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PR3152 (cleefy) > PR3152 IC10 > Flashcards

PR3152 IC10 Flashcards

1
Q

what is the mechanism of action of tamoxifen

A

SERM = selective estrogen receptor modulator

it prevents binding of endogenous estrogen to the estrogen receptor by forming tamoxifen-ER complex = alter gene expression = prevent cell activation and proliferation

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2
Q

isomerism of tamoxifen?

A

it exists as cis trans stereoisomer
cis isomer = estrogenic activity
trans isomer = anti-estrogenic activity

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3
Q

absorption of tamoxifen

BA, peak, Css

A

oral
~100% bioavailability
peak 5hours
takes 3-4 weeks for Css (up to 16 weeks)

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3
Q

distribution of tamoxifen

percentage binding, Vd

A

> 98% plasma protein binding
high Vd 50-60L/kg
multi organ involvement
concentrates at the uterus and breast (10fold)

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3
Q

metabolism of tamoxifen

CL, t1/2, enzymes

A

CL 1.4ml/min/kg
t1/2 5-7 days
phase 1: hydroxylation, n-oxidation, dealkylation
phase 2: glucoronidation, sulphation
major pathway = n-demethylation primarily by CYP3A4 = N-desmethyltamoxifen

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4
Q

half life of N-demethyltamoxifen

A

14 days

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4
Q

what is the other metabolism route for tamoxifen (NAME the CYP)

A

cyp2D6
4-oh-tamoxifen and 4-oh-desmethyltamoxifen
minor metabolites
exhibit strong affinity to the estrogen receptors

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5
Q

specific counselling points for tamoxifen (food/drug)

A

GRAPEFRUIT JUICE : 3A4 INHIBITOR
SSRI, antidepressants: 2D6 inhibitor

diphenhydramine is a 2c6 inhibitor

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5
Q

clinical uses of tamoxifen

A

breast cancer (early and metastatic)
both pre and post menopausal women
may be useful in chemoprevention of breast cancer in high risk women
side benefit of reducing osteoporosis risk

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6
Q

side effects of tamoxifen

A

Lower estrogen = hot flashes similar to menopause:
* Hot flashes

Acting on the estrogen receptor in the uterus, similar to COCs:
* ↑ risk of endometrial cancer
* Venous thromboembolic events (DVT)
* Menstrual irregularities
* Vaginal bleeding and discharge

Others:
* Nausea, vomiting

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7
Q

toxicity of tamoxifen?

A
  • High doses could lead to acute neurotoxicity (tremor, hyperreflexia, unsteady gait, dizziness.
  • Patients experiencing an overdose should be given support treatment; no specific treatment for overdose is suggested.
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8
Q

excretion of tamoxifen

A

mainly fecal
negligible urine excretion (<1%)

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9
Q

mechanism of action of pembrolizumab

A

bind to PD1 receptor on T cells to prevent activation of PD1 pathway mediated inhibition of T cell activities

  • prevents binding of PDL1 expressed by tumor cells to evade immune respnose from T-cells

inhibits cancer metastasis (for cervical cancer)

PD1 receptor BLOCKERS

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10
Q

what is the ADME of prembrolizumab?

t1/2
css

vd

A

A: nil
D: poor Vd (~7), low extravascular circulation
M: by non specific catabolism
t1/2 = ~27 days, Css after 19 weeks
E: unknown

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11
Q

what is the dosing instructions for pembrolizumab?

A

200mg IV over 30 min x every 3 week

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12
Q

factors influencing clearance of pembrolizumab

A

gender (female lower CL)
type of cancer

13
Q

side effects of pembrolizumab

A
  • Infusion-relation S/Es such as
    Rash, itchiness
  • Fatigue
  • Diarrhoea
  • Nausea
  • Joint pain
  • (Life threatening) Immune-related inflammation on lung, endocrine organs, liver, kidney, sepsis.
14
Q

contraindications of pembrolizumab

A

X corticosteroids
X pregnancy (increase miscarriage risk)
X history of severe reaction to another antibody therapy
X illnesses e.g., infection, liver/kidney disease etc.

15
Q

mechanism of action of leuprorelin

A

GnRH analogue = agonist at the pituitary GnRH receptors = continuous administration = inhibit LH and FSH = suppress androgen production at testes = inhibits stimulatory effect on prostate cancer cells = apoptosis

16
Q

monitoring after leuprorelin administration

A

1) prostate specific antigen in the first few weeks
2) LH, FSH, serum testosterone after 4 weeks .

17
Q

absorption of leuprorelin

PEAK CSS

A

SC IM dosing interval 1,3,4 weeks depending on the dose

peak = 1-3hours
Css = ~4 weeks

18
Q

distribution of leuprorelin

vd
ppm

A

Vd for IV = 27L/kg
not known for IM SC
plasma protein binding ~45% in vitro

18
Q

metabolism of leuprorelin

t1/2

A

by proteolysis
t1/2 = 3 hours due to a single D isomer of leucyl residue that increases t1/2 from 3-4 min

not metabolised by liver cyp450

18
Q

excretion of leuprorelin

A

<5% excreted via urine

19
Q

side effects of leuprorelin

A
  • Local pain & redness @ injection site (~10% cases)
  • Hot flushes during first few weeks of Tx
  • Headaches/dizziness
  • GI disturbances
  • Altered mood
  • Hyperglycemia
  • decreased libido
20
Q

contraindications of leuprorelin

A
  • Hypersensitivities to Leuprorelin or other GnRH agonists
  • Pre-existing heart disease
  • Patients with risks for osteoporosis
21
Q

moa of bicalutamide

A

Anti-androgen
Acts competitively to antagonize androgen receptor

Inhibits nuclear translocation of the AR and interaction of the AR with the promoter at the AR response element.

The inhibition of AR-dependent transcription impairs cell proliferation and triggers apoptosis in cancer cells.

Used in conjunction with GnRH agonists at initiation to reduce effects of serum testosterone surge (tumour flare)

Prostate growth req androgens, so androgen dep ↓ prog of prostate cancer

22
Q

clinical use of bicalutamide

A

Prostate cancer

For locally advanced disease (in conjunction with radiation therapy or surgery = ↑survival)

23
Q

absorption of bicalutamide

A

well absorbed orally
oral dose once daily with GnRH agonist

24
Q

distribution of bicalutamide

protein binding

A

highly plasma protein bound (racemic 96%; (R)-bicalutamide >99%)

25
Q

metabolism of bicalutamide

t1/2

A

extensively metabolized in Liver

Racemic; Stereoselective

(S)-bicalutamide [inactive]: rapidly cleared by glucuronidation

(R)-Bicalutamide [active]: slow hydroxylation (CYP 3A4) = glucuronidation

t1/2 6 hours for R-bicalutamide

26
Q

elimination of bicalutamide

A

parent drug & metabolites via bile and urine

27
Q

side effects of bicalutamide

A
  • Hot flushes
  • N/V/D
  • ↓libido
  • Fatigue
  • Constipation
  • Mild swelling ankles/legs/feet
28
Q

contraindications of bicalutamide

A

women and children

known hypersensitivity to bicalutamide or any excipients

PR3152 (cleefy) (13 decks)

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