Chemo Flashcards
1
Q
Targets of HIV treatment
A
reverse transcriptase
Protease
2
Q
NRTI
A
zidovudine
didanosine
zalcitabine
3
Q
NNRTI
A
efavirenz
nevirapine
etravirine
delaviridine
4
Q
PI
A
saquinivir
nelfinivir
5
Q
NS3 Inhibitors
A
1- telaprevir, boceprevir
2- simeprevir, voxilaprevir
6
Q
NS5A Inhibitors
A
1- daclatavir, ledipasvir
2- velpatsvir
7
Q
NS5B Inhibitors
A
sofosbuvir
8
Q
Hepatitis C
A
single stranded RNA genome
9
Q
function of NS5B inhibitors
A
inhibit RNA dependent RNA polymerase
–>prevents RNA replication
10
Q
genital herpes
A
HHV1+2
11
Q
herpes zoster
A
HHV3
shingles and chickenpox
12
Q
cidofovir
A
new and treats herpes zoster
selectively inhibits DNA polymerase
–>prevents viral DNA replication and transcription
it is phosphorylated by cellular kinases- toxicity
13
Q
HA receptor
A
it recognises sialic acid on epithelial cells and binds to the cell
cell is internalised in an endosome
14
Q
M2 receptor
A
acts as an ion channel
influx of H+ breaks down the matrix layer
segments go into cytosol
15
Q
antigenic drift
A
virus makes mistakes when copying its genes
16
Q
antigenic shift
A
one cell is infected by 2 viruses so the segments are mixed around
17
Q
targets for influenza antiviral
A
M2- endosome escape
NA- release from the cell
18
Q
M2 channel inhibitors
A
amantadine and rimantadine
19
Q
neuraminidase inhibitors
A
zanamir (relenza)
oseltamivir (tamiflu)
20
Q
ribavirin FDA approved to treat
A
hepatitis C
human respiratory syncytial virus
21
Q
antibiotic
A
natural substance made by a microorganism which prevents/ stops the growth of another
22
Q
antibacterial
A
compounds capable of killing/ inhibiting bacteria
can be synthetic or semi-synthetic
23
Q
disinfectants
A
kill microorganisms but are too toxic to be used in humans
24
Q
mupirocin
A
narrow spectrum
gram +ve bacteria
topical ointment
inhibits iso-leucyl tRNA synthetase
25
linezolid and tedizolid
oxazolidinone
bacteriostatic
bind to 50S subunit of Gram +ve
26
lipophilic tetracyclines
minocycline
| doxycycline
27
hydrophilic tetracycline
tetracycline
28
aminoglycosides treat:
severe sepsis by Enterobacteriaceae
plague and tularaemia
enterococcal endocarditis
combination- anaerobic infections and TB
29
30S and 50S aminoglycosides
tobramycin
| kanamycin
30
chloramphenicol treats
used in the treatment of typhoid and paratyphoid fever
31
adverse effects of tetracycline
GI disturbances
| deposits in calcium- pregnant and young children
32
adverse effects of aminoglycosides
ototoxicity
| nephrotoxicity
33
adverse effects of chloramphenicol
myelosuppression
| Gray syndrome
34
macrolides
erythromycin
| azithromycin
35
what effects erthyromycins availability
it is acid labile
36
targets for drugs for bacterial cell membrane
synthesis of peptidoglycan
| bacterial membranes
37
transglycosylation
disaccharide incorporated into existing glycan strand
38
transpeptidation
stem peptides undergo cross linking to give rigidity in the cell wall
final amino acid is cleaved from the peptide
39
what does clavulanic acid do?
bind more efficiently to beta lactamase and make it inactive so beta-lactam can still work
40
4 types of beta lactam
penicillins
cephalosporins
monobactams
carbapenems
41
applications of vancomycin
gram +ve infections caused by S.aureus and MRSA
can be given orally for diarrhoea as will stay there
given to patients hypersensitive to b-lactam
42
MAO of polymyxin B and E
1- initially through lipopolysaccharide
2- goes through outer membrane into inner membrane
3- destabilisation and affects depolarisation so leakage of proteins
43
adverse effects of vancomycin
red man syndrome due to release of histamines
44
MAO for ribavirin
1- inhibits inosine monophosphate deyhydrogenase- reduces RNA synthesis
2- induces errors/ mutations- can bind to C or U
3- slows down RNA dependent RNA polymerase- longer for immune response
45
linezolid treats
community and hospital acquired pneumonia
| skin and soft tissue infections
46
tedizolid treats
reduced myelosuppression
| increased antibacterial potency
47
what does azithromycin treat?
chlamydia and respiratory tract infections
48
what is benzylpenicillin used to treat?
syphillis by streptococci
49
what is daptomycin used to treat?
complicated skin and soft tissue infections (S.aureus and MRSA)
50
what is tetrahydrofolate important for?
it is an essential precursor to DNA
| -->if blocked, DNA synthesis is prevented
51
target for sulphonamides
competitive inhibitors of dihydropteroate synthase
52
target for trimethoprim
inhibitor of dihydrofolate reductase
53
applications of sulphonamides and trimethoprim
short-term and prophylaxis of respiratory, urinary or digestive tract infections
pneumonia in HIV
together they are cotrimoxazole
54
what is cotrimoxazole
sulphonamide and trimethoprim combined
55
what does topoisomerase 4 do?
creates a transient double stranded break in one chromosome to allow the other to pass through
56
what does gyrase do?
mediates negative supercoiling
57
MAO of quinolones
bind to 5' end of enzymes topoisomerase and gyrase
traps the enzymes on DNA so the enzymes keep breaking up DNA
this blocks DNA replication and transcription
58
MAO of nitroheterolytic drugs
nitro group acts as an electron donor
| oxygen free environments
59
MAO of rifamycin
interferes with RNA polymerase
| occludes the entrance of RNA exit channel, RNA cannot leave the enzyme
60
Applications of rifamycin
Gram positive infections
tuberculosis
leprosy
penicillin resistant S.pneumoniae
61
saprophytism
usually from dead organic material
62
dermatophytes
exploit keratin found in skin, hair and nails
63
risk factors for candidosis
```
gut surgery
antibiotics
central venous catheters
IV drug abuse
immune suppression
prematurity
diabetes
cancer
```
64
30S aminoglycosides
streptomycin and spectinomycin
65
daptomycin
gram +ve
| IV
66
MAO of daptomycin
uses Ca2+ and lipophilic tail to enter membrane
then aggregates
causes depolarisation so contents leak
67
Daptomycin applications
skin and soft tissue infections (S.aureus and MRSA)
68
Polymyxin applications
inhalation therapy for cystic fibrosis
| burns
69
Nitroheterolytic drugs
metrodizaole and tinizaole
| need oxygen free environment
70
what does cryptococcus cause
pulmonary disease
| meningitis
71
what is aspergillis terreus resistant to?
amphotericin B
72
MAO of 5-fluorocytosine
converted to fluorouracil
either: - disrupts translation by incorporated into RNA
or: - inhibit DNA synthesis by inhibiting thymidylate synthetase
73
what does 5-flurocytosine and Amphotericin B treat?
cryptococcal meningitis
74
examples of polyene antifungals
Amphotericin B and nystatin
75
MAO of polyene antifungals
bind to sterols (ergosterol)
| increases cell permeability
76
what is amphotericin B used to treat
empirical treatment in immunocomprised patients
treatment where fungi isn't known
candidosis etc.
IV
77
what is nystatin used to treat?
vaginal and oral candidosis
| it is a topical cream (too toxic for IV)
78
yeast fungi
candida
| cryptococcus
79
mould fungi
Aspergillosis
| mucromycosis
80
dimorphic fungi
histoplasmosis
81
MAO of echinocandins
bind to FKS1P subunit of gluten synthase and inhibit
| -->inhibit the cell wall synthesis
82
spectrum of activity for echinocandins
Aspergillosis and candida
| narrow spectrum
83
examples of echinocandins
caspofungin
anidulafungin
micafungin
84
MAO for terbinafine
inhibits squalene epoxidase
| prevents ergosterol synthesis
85
What is terbinafine used for?
treats dermatophyte infections of skin and nail
| topical/oral/inhalation
86
neuroplasia
another name for cancer
87
metastasis
process of formation of distant secondary products
88
angiogenesis
tumours and cancer cells forming stroma
| including blood and lymphatic vessels
89
palliative chemotherapy
when cancers resistant to all drugs and treatment
| -->offer care- quality of life maintained
90
MAO of methotrexate
competitive inhibitor of dihydrofolate reductase
91
how can methotrexate toxicity be rescued?
leucovorin
92
MAO of 6-mercaptopurine
inhibits purine synthesis
| gets incorporated into DNA and RNA--> non-functional molecules
93
Gemcitabine
analogue of deoxycytidine
| used in the treatment of advanced metastatic pancreatic cancer
94
MAO of cytarabine
chain terminator of DNA synthesis
phosphorylated and incorporated into DNA
inhibits DNA polymerases
95
MAO of antimetabolites
inhibit or interfere with DNA/RNA synthesis
96
MAO of antibiotics
bind to DNA
| disrupt function of DNA
97
MAO dactinomycin
Intercalates into minor groove of DNA- more sensitive to strand breaks and chromosomal rearrangements
binds to DNA and interferes with transcription and replication
resistance due to P-glycoprotein
98
MAO anthrayclines
intercalate into DNA
generates free radicals that break DNA strands
targets cells in S and G2 phases
form cross links with GG making DNA unstable
99
examples of anthracyclines
doxorubicin and daunorubicin
100
```
mechlorethamine
cyclophosphamide
ifosphamide
carmustine
dacarbazine
temzolamide
```
alkylating agents
101
MAO platinum drugs
form intra and inter strand cross links
interfere with DNA replication and transcription
act in G1 and S phases
102
Topoisomerase 1 inhibitors
topotecan- ovarian and lung cancer
| irinotecan- colon and rectal cancer
103
MAO of topoisomerase 1 inhibitors
prevent re-ligation of DN strands
S phase specific
need to be activated in cancer cells
104
Topoisomerase 2 inhibitors
daunorubicin and doxorubicin- break DNA strands that cannot be repaired
Etoposide and teniposide- double strand breaks in DNA
105
Telomerase Inhibitors
Imetelsat- direct enzyme inhibitors
| compete for binding with telomerase RNA
106
Mitosis inhibitors
bind to tubin and inhibit polymerisation into microtubules
| -->induce spindle dysfunction
107
Vinca alkaloids
block mitosis in metaphase by binding to tubular and preventing polymerisation into microtubules
induce spindle dysfunction
108
Taxanes
active in G2/M phase of cell cycle
stabilise microtubules, preventing chromosome segregation
used to treat ovarian and breast cancers
109
what are anthracyclines used for?
breast, lung and leukaemia
| IV
110
telomerase
binds to the end of chromosome and replicates it
integrity of chromosome maintained
active in stem cells
111
examples of vine alkaloid
vincristine and vinblastine
112
examples of taxanes
paclitaxel and docetaxel
113
if resistant to vinka alkaloids
also resistant to dactinomycin
114
hormone responsive
cancer regresses on hormone treatment
115
hormone dependent
cancer regresses when hormone removed
116
tamoxifen
selective oestrogen receptor modulator
competitively inhibits oestrogen receptor
lowers oestrogen levels
used with leucorvorin in premenopausal
117
Flutamide, nilutamide and bicalutimide
non steroidal anti-androgens
| compete for binding with androgen for the androgen receptor
118
iressa and tarceva
inhibit tyrosine kinase
show promise as lung cancer therapy
Japanese 3x more likely to respond to iressa than american
119
BCR-ABL
in CML patients a fusion protein is formed
it has tyrosine kinase activity
only found in CML patients
120
Gleevac
small molecule inhibitor of BCR-ABL
121
MDM2
enzyme that attaches ubiquitin to p53, then directs p53 to proteasome where it gets degraded
122
nutlin
binds to MDM2 and releases p53 and triggers apoptosis
cannot be used clinically
proof of concept
123
nexavar
renal cancer
| inhibits tyrosine kinase- could have wider applications
124
herceptin uses
breast and ovarian cancers that do not express the oestrogen receptor
125
target for herceptin
HER-2- tyrosine kinase
| it is over-expressed in 30% breast cancers
126
development of herceptin
linked with emtansine (toxic tubulin inhibitor)
| delivers second punch to cells
127
bevacizumab uses
given with 5-FU for colorectal cancer
128
MAO of bevacizumab
prevents angiogenesis by binding to vascular endothelial growth factors (VEGF)
129
adverse effects of bevacizumab
hypertension and intestinal bleeding
| effects on vascular system
130
Rituximab target
binds to CD20 on B cells of non-Hodgkin lymphoma
| not other bone marrow cells--> doesn't deplete bone marrow
131
Rituximab uses
therapy for NHL, other lymphomas and leukaemias
| also macular degeneration of the eye
132
adverse effects of rituximab
hypotension, fever, cardiac problems
133
cetuximab
targets EGF receptor- tyrosine kinase activity
| used in colorectal cancers
134
L-asparaginase
depletes supply of asparagine
given in cancers where dependent on exogenous sources
normal cells not affected
therapy in childhood ALL
135
interferon
1- alpha and gamma- epithelial and fibroblast cells
2- gamma- immune system- fight pathogens
promote cell apoptosis and stimulate immune cells to recognise and kill cancer
136
interferon alpha
can be made in bacteria- isn't post-translationally modified
137
resistance
situation where disease causing agents are able to survive and grow in the presence of chemotherapeutic drugs
138
types of acquired antibiotic resistance
1- endogenous- spontaneous mutation which leads to subtle change
2- horizontal- bacteria acquire resistant gene from a bacteria that is already
139
mechanisms for antibacterial resistance
1- altered target site
2- decreased uptake
3-enzymatic inactivation
4- bypass
140
A, C and D beta-lactamases
have a serine which provide nucleophilic attack on the cyclic amide bond- breaking open the beta-lactam ring
141
B beta-lactamase
zinc ions which perform reaction
