Cancer and Pain Flashcards
Name 2 bisphosphonates
- alendronic acid
- discodium pamidronate
- zolendronic acid
Suggest 3 indications for the use of bisphosphonates:
- protection vs. osteoporotic fragility fractures (alendronic acid)
- treatment of severe hypercalcaemia of malignancy after IV rehydration (pamidronate, zolendronic)
- protection vs. pathological fractures, cord compression and need for radiotherapy/surgery in pts with myeloma and breast cancer with bone mets
- 1st line rx for metabolically active Paget’s disease to reduce bone turnover and pain
how do bisphosphonates reduce bone turnover?
- they are readily incorporated into bone, where they accumulate and inhibit the action of osteoclasts
- and promote apoptosis of osteoclasts so less bone is resorbed and bone mass is improved
2 SEs of bisphosphonates:
how is the most common protected against?
- oesophagitis when taken orally and hypophosphatemia
- –> swallow whole 30mins before breakfast with plenty of water, stay upright for 30mins after
- rare: osteonecrosis of jaw (higher risk with IV high doses)
- atypical femoral fracture
2 CIs and a caution in the administration of bisphosphonates?
-CI: SEVERE RENAL IMPAIRMENT (as renally excreted)
-CI: HYPOCALCAEMIA (bisphosphonates bind calcium)
-CI: UPPER GI DISORDERS
Caution: smokers and pts with major dental disease (osteonecrosis risk)
Bisphosphonates bind calcium so absorption is reduced if taken with what?
- calcium salts inc milk
- antacids
- iron salts
Name 2 sex hormone antagonists used for breast cancer, which types of breast cancer are they indicated for?
- tamoxifen, anastrozole, letrozole
- early and locally advanced ER positive breast cancer (as adjuvant post op to reduce recurrence)
- advanced ER-positive breast cancer to slow disease progression (if HER negative)
What is the difference between tamoxifen and anastrozole and letrozole, in what women are they used?
- tamoxifen is a SERM (selective oestrogen receptor modulator) that prevents oestrogen binding to its receptor (and stimulating cell proliferation) Tamoxifen is used in pre-menopausal women.
- anastrozole and letrozole are aromatase inhibitors that interfere with oestrogen synthesis outside the ovary (in muscle and fat), used for post-menopausal women but not for used in women with functioning ovaries
anastrozole and letrozole are aromatase inhibitors that interfere with oestrogen synthesis outside the ovary (in muscle and fat), used for post-menopausal women but not for used in women with functioning ovaries, why?
-they have little effect on ovarian oestrogen synthesis (may even cause it to rise)
NB: anti-oestrogen therapies are only effective if the tumour expresses oestrogen receptors
Name 4 SEs of tamoxifen and aromatase inhibitors e.g. anastrozole and letrozole
(sx of oestrogen depletion)
- vaginal dryness
- hot flushes
- loss of bone density
- tamoxifen increases risk of VTE and endometrial cancer
- GI upset
- headache
- rarely can –> agranulocytosis and liver failure
2 CIs for tamoxifen and aromatase inhibitors e.g. anastrozole and letrozole
- tamoxifen CI: PREGNANCY
- tamoxifen CI: LACTATION
- aromatase inhibitors CI: PRE-MENOPAUSAL WOMEN (unless ovarian function supressed/ablated)
Tamoxifen ____ CYP2C9 enzyme responsible for metabolising ____ so increases the risk of bleeding
The SSRIs fluoxetine and paroxetine ___ hepatic activation of tamoxifen
- inhibits, warfarin
- inhibits
2 Indications for allopurinol
-preventing…..
- preventing recurrent attacks of gout
- preventing uric acid and calcium oxalate renal stones
- preventing hyperuricaemia and tumour lysis syndrome associated with chemo
Allopurinal MOA
- it is a ____ ____ inhibitor
- ____ ____ metabolises ___ (produced from purines) to ____ ___
- so inhibition of it lowers plasma ___ ___ concentrations and reduces ______ of it in the ____ or ____
- xanthine oxidase
- xanthine oxidase metabolises xanthine to uric acid
- lowers plasma uric acid and reduces precipitation of it in the joints and kidneys
3 SEs of allopurinol
- starting can trigger/worsen an acute gout attack (risk reduced if NSAID or colchicine co-prescribed)
- skin rash (can be mild or Steven-Johnson’s or toxic epidermal necrolysis
- allopurinol hypersensitivity syndrome: rare: fever, eosinophiliia, lymphadenopathy and other organ involvement
3 CIs to allopurinol (relate directly to the 3 SEs) and 1 caution
- CI: DURING ACUTE GOUT ATTACK
- CI: RECURRENT SKIN RASH
- CI: SIGNS OF SEVERE HYPERSENSITIVITY
- Caution in severe renal or hepatic impairment
Describe the interaction of allopurinol (a xanthine oxidase inhibitor) with azathioprine and ACE inhibitor and with amoxicillin:
- mercaptopurine the active metabolite of azathioprine is metabolised by xanthine oxidase so use of both increases risk of toxicity
- co-prescription with ACEi or thiazide diuretics increases risk of hypersensitivity reactions
- co-prescription w Amoxicillin increases risk of the rash
when starting allopurinol NSAID/colchicine should also be prescribed for how long for what?
-continue for 1 month+ after serum uric acid levels return to normal to avoid triggering an acute attack
Ondansetron and Granistron are anti-emetics useful in prophylaxis and rx of what? esp. in what context? They are antagnoists of which receptor?
- of N&V esp in context of general anaesthesia and chemotherapy
- 5-HT3-receptor antagonists
NB: unsilenced but effective for hyperemesis gravidarium where benefits > risks
Explain MOA of 5-HT3-R antagonists e.g. ondansetron
- there is a high density of these receptors in the CTZ (senses emetogenic substances in blood)
- 5-HT is a key NT released by gut in response to emetogenic stimuli
- Ondansetron blocks these effects
5-HT3-R antagonists e.g. ondansetron SEs / 1 adverse consequence
- rare but constipation, diarrhoea, headaches are possible
- rarely high doses can cause QT prolongation so avoid in pts with this already and avoid if pt is on other drugs that also have this effect e.g. anti-psychotics, quinine, SSRIs…
Typical starting dose for 5-HT3-R antagonists e.g. ondansetron is ___mg 12-hrly can be oral, IV or?
8-12mg
-also rectal and injectable IM preparations are available
Paracetamol is a weak inhibitor of ____ the enzyme involved in ____ metabolism. This increased pain threshold and decreases _____ E2 (PGE2) conc in thermoreg area of _____ therefore controls fever
- COX (cox-2 selective)
- prostaglandin
- decreases prostaglandin E2
- hypothalamus
paracetamol is cox-2 selective, it is v safe with few SEs, what difference to NSAIDs mean it doesn’t cause peptic ulcers/renal impairment/risk of CVS event?
-lack of cox-1 inhibition
