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Semester 4 - Clinical Pharmacology And Therapeutics > Chemotherapy > Flashcards

Chemotherapy Flashcards

1
Q

How do they discover chemotherapy?

A

Chance
Screening of compounds
Chemical engineering
Experiments

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2
Q

How do you know when to give chemotherapy?

A

The fractional cell kill hypothesis which states that a defined chemotherapy concentration, applied for a defined time period, will kill a constant fraction of the cells in a population, independent of the absolute number of cells.
So, you give it when bone marrow has increased but cancer cells haven’t re-grown by as much.

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3
Q

What tumours are highly sensitive to chemotherapy?

A 
Lymphomas
Germ cell tumours
Small cell lung
Neuroblastoma
Wilm's tumour
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4
Q

What cancers are moderately sensitive to chemotherapy?

A 
Breast
Colorectal
Bladder
Ovary
Cervix
Lung
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5
Q

What cancers have a low sensitive to chemotherapy?

A

Prostate
Renal cell
Brain tumour
Endometrial

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6
Q

How can different chemo therapies work?

A

Antimetabolites (on DNA synthesis)

Alkylation agents (on DNA)

Intercalating agents (on DNA transcription and duplication

Spindle poisons (on mitosis)

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7
Q

How do alkalating agents work?

A

Damage DNA to prevent replication

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8
Q

How are platinum compounds formed?

A

They are formed from platinated inter and intrastrand adducts leading to inhibition of DNA synthesis.

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9
Q

MOA of methotrexate or 5-fluorouracil (anti-metabolites)

A

They both interfere with the folate cycle

Inhibit Thymidylate Synthase - 5FU

Inhibit dihydrofolate reductive to prevent tetrahydrofolate formation - methotrexate

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10
Q

Describe the MOA of spindle poisons

A

Once chromosome are aligned at metaphase, spindle microtubules depolymerise, moving sister chromatids towards opposite poles.

The nuclear membrane then re-forms and the cytoplasm divides.

Spindle poisons disrupt this.

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11
Q

How do microtubule binding agents work?

A

Micro-tubule binding agents affect microtubules by:

  • Inhibiting polymerisation
  • Stimulating polymerisation and preventing depolymerisation
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12
Q

Describe, on a cellular level, the MOA of specific spindle poisons

A

Taxoids - promote spindle microtubule assembly and prevent disassembly.

Vinca alkaloids - Prevent spindle formation

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13
Q

How do alkylation agents become resistant?

A
  1. Decreased entry or increased exit of agent
  2. Inactivation of agent in cel
  3. Enhanced repair of DNA lesions produced by alkylation
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14
Q

What are the clinical indications of chemotherapy?

A

Cancer!
But, aim is different in different malignancies.

Performance score (how active)
Clinical stage
Prognostic factors or score
Molecular or cytogenetic markers

Basically, look at side effects vs the anticipated or best outcome.

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15
Q

How do you normally give chemotherapy?

A

IV - most common - bolus, infusional bag, continuous pump infusion. (PICC or Hickman line)

PO - convenient but depends on oral bioavailability

SC - convenient in a community setting

Into a body cavity - Bladder, pleural effusion

Intralesional - directly to cancerous area - consider pH

Intrathecal - into CSF - by lumbar puncture or omaya reservoir

Topical - onto the skin

IM - rarely

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16
Q

What are the common side effects of chemotherapy?

A 
Alopecia 
Mucositis 
Pulmonary fibrosis
Nausea / vomiting 
Diarrhoea 
Cardiotoxicity 
Local reaction 
Cystitis
Sterility 
Renal failure 
Myalgia 
Myelosuppession 
Phlebitis 
Neuropathy
17
Q

What effects of chemo can occur as a result of tumour dying?

A

Acute renal failure - hyperuricaemia caused by rapid tumour lysis leads to precipitation of urate crystals in renal tubules

GI perforation at site of tumour - reported in lymphoma

Disseminated Intravascular Coagulopathy - occurs in AML

18
Q

Describe the vomiting that occurs as a result of chemotherapy

A

Multifactoral but includes direct action of chemotherapy drugs on the CTZ.

Patterns of emesis:
Acute phase - 4-12hours
Delayed onset - 2-5days later
Chronic phase - may persist, up to 14 days.

19
Q

Describe how alopecia occurs as a result of chemotherapy

A

Hair thins at 2-3 weeks
May be total
May re-grow during therapy
Marked with doxorubicin, vinca alkaloids, cyclophosphamide
Minimal with platinums
Help sometimes with scalp cooling (could just become patchy)

20
Q

Describe skin toxicity occurring with chemotherapy

A

Local:

  • irritation and thrombophlebitis of veins
  • Extravasaion

General:

  • Bleomycin; hyperkeratosis, hyperpigmentation, ulcerated pressure sores
  • Busulphan, doxorubicin, cyclophosphamide, actinomycin D - Hyperpigmentation.
21
Q

Describe mucositis occurring with chemotherapy

A

GI tract epithelial damage
May be profound and involve the whole tract
Most commonly worse in oropharynx

Presents as:
Sore mouth / throat
Diarrhoea
GI bleeding

22
Q

Describe cardio toxicity occurring with chemotherapy

A

Cardio-myopathy - worse with doxorubicin and high dose cyclophosphamide. Mortality is approximately 50%.

Arrhythmias:
Cyclophosphamide
Etoposide

23
Q

Describe lung toxicity occurring with chemotherapy

A

Bleomycin - pulmonary fibrosis

Mitomycin C, cyclophosphamide, melphalan, chlorambucil - pulmonary fibrosis

24
Q

Describe haematological toxicity occurring with chemotherapy

A

Most frequent dose limiting toxicity

Most frequent cause of death from toxicity

Different agents cause variable effects on degree and lineages:

  • Neutrophils (neutropenia)
  • Platelets
25
Q

The dose of chemotherapy needs to be altered depends on the individual patient, what is the dose based on?

A

SA and/ or BMI

Drug handling ability (liver function, renal function)

General wellbeing (performance status and comorbidity)

26
Q

What are some important DDIs with chemotherapy?

A

Drugs may increase plasma levels of the chemotherapy drugs:

Vincristine and itraconazome leads to more neuropathy

Capecitabine (aral 5FU0 and warfarin

Methotrexate - penecillin and NSAIDs

Capecitabine and St Johns Wart, Grapefruit juice

27
Q

How do you monitor chemotherapy during treatment?

A

Response of cancer

  • Radiological imaging
  • Tumour marker blood tests
  • Bone marrow / cytogenetics

Drug levels
-E.g. methotrexate drug assays taken on serial days to ensure clearance from the blood after folinic acid rescue

Check for organ damage

  • Creatinine clearance
  • Echocardiogram
28
Q

How do drugs drugs get from bench to bedside?

A
  1. Chemical engineering
  2. Pre-clinical studies e.g. animals
  3. Clinical trials program (phase I,II,III)
  4. Licensed by FDA
  5. Clinics and Nice
29
Q

What things need to be taken into account when deciding the treatment phasing?

A

Growth fraction
The ‘cell kill’ of each cycle of the chemotherapy regiment
Marrow and GI recovery before next cycle
How tolerable it is.

30
Q

What causes variability in the amount of drug that ends up in the blood?

A

Abnormalities in absorption - N&V, compliance, gut problems

Abnormalities in distribution - weight loss, reduced body fat, ascites

Abnormalities in elimination - liver & renal dysfunction, other meds

Abnormalities in protein binding - low albumin, other drugs

Semester 4 - Clinical Pharmacology And Therapeutics (26 decks)

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