CANCER Flashcards
(34 cards)
tamoxifen - general
- cis isomer: oestrogenic activity
- trans isomer: anti-oestrogenic activity
tamoxifen indication
1) breast cancer
2) pre & post menopausal women
3) useful in chemoprevention of breast cancer at high risk
4) reduce severity of osteoporosis
tamoxifen - MOA
- tumour cell respond to oestrogen -> proliferate & grow
- competitively block endogenous oestrogen binding to oestrogen receptor in target tissue -> prevent binding & dissociate from AF-2 -> partially block translation & transcription
- tamoxifen ER complex enter nucleus -> bind to DNA -> suppress cell division & proliferation protein & signals
tamoxifen - PK - absorption
- oral
- rapidly & extensively absorbed in intestine
- peak time 5 hrs after ingestion
- Css after 3-4 wks up to 16 wks
tamoxifen - PK - distribution
- albumin bound
- Vd 50-60 L/kg
- concentrate in breast, uterus, ovary tissue
tamoxifen - PK - metabolism
1) CYP2D6
- 4-OH-tamoxifen (anticancer) -> by CYP3A4 -> endoxifen
2) CYP3A4 -> N-desmethyl-tamoxifen -> by CYP2D6 -> endoxifen (most active metabolite)
tamoxifen - PK - elimination
shit
tamoxifen - interactions
1) food drug: grapefruit juice
2) DDI: diphenhydramine
tamoxifen SE
1) hot flash
2) increase risk of endometrial cancer
3) DVT
4) menstrual irregularities
5) vaginal bleeding & discharge
6) N/V
tamoxifen tox
- high dose
- neurotox: tremor, hyperreflexia, unsteady gait, dizziness
pembrolizumab - indication
cervical cancer
pembrolizumab - MOA
1) PD-1
- expressed by T cell
- recognise certain ligands (PD-L1, PD-L2)
- PD-1 + PD-L1 -> inhibit T cell activation -> evade immune system
2) PD-1 blocker
- bind to PD-1 -> prevent PD-L1 & PD-L2 from cancer cells from binding -> release PD-1 pathway mediated inhibition of T cell activities
- block cancer metastasis
pembrolizumab - dose
IV 200mg over 30 mins every 3 wks
pembrolizumab - PK
- distribution: small Vd, limited extravascular distribution
- metabolism: nonspecific
- t1/2 27 days, Css after 19 wks
pembrolizumab - SE
1) infusion related SE
2) Fatigue
3) N/D
4) joint pain
5) life-threatening
- immune-related inflammation on lung, endocrine organs, liver, kidney, sepsis
pembrolizumab - CI
1) corticosteroids/immunosuppressant
- stop -> start pembrolizumab -> continue
2) X pregnant (increase miscarriage risk)
3) hypersensitivity to other Ab therapy
45) infection, kidney/liver disease
S&S of prostate cancer
1) difficulty urinating
2) low stream of urine
3) frequent nocturia
4) constant need to pee
5) dark reddish urine
6) weak/swollen lower limb
7) back pain
lab values for prostate cancer
prostate specific antigen
- 10 - 100 range
- normal below 5
how to achieve androgen deprivation
1) inhibit pituitary gonadotropin release
- Leuprorelin
2) inhibit androgen synthesis
- finasteride
3) inhibit androgen binding
- androgen receptor blockers (flutamide)
4) surgical extirpation of glands
- castration, adrenalectomy
pharmaco strategies for prostate cancer - list
1) target upstream pathway/trigger: leuprorelin
2) direct blockage of hormone acting on its receptor: bicalutamide
leuprorelin - general
- GnRH analogue
- GLP-1 agonist
leuprorelin - MOA
- decreased androgen (testosterone) production in testes -> minimise positive effect on androgen-sensitive prostate cancer cell -> cancer cell apoptosis
- continuous administration -> decrease FSH & LH release -> suppress androgen synthesis
leuprorelin - monitoring
- prostate-specific antigen (PSA)
- LH, FSH, serum testosterone after 4 wks of therapy
leuprorelin - PK - absorption
- SC/IM single dose long acting depot
- interval between injection vary depending on dose (1/3/4 month interval)
- Cmax 1-3 hrs
- Css 4 wks
