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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
Etoposide toxicities
Dose limiting myelosuppression | Hypotension if infusion too quick
26
Anthracyclines
``` Doxorubicin Daunorubicin Epirubicin Idarubicin Liposomal doxorubicin Mitoxantrone ```
27
Anthracyclines MOA
Inhibition of topoisomerase II Intercalations between base pairs Metabolised in liver to form oxygen free radicals
28
Anthracyclines toxicity
``` Dose limiting myelosuppression Cardiotoxicity Alopecia Acute NV Vesicant Red discolouration of urine ```
29
Anthracyclines cardiotoxicity
Acute (24h): Arrhythmias, pericarditis Subacute (weeks to months): tachycardia Late (>5y): cardiomyopathy
30
Anthracyclines cardiotoxicity risk factors
``` Cumulative doses Administrative schedule Age Mediastinal radiation Known cardiac disease ```
31
Anthracycline-induced cardiotoxicity prevention
``` Baseline MUGA for LVEF Limit cumulative dose Less cardiotoxic anthracycline/analogue - liposomal doxorubicin - mitoxantrone Use dexrazoxane ```
32
Antimetabolites mechanism of action
Compete for binding sites on enzyme - antifolate (mtx) Incorporate directly into DNA or RNA
33
Methotrexate
Indicated for all cancers, GVHD, rheumatoid diseases
34
MTX toxicities
``` Dose limiting myelosuppression CNS toxicity Mucositis Pulmonary pneumonitis Hepatits Nephrotoxicity Diarrhoea ```
35
5-Fluorouracil
Pyrimidine analogue -- acts as an antagonist | Available as injection
36
5-FU Toxicities
Myelosuppression with bolus administration Hand-foot syndrome (PPE) and diarrhoea with continuous infusion Skin discoloration Nail changes Photosensitivity Neurologic toxicity Vasospastic angina
37
Capecitabine
Pyrimidine analogue selectively activated by tumour cells Indicated for breast and colorectal cancer Administered with food
38
Capecitabine toxicity
Dose limiting hand-foot syndrome, mucositis and diarrhoea CINV Fatigue Rash
39
Vinca alkaloids
Vincristine Vinblastine Vinorelbine
40
Vinca-induced toxicities
``` Vesicant Alopecia Constipation Vincristine - peripheral neuropathy (max 2mg/w) - ileus Vinblastine/Vinorelbine - dose limiting neutropenia and thrombocytopenia - neurologic toxicity ```
41
Taxanes and premedications
Paclitaxel - H1 blocker, H2 blocker, corticosteroids | Docetaxel - Dexamethasone
42
Paclitaxel toxicities
``` Myelosuppression - WBC nadie 8-11d, recovery 15-21d Peripheral neuropathy Myalgias Hypersensitivity reactions Mucositis ```
43
Docetaxel toxicities
More neutropenia Alopecia Less peripheral neuropathy, hypersensitivity reactions and asthenia
44
Tamoxifen
Selective estrogen receptor modulators | Indicated for estrogen-receptor positive breast cancer
45
Tamoxifen toxicities
Increased risk of endometrial cancer agonistic effect on bone, lipids, endometrium Hot flashes Thromboembolic events
46
Aromatase inihibitors
Anastrozole Letrozole Exemestane Reversible competitive inhibitor
47
Aromatase inhibitors SE
Fatigue Hot flashes Myalgia/Athralgia Bone-related adverse effects
48
BCR/ABL tyrosine kinase inhibitor
Imatinib, Dasatinib, nilotinib | Indicated for leukemia, gastrointestinal stromal tumor
49
BCR/ABL tyrosine kinase inhibitor toxicities
``` CINV Dose limiting myelosuppression Fluid retention Increase in LFTs CYP3A4 interactions ```
50
EGFR tyrosine kinse inhibitors
Gefitinib Erlotinib Afatinib Indicated for lung cancer, pancreatic cancer (erlotinib)
51
EGFR TK inhibitors SE
``` Dermatological toxicities - Pruritis - papulopustular rash - alopecia - Xerosis - Nail changes GI side effects -- diarrhoea ```
52
Rituximab considerations
Infusion related reactions - fever, rigors, bronchospams, hypotension Premedicate with paracetamol and diphenhydramine Start infusion slow and increase rate over time if no reactions
53
Bevacizumab
VEGF inhibitor | Indicated in colorectal, lung, kidney cancer
54
Bevacizumab CI
``` High risk of bleeds High risk of CNS metastasis Hypertension Proteinuria -- discontinue in nephrotic syndrome Risk of stroke ```
55
Trastuzumab
HER2/Neu receptor antagonist | Indicated for breast, gastric cancer (HER2+)
56
Trastuzumab toxicities
Cardiotoxicity | Hypersensitivity - premedicate with paracetamol
57
Ipilimumab
Blocks CTLA-4 inhibitory signal to kill cancer cells Indicated for treatment of melanoma SE: rash, diarrhoea, thyroid
58
PD-1 Inhibitors
Pembrolizumab Nivolumab Cemepilimab
59
PD-L1 inhibitors
Atezolizumab Avelumab Durvalumab
60
Immune related adverse effects
``` Hypophysitis Thyroiditis Pneumonitis Hepatitis Pancreatitis Adrenal insufficiency Colitis Motor and sensory neuropathies Dermatitis/rash Arthritis ```

Oncology (3 decks)

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