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Pharmacology for FRCR CO1 > 2.4 Clinical use of systemic therapies > Flashcards

2.4 Clinical use of systemic therapies Flashcards

1
Q

Describe the dose response curve

A

Determines:
- Required dose
- Frequency of dosing
- Therapuetic index

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2
Q

At what stage of drug development is the dosing schedule for a drug established?

A

Phase I trial

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3
Q

What is the Threshold Dose?

A

The lowest dose where an effect occurs

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4
Q

What does the slope of the curve describe?

A

The rate at which injury builds up

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5
Q

What is the Efficacy of the drug?

A

Maximum effect the drug can produce based on the therapeutic goal

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6
Q

What is the Effective Dose?

A

Minimum drug required to acheive maximal effect

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7
Q

What is the ED50?

A

Aka Potency; dose required to produce 50% of the maximum possible response

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8
Q

What des potency depend on?

A

Efficacy
Success of binding at target site

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9
Q

What is the Lethal Dose (LD)?

A

Dose that is lethal 100% of the time

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10
Q

What is LD50?

A

Dose that is letha 50% of the time

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11
Q

What is the Therapeutic Index?

A

LD50/ED50

The higher the Therapeutic index the safer the drug as there is less risk of toxicity/overdose

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12
Q

What is Dose Intensity?

A

Amount of treatment delivered per unit of time, usually

mg/m2/week

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13
Q

Why is dose intensity important in cancer treatment?

A

Dose intensity can improve tumour control by reducing the chance the cancer cells have to recover or develop resistance

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14
Q

How is increased dose density achieved?

A
  • Increase dose
  • Shorten intervals
    or both

Needs to be balanced against toxicity

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15
Q

What dose Dose Dense mean?

A

The interval between treatments is shortened compared to the standard regimen

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16
Q

How is combining treatments useful in treating cancer?

A
  • Make use of different mechanisms - different stages of cell cycle
  • Reduce chance of resistance
  • Diversify toxicity profiles
17
Q

What are the 7 types of regional therapy?

A
  1. HIPEC
  2. Intravesical
  3. Intrapleural
  4. Intralesional
  5. Intra-arterial
  6. Isolated limb infusion/perfusion
  7. Intrathecal
18
Q

What happens during HIPEC?

A
  • Resect tumour
  • Heated chemo 40-48’C infused into abdomen, sits for 2 hours then drained

Peritoneal carcinomatosis
Peritoneal mesothelioma

19
Q

What is an example of intravesical treatment?

A

Mytomicin C infused into bladder after TURBT

20
Q

What are the features of safe practice in giving intrathecal chemotherapy?

A
  • Designated areas - that are regularly used for this
  • Qualified staff
  • Time-out - 2 people should verify and document drug, dose, and route
  • Sterile
  • Formal checking procedure
  • Correct medications for intrathecal use - isotonic, preservative free (should be kept separately and in a designated container)
  • Check patient is ok, check bloods
  • Consent and warn of side effects
  • Patient lies flat 30-60 minutes
21
Q

What is high-dose chemotherapy?

A

Intensive drug treatment to kill cancers cells and overcome resistant. most chemos have a dose dependent effect (bigger dose = more kill) - curative intent

Also destroys bone marrow (myeloablation)

Then followed by bone marrow or stem cell transplant

High toxicity

22
Q

How do systemic therapies interact with other treatment modalities?

A
  1. Surgery
  2. Radiotherapy
  3. Targeted or immunotherapies
  4. Locoregional
  5. Methods to alter pharmacokinetic and dynamic interactions e.g. drug metabolism or TME
23
Q

How is SACT used alongisde surgery?

A
  1. Neoadjuvant - mciromets, better resection, preserve organ
  2. Adjuvant - micromets and recurrence

Challenegs: impaired wound healing, surgery delay due to treatment tox

24
Q

How is SACT used alongside RT?

A
  1. Concurrent - act as radiosensitiesers - enhance the efficacy of radiation by imapiring DNA repair in tumour cells (e.g. cisplatin in cervical and h&n)
  2. Sequential - delivered sequentially to avoid tox

Radiation recall - some sact can cause inflammatory reactions in tissues that have been irradiated previously

May need extra toxicity management

25
Q

How do different types of SACT i.e. chemo, immuno, targeted interact?

A
  1. Synergistic
  2. Sequencing

Toxicity potentially high

26
Q

How are locaoregional therapies used alongside SACT?

A

SACT before or after HIPEC
Transarterial chemoembolisation - intraarterial delivery to HCC

Locoregional therapies could alter systemic drug pharamcokinetics or increase tox

27
Q

How can altering pharmacokinetics and dynamics impact SACT?

A
  1. Other treatments may alter SACT metabolism or TME
    e.g. radiation induced vascular permeability may influence delivery and efficacy of systemic agents

Must consider interactions between SACT and supportive medications

Pharmacology for FRCR CO1 (7 decks)

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