Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

endo y3s1 > IC10 PK of drugs for endocrine cancers > Flashcards

IC10 PK of drugs for endocrine cancers Flashcards

1
Q

tamoxifen drug type

A

Selective oestrogen receptor modulator

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

tamoxifen MOA

A

Completely blocks endogenous oestrogen binding in target tissue [breast]

  • tamoxifen-ER complex alters oestrogen-responsive gene expression
    (Enters nucleus & bind to DNA)
  • Prevention of cell activation & proliferation
    (Suppressing cell division & proliferation of proteins & signals)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

tamoxifen PK
Absorption

administration, F, peak conc, Css

A
  • PO tablets
  • Rapidly & extensively absorbed in intestines (F = ~100%)
  • Peak time: 5 hours (within range of 3-7 hours)
  • Css reached typically after 3-4 weeks; may be possible up to 16 weeks
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

tamoxifen PK
distribution

plasma protein binding, Vd, concentration in tissues

A

Plasma protein binding > 98%

Vd: 50-60 L/kg (large)

High concentrations of tamoxifen found in breast, uterus, liver, kidney, lung, pancreas & ovary tissue
* Greater selectivity in breast & uterus ⇒ exert anti-estrogenic & anti-cancer effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

tamoxifen PK
metabolism - t1/2

A

5-7 days

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

tamoxifen PK
metabolism - phases

A

1: Hydroxylation, N-oxidation, dealkylation
2: Glucuronidation, sulphation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

tamoxifen PK
metabolism - pathways

A

Major: N-desmethyl tamoxifen by CYP3A4
* t1/2 ~14 days: takes longer time to reach Css

Minor: active metabolites by CYP2D6
* 4-hydroxytamoxifen & 4-hydroxy-N-desmethyltamoxifen (endoxifen)
* Exhibits affinity for oestrogen receptor; greater than tamoxifen
* CYP2D6 can be inhibited by diphenhydramine (impt to replace antihistamine choice)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

tamoxifen PK
metabolism - end product

A

endoxifen ⇒ most active metabolite

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

tamoxifen PK
excretion

Negligible urinary

A

Mainly excreted in faeces (most metabolism in liver)
Negligible urinary excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

tamoxifen clinical uses

A
  1. Breast cancer (early & metastatic)
  2. Both pre- & post-menopausal women ⇒ regulation of oestrogen levels
  3. May be useful in chemoprevention of breast cancer in women @ high risk
  4. Reduces severity of osteoporosis
    * not used for that indication due to availability of agents with better SE profiles
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

tamoxifen toxicity

A

High doses → acute neurotoxicity (tremor, hyperreflexia, unsteady gait, dizziness)
Patients experiencing overdose should be given support treatment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

tamoxifen SE

A
  • Hot flashes → upper body (face, chest & neck) feeling warm
  • ↑ risk of endometrial cancer
  • Venous thromboembolic events (VTE): ie DVT
  • Menstrual irregularities; vaginal bleeding & discharge
  • Nausea, vomiting ⇒ common for anti-cancer drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Pembrolizumab
role of PD1 receptors (normal)

A

Expressed by T cells → can detect cancer cells via cancer Ag expressed on tumour cell surface → T cell activation (immunity against cancer)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Pembrolizumab
role of PD1 receptors (cancer)

A

Engagement with PD-L1 on cancer cell ⇒ inhibits T cell activation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Pembrolizumab MOA

A
  • Prevents PD-L1 expressed on cancer cells to interact with PD-1 ⇒ PD-L1 do not bind to PD-1
  • Hence T cells still can be activated
  • Releases PD-1 pathway-mediated inhibition of T cell activities
  • Inhibits cancer metastasis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Pembrolizumab
Formulation & dosage

A

Humanised Ab (from mouse) ⇒ have high affinity to PD-1 receptors
Recombinant; manufactured from CHO cells

Dose (adults): IV 200mg, every 3 weeks (IV infusion over 30 mins)
may last longer than 8 months → depends on severity of cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Pembrolizumab PK
distribution

Vd

A

Small Vd (~7L; close to circulatory volume)
Limited extravascular distribution ⇒ mostly in plasma, lesser in tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Pembrolizumab PK
Metabolism

A

Clearance from circulation through non-specific catabolism (breakdown to small amino acids by enzymes)

19
Q

Pembrolizumab PK
factors affecting CL

A

Types of cancer
Gender ⇒ lower in females

20
Q

Pembrolizumab SE

A

Infusion-relation: rash & itchiness
* Hypersensitivity to drug & components at site of injection

Fatigue, Joint pain
Diarrhoea, Nausea
(Life threatening) Immune-related inflammation on lung, endocrine organs, liver, kidney, sepsis.

21
Q

Pembrolizumab contraindications

A
  1. Patients taking corticosteroids/ immunosuppressants
    Should stop before starting on pembrolizumab
    May interfere with pembrolizumab
    Can be used AFTER pembrolizumab → for immune-related AE
  2. Pregnant women
    Increases risk of miscarriage
  3. Patients with history of severe reaction (ie: hypersensitivity) to another antibody therapy OR have other illnesses (ie: infection, liver/kidney diseases)
22
Q

leuprorelin drug type

A

Synthetic gonadotropin releasing hormone (GnRH) → agonist at pituitary GnRH receptors

23
Q

leuprorelin MOA

A
  • Constant stimulation of pituitary → reduces FSH & LH release ⇒ suppress androgen release (via negative feedback)
  • Decreased androgen (testosterone) production in testes ⇒ minimises + effect on androgen-sensitive prostate cancer cell
  • Cancer cell will undergo apoptosis
24
Q

leuprorelin monitoring

A
  1. Prostate-specific antigen (PSA) in first few weeks of therapy
    Normal: <5 & Cancer: >10
    Generally shows decrease = effectiveness of treatment
  2. LH, FSH levels & serum testosterone after 4 weeks of therapy
25
Q

leuprorelin PK
absorption - route of administration

A

SC/ IM dosage forms → single-dose long-acting depot
Slow release upon injection

Possible IV infusion

26
Q

leuprorelin PK
absorption - dosing interval

A

vary depending on dose at 1,3 or 4 months interval (depends on preparation)

27
Q

leuprorelin PK
absorption - Cmax & Css

A

Cmax = within 1-3 hours
Css = after 4 weeks

28
Q

leuprorelin PK
distribution

Vd, plasma protein binding

A

Vd ~27L after IV ⇒ can distribute to tissues (prostate)
No data on Vd after SC/ IM

~45% plasma protein binding

29
Q

leuprorelin PK
Metabolism

how it occurs & t1/2

A

Polypeptide degraded proteolytically into inactive peptides
Potentially by peptidases

t1/2 ~ 3hrs
due to Single D-amino acid (D-leucyl) residue

30
Q

leuprorelin PK
excretion

A

<5% via urine

31
Q

leuprorelin SE

P&R, HF, L, H/D/AM, HG, GI

A

Local pain & redness @ injection site (~10% cases)
Hot flushes during first few weeks of treatment
Headaches/dizziness, altered mood
GI disturbances
Hyperglycemia
decreased libido (due to lesser testosterone production)

32
Q

leuprorelin contraindications

A

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

33
Q

Bicalutamide
drug type

A

Androgen receptor antagonist [anti-androgen]

34
Q

Bicalutamide
reason for combination with GnRH agonist

A

(GnRH agonists) Initial stages: Blocks AR → ↑LH secretion → (+) higher serum testosterone levels

Used primarily together with GnRH analogue ⇒ reduce effects of testosterone surge (tumour flare) that occurs with GnRH agonist in treatment of metastatic prostate cancer

35
Q

Bicalutamide MOA

A

Anti-androgen, acts competitively to antagonise androgen receptor

  1. Inhibits nuclear translocation of AR + interaction of AR with promoter at AR response element
    * Inhibition of AR-dependent transcription → impairs cell proliferation ⇒ triggers apoptosis in cancer cells
  2. Androgen deprivation ⇒ decreases progression of prostate cancer
36
Q

Bicalutamide clinical uses

A
  1. Prostate cancer
  2. Androgen deprivation therapy
    used during the initiation of androgen deprivation therapy with a LHRH agonist to reduce the symptoms of tumour flare in patients with metastatic prostate cancer
  3. For locally advanced disease (in conjunction with radiation therapy or surgery ↑ survival)
37
Q

General prostate cancer treatment outline

A

Drug treatment
radiation/ surgical removal of prostate

38
Q

Bicalutamide PK
absorption

route of administration, bioavailability with food

A

PO tablets → absorbed well orally
Bioavailability not affected by food ⇒ can take before/ after food
Taken OD together with GnRH analogue

39
Q

Bicalutamide PK
distribution

A

Highly plasma protein bound

40
Q

Bicalutamide PK
metabolism

(S) & (R); t1/2 of (R)

A

Extensive in liver

(S)-bicalutamide [inactive]: rapidly cleared by glucuronidation
(R)-Bicalutamide [active]: slowly hydroxylation (CYP3A4) ⇒ glucuronidation
* t1/2 = 6 days

41
Q

Bicalutamide PK
excretion

A

Parent drug & metabolite via bile & urine

42
Q

Bicalutamide SE

HF, NVDC, L, F, S

A
  • Hot flushes
  • Nausea/ vomiting, constipation/ diarrhoea
  • ↓ Sexual desire/ ability (decreased libido)
  • Fatigue
  • Mild swelling ankles/ legs/ feet
43
Q

Bicalutamide contraindications

A

Women & children

Patients with known hypersensitivity reaction to bicalutamide OR to any excipients of this product

endo y3s1 (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions