Pharmacology

Question 1

When do antimetabolites act in the cell cycle?

Answer 1

S phase - therefore effective in cells with high proliferation

Question 2

What examples of antimetabolites are there?

Answer 2

MTX, purine and pyramiding analogues

Question 3

What enzyme does MTX inhibit?

Answer 3

Dihydropholate reductase

Question 4

What medication can rescue a patient undergoing MTX treatment?

Answer 4

Folic acid

Question 5

What needs monitoring for MTX?

Answer 5

LFT -liver metabolised
UE - Renal excretion
FBC - myelosupression

Question 6

What medication interact with MTX?

Answer 6

It is uses protein bound carriers and therefore interacts with: phenytoin, aspirin etc.

Question 7

What can aid renal excretion of MTX?

Answer 7

IVF and alienation of brine using bicarbonate

Question 8

What effects do 2rd spaces (Ascities, effusions) have on MTX?

Answer 8

Prolonges the t1/2

Question 9

What toxicities are common with MTX?

Answer 9

Myelosupression
Mucocitis
pneumonitis
Hepato and real toxicity

Question 10

What classical side effect occurs in children using MTX?

Answer 10

Demylinating encephalolpathy

Question 11

What enzyme does 5-FU effect?

Answer 11

thymidylate synthase inhibitor therefore stopping pyramiding synthesis

Question 12

5FU cis effected by st past metabolism, what is used to overcomes this? (sorry bodily worded question)

Answer 12

De Gramont - IV delivery via 48 hour pump

Question 13

What prolongs the half life of 5 FU?

Answer 13

Prolongs half life of the 5 FU

Question 14

What marker can cause increased toxicity experienced by patients with 5FU?

Answer 14

Dihydropyrimidine dehydrogenase deficiency

Question 15

What is capecitabine?

Answer 15

Oral 5FU prodrug

Question 16

What SE are typical with capecitabine?

Answer 16

Palmar-planatar syndrome
mucositis
myelosupression
diarrheoa

Question 17

What cardiac SE does capecitabine have?

Answer 17

Coronary artery spasm inducing MI symptoms. Although this isn’t a thromboembolism it does need a AE

Question 18

What is Gemcitabine?

Answer 18

An analogue of cytosine, therefore inhibiting DNA replication.

Question 19

Name some anti-tumour antibiotics?

Answer 19

• Anthracyclines
• Bleomycin
• Mitomycin C

Question 20

What is an AE with bleomycin?

Answer 20

pulmonary toxicity

Question 21

How does Mitomycin C work?

Answer 21

Alkylation resulting in G-G cross linkage

Question 22

What types of microtubule agents are there?

Answer 22

Vinca alkaloids

Taxane

Question 23

what medication inhibits tubule break down?

Answer 23

taxane

Question 24

What medication prevent tuble polymerisation?

Answer 24

Vinca alkaloids

Question 25

How do alkylation agents work?

Answer 25

- Covalently binds G to alkyl group of drug

Question 26

What are examples of alkylating agents?

Answer 26

cyclophosphamide, Ifosphemide

Question 27

What causes hemorrhagic cystitis?

Answer 27

MTX metabolised by liver leading to urinary excretion of toxic metabolite: acrolein

Question 28

How is hemorrhagic cystitis treated?

Answer 28

IVF, MESNA

Question 29

What is a sig AE of Ifosphemide?

Answer 29

Neorotoxicity vivid dreams > drowsy > coma > death

Question 30

how do platinum agents work?

Answer 30

- Cross links with G and A residues

Question 31

What is the difference between carboplatin and cisplatin?

Answer 31

carboplatin has a longer t1/2

Question 32

What is a 3rd gen platinum agent?

Answer 32

aims to ovrecome platinum resistance Oxaliplatin

Question 33

What is an example of TOP 1 inhibitor?

Answer 33

irinotecan, topotecan

Question 34

What is an example of TOP 2 inhibitor?

Answer 34

anthrocylines, etoposide

Question 35

what SE of irinotecan should be aware of? how to tx?

Answer 35

o Acute cholinergic syndrome Tx with atropine

Question 36

What is the philidelphia chromosome?

Answer 36

Translocation between chromosome 9 and 22 with fusion of ABL and BCR gene causing a constitutively active tyrosine kinase

Question 37

What medication stop dimerisation of HER 2?

Answer 37

pertuzumab

Question 38

Are tumour capillaries good?

Answer 38

No, leaky, blind ends. poor delivery of nutrition

Question 39

The tumour microenvironment is naturally resistant to chemo due to... (3)

Answer 39

- ROS drugs are less effective - hypoxic slow proliferation - reduced drug delivery

Question 40

What happens to interstitial pressure in TME?

Answer 40

elevated - poor lymph drainage - plasma protein enter tissue (decrease in oncogenic pressure)

Question 41

What does p-Glycoprotein do?

Answer 41

Multi drug efflux

Question 42

What acronym is used for pharmacokinetics?

Answer 42

Absoprtion Distribution Metabolism Excretion

Question 43

How is volume of distribution calculated?

Answer 43

dose/serum conc.

Question 44

Hoe is t1/2 calculated?

Answer 44

C^0 = concnentration at time 0

Question 45

What is F in pharmacokinetics?

Answer 45

bioavailibilty

Question 46

How is bioavailibilty calculated?

Answer 46

(AUC(po)*Dose(iv)/AUC (iv)*Dose(po))*100

Question 47

What medication effect the descending pathway?

Answer 47

tricyclics SNRI tramdol/ tapentadol

Question 48

What is SRI?

Answer 48

dose of drug required to produces partial or complete response

Question 49

What is the significance of cd34?

Answer 49

marker for WCC progenitors before maturity

Question 50

What medication be stimulate WCC increase?

Answer 50

GCSF and plerixiform

Question 51

What is the chance of a sibling being a HLA match?

Answer 51

1/4

Question 52

Apart from matching, what else needs to be considered when finding a WCC donor?

Answer 52

male age CMV history

Question 53

What medication is used 1st lin in graft-versus host disease?

Answer 53

cyclophosphermide

Question 54

What does a prognostic marker indicate?

Answer 54

something which helps indicate a difference in survival

Question 55

What is a predictive marker?

Answer 55

predicts response to treatment

Question 56

What is a biomarker for increased toxicity in 5-FU therapy?

Answer 56

DPD deficiency

Question 57

Does TAS-102 have the same DPD problems?

Answer 57

No

Question 58

What biomarker indicates Irinotecan toxicity?

Answer 58

UGT1a1 - Glucoronidaiton to SN38 (active metabolite) for bile excretion

Question 59

What does microsatalite instability indicate?

Answer 59

?MMR

Question 60

What is the pathopysiology of sporadic MMR deficiency?

Answer 60

Hypermethylation of MLH1 promotor

Question 61

What features make sporadic MMR more likely?

Answer 61

BRAF | increased age

Question 62

What does Ca are classical involved in lynch syndrome?

Answer 62

CRC | endometrial

Question 63

What is the MOA of tamoxifen?

Answer 63

Selective estrogen receptor agonist

Question 64

What are the symptoms of tamoxifen agonism?

Answer 64

menopause - hot flush, vaginal drones | also tumour responce

Question 65

What are the symptoms of tamoxifen antagonism?

Answer 65

increased VTE Endometrial hyperplasia Increased bone health cholesterol reduction

Question 66

What enzyme forms androsterdiol from cholesterol

Answer 66

- 2-beta hydroyl steroid dehydrogenase

Question 67

What enzyme converts testosterone to oestrogen?

Answer 67

aromatase

Question 68

What is first line therapy for post menopausal women?

Answer 68

Aromatase inhibitor and a CKD4 inhibitor

Question 69

What medication targets mTOR?

Answer 69

Evolimus

Question 70

What is first line in ovarian cancer?

Answer 70

PARP inhibitor and Bevacizumab

Question 71

What SE of VEGF inhibitor?

Answer 71

Same as pre eclampsia! - HTN - Proteinurea - thrombosis

Question 72

How can AUC be calculated (not graphically)?

Answer 72

AUC = (initial dose * bioavailability) / clearance

Question 73

What is the bioavailability of IV drugs?

Answer 73

1 - all of it is "absorbed" into the blood

Question 74

What is a high volume of distribution and what does it indicate?

Answer 74

Body has 42 L of water > 42 = a high Vd and therefore the drug is distributed into the tissue

Question 75

What indications are there for allogenic cell transplantation?

Answer 75

Leukaemia, MDS, marrow failure

Question 76

What indications are there for autologous cell transplantation?

Answer 76

Lymphoma, myeloma, germ cell

Question 77

5FU metabolism by DPD to a waste product can cause what SE?

Answer 77

Hand foot syndrome, cardio toxicity and neurotoxicity

Question 78

What can inhibit the side effect of 5FU metabolite by DPD?

Answer 78

Gimeracil

Question 79

What enzyme metabolises 5 FU and were is its mostly expressed?

Answer 79

OPRT, more in the tumour than normal cells

Question 80

What medication targets OPRT metabolism of 5FU in normal cells?

Answer 80

Oteracil

Question 81

What SE does activated 5FU have in normal cells?

Answer 81

Myelosupression, GI toxicity, Alopecia