Cytotoxic drugs and immunotherapy Flashcards
1
Q
what are the side effects associated with cyclophosphamide and ifosfamide
A
Haemorrhagic cystitis due to urinary metabolite acreolein which is prevented by increasing fluid intake for 24-48 hrs after IV injection
mesna is given routinely with Ifosfamide and with high doses of cyclophosphamide e.g over 2g or when pt is considered high risk to prevent haemorrhagic cystitis as well
2
Q
Cyclophosphamide, Ifosdamide, Melphan and Crmustine are all examples of which type of agents
A
alkylating
3
Q
For ifosfamide what are the monitoring requirements
A
GFR and tubular refill rate need to be checked before each cycle
need to endure satisfactory electrolyte balance and renal function before wach course
4
Q
what is melphalan and what is it used for
A
derivative of nitrogen mustard and phelyalanine making it slightly more selective towards rapidly dividing cells
multiple myeloma , carcinoma and advcaned breast cancer
5
Q
what are the side effects of melphalan
A
monitor blood count before and throughout
6
Q
what are the side effects associated with Carmustine
A
Pulmonary toxicity - dose related, cumulative and may be delayed
Hepatoxicity- high IV doses, may be delayed up to 60 days aftre admin, usually reversible
7
Q
what is carmustine and what is it used for
A
a small lipohilic molecule used in CNS tumours and haematological malignancy -myeloma and lymphoma.
hodgskins, leukaemia and brain tumour, intralesional implants for treatment of recurrent glioblastoma and malignant glioma
8
Q
what type of drugs are doxorubicin, epirubicin and daunorubicin
A
antibiotics anthracyclines
9
Q
what are the side effects assocaiated with doxorubicin
A
Cardiomyopathy - higher cumulative doses. limit 450ng/m2
liposomal formulations- reduce cardiotoxicty and local necrosis, however can cause infusion reactions
liposomal can cause hand-foot syndrome
elevelates bilirubin coc
10
Q
what are the monitoring requirements for doxorubicin
A
befrore treatment echocardiogram
cardiac monitoring
11
Q
what are the s/e of epirubicin
A
c aution with cumulative doses exceeding 900mg/m2 dur to risk of congestive heart failure increased
12
Q
what are the side effects of daunorubicin
A
cardiotoxicity is cumulative and may be reverible
13
Q
moa of alkalting agents
A
non specific so act on all rapidly dividing cells
transfer alkyl group to purine bases on DNA - adenine and guanine resulting in cross linking = apoptosis
14
Q
what are the general side effects of alkylating agents
A
anaemia, pancytopenia, amenorrhoea, mucosal damage, alopecia, increased risk of malignancy
15
Q
which enzyme are cyclophosphamide and ifosfamide metabolized by
A
cytochrome P450 enzyme
16
Q
what is chlorambucil
A
an alkylating agent that is a well absorbed nitrogen mustard derivative
17
Q
name the alkylating agents
A
melphalan Cyclophosphamide Ifosfamide Chlorambucil Camustine
18
Q
name the anti-tumour antibiotics
A
anthracyclines- doxorubicin , daunorubicin, epirubicin, idarubicin
mitomycin
dactinomycin
19
Q
moa of dactinomycin
A
binds to DNA and inhibits the synthesis of RNA and proteins
20
Q
s/e of mitomycin
A
myelosuppression esp thrombocytopenia
21
Q
What is the moa of anthracyclines
A
act on signal transduction
generate free radicals
target topoisomerase II leading to strand breaks and cell death
22
Q
what the s/e of anthracyclines
A
myelosuppression
mucosistis
alopecia
cardiotoxicity- due to generate of free radicals in the heart ECHO required before treatment with anthracyclinesand during treatment. Lifetime dose can not be exceeded
23
Q
what is the moa of plant alkaloids amd the two types
A
tubulin interactive agents that act by binding to tubulin (protein that forms cellular microtubules used for cell division- specifically metaphase)
Vinka alkaloids
Taxanes
24
Q
name the vinka alkaloids
A
vinblastine, vincristine, vinorelbine
25
name the taxanes
Docetaxel, paciltaxel, cabazitxel
26
s/e of vinka alkaloids
neurotoxicity, extravasation, myelosuppression
| must not be given intrathecally- cn cause severe neurotoxicty that is fatal
27
s/e of taxanes
Hypersensitivity reactions so may require steroids and antihistamies pre treatment
28
name the antimetabolites and general moa
```
methotrexate
fluorouracil
pemetrexed
cytarabine
gemcitabine
fludarabine
hydroxycarbamide
Structurally related to natural compounds. They interefrer with cell metabolism of nuceli acids necessary for DNA, RNA and protein synthesis. Specifically the S phase.
```
29
moa and s/e of methotrexate
| what is used in addition to MTX for high doses
inhibits folate metabolism thereby inhibiting synethesis of purines and pyramidines required for DNA and RNA synthesis
toxicities: myelosuppression, mucositits, nephrotoxicity
folinic acid given after high dose to promote clearance of MTX and reduce toxicity
30
moa and s/e of fluorouracil
pro-drug which is activiated within the cell. metabolites act by inhibiting the synthesiis of pyradines. short half life with significant renal and lung clearance
s/e hand and foot syndrome, due to prolonged infusion, diarrhoea, neurotoxicity, myelosuppression, stomatitis, cardiotoxity
can be delivered over 1 weeks via infusion pump
31
what are the oa and s/e of capectiabine
orally admin pro drug of fluorouracil activated in the tumour itself and in the liver. It can potentially be usd to replace continous infusion of fluourouracil
dose limiting diarrhoea can result in dose reduction or cessation of tretament
can also result in hand and foot syndrome
32
mos of pemetrexed and how toxicity is reduced
anti-purine whihc acts as an antagonist against enzymes involved in folate dependent pathways whihc results in a decrease of intracellular
toxicity reducd by co-admin of folate supplements and b12
33
cytarabine moa and s/e
cytosine analogue that competes for cytosine for incorporation into DNA nad RNA
Toxicity: vomiting, myelosuppresion, alopecia
due to rapid clearnace- more effective as continued infusion
34
moa and s/e of gemcitabine
cytosine analogue. better cell permeation than cytarabine. Toxicities include myelosuppression, oedema, flu-like symptoms, nephrotoxicity
35
moa and s/e of Fludarabine
adenosine analogue that competes with adenosisne for incorporation into RNA, DNA Before incorporation it is phosphorylated
toxicities include myelosuppression and haemolytic anaemia (abnormal breakdown of rbc)
36
moa and s/e of hydroxycarbamide
reduced availability of nucleotides by inhibiting ribonucleatide reductase
toxicities: myelosuppression, GI toxicity and hypermigmentation of the skin
37
moa of platinum complexes and examples
interfere and disrupt teh structure of teh double helix in DNA. they also form cross links whihc are similar to those of alkylating agents
causes electrolyes imbalance especially low magnesium
cisplatin
carboplatin
oxaliplatin
38
MOA of cisplatin and s/e
bind directly to DNA and forms cross links within strands which Ultimately inhibits DNA synethsis by disrupting the structure
s/e- dose dependenat nephrotoxicity, peripheral neuropathy and ototoxicity. highly emetogenic
initial claerance is fast followed by reduced rate due to plasma binding. renal impairment affects clearncance
39
what is carboplatin analogue of and what are the s/e
cisplatin analogue - therfore forms cross links with DNA altering strands
tocities- thrombocytopenia , nephotoxicity, ototoxicity, neurotoxicity, alopecia and nausea and vomiting
less toxic than cisplatin other than the thrombocytopenia
clearance dependeant on renal function
40
moa and s/e of oxaliplatin
Platinum analogue broader spectrum cross links DNA
dose limiting peripheral neuropathy whihc can reverse with withdrawal of oxaliplatin
also diarrhoea, n/v bone marrow suppression and ototoxicity
41
what is the moa and examples Topoisomerase inhibitors
Enzymes are involved in regulation of the winding of dna
To poison erase 1 cleaved apart double strand of dna. These relaxed strands are used for replication, transcription and recombination
Top 2 cuts both dna strands allowing another strand of dna to pass through stopping them tangles
Top 1- irinotecan and topotecan both block action of top 1 whose activity is usually increased in cancer cells
Top 2 - etoposide and teniposide both inhibit action of top 2 by: preventing the enzyme from regulating cleaved dna, generating large amounts dna with breaks, irreversible double stranded breaks, inconceivable recombination, apoptosis
42
Toxicities of topoismerase 2 inhibitors
Blood pressure changes when infused, neutropenia, alopecia, mucositis, hypersensitivity
Highly protein bound so higher toxicity in those with low albumin
43
Toxicity of top 1
Neutropenia diarrhoea, n/v. Anaemia thrombocytopenia alopecia
44
Which drugs are associated with oral mucositis
Anthracyclines
Fluorouracil
Methotrexate
Radiotherapy to the head or neck
45
How can u prevent oral mucositis
Good oral hygiene
Soft toothbrush
Sucking ice chips during infusion (reduced blood flow to mouth due to vasoconstriction so less blood flows there
Artificial mouth saliva mouth wash and gels
46
what is the treatment for the side effect associated with anti cancer medications: oral mucositis
anti-inflam mouthwash e.g benzydamine
saline mouth wash
palifermin (human keratinocyte growth factor)
pain meds
poor oral hygiene leads to fungal infections and systemic ones
47
what is classified as acute vs what is classified as delayed vs anticipatory nausea and vomiting
acute within 24 hrs of treatment
delayed after 24 hrs of treatment
anticipatory before treatment has started due to anxiety
48
what anti-emetic is used for n and v in chemo
ondansetron
49
which anxiolytic is used for anticipatory n and v
lorazepam
50
how is n and v reduced in treatment
steroid given before treatment e.g dexamethasone
51
name one of the indications of chlopromazine other than schizophrenia
iratractable hiccup
52
when does alopecia usually occur during treatment and what methods can be used to reduce this
within 3 - 6 weeks after the first dose of chemo
reversible hair loss is common
no pharmalogical methods available
cold caps worn during treatment to minimise the concentration of cytotoxic drug reaching hair follicles through vasoconstriction
53
which drugs are associated with ototoxicity and nephrotoxicity
cisplatin and carboplatin
54
which drugs are associated with peripheral neuopathy
vincristine
55
which drugs are associated with pulmonary fibrosis
| b like boobs
bleomycin and busulfan
56
Which drugs are associated with cardiotoxicity
trastuzumab and doxorubicin
57
what drug is associated with haemorrhagic cystitis
Cyclophosphamide
| ifosfmide
58
whihc drugs are associated with myelosuppression
Methotrexate
fluorouracil
mercaptopurine
59
how do monoclonal antibodies work and examples
ipilimumab, nivolumab, pembrolizumab, atezolizumab,
block activity of abnormal proteins made in the cancerous cells
can be used as checkpoint inhibitors so these cells cant bypass the immune response
they can target specific genes
60
what toxicities are assocaited immunotherapy
```
skin
thyroid
Hepatotoxicity
Gastrointestinal
pneumonitis
```
61
which immunotherapy’s cause skin toxicities
how does this present
how is it managed
e.g ipilimumab, nivolumab, pembrolizumab
can cause a rash, pruitis, vitiligo, alopecia, stomatitis, dry skin, photosensitivity
treatment: topical emollieoral antihistamines, topical corticosteroids
if severe systemic steroids
62
which immunotherapy’s cause thyroid toxicities
how does this present
how is it managed
all
TFT baseline before treatment
treat accordingly: levo for hypo and carbimazole, beta blockers or setroids for hyperthyroidism
63
which immunotherapy’s cause hepatic toxicities
how does this present
how is it managed
occurs: ipilinumumab, nivolumab, pembrolizumab
al pt should have billirubicin and serum transaminases should be taken before to test for hepatoxicity
management: witholding therapy. setroids if persistent and if no response to steroids then mycophenolate mofetil
64
what is the most side effect from immunotherapy
diarrhoea
65
how is diarrhoea managed in immunotherapy
non-severe diarrhoea = antidiarrhoea meds, fluids, electrolyte imbalances
severe diarrhoea = treatment cessation and steroids. infliximab can be used for those who dont respond to steroids
66
how is pneumonitis managed and how does it present
URTI, SOB, new cough
managed with steroids, antibiotics if infection
if no repsonse to steroids then infliximab, mycophenolate or cyclophosphamide
67
what can cause hypercalcaemia in oncology
what is the treatemnt
which cancers is it most commonly associated with
common in mutiple myeloma and solid tumours
majority due to production of parathyroid hormone related peptide whihc act on the bone, gi and kidney to increase calcium levels also due to reabsoption of bone to osetoclasts
treatment: rehydration, bisphosphinates e.g palmidronate, zolendronic acid. calcitonin, octreotide
68
what causes tumour lysis syndrome
how does it present
what is the treatment
which cancers is it most commonly associated with
rapid destruction of cancerous cells leading to mass release of cellular contents into blood stream
most commonly lymphomas and leukaemias
Signs: hyperuricaemia, hyperphosphataemia, hyperkalaemia, hypocalceamia, hypomagnesaemia, acute renal failure, metabolic acidosis
prevention: rasburicase for high risk and allopurinol for low/moderate risk
treatment/l raburicase
69
what is raburicase used for
treatment and prevention in high risk pateints for tumour lysis syndrome
70
what causes bone marrow suppression/neutropenic sepsis
how does it present
what is the treatment
which cancers is it most commonly associated with
caused by cytotoxics apasrt vincristine and bleomycin
blood counts required before each treatments
neutropenia is under 0.5 x 10^9/L
Fever in neutropenic pt use immediate broad spec antibiotics
tretment of neutropenia: filgrastim
71
what causes spinal cord compression
how does it present
what is the treatment
which cancers is it most commonly associated with
causes: tumour in the veterbrae, collapse of vertebra or spinal cord tumour
diagnosed through MRI
signs: motor weakness, vertebrae pain, sensory changes, numbness
Treatment:
-pt started on high dose steroids: dexa 8mg BD Oral
or radiotherapy
-or surgery
pts should lie flat whilst investigating
72
what causes supervior vena cava obstruction
how does it present
what is the treatment
which cancers is it most commonly associated with
most common with lung cancer
signs : distended neck and head veins, skin discolouration, headaches, oedema
pt should be sat upright and given oxygen for breathlessness
treatment includes: opioids for pain and high dose steroids for oedema
best treatment is stenting SVC and radiotherapy
73
what causes inappropriate antidiuresis
how does it present
what is the treatment
which cancers is it most commonly associated with
diagnosis based in plasma osmolarity, plasma sodium , urine osmolarity, urinary sodium
treatment: fluid restriction, hypertonic saline, demeclocyline
loop diuretics can correct hypernatraemia but should be used caution
74
name antiprofilitic drugs
azathiopurine
mercaptopurine
myclophenadate
Cyclophosphamide
75
name calciurin inhibitors
ciclosporin
tacrolimus
sirolimus
76
which drugs are only mildly emetogenic
```
fluorouracil
methotrexate
etoposide
vinca alkaloids
abdominal radiotherapy
```
77
name drugs that are moderately emetogenic
taxanes
doxorubicin
Intermediate and low doses of cyclophosphamide
high dose of methotrexate, mitoxanthrone
78
name drugs that are highly emetogenic
cicplatin
high dose cyclophosphamide
dacarbazine
79
what drugs are used for the treatment of multiple sclerosis
interferon beta
glatiramer
fingolimod- taken orally for highly active disease
natalizumab- rapidly evolving severe relapsisng remitting ms
80
What are the methotrexate interactions
NSAIDS- increase the risk of toxicity
penicillins- increases risk of methotrexate toxicity
aspirin (high dose) - increased risk of toxicity
PPI's - decrease clearance of mtx
statins- increase risk of hepatotoxicity
most antibiotics- hepatoxocity
trimethoprim- increased risk of adverse reactions
81
the use of radiotherapy and cyctotoxic antibiotics increases the risk of?
toxicity
82
what colour does anthracyclines colour urine
red
83
what is hand and foot syndrome and which drugs cause it the most and how is it avoided
anthracyclines
antimetabolites; fluorouracil and capacitabine
reddening of hands and foot
reduced bu cooling down- no socks, tight shoes, gloves
84
what type of doxorubicin formulations are more likley to cause hand and foot syndrome but less likley to cause necrosis and cardiotoxicity
liposomal formulations
85
which type of vaccines should be avoided in pts who are recieveing immunotherapy
live vaccines
| oonly under specialist supervision
86
when is ciclosporin contra-indicated
uncontroolled blood glucose or infection or malignancy
| systemic use: atopic dermatitis and psoriasis
87
what electrolyte imbabalnce does ciclosporin cause
hypomagnesia
| hyperkalcaemia
88
how often is folic acid given with methotrexate
once a week
89
when is azathiopurine indicated
IBD, RA, autoimmune disease, suppress transplant rejection
90
what drug interacts with azathiopurine and how do u reduce the dose
reduce dose to 1/4 with allopurinol due to risk of haematologival toxicity
91
what pre screening is required for azathiopurine
TMPT thiopurine methyltransferase
absent then do not give
reduced then under specialist supervision
92
what are the monitoring requirements of azathiopurine
FBC weekly for first 4-8 weeks
| then every 3 months
93
what are the monitoring requirements for ciclosporin
FBC weekly until stable
monthly for 2-3 months then every 3 months
switch to oral if iv is irritant
94
which immunotherapy drugs must be precribed by brand
ciclosporin
azathiopurine
tacrolimus
95
what are the signs of bone marrow suppression
bruising
bleeding
infection
blood disorders
96
why might azathiopurine and myclophenalate be used together
reduce risk of rejection of transplant howver more likely side effects
mycloph is more selective
97
s/e of myclophenadate
| what needs to be measures
hypogammagliobulinemia- reduced antibiotics
bronchiectasis- widened bronchi so infections more likely
skin cancer- avoid sun
measure immunoglobulin levels
watch out for pulmonary fibrosis- SOB, cough
98
what are the contrception requirements for myclophenadate
```
2 pregnancy tests 8-10 days apart
use two forms of contraception before during and 6 weeks after treatment
females for 90 days after admin
females join PPP
found in semen
```
99
what food interacts with mycophenolate
pomelo juice whihc increases exposure
| purple grape juice decreases exposure
100
what need to be monitored whilst on ciclosporin
```
renal and liver
verty nephrotoxic
blood pressure- hypertension discontinue
hyperkalaemia
hypomagnesia
blood lipids before treatment and the month after starting
```
101
s/e of tacrolimus
cardiomyopathy
hyperglycaemia
hyperkalaemia
avoid sunlight
