Cancer Agents Flashcards
Describe the mode of action of tamoxifen
Competitively block endogenous estrogen receptors in target tissue
Tamoxifen-ER alters estrogen responsive gene expression
Prevents cancer cell proliferation and activation
What are some characteristics of Tamxoifen?
Stereoisomer has estrogenic and anti-estrogenic activity
- Cis isomer: estrogenic
- Trans isomer: anti-estrogenic
Tissue specific effect
How is Tamoxifen absorbed?
Orally; rapid and extensive in the intestines
What is the distribution of Tamoxifen like? Why so?
Plasma protein binding is high. High concentrations of tamoxifen are found to be concentrated in breast, uterus, liver, kidney, lung and pancreas
How is Tamoxifen metabolized?
Phase I: Hydroxylation, N-oxidation and dealkylation
Phase II: Glucuronidation and sulfation
What is the major metabolic pathway of Tamoxifen? What is formed?
N-demethylation which is catalyzed by CYP3A4 forms N-desmethyl-tamoxifen
Upon metabolism, what is the active form of tamoxifen?
Endoxifen
What is the minor metabolic pathway of Tamoxifen and what is formed?
Hydroxylation by CYP2D6 forms 4-OH-tamoxifen
What are the CYP enzymes involved in metabolism of tamoxifen?
CYP2D6 and CYP3A4
How is Tamoxifen eliminated?
Faeces
What are some DDI to watch out for the metabolism of tamoxifen?
CYP2D6: Grapefruit juice
CYP3A4: Diphenhydramine
List the clinical use of tamoxifen
Breast cancer: early and metastatic
Pre and postmenopausal women
Chemoprevention for breast cancer for those with high risk
Breast cancer + osteoporosis
Name some of the minor adverse effects of Tamoxifen.
Hot flashes
Menstrual irregularities
Vaginal bleeding and discharge
N/V
Name the major adverse effects of Tamoxifen
Endometrial cancer
VTE
Acute neurotoxicity
Describe the mode of action of pembrolizumab
Binding to PD-L1 on cancer cells allow the release of PD-1 pathway mediated inhibition of T cell activities. Thus, allow T cell activation and killing of cancer cells to occur.
How is pembrolizumab absorbed?
IV administration
How is pembrolizumab’s distribution?
Limited extravascular distribution as limited binding to plasma protein
How is pembrolizumab metabolized?
Metabolized by non-specific catabolism where larger molecules are broken down to smaller ones
What are the factors that can affect pembrolizumab clearance?
Albumin
Bilirubin level
Type of cancer
Gender: lesser in females
List the adverse drug reactions associated with pembrolizumab
Infusion related side effects such as rash or itchiness
Fatigue
Diarrhea
Nausea
Joint pain
Immune related inflammation on lungs, endocrine, liver and kidney
Which groups of patient are contraindicated in the use of pembrolizumab?
Those on corticosteroids and immunosuppressants
Pregnant women
Patient with history of severe reaction to another antibody therapy or other illnesses
Describe the mode of action of leuprorelin
Acts as GLP-1 agonist by mimicking GnRH
Decreases androgen production in testes
Minimal positive effect on androgen sensitive prostate cancer cells
Cancer cells undergo apoptosis
What are the monitoring parameters for those on leuprorelin? How frequent should they be monitored?
PSA
FSH and LH
Testosterone levels
After 4 weeks of therapy
How is leuprorelin absorbed? How frequent is it dosed?
SC/IM
At 1, 3 and 4 months interval
How is leuprorelin metabolized?
Proteolytically by peptidases into inactive peptides
How is leuprorelin excreted?
Small proportion of 5% by urine
What are some of the adverse side effects of leuprorelin?
Local pain at injection site
Flushes
Headache
GI disturbances
Altered mood
Hyperglycemia
Hyperlipidemia
Loss of libido
Which group of patients are contraindicated in the use of leuprorelin?
Hypersensitivity to GnRH agonist
Preexisting heart disease
Patient with risk of osteoporosis
Why is Bicalutamide prohibited from use as monotherapy?
Bicalutamide act as androgen receptor inhibitor
Blocking it will cause LH to increase due to the shift in equilibrium and hence, cause an increase in testosterone
Not ideal for prostate cancer
What is the mode of action of bicalutamide?
Act competitively to antagonize androgen receptors
Inhibit the nuclear translocation of androgen receptor with promoter at AR response element
Impairs cell proliferation and triggers apoptosis
Decreases prostate size as lesser amount of testosterone
How should it be used?
With GnRH analogue (leuprorelin) to alleviate testosterone surge
Name the clinical indications of bicalutamide
Prostate cancer
Androgen deprivation therapy
Locally advanced disease
How is bicalutamide absorbed?
Orally
How is the distribution of bicalutamide like?
Highly plasma protein bound
How is bicalutamide metabolized?
Via the liver
Which stereoisomer (R or S) is the active form of Bicalutamide? How is it formed?
R-Bicalutamide
Formed when bicalutamide undergoes hydroxylation then glucuronidation
How is bicalutamide eliminated?
Bile and urine
Name the adverse effects associated with bicalutamide
Gynecomastia
Sexual dysfunction
Fatigue
GI disturbance
RARE; Seizures
