medicinal chemistry Flashcards
1
Q
the four types of administration routes are…
1. oral
2. ???
3. rectal
4. topical
A
parental
2
Q
capsules, suspensions, solutions and tablets are all ______ administrated
A
orally
3
Q
what are two rectal dosage forms?
A
suppositories, creams
4
Q
what are three types of injections
A
- intravenous
- subcutaneous
- muscular
5
Q
why are there different administrative routes? (2 short)
A
- increase bioavailability of drug
- prevents degradation by acidic pH in the stomach environment
- incr patient compliance
6
Q
what is bioavailability?
A
fraction of of administered dosage that enters the blood stream
7
Q
which type of administration has 100% bioavailability?
A
parental
8
Q
what is pharmocokinetics? (short recap)
A
what the body does to the drug after it enters the body
9
Q
the four processes of pharmokinetics are…
A
- absorption
- distribution
- metabolism
- elimination
(All Dogs Make Eggs)
10
Q
what is one way absorption is negatively affected?
A
poor solubility in water -> poor uptake
11
Q
distribution is affected by the _______ity and _____ity of drugs
A
hydrophilicity, lipophilicity
12
Q
what affects the hydrophilicity and lipophilicity of drugs?
A
the functional groups present on compounds
13
Q
what type of drug administration is usually affected by metabolism?
A
oral
14
Q
drugs that become metabolites undergo ______________
A
first pass metabolism
15
Q
how does metabolism affect bioavailability? (3)
A
- drugs experience ‘first-pass metabolism’ by the liver
- cannot exert therapeutic affects
- this significantly affects F
16
Q
what is the therapeutic window? (short def.)
A
the range of acceptable dosage strengths where the drug will exert its therapeutic effect without causing toxic effects
17
Q
what is the formula for therapeutic index for animals
A
LD50/ED50
18
Q
what is the formula for therapeutic index for humans
A
TD50/ED50
19
Q
is a high therapeutic index good? why?
A
- yes
- greater safety margin btw effective and toxic/lethal dose
- when taken in higher doses than required for it to exert therapeutic effect, the drug will still be safe
20
Q
how does aspirin work as a mild analgesic?
A
it binds to COX 2 enzyme and prevents it from releasing prostaglandin
21
Q
aspirin prevents pain detection at the source by
A
preventing nerve messages from being sent to the brain
22
Q
aspirin reduces swelling by
A
- preventing dilation of blood vessels
- decr swelling
- reduces inflammatory response
23
Q
what does prostaglandin do? (2)
A
- send nerve messages to brain -> pain detection at source
- causes inflammatory response -> dilation of blood vessels -> swelling -> incr pain
24
Q
what reagents and conditions are required for the synthesis of aspirin?
A
- reagents: salicylic acid, ethanoic anhydride
- cond: catalyst H2SO4, warm e mixture
25
what are the products of aspirin synthesis
aspirin + ethanoic acid
26
write out the reaction of aspirin synthesis
-
27
how is aspirin purified from aspirin synthesis?
- dissolved and heated in ethanol
- recrystallisation in ethanol -> due to low solubility
- filtration
28
what does a lower than expected melting point of aspirin tell us?
there are impurities
29
what is the m.p. of salicylic acid?
159ºC
30
what is the m.p. of aspirin
138-140ºC
31
what method can be used to differentiate between aspirin and salicylic acid?
- IR spectroscopy
- aspirin: presence of C=O peak
- salicylic acid: presence of O-H peak
32
what does synergistic mean?
when taken together, the drugs have a greater combined effect than individual effects
33
what are 2 other purposes for aspirin?
- anticoagulant
- synergistic effects w alcohol
34
why is aspirin made into a salt?
- improve solubility of aspirin in water
- incr F
35
write the reaction of how aspirin is made into a salt
-
36
what is penicillin
an antibiotic
37
why is penicillin so reactive?
it has a beta-lactam ring which has ring strain
38
how does the beta-lactam ring in penicillin kill bacteria? (2)
- binds irreversibly to enzyme transpeptidase in bacteria
- disrupts formation of bacterial cell wall
- when water enters bacteria, bacteria lyses
39
why is penicillin modified? (2)
1. to improve stability of drug in low pH environment
- improve oral F
2. overcome antibiotic resistant bacteria
- has enzyme penicillinase which prematurely opens up beta-lactam ring
- prevents bacteria fr recognising drug
40
why is there increased antibiotic resistance?
- overprescription of antibiotics
- when patients do not complete the full course of antib
- use of antibodies in animal feed -> enters food chain -> humans end up eating it
41
how do opiates function as strong analgesics?
- bind reversibly to opiate receptors in CNS
- prevents transmission of nerve impulses
42
how is morphine derived?
from opium
43
which opiate is methylated morphine?
codeine
44
diamorphine is the ________ form of morphine
esterified
45
why is diamorphine the most potent?
- it is least polar
- it can cross the lipophilic blood brain barrier most easily
46
codeine and diamorphine are _____, precursors to the active form morphine
pro-drugs
47
what are pro-drugs
- inactive form of drug
- metabolised in the body into active form
48
what reagent can be used to react convert morphine into diamorphine
ethanoic anhydride
49
what are 2 advantages of opiate usage?
- provides stronger + faster pain relief
- suppresses cough reflex
50
what are 3 disadvantages of opiate usage?
- addiction
- tolerance -> overdose
- constipation
51
what is tolerance?
it is when a higher dosage is required to exert the same effect
52
why is tolerance dangerous?
higher dosages may reach lethal dosage --> overdose
53
what condition is caused by excessive production of HCl?
dyspepsia
54
what are three things you can take to counter dyspepsia
- ranitidine
- omeprazole/esomeprazole
- antacids
55
how does ranitidine counter dyspepsia?
- competitive inhibitor of H2-receptor
- prevents histamine from binding
- prevents parietal cells from releasing HCl
56
ranitidine inhibits ____ while omeprazole/esomeprazole inhibits ____
H2-receptor, proton pump
57
how does omeprazole/esomeprazole counter dyspepsia?
- inhibits proton pumps
- directly prevents parietal cells from releasing H+
58
antacids counter dyspepsia by...
neutralising excess acid
59
why aren't strong bases used as antacids?
- they are strong bases --> caustic
- damage stomach lining
60
what's the difference between viruses and bacteria? (focus on virus) (2)
- viruses need a host to replicate and survive (bacteria don't need)
- viruses consist of proteins and RNA (bacteria has a complex cellular structure)
61
antivirals function to _________ with host or virus
interfere
62
how do antivirals work? (3 short)
- interfere w host DNA -> virus cannot replicate
- interfere w host cell membrane -> virus cannot enter
- interfere w virus -> virus cannot leave
63
what does oseltamivir/zanamivir act against?
influenza
64
how does oseltamivir/zanamivir work as an antiviral? (4)
- competitive inhibitors of neuraminidase enzyme
- neuraminidase cleaves a sialic acid moiety from the host cell -> allows virus to leave
- oseltamivir competes with sialic acid moiety for the active site
- prevents exit of viral molecules
65
why must oseltamivir/zanamivir be administered promptly upon infection?
- otherwise the virus would have already proliferated
- this renders the drug ineffective
66
why is HIV so difficult to kill (3)
- kills T helper cells
- mutates rapidly -> develops resistance
- remains dormant
67
where is taxol obtained from
bark of pacific yew trees
68
why is taxol synthetically produced
extremely low yield fr the trees
69
taxol synthetically produced by... (short)
using 10-deacylbaccatin from needles and leaves of European yew trees
70
production of taxol is highly controlled by ________
chiral auxillaries
71
why are chiral auxillaries necessary in the production of taxol?
- chiral auxilliaries are used to ensure only products w desired stereochemistry is produced
- otherwise taxol could potentially bind to off-target and lead to toxicity
72
why does the production of taxol need to be highly controlled?
- taxol has 11 chiral centres
- if it binds to off targets it could lead to toxicity
73
how are chiral auxillaries used to produce the desired enantiomer of Taxol?
- the chiral auxiliary combines with the **non-chiral reactant** to form a chiral intermediate
- ensures only the desired enantiomer is produced
- removed and recycled
74
in chemotherapy, taxol is used to bind to _______ in ________ cells
tubulin in cancer cells
75
how does the binding of taxol to tublin prevent the proliferation of cancer cells
- prevents spindle fibres from breaking down
- prevents cell division
76
what is emitted in alpha decay
helium nucleus, 4,2 He
77
what is emitted in beta decay
electron, 0, -1 e-
78
what is the equation used to find the rate constant?
t1/2= ln2/k
t1/2 – half life of isotope
k = decay constant
79
what are the types of diagnostic imaging?
- nuclear imaging
- magnetic resonance imaging (MRI)
80
what is nuclear imaging?
diagnostic technique that uses tracers that emit radiation and can be detected by using positron emission tomography (PET)
81
what type of diagnostic imaging uses gamma radiation?
nuclear imaging
82
how can gamma radiation be detected in nuclear imaging?
with positron emission tomography (PET)
83
what tracer is used for nuclear imaging?
Technetium-99m
84
why is Technetium-99m used as a tracer for nuclear imaging? (3)
1. it has a **short half-life** -> minimises exposure for the patient
2. **emits low-energy radiation** -> safe for the patient
3. **binds to a range of biologically-active substances** -> versatile
85
magnetic resonance imaging employs the theories of _______ spectroscopy to provide ____ images
NMR, 2D/3D
86
why is MRI preferred over nuclear imaging?
it does not use ionising radiation
87
________ emit high energy radiation that kills off cancer cells
radionuclides
88
how does radiotherapy work?
it uses radionuclides that emit **high energy radiation** that can kill off cancer cells
89
what are radionuclides used for?
1. cancer treatment
2. medical imaging
90
what are 2 common radionuclides used in radiotherapy?
- Lutetium-177
- Yttrium-90
91
why are Lutetium-177 and Yttrium-90 used as radionuclides for radiotherapy?
- they emit beta radiation that destroys cancer cells
- Lut-177 also emits gamma radiation that allows for imaging
92
Cobalt-60 is used for...
external radiotherapy
93
how is Cobalt-60 effective in damaging cancer cells for external radiotherapy?
- fired at site of cancer from external source
- undergoes beta decay
- it emits gamma radiation that can penetrate and damage cancer cells
94
what is Lead-212 is used for?
internal radiotherapy
95
gamma radiation in external radiotherapy is from an _________ source
external
96
internal radiotherapy requires a _________
carrier drug/protein/antibody
97
how does internal radiotherapy work?
a radioactive material is ingested into the body with a carrier drug/protein/antibody to allow for treatment to work
98
name two types of internal radiotherapy
1. targeted alpha therapy (TAT)
2. boron neutron capture therapy (BNCT)
99
what element is involved in targeted alpha therapy (TAT)?
Lead-212
100
how does Lead-212 treat cancer?
it undergoes alpha decay which can kill target cells
101
what treatment would be used for cancers that have metastasised?
- internal radiotherapy
- targeted alpha therapy (TAT) where Lead-212 is used
102
why is TAT used for treating metastasised cancers?
- carrier drug carries radiation source directly to cancer cells
- several sites in the body can be targeted at the same time
103
which therapy uses Boron-10?
- internal therapy
- boron neutron capture treatment
104
which therapy uses Cobalt-60?
external
105
how does boron neutron capture therapy (BNCT) work?
- it employs Boron-10 which 'captures' neutrons which are fired at it from an external source
- forms Boron-11 which undergoes alpha decay
106
how is Boron-10 is administered?
via intravenous injection
107
what is the equation for the decay of Boron-10 in BNCT?
-
108
for treatment of neck/head/brain cancer, what therapy would be used?
boron neutron capture therapy (BNCT)
109
why are alpha particles effective for head cancer therapies?
- they have **high ionising density** -> thus high probability of killing cells at target
- alpha particle radiation is **short range** -> **minimises unwanted irradiation** of normal tissue surrounding targeted cancer cells
110
what are the side effects of radiotherapy? (3)
- fatigue
- nausea
- hair loss
111
why does radiotherapy have side effects?
- radionuclides emit ionising radiation
- this causes formation of reactive radicals and damages DNA
112
why is hair loss a common effect of radiotherapy?
radionuclides damage DNA of hair follicles
113
how can substances be isolated? (2)
1. solvent extraction
2. fractional distillation
114
what is the principle that solvent extraction uses?
it separates compounds based on their preference for water or organic solvent
115
how does solvent extraction work? (5)
- hexane and water are added to a **separating funnel**
- solid mixture is added and shaken vigorously
- compound will separate out based on their hydrophilicity and lipophilicity -
- empty the funnel to obtain desired layer
- let the solvent evaporate -> thus obtaining the desired compound
116
what is the principle that fractional distillation uses?
separates compounds based on their difference in volatilities
117
what is the eqn for mole fraction of A in vapour?
vapour pressure of A / total vapour pressure
118
how does fractional distillation work?
1. components w lower bp evaporate first
2. it rises through the fractionating column where it repeatedly evaporates and condenses
3. vapour enters condenser, is cooled to form a liq and collected
119
what is the equation for vapour pressure
Xa x Pa
Xa= mole fraction of A in mixutre
Pa= vapour pressure of pure A
120
what is the equation for total vapour pressure
Xa x Pa + Pb x Xb
| where P is vapour pressure
and X is mole fraction
121
what is the equation for mole fraction
vapour pressure of benzene /total vapour pressure
122
how are steroids detected?
by using gas chromatography-mass spectrometry (GCMS)
123
how does gas chromatography-mass spectrometry (GCMS) work?
- sample is vaporised
- separated based on boiling points --> more volatile cmpds move faster
- separated based on affinity for stationary and mobile phase --> cmpds w greater affinity for stationary are retained longer
- mass spec then can be compared to known compounds for identification
124
what is the principle of GCMS?
- components are separated by affinity for stationary and mobile phase
- AND b.p.s
125
what are the two ways to detect ethanol?
1. breathalysers
2. intoximeters
126
intoximeters use ______ _____ of which the _______________ generated can be detected
fuel cells, electric current
127
how do breathalysers work?
- they detect ethanol when K2Cr2O7 oxidises ethanol to ethanoic acid
- colour change is detected -> orange to green
128
how do fuel cell breathalysers work?
- at the anode, ethanol in breath is oxidised to ethanoic acid
- electrons pass through external circuit to the cathode
- at the cathode, O2 is reduced to H2O
- current is proportional to alcohol concentration in blood
129
what are the 3 principles of green chemistry you should note?
1. safer solvents and auxillaries
2. atom economy
3. waste prevention
130
why are some solvents unsafe? (3)
- they may be carcinogenic
- highly flammable and explosive
- contaminate the environment
131
what are 2 safe solvents
- water
- ethanol
132
what is an example of a switch to safer solvent?
- synthesis of analgesic Lyrica
- reduces 3 million tonnes of CO2 emissions by switching to water as the main solvent
133
increasing atom economy reduces...
the no. of byproducts in a synthetic route
134
what is an example for increased atom economy?
- synthesis of ibuprofen
- 6 steps reduced to 3
- increased atom economy from 40% to 77%
135
what is waste prevention in green chemistry?
prioritising reducing the amount of waste created instead of cleaning up and treating waste
136
what is an example of improved waste prevention
- production of Viagra
- used a modified reaction route that reduced waste by 75%
137
what are the types of waste?
1. nuclear
2. antibiotic
138
what are the types of nuclear waste?
- high-lvl waste
- low-lvl waste
139
what is high-lvl waste?
waste that gives off large amts of ionising radiation with a long half life
140
what is short-lvl waste?
waste that gives off short amts of ionising radiation w a short half life
141
how can you dispose of high-lvl waste?
- stored under water in cooling ponds for 5-10 yrs
- transferred to dry storage in heavily shielded structure buried underground
142
how can you dispose of low-lvl nuclear waste?
- stored in shielded containers until the radiation drops to a safe level
- disposed in landfills
143
why is antibiotic waste bad?
- if antibiotics are improperly disposed and overprescribed -> this incrs exposure of bacteria to the antibiotic
- hastens genetic mutation of bacteria
- allows bacteria to develop antibiotic resistance
144
how can we prevent antibiotic waste? (4)
- minimised release of antibiotics into the environment
- destruction of activity of the drug before disposal
- consumers must avoid overuse
- consumers must complete the full course of prescribed med
