IMMUNE SYSTEM & MALIGNANT DISEASE Flashcards
AZATHIOPRINE
How does it work?
Antimetabolite-> breaks down into mercaptopurine which inhibits the reimpairment+making of DNA
AZATHIOPRINE
PRE-TREATMENT SCREENING?
CHECK TPMT LEVELS as TPMT metabolises thiopurine drugs (azathiopurine, mercaptopurine & tioguanine)
Reduced activity of enzyme? risk of myelosuppression
AZATHIOPRINE- SIDE-EFFECTS? HN^2T
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
AZATHIOPRINE- MONITORING REQUIREMENTS?
TPMT
REGULAR LFT/FBC, more often in liver/renal impairment
FBC weekly for first 4 weeks, then at least /3 months
AZATHIOPRINE- INTERACTIONS?
AZATHIOPRINE+ALLOPURINOL? haematological toxicity-> reduce AZA dose to 1/4 of usual dose
AZATHIOPRINE+ACE-i? anaemia/leucopenia-> AVOID concomitant use
CALCINEURIN INHIBITORS- Examples?
Ciclosporin
Tacrolimus
CICLOSPORIN/TACROLIMUS
How does it work?
inhibits lymphokines-> suppresses cell-mediated response
CICLOSPORIN/TACROLIMUS- MHRA WARNING?
PRESCRIBE AND DISPENSE BY BRAND NAME ONLY
CICLOSPORIN- SIDE-EFFECTS?
bit longer start
HYPER- glycaemia/uricemia/kalaemia/lipidaemia/tension HYPO- magnesaemia Renal/Liver Impairment Skin Reactions Gingival Hyperplasia Hair changes (hirsutism) Eye inflammation/vision Ls (topical)
CICLOSPORIN/TACROLIMUS- AVOID IN..?
PREGNANCY
BREAST-FEEDING
malignancy
uncontrolled hypertension/infections
CICLOSPORIN- INTERACTIONS
Increases exposure? GPOM
Decreases exposure? PG
Can mix with?
GRAPEFRUIT+POMELO juice-> increased ciclosporin exposure
PURPLE GRAPE JUICE-> decreased ciclosporin exposure
BUT…
Can mix with orange/apple juice to improve taste
CICLOSPORIN- PRE-SCREENING?
Exclude malignancies obvs
CICLOSPORIN- MONITORING & ADVICE?
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
TACROLIMUS- SIDE-EFFECTS?
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
LEARN CICLO/TACRO TOGETHER!
SIMILAR/DIFFERENCES
TACROLIMUS- INTERACTIONS? GP^2
Patient has hypersensitivity to macrolide?
GRAPEFRUIT/POMEGRANATE/POMELO juice- INCREASES tacrolimus levels
Patient has hypersensitivity to macrolide? DO NOT USE
TACROLIMUS- MONITORING & ADVICE?
Bob and Eve Baked Lovely Egg Cakes Blood pressure ECG Blood glucose LFT Electrolytes CrCL
AVOID EXPOSURE TO UV/sunlight
Driving/skilled L
MYCOPHENOLATE MOFETIL
How does it work?
Inhibits purine synthesis
MYCOPHENOLATE MOFETIL- RISKY SIDE-EFFECTS?
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
MYCOPHENOLATE MOFETIL- MHRA CONTRACEPTION ADVICE (TERATOGENIC)
WOMEN?
MEN?
WOMEN? 1 effective contraceptive before+during+6 weeks after treatment (2 methods preferred)
MEN? during treatment+90 days after-> OR female partner
MULTIPLE SCLEROSIS
What is it?
Chronic autoimmune disease demyelinating the CNS
MULTIPLE SCLEROSIS
Can be relapsing/progressive/both
Active disease?
At least 2 big relapses in the past 2 years, despite interferon beta treatment
MULTIPLE SCLEROSIS- MANAGING SYMPTOMS
SPASTICITY? RELPASES? OSCILLOPSIA? MOOD ALTERATION? FATIGUE?
SPASTICITY? baclofen/diazepam/tizanidine/dantrolene
RELPASES? methylprednisolone
OSCILLOPSIA? objects vibrate-> gabapentin
MOOD ALTERATION? amitriptyline
FATIGUE? amantadine/fampridine
BACLOFEN- DOSE ADVICE?
Increase dose slowly
Risk of sedation/hypotonia (abnormally low level of muscle tone)
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
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
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).
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
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
CYTOTOXIC SIDE-EFFECTS
TUMOUR LSYIS SYNDROME CAUSES..?
HYPER kalaemia/uricaemia/phosphataemia
HYPO calcaemia (P&C linked)
ALL can lead to renal damage/arrhythmias :(
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
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
CYTOTOXIC SIDE-EFFECTS
Alopecia- common
Thromboembolism? Chemo increases risk
CYTOTOXIC SIDE-EFFECTS
UROTHELIAL TOXICITY
Causes?
Common in?
Treatment?
UROTHELIAL TOXICITY
Causes? Haemorrhage in urinary tract
Common in? ALKYLATING- Cyclophosphamide/Ifosfamide
Treatment? Mesna
CYTOTOXIC SIDE-EFFECTS
MYELOSUPPRESSION
Caused by?
Treatment?
MYELOSUPPRESSION
Caused by? Methotrexate
Treatment? Folinic Acid
CYTOTOXIC DRUGS- PREGNANCY/REPRODUCTIVE SYSTEM
TECU?
Teratogenic
Exclude pregnancy pre-treatment w/ drugs
Contraceptive advice pre-therapy
Use contraception during+after treatment
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
CYTOTOXIC NAUSEA & VOMITING
Types of symptoms?
Acute/delayed/anticipatory
Delayed/anticipatory the worst
CYTOTOXIC CAUSES OF NAUSEA & VOMITING
just know a few…
MILD?
FLUOROURACIL
METHOTREXATE
VINCRISTINE
ETOPOSIDE
CYTOTOXIC CAUSES OF NAUSEA & VOMITING
just know a few…
MODERATE?
DOCETAXEL DOXORUBICIN LOW CYCLOPOHSPHAMIDE DOSES HIGH METHOTREXATE DOSES MITOXANTRONE
CYTOTOXIC CAUSES OF NAUSEA & VOMITING
just know a few…
SEVERE?
CISPLATIN
HIGH DOSES OF CYCLOPHOSPHAMIDE
DACARBAZINE
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
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)
CYTOTOXIC NAUSEA & VOMITING
PREVENTION OF ANTICIPATORY SYMPTOMS (occurs pre-treatment)?
LORAZEPAM
ALKYLATING AGENTS- KEY POINTS
EXAMPLES?
SIDE-EFFECTS?
CYCLOPHOSPHAMIDE/IFOSOFAMIDE/MELPHALAN
UROTHELIAL TOXICITY
RISK OF PERMANENT MALE STERILITY
ANTHRACYCLINES- EXAMPLES?
DAUNORUBICIN (RUBY-RED URINE!)
DOXORUBICIN
EPIRUBICIN
IDARUBICIN
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
ANTIMETABOLITES
EXAMPLES?
SIDE-EFFECTS?
EXAMPLES? CYTARABINE FLUOROURACIL METHOTREXATE MERCAPTOPURINE
SIDE-EFFECTS?
MUCOSITIS
MYELOSUPPRESSION
CYTOTOXIC ANTIBIOTICS
EXAMPLES?
SIDE-EFFECTS?
EXAMPLES?
BLEOMYCIN
MITOMYCIN
SIDE-EFFECTS?
PROGRESSIVE PULMONARY FIBROSIS
PULMONARY TOXICITY
TAXANES- EXAMPLES?
CABAZITAXEL
DOCETAXEL
PACLITAXEL
TAXANES- SIDE-EFFECTS/MONITORING?
HYPERSENTIVITY-> premedicate w/ corticosteroids+antihistamines MONITOR: Cardiac output S+s of pneumonitis+sepsis Contraception during+6 months after
VINCA ALKALOIDS
EXAMPLES?
SIDE-EFFECTS?
EXAMPLES?
VINBLASTINE
VINCRISTINE
VINDESINE
SIDE-EFFECTS?
INTRAVENOUS ADMINISTRATION ONLY (INTRATHECAL= fatal)
BRONCHOSPASM
NEUROTOXICITY- neuropathy/motor weakness/myalgia
2 DRUGS THAT DO NOT CAUSE BONE MARROW SUPPRESSION, SPECIFIC ONLY 2?
VINCRSTINE
BLEOmycin
MITOmycin does L
- 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
gingival?
ONLY WITH CICLOSPORIN!
Cyclophosphamide/alkylating agents
BIG BOY RISK?
Neutropenia
contraception during+3 months after
Cisplatin- during+6 months after
