with iodomethane (CH3I) in alkaline solution
44
The synthesis of codeine from morphine is a ___ reaction
Nucleophilic substitution
45
Why does codeine have to be metabolised into morphine first?
- Steric hindrance of methyl group
- Codeine cannot bind directly to opioid receptors
46
Method to synthesise diamorphine from morphine
Heat morphine with ethanoic anhydride
47
The synthesis of diamorphine from morphine is a ___ reaction
Condensation
48
Outline the role of hydrochloric acid in the stomach
- Provides denature proteins
- Provides the optimum condition for pepsins and other enzymes to digest food
- Kills bacteria ingested with food
49
Outline the role of hydrogen carbonates and gastric mucus in the stomach
Prevents the gastric juice from digesting the stomach
50
Effect of excess HCl in the stomach
- Indigestion
- Gastritis
- Peptic ulcer
51
How does an antacid combat excess HCl in the stomach?
Quickly reduces the acidity of the gastric juice by neutralising excess acid and increasing the pH
52
Why do antacids usually contain a mixture of 2 or more ingredients?
- Counteract undesirable side effects
- Some ingredients might be slower
53
Define the role of antifoaming agents in antacids
Relieve bloating by allowing CO2 to coalesce and leave as flatulence
54
Define the role of alginates in antacids
Produces protective layer that floats on stomach content and prevents heartburn
55
Outline how Ranitidine and Zantac work
Binds to H2 histamine receptor which stops the production of acid
- Binds to same H2 receptors as histamine --> Blocks histamine binding to H2 receptor
56
Outline how Omeprazole and Esomeprazole work
Binds to gastric proton pump thus preventing the release of H+ ions into the stomach
57
Outline how metabolites work
Drugs are changed into the active form (metabolites) after being processed by the body
58
Reasons for making drugs in different forms (metabolites)
- Avoid side effect
- Longer shelf life
- Easier storage
- Allow drug to be more soluble in water
- Target drugs for specific areas
59
Why is it important to maintain the pH of the body within certain strict limits
To ensure enzymes function correctly
60
Define a buffer solution
Solution which resists changes in pH when small amounts of acid or alkali are added to them
61
Data booklet:
pH = pKa + log [A-]/[HA]
What do A- and HA mean?
[A-] = Concentration of conjugate base
[HA] = Concentration of acid
62
Difference between virus and bacteria
- Bacteria have cell walls and viruses do not
- Bacteria perform living functions on their own and viruses do not without a host cell
- Bacteria affected by antibiotics while viruses are not
63
Why are viruses considered non-living organisms?
Viruses lack cell structure and do not grow or reproduce
64
Ways in which antiviral drugs work
- Prevents attachment of virus to host cell
- Blocks enzyme activity in the host cell so viruses cannot use it to multiply
- Prevents new virus from leaving host cell
65
Outline how Oseltamivir and Zanamivir work
- Blocks NA viral enzyme which allows viruses to pass through cell membrane
- Prevents virus from leaving host cell so it cannot infect other cells
66
Functional groups present in both Oseltamivir and Zanamivir are ___
- Carboxamide
- Ether
- Carbonyl
- Amino
- Alkenyl
67
Why is oseltamivir inactive in its original form?
- Presence of ester group
- Turned into acidic metabolite once ester is hydrolysed in body
68
Difficulties with eradicating AIDS/HIV virus include ___
- Virus mutates quickly (can adapt to drugs)
- Makes people vulnerable to other infections
- Virus attacks immune system
- Each kind of virus requires special drugs
- Difficult to attack virus without attacking host cell
69
Source of pharmacologically active compounds (waste)
- Incorrect disposal of drugs in hospitals and pharmacological industries
- Incorrect disposal of waste products from pharmacological industries in particular organic and/or chlorinated solvents
- Use of antibacterial drugs in agriculture and animal husbandry
70
Detrimental effects of pharmacologically active compounds (waste) in the environment
- Increased resistance of bacteria to current drugs
- Carcinogenic
- Cause damage to internal organs of living organisms
- Changes in metabolism and behaviours of organism
71
Environmental effect of chlorinated solvents
Contribute to greenhouse gases and ozone depletion
72
Why must chlorinated solvents be incinerated at high temperatures?
To prevent the formation of carcinogens
73
Preventive/corrective measures for pharmacologically active compounds (waste)
- Ensure proper treatment of drugs before disposal
- Restrict antibiotic therapy to bacterial infections
- Controlled use in agriculture
- Use of alternative solvents such as supercritical fluid
74
Define low-level nuclear waste
Nuclear waste that has low radioactivity and usually contains isotopes with short half-lives
75
Source of low-level nuclear waste
Contaminated surgical/clinical instruments
76
Outline the proper disposal of low-level nuclear waste
- Stored on site until decay activity is safe and then disposed of as ordinary waste
- Incineration
77
Define high-level nuclear waste
Nuclear waste that has high radioactivity and usually contains isotopes with longer half-lives
78
Source of high-level nuclear waste
Nuclear reactors
79
Outline the proper disposal of high-level nuclear waste
- Vitrification
- Storage underground in concrete bunkers
80
Dangers of high-level nuclear waste
- Carcinogenic
- Can cause birth defects
- Weaken immune system
- Cause DNA mutation in living organisms especially in bacteria
81
Outline some principles of green chemistry
- Minimise number of steps in synthesis
- Maximise atom economy
- Use as little solvent and energy as possible
- Recover/reuse solvents
- Use water as a solvent
82
How can antibiotic use affect the environment?
- Leads to antibiotic resistance in bacteria/microorganisms
- Destroys useful bacteria
83
Outline the synthesis of oseltamivir using green chemistry
- Synthesis from petrochemicals involves huge quantity of materials and generates large amounts of waste
- Current synthesis uses shikimic acid, a natural product extracted from Chinese star anise or fermentation of glucose by GM bacteria
- Current synthesis cuts down on number of steps and reduces energy consumption
84
Common hazardous solvents
- Methanol
- Formaldehyde
- Chlorinated solvents
- Benzene
85
Give some green solutions to the problem of organic solvent waste
- Use of alternative solvents such as supercritical fluids
- Use of water as solvent
- Use solvent-free reactions
- Recycle waste solvents
- Catalysis that leads to better/higher yield
- Reducing number of steps
