S13: chemotherapy & anaesthetics Flashcards
Describe growth fraction
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
What is the fractional cell hypothesis?
A given dose kills a constant proportion of a tumour cell population
Repeated doses are required
Frequency and duration of treatment limited by toxicities
Describe platinum compounds
Cisplatin
Formation of platinated inter- and intrastrand adducts, leading to inhibition of DNA synthesis
Describe antimetabolites
5-fluorouracil inhibits thymidylate synthase
Methotrexate inhibits dihydrofolate reductase
Describe vinca alkaloids
Vincristine
Microtubule assembly inhibitor – prevent the formation of the spindles
Describe taxanes
Paclitaxel
Microtubule depolymerisation inhibitor
List side effects of chemotherapy
Alopecia Mucositis Nausea/vomiting Cardiotoxicity Sterility Neuropathy
List certain chemotoxicities of chemotherapeutic agents
Cisplatin – ototoxicity & nephrotoxicity
Vincristine – peripheral neuropathy
Cyclophosphamide – haemorrhagic cystitis
Methotrexate & 5-FU – myelosuppression
List different routes of administration of chemotherapy
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
What causes variability in pharmacokinetics of chemotherapeutic agents?
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
List important drug interactions of some chemotherapeutic agents
Vincristine and itraconazole leads to more neuropathy
Capecitabine (oral 5FU) and warfarin
Methotrexate – caution with prescribing penicillin & NSAIDs
List adverse effects of chemotherapy due to effect of treatment on the tumour
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
Describe the monitoring of chemotherapy during treatment
Response of cancer – radiological imaging, tumour marker blood tests & bone marrow/cytogenetics
Drug levels
Checks for organ damage – creatinine clearance & echocardiogram
Describe Guedel’s signs
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
What is volatile anaesthetic potency?
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
Outline factors affecting induction and recovery
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
What affects MAC?
Age (higher in infants, lower in elderly)
Pregnancy (increased)
Alcoholism (increased)
Other anaesthetics & sedatives (decreased)
Opioids (decreased)
Describe GABAa receptors
Critical target for anaesthetics
Potentiate GABAa medicated Cl- conductance to depress CNS activity
Potentiate GABA activity – anxiolysis, sedation, anaesthesia
How is intravenous anaesthetic potency described?
Plasma concentration to achieve a specific end point
For induction in mixed anaesthesia – bolus to end point then switch to volatile
List examples of local anaesthetics
Lidocaine
Bupivacaine
Ropivacaine
NB: block voltage-gated sodium channels
Describe regional anaesthesia
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
List main anaesthetic side effects
Peri-operative nausea & vomiting
CVS – hypotension
Chest infection
Why may a vasoconstricting agent be used in conjunction with a local anaesthetic?
1) decrease peak plasma concentration of local anaesthetic
2) decrease the minimum effective dose, increase the duration of anaesthesia
List patient factors to consider in order to calculate an appropriate regime for chemotherapy
BMI
Liver function
Kidney function
Performance status
What does a higher MAC suggest?
Higher MAC would suggest the anaesthetic is less potent
More is required to achieve surgical anaesthesia
