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IMMUNE SYSTEM & MALIGNANT DISEASE Flashcards

1
Q

AZATHIOPRINE

How does it work?

A

Antimetabolite-> breaks down into mercaptopurine which inhibits the reimpairment+making of DNA

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2
Q

AZATHIOPRINE

PRE-TREATMENT SCREENING?

A

CHECK TPMT LEVELS as TPMT metabolises thiopurine drugs (azathiopurine, mercaptopurine & tioguanine)

Reduced activity of enzyme? risk of myelosuppression

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3
Q

AZATHIOPRINE- SIDE-EFFECTS? HN^2T

A

HN^2T
HYPERSENSITIVITY-> malaise/dizziness/D+V/fever
NEUTROPENIA/THROMBOCYTOPENIA-> sore throat/bruising/bleeding
NAUSEA-> common at start, resolves over time
TERATOGENIC-> avoid in pregnancy

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4
Q

AZATHIOPRINE- MONITORING REQUIREMENTS?

A

TPMT
REGULAR LFT/FBC, more often in liver/renal impairment
FBC weekly for first 4 weeks, then at least /3 months

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5
Q

AZATHIOPRINE- INTERACTIONS?

A

AZATHIOPRINE+ALLOPURINOL? haematological toxicity-> reduce AZA dose to 1/4 of usual dose

AZATHIOPRINE+ACE-i? anaemia/leucopenia-> AVOID concomitant use

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6
Q

CALCINEURIN INHIBITORS- Examples?

A

Ciclosporin

Tacrolimus

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7
Q

CICLOSPORIN/TACROLIMUS

How does it work?

A

inhibits lymphokines-> suppresses cell-mediated response

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8
Q

CICLOSPORIN/TACROLIMUS- MHRA WARNING?

A

PRESCRIBE AND DISPENSE BY BRAND NAME ONLY

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9
Q

CICLOSPORIN- SIDE-EFFECTS?

bit longer start

A 
HYPER- glycaemia/uricemia/kalaemia/lipidaemia/tension
HYPO- magnesaemia
Renal/Liver Impairment
Skin Reactions
Gingival Hyperplasia
Hair changes (hirsutism)
Eye inflammation/vision Ls (topical)
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10
Q

CICLOSPORIN/TACROLIMUS- AVOID IN..?

A

PREGNANCY
BREAST-FEEDING
malignancy
uncontrolled hypertension/infections

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11
Q

CICLOSPORIN- INTERACTIONS

Increases exposure? GPOM

Decreases exposure? PG

Can mix with?

A

GRAPEFRUIT+POMELO juice-> increased ciclosporin exposure

PURPLE GRAPE JUICE-> decreased ciclosporin exposure

BUT…
Can mix with orange/apple juice to improve taste

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12
Q

CICLOSPORIN- PRE-SCREENING?

A

Exclude malignancies obvs

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13
Q

CICLOSPORIN- MONITORING & ADVICE?

A 
Cameron Loves Money | Polly Loves Chanel Bags
Ciclosporin trough levels
LFT
Magnesium
Potassium
Lipids
CrCl
Blood Pressure

AVOID EXPOSURE TO UV/SUNLIGHT
TOPICAL? can affect driving/skilled etc

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14
Q

TACROLIMUS- SIDE-EFFECTS?

A 
HYPER-glycaemia+uricaemia/kalaemia
HYPO/HYPERtension
RENAL/LIVER IMPAIRMENT
SKIN REACTIONS
VISUAL DISTURBANCES
BLOOD DYSCRASIA
CVD (QT prolongation/cardiomyopathy in children)
Nervous system disorder/peripheral neuropathy
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15
Q

LEARN CICLO/TACRO TOGETHER!

SIMILAR/DIFFERENCES

A
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16
Q

TACROLIMUS- INTERACTIONS? GP^2

Patient has hypersensitivity to macrolide?

A

GRAPEFRUIT/POMEGRANATE/POMELO juice- INCREASES tacrolimus levels

Patient has hypersensitivity to macrolide? DO NOT USE

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17
Q

TACROLIMUS- MONITORING & ADVICE?

A 
Bob and Eve Baked Lovely Egg Cakes
Blood pressure
ECG
Blood glucose
LFT
Electrolytes
CrCL

AVOID EXPOSURE TO UV/sunlight
Driving/skilled L

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18
Q

MYCOPHENOLATE MOFETIL

How does it work?

A

Inhibits purine synthesis

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19
Q

MYCOPHENOLATE MOFETIL- RISKY SIDE-EFFECTS?

A

BONE MARROW SUPPRESSION->report infection/bruising/bleeding
PURE RED CELL APLASIA-> reduce dose/discontinue
HYPOGAMMAGLOBULINAEMIA-> measure immunoglobulin levels in recurrent infection
BRONCHIECTASIS-> persistent cough/SOB develops

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20
Q

MYCOPHENOLATE MOFETIL- MHRA CONTRACEPTION ADVICE (TERATOGENIC)

WOMEN?
MEN?

A

WOMEN? 1 effective contraceptive before+during+6 weeks after treatment (2 methods preferred)
MEN? during treatment+90 days after-> OR female partner

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21
Q

MULTIPLE SCLEROSIS

What is it?

A

Chronic autoimmune disease demyelinating the CNS

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22
Q

MULTIPLE SCLEROSIS

Can be relapsing/progressive/both

Active disease?

A

At least 2 big relapses in the past 2 years, despite interferon beta treatment

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23
Q

MULTIPLE SCLEROSIS- MANAGING SYMPTOMS

SPASTICITY?
RELPASES?
OSCILLOPSIA?
MOOD ALTERATION?
FATIGUE?
A

SPASTICITY? baclofen/diazepam/tizanidine/dantrolene
RELPASES? methylprednisolone
OSCILLOPSIA? objects vibrate-> gabapentin
MOOD ALTERATION? amitriptyline
FATIGUE? amantadine/fampridine

24
Q

BACLOFEN- DOSE ADVICE?

A

Increase dose slowly

Risk of sedation/hypotonia (abnormally low level of muscle tone)

25
CYTOTOXIC DRUGS DRUG HANDLING?
Reconstituted by trained personnel Reconstituted in designated pharmacy areas Protective clothing Eye protection X Pregnant staff Use local procedures-> spillages/safe disposal/syringes/containers/absorbent material Monitor staff exposure
26
CYTOTOXIC DRUG CLASSES ``` ALKYLATING AGENTS? ANTHRACYCLINES? ANTIMETABOLITES? CYTOTOXIC ANTIBIOTICS? PLATINUM COMPOUNDS? TAXANES? VINCA ALKALOIDS? ```
ALKYLATING AGENTS? cyclosphosphamide/ifosofamide/melphalan ANTHRACYCLINES? daunorubicin/doxorubicin/epirubicin/idarubicin ANTIMETABOLITES? cytarabine/fluorouracil/methotrexate/mercaptopurine CYTOTOXIC ANTIBIOTICS? bleomycin/mitomycin PLATINUM COMPOUNDS? carboplatin/cisplatin/oxaliplatin TAXANES? cabazitaxel/docetaxel/paclitaxel VINCA ALKALOIDS? vinblastine/vincristine/vindesine
27
CYTOTOXIC SIDE-EFFECTS EXTRAVASTAION OF IV drugs?
Tissues necrosis occurs due to leakage, trained staff only If extravasation is suspected the infusion should be stopped immediately but the cannula should not be removed until after an attempt has been made to aspirate the area (through the cannula) in order to remove as much of the drug as possible. Aspiration is sometimes possible if the extravasation presents with a raised bleb or blister at the injection site and is surrounded by hardened tissue, but it is often unsuccessful if the tissue is soft or soggy. Corticosteroids are usually given to treat inflammation, although there is little evidence to support their use in extravasation. Hydrocortisone or dexamethasone can be given either locally by subcutaneous injection or intravenously at a site distant from the injury. Antihistamines and analgesics may be required for symptom relief. The management of extravasation beyond these measures is not well standardised and calls for specialist advice. Treatment depends on the nature of the offending substance; one approach is to localise and neutralise the substance whereas another is to spread and dilute it. The first method may be appropriate following extravasation of vesicant drugs and involves administration of an antidote (if available) and the application of cold compresses 3–4 times a day (consult specialist literature for details of specific antidotes). Spreading and diluting the offending substance involves infiltrating the area with physiological saline, applying warm compresses, elevating the affected limb, and administering hyaluronidase. A saline flush-out technique (involving flushing the subcutaneous tissue with physiological saline) may be effective but requires specialist advice. Hyaluronidase should not be administered following extravasation of vesicant drugs (unless it is either specifically indicated or used in the saline flush-out technique).
28
CYTOTOXIC SIDE-EFFECTS ORAL MUCOSITIS Sore mouth associated w/? Advice? Preventing>Treating, treat w? If caused by methotrexate? Methotrexate rescue therapy/OD?
ORAL MUCOSITIS Sore mouth associated w/? Fluorouracil/Methotrexate/Anthracyclines Advice? Good oral hygiene, suck ice chips w/ fluorouracil Preventing>Treating, treat w? Saline mouthwash If caused by methotrexate? Folinic acid Methotrexate rescue therapy/OD? Levofolinic acid, also given w/ fluorouracil for colorectal cancer
29
CYTOTOXIC- TUMOUR LYSIS SYNDROME Why does it occur? Higher risk in...?
Why does it occur? Due to rapid destruction of malignant cells Higher risk in...? Non-Hodgkin's/Burkitt lymphoma/ALL/AML & Pre-existing hyperuricaemia/Dehydration/Renal Impairment
30
CYTOTOXIC SIDE-EFFECTS TUMOUR LSYIS SYNDROME CAUSES..?
HYPER kalaemia/uricaemia/phosphataemia HYPO calcaemia (P&C linked) ALL can lead to renal damage/arrhythmias :(
31
TUMOUR LYSIS SYNDROME- HYPERURICAEMIA More present in..? LL What drug+advice 24hrs pre-treatment? aLL Alternative?
More present in High-grade Lymphoma/Leukaemia What drug+advice 24hrs pre-treatment? Allopurinol+adequate hydration Alternative? Febuxostat 2 days pre-treatment
32
CYTOTOXIC SIDE-EFFECTS ``` BONE-MARROW SUPPRESSION Caused by all of them except..? When does it occur? What counts do you check pre-treatment? Reduce? AVOID treatment during..? Neutropenic fever immediate treatment? ```
Caused by all of them except Vincristine/Bleomycin When does it occur? 7-10 days after administration What counts do you check pre-treatment? Reduce? Check blood count, reduce dose if bone marrow an L AVOID treatment during..? Acute infection/seek help asap! Neutropenic fever immediate treatment? Broad-spectrum antibiotic
33
CYTOTOXIC SIDE-EFFECTS Alopecia- common Thromboembolism? Chemo increases risk
34
CYTOTOXIC SIDE-EFFECTS UROTHELIAL TOXICITY Causes? Common in? Treatment?
UROTHELIAL TOXICITY Causes? Haemorrhage in urinary tract Common in? ALKYLATING- Cyclophosphamide/Ifosfamide Treatment? Mesna
35
CYTOTOXIC SIDE-EFFECTS MYELOSUPPRESSION Caused by? Treatment?
MYELOSUPPRESSION Caused by? Methotrexate Treatment? Folinic Acid
36
CYTOTOXIC DRUGS- PREGNANCY/REPRODUCTIVE SYSTEM TECU?
Teratogenic Exclude pregnancy pre-treatment w/ drugs Contraceptive advice pre-therapy Use contraception during+after treatment
37
CYTOTOXIC DRUGS ALKYLATING DRUGS/PROCARBAZINE Increased risk of?
Cyclophosphamide/Ifosfamie/Melphalan Increased risk of? Urothelial toxicity Male sterility Women affected less, may cause onset of premature menopause
38
CYTOTOXIC NAUSEA & VOMITING Types of symptoms?
Acute/delayed/anticipatory Delayed/anticipatory the worst
39
CYTOTOXIC CAUSES OF NAUSEA & VOMITING just know a few... MILD?
FLUOROURACIL METHOTREXATE VINCRISTINE ETOPOSIDE
40
CYTOTOXIC CAUSES OF NAUSEA & VOMITING just know a few... MODERATE?
``` DOCETAXEL DOXORUBICIN LOW CYCLOPOHSPHAMIDE DOSES HIGH METHOTREXATE DOSES MITOXANTRONE ```
41
CYTOTOXIC CAUSES OF NAUSEA & VOMITING just know a few... SEVERE?
CISPLATIN HIGH DOSES OF CYCLOPHOSPHAMIDE DACARBAZINE
42
CYTOTOXIC NAUSEA AND VOMITING PREVENTION OF ACUTE symptoms (within 24hrs of treatment) LOW-RISK? HIGH-RISK?
LOW-RISK? dexamethasone OR lorazepam HIGH-RISK? ondansetron+dexaxmethasone+aprepitant
43
CYTOTOXIC NAUSEA & VOMITING PREVENTION OF DELAYED SYMPTOMS (after 24hrs of treatment) MODERATELY EMETOGENIC THERAPY? HIGHLY EMETOGENIC THERAPY?
MODERATELY EMETOGENIC THERAPY? dexamethasone+ondansetron (5HT-3 receptor antagonist) HIGHLY EMETOGENIC THERAPY? dexamethasone+aprepitant (neurokinin receptor antagonist)
44
CYTOTOXIC NAUSEA & VOMITING PREVENTION OF ANTICIPATORY SYMPTOMS (occurs pre-treatment)?
LORAZEPAM
45
ALKYLATING AGENTS- KEY POINTS EXAMPLES? SIDE-EFFECTS?
CYCLOPHOSPHAMIDE/IFOSOFAMIDE/MELPHALAN UROTHELIAL TOXICITY RISK OF PERMANENT MALE STERILITY
46
ANTHRACYCLINES- EXAMPLES?
DAUNORUBICIN (RUBY-RED URINE!) DOXORUBICIN EPIRUBICIN IDARUBICIN
47
ANTHRACYCLINES- DOXORUBICIN KEY POINTS?
RUBY-RED URINE FORMULATIONS NOT INTERCHANGEABLE (conventional/liposomal/pegylated liposomal) CARDIOTOXIC SIDE-EFFECTS LIPOSOMAL formulations-> reduced cardiotoxicity but causes painful macular skin eruptions -> Prevents skin eruptions by cooling hands/feet/avoid gloves&socks
48
ANTIMETABOLITES EXAMPLES? SIDE-EFFECTS?
``` EXAMPLES? CYTARABINE FLUOROURACIL METHOTREXATE MERCAPTOPURINE ``` SIDE-EFFECTS? MUCOSITIS MYELOSUPPRESSION
49
CYTOTOXIC ANTIBIOTICS EXAMPLES? SIDE-EFFECTS?
EXAMPLES? BLEOMYCIN MITOMYCIN SIDE-EFFECTS? PROGRESSIVE PULMONARY FIBROSIS PULMONARY TOXICITY
50
TAXANES- EXAMPLES?
CABAZITAXEL DOCETAXEL PACLITAXEL
51
TAXANES- SIDE-EFFECTS/MONITORING?
``` HYPERSENTIVITY-> premedicate w/ corticosteroids+antihistamines MONITOR: Cardiac output S+s of pneumonitis+sepsis Contraception during+6 months after ```
52
VINCA ALKALOIDS EXAMPLES? SIDE-EFFECTS?
EXAMPLES? VINBLASTINE VINCRISTINE VINDESINE SIDE-EFFECTS? INTRAVENOUS ADMINISTRATION ONLY (INTRATHECAL= fatal) BRONCHOSPASM NEUROTOXICITY- neuropathy/motor weakness/myalgia
53
2 DRUGS THAT DO NOT CAUSE BONE MARROW SUPPRESSION, SPECIFIC ONLY 2?
VINCRSTINE BLEOmycin MITOmycin does L
54
106. A 34-year-old man has been prescribed a drug to prevent organ rejection following a kidney transplant. The drug must be prescribed by brand and is known to have a drug interaction with grapefruit juice, whereby the concentration of the drug in context is increased. A common adverse effect is gingival hyperplasia
B (ciclosporin} Best way to tackle this form of question is to rule out the options based on the characteristic for example: - Brand specific drugs listed: ciclosporin, mycophenolate and tacrolimus - Ciclosporin and tacrolimus have a drug interaction with grapefruit juice which increases the drug exposure, - Phenytoin, ciclosporin, and nifedipine are the most common causes of gingival overgrowth. Tacrolimus is not known to cause gingival hyperplasia
55
gingival?
ONLY WITH CICLOSPORIN!
56
Cyclophosphamide/alkylating agents | BIG BOY RISK?
Neutropenia contraception during+3 months after Cisplatin- during+6 months after

GPhC BNF (48 decks)

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