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Oncology > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

Biochemical classification

A 
Alkylating agents 
Topoisomerase inhibitors 
Targeted therapies 
Antimetabolites 
Anti-microtubules
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2
Q

MOA

A

Preferentially kill proliferating cells

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3
Q

Non-phase specific agents

A 
Exert cytotoxic effect throughout cell cycle 
Cell kill proportional to dose 
Alkylating agents
Anthracycline antibiotics 
Antitumor antibiotics 
Nitrosoureas
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4
Q

Nitrogen mustards

A 
Cyclophosphamide
Ifosfamide
Bendamustine 
Chlorambucil 
Melphalan 
Mechlorethamine
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5
Q

Platinum analogues

A

Carboplatin
Cisplatin
Oxaliplatin

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6
Q

Alkylating agents MOA

A

Formation of positively charged carbonium ion which binds to electron-rich nucleophilic sites
Cytotoxic effects from:
- inhibition of DNA replication and transcription
- mispairing of DNA
- strand breakage

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7
Q

Alkylating agents toxicity

A

Myelosuppression*
- nadir at 6-10d, recovery in 14-21d (except nitrosourea)
Mucositis
CINV
Neurotoxicity
Alopecia
Long term (4y): pulmonary fibrosis, infertility, secondary leukemia

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8
Q

Cyclophosphamide

A

Must be activated in the liver to active metabolite
Indications:
- lymphomas and breast cancer (low doses)
- bone marrow transplants (high dose)

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9
Q

Cyclophosphamide toxicities

A 
CINV (dose-related)
SIADH 
Hemorrhagic cystitis (high doses/long term) 
Myelosuppression
Cardiac dysfunction in high dose
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10
Q

Ifosfamide

A

Analogue of cyclophosphamide activated by CYP3A4

MOA through DNA crosslinks at guanine N-7 positions

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11
Q

Ifosfamide indications and administration

A

Testicular cancer VIP regimen
Diffuse large B-cell lymphoma RICE regimen
Must be administered with MESNA
Vigorous hydration with 1.5-2L of NS pre and post hydration; increase fluid intake

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12
Q

Ifosfamide toxicities

A

CINV
CNS Toxicity
Nephrotoxicity
Dose limiting haemorrhagic cystitis

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13
Q

Ifosfamide neurotoxicity

A 
From accumulation of chloroacetaldehyde 
Presentation: 
- hallucinations 
- confusion 
- somnolence
Symptoms begin 2-5d after start of ifosfamide
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14
Q

Ifosfamide neurotoxicity prevention/management

A 
Caution in elderly patients, renal dysfunction 
Increase infusion time 
Avoid concurrent CNS active drugs 
Decrease dose/discontinue with onset 
Methylene blue antidote
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15
Q

Cisplatin

A

Indicated for solid tumours
CI in renal impairment (SCr < 1.5mg/dL)
Vigorous hydration required
Must be given with antiemetic

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16
Q

Cisplatin toxicity

A 
Dose limiting acute and delayed CINV
- Must always be given with antiemetics
Ototoxicity (high peak doses)
Peripheral neuropathy
- Limit cumulative doses 
- Decrease dose or discontinue treatment 
- Substitute with carboplatin 
Irritant to veins
Nephrotoxicity
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17
Q

Cisplatin induced nephrotoxicity prevention strategies

A 
Hydration w at least 1-2L 0.9% NaCl IV pre and concurrent, with K and Mg supplementation 
Maintain urine output 100mL 
Provide mannitol/furosemide
Prolong infusion time (24h)
Amifostin
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18
Q

Carboplatin

A

Indicated for solid tumours
Dose = AUC x (GFR + 25)
- AUC = 2 for weekly; 5/6 for every 3 weekly

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19
Q

Carboplatin toxicities

A

Dose limiting myelosuppression (thrombocytopenia)
Hypersensitivity after 6-7 doses
Lower incidences of nephro and ototoxicity, CINV

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20
Q

Oxaliplatin

A

Indicated for colorectal cancer

Stable only in D5W

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21
Q

Oxaliplatin toxicity

A

Cumulative peripheral neuropathy from injury to small sensory fibres
- Acute occurs in first 2 days, reversible and exacerbated by cold surfaces
- Persistent (paresthesia) lasts > 14d, may improve upon discontinuation
Myelosuppression
Nephrotoxicity
Hypersensitivity

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22
Q

Irinotecan

A

Inhibition of topoisomerase I

Cell cycle phase specific (S phase)

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23
Q

Irinotecan toxicities and management

A

Dose limiting diarrhoea
- Loperamide 4mg at earliest sign, followed by 2mg PO q2h until diarrhea free for 12h
Cholinergic syndrome
- premedicate w IV/SC Atropine 0.25-1mg)
UGT1A1 deficiency - reduction in starting dose

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24
Q

Etoposide

A

Inhibition of topoisomerase II
Indicated for solid tumours
IV infusion at least 1h to avoid hypotension, <0.4mg/mL, non-PVC tubing
PO dose twice of IV

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25
Q

Etoposide toxicities

A

Dose limiting myelosuppression

Hypotension if infusion too quick

26
Q

Anthracyclines

A 
Doxorubicin
Daunorubicin 
Epirubicin
Idarubicin 
Liposomal doxorubicin 
Mitoxantrone
27
Q

Anthracyclines MOA

A

Inhibition of topoisomerase II
Intercalations between base pairs
Metabolised in liver to form oxygen free radicals

28
Q

Anthracyclines toxicity

A 
Dose limiting myelosuppression 
Cardiotoxicity
Alopecia 
Acute NV
Vesicant 
Red discolouration of urine
29
Q

Anthracyclines cardiotoxicity

A

Acute (24h): Arrhythmias, pericarditis
Subacute (weeks to months): tachycardia
Late (>5y): cardiomyopathy

30
Q

Anthracyclines cardiotoxicity risk factors

A 
Cumulative doses
Administrative schedule 
Age
Mediastinal radiation 
Known cardiac disease
31
Q

Anthracycline-induced cardiotoxicity prevention

A 
Baseline MUGA for LVEF
Limit cumulative dose 
Less cardiotoxic anthracycline/analogue 
- liposomal doxorubicin 
- mitoxantrone 
Use dexrazoxane
32
Q

Antimetabolites mechanism of action

A

Compete for binding sites on enzyme
- antifolate (mtx)
Incorporate directly into DNA or RNA

33
Q

Methotrexate

A

Indicated for all cancers, GVHD, rheumatoid diseases

34
Q

MTX toxicities

A 
Dose limiting myelosuppression
CNS toxicity 
Mucositis
Pulmonary pneumonitis
Hepatits
Nephrotoxicity 
Diarrhoea
35
Q

5-Fluorouracil

A

Pyrimidine analogue – acts as an antagonist

Available as injection

36
Q

5-FU Toxicities

A

Myelosuppression with bolus administration
Hand-foot syndrome (PPE) and diarrhoea with continuous infusion
Skin discoloration
Nail changes
Photosensitivity
Neurologic toxicity
Vasospastic angina

37
Q

Capecitabine

A

Pyrimidine analogue selectively activated by tumour cells
Indicated for breast and colorectal cancer
Administered with food

38
Q

Capecitabine toxicity

A

Dose limiting hand-foot syndrome, mucositis and diarrhoea
CINV
Fatigue
Rash

39
Q

Vinca alkaloids

A

Vincristine
Vinblastine
Vinorelbine

40
Q

Vinca-induced toxicities

A 
Vesicant 
Alopecia 
Constipation
Vincristine 
- peripheral neuropathy (max 2mg/w) 
- ileus
Vinblastine/Vinorelbine 
- dose limiting neutropenia and thrombocytopenia
- neurologic toxicity
41
Q

Taxanes and premedications

A

Paclitaxel - H1 blocker, H2 blocker, corticosteroids

Docetaxel - Dexamethasone

42
Q

Paclitaxel toxicities

A 
Myelosuppression - WBC nadie 8-11d, recovery 15-21d 
Peripheral neuropathy
Myalgias
Hypersensitivity reactions 
Mucositis
43
Q

Docetaxel toxicities

A

More neutropenia
Alopecia
Less peripheral neuropathy, hypersensitivity reactions and asthenia

44
Q

Tamoxifen

A

Selective estrogen receptor modulators

Indicated for estrogen-receptor positive breast cancer

45
Q

Tamoxifen toxicities

A

Increased risk of endometrial cancer
agonistic effect on bone, lipids, endometrium
Hot flashes
Thromboembolic events

46
Q

Aromatase inihibitors

A

Anastrozole
Letrozole
Exemestane
Reversible competitive inhibitor

47
Q

Aromatase inhibitors SE

A

Fatigue
Hot flashes
Myalgia/Athralgia
Bone-related adverse effects

48
Q

BCR/ABL tyrosine kinase inhibitor

A

Imatinib, Dasatinib, nilotinib

Indicated for leukemia, gastrointestinal stromal tumor

49
Q

BCR/ABL tyrosine kinase inhibitor toxicities

A 
CINV
Dose limiting myelosuppression 
Fluid retention 
Increase in LFTs 
CYP3A4 interactions
50
Q

EGFR tyrosine kinse inhibitors

A

Gefitinib
Erlotinib
Afatinib
Indicated for lung cancer, pancreatic cancer (erlotinib)

51
Q

EGFR TK inhibitors SE

A 
Dermatological toxicities 
- Pruritis 
- papulopustular rash
- alopecia 
- Xerosis 
- Nail changes 
GI side effects -- diarrhoea
52
Q

Rituximab considerations

A

Infusion related reactions - fever, rigors, bronchospams, hypotension
Premedicate with paracetamol and diphenhydramine
Start infusion slow and increase rate over time if no reactions

53
Q

Bevacizumab

A

VEGF inhibitor

Indicated in colorectal, lung, kidney cancer

54
Q

Bevacizumab CI

A 
High risk of bleeds
High risk of CNS metastasis 
Hypertension 
Proteinuria -- discontinue in nephrotic syndrome 
Risk of stroke
55
Q

Trastuzumab

A

HER2/Neu receptor antagonist

Indicated for breast, gastric cancer (HER2+)

56
Q

Trastuzumab toxicities

A

Cardiotoxicity

Hypersensitivity - premedicate with paracetamol

57
Q

Ipilimumab

A

Blocks CTLA-4 inhibitory signal to kill cancer cells
Indicated for treatment of melanoma
SE: rash, diarrhoea, thyroid

58
Q

PD-1 Inhibitors

A

Pembrolizumab
Nivolumab
Cemepilimab

59
Q

PD-L1 inhibitors

A

Atezolizumab
Avelumab
Durvalumab

60
Q

Immune related adverse effects

A 
Hypophysitis 
Thyroiditis 
Pneumonitis 
Hepatitis 
Pancreatitis 
Adrenal insufficiency 
Colitis 
Motor and sensory neuropathies 
Dermatitis/rash 
Arthritis

Oncology (3 decks)

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