S13: chemotherapy & anaesthetics

Question 1

Describe growth fraction

Answer 1

Proportion of cells dividing at any given time
Useful indicator of sensitivity to chemotherapeutic agents – more responsive tumours are those with large growth fractions
Repeated cycles are required to eradicate remaining and re-growing cells

Question 2

What is the fractional cell hypothesis?

Answer 2

A given dose kills a constant proportion of a tumour cell population
Repeated doses are required
Frequency and duration of treatment limited by toxicities

Question 3

Describe platinum compounds

Answer 3

Cisplatin

Formation of platinated inter- and intrastrand adducts, leading to inhibition of DNA synthesis

Question 4

Describe antimetabolites

Answer 4

5-fluorouracil inhibits thymidylate synthase

Methotrexate inhibits dihydrofolate reductase

Question 5

Describe vinca alkaloids

Answer 5

Vincristine

Microtubule assembly inhibitor – prevent the formation of the spindles

Question 6

Describe taxanes

Answer 6

Paclitaxel

Microtubule depolymerisation inhibitor

Question 7

List side effects of chemotherapy

Answer 7

Alopecia 
Mucositis 
Nausea/vomiting 
Cardiotoxicity 
Sterility 
Neuropathy

Question 8

List certain chemotoxicities of chemotherapeutic agents

Answer 8

Cisplatin – ototoxicity & nephrotoxicity
Vincristine – peripheral neuropathy
Cyclophosphamide – haemorrhagic cystitis
Methotrexate & 5-FU – myelosuppression

Question 9

List different routes of administration of chemotherapy

Answer 9

IV is most common
PO convenient, dependant on oral bioavailability
SC convenient in community setting
Into a body cavity – bladder & pleural effusion
Intralesional – directly into a cancerous area – consider pH

Question 10

What causes variability in pharmacokinetics of chemotherapeutic agents?

Answer 10

Abnormalities in absorption – N+V, compliance, gut problems
Abnormalities in distribution – weight loss, reduced body fat, ascites
Abnormalities in elimination – liver and renal dysfunction, other meds
Abnormalities in protein binding – lower albumin, other drugs

Question 11

List important drug interactions of some chemotherapeutic agents

Answer 11

Vincristine and itraconazole leads to more neuropathy
Capecitabine (oral 5FU) and warfarin
Methotrexate – caution with prescribing penicillin & NSAIDs

Question 12

List adverse effects of chemotherapy due to effect of treatment on the tumour

Answer 12

1) Acute renal failure – hyperuricaemia caused by rapid tumour lysis leads to precipitation on urate crystals in renal tubules
2) GI perforation at site of tumour
3) Disseminated intravascular coagulopathy

Question 13

Describe the monitoring of chemotherapy during treatment

Answer 13

Response of cancer – radiological imaging, tumour marker blood tests & bone marrow/cytogenetics
Drug levels
Checks for organ damage – creatinine clearance & echocardiogram

Question 14

Describe Guedel’s signs

Answer 14

Stage 1 – analgesia & consciousness
Stage 2 – unconscious, breathing erratic but delirium could occur, leading to an excitement phase
Stage 3 – surgical anaesthesia, with four levels describing increasing depth until breathing weak
Stage 4 – respiratory paralysis and death

Question 15

What is volatile anaesthetic potency?

Answer 15

Described by MAC (minimum alveolar concentration)
[alveolar] at which 50% of subjects fail to move to surgical stimulus
At equilibrium [alveolar] = [spinal cord]
Anatomical substrate for MAC is spinal cord

Question 16

Outline factors affecting induction and recovery

Answer 16

Blood:gas partition (in the blood) – low value, fast induction & recovery
Oil:gas partition (in fat) – determines potency and slow accumulation due to partition into fat

Question 17

What affects MAC?

Answer 17

Age (higher in infants, lower in elderly)
Pregnancy (increased)
Alcoholism (increased)
Other anaesthetics & sedatives (decreased)
Opioids (decreased)

Question 18

Describe GABAa receptors

Answer 18

Critical target for anaesthetics
Potentiate GABAa medicated Cl- conductance to depress CNS activity
Potentiate GABA activity – anxiolysis, sedation, anaesthesia

Question 19

How is intravenous anaesthetic potency described?

Answer 19

Plasma concentration to achieve a specific end point

For induction in mixed anaesthesia – bolus to end point then switch to volatile

Question 20

List examples of local anaesthetics

Answer 20

Lidocaine
Bupivacaine
Ropivacaine
NB: block voltage-gated sodium channels

Question 21

Describe regional anaesthesia

Answer 21

Selectively anaesthetising a part of the body
Often described as a ‘block’ of a nerve and hence the patient remain awake
Uses local anaesthetic/opioid

Question 22

List main anaesthetic side effects

Answer 22

Peri-operative nausea & vomiting
CVS – hypotension
Chest infection

Question 23

Why may a vasoconstricting agent be used in conjunction with a local anaesthetic?

Answer 23

1) decrease peak plasma concentration of local anaesthetic

2) decrease the minimum effective dose, increase the duration of anaesthesia

Question 24

List patient factors to consider in order to calculate an appropriate regime for chemotherapy

Answer 24

BMI
Liver function
Kidney function
Performance status

Question 25

What does a higher MAC suggest?

Answer 25

Higher MAC would suggest the anaesthetic is less potent

More is required to achieve surgical anaesthesia