IMMUNE + MALIGNANT DISEASE

What meds are used to suppress rejection in organ transplant?

• antiproliferative drugs = azathioprine (metabolised to 6MP)… MUST dose reduce with allopurinol; another antiproh = mycophenolate mofetil (more selective)

• calcineurin inhibitors = ciclosporin OR tacrolimus, corticosteroids, OR sirolimus

• corticosteroids

must look out for signs of infection in the above

What chemo is most emotogenic?

Cisplatin, cyclophoshomide

S/E of cytotoxic drugs?

Bleomycin - pulmonary fibrosis

Doxorubicin - cardiotoxic

Cisplatin, carboplatin - nephrotoxic + ototoxic

Cyclophosphamides - haemorrhagic cystitis => musr give Mesna too

Vinca alkoloids AND taxanes - peripheral neuropathy

Methotrexate, 5FU - immunosuppression

Nitrosomes eg lomustine - neurotoxic crosses BBB

what to do if allopurinol and mercaptopurine or azathioprine given together?

reduce dose of mercaptopurine or azathioprine as allo prevents breakdown of M and => bone marrow suppression and toxicity

which chemo least likely to cause bone marrow suppression?

vincristine and bleomycin

what are the different levels of chemo emetogenicity?

mildly emetogenic = 5FU, methotrexate, etopside

moderately = taxanes, doxorubicin, cyclophosphamide, high dose methotrexate

highly - cisplatin, cyclophosphamide, dacarbazine

what anti-emetic mostly used in chemo?

dexa

lorazepam

what chemo should never be combined with radiotherapy?

doxorubicin, daunrubicin, epirubicin - all similar to radio => risk of toxicity

Where to report and score cytotoxic drug S/E ?

• common toxicity criteria for adverse events (CTCAE)

Those who are more susceptible to N+V during chemo?

• women

• Those who suffer form motion sickness

• Under 50 year olds

• Taking opioids

• Anxious patients

• Repeated exposure to the cytotoxic drug

What to give low and high risk N+V patients

Low risk - metoclop (pro-kinetic/DA antagonist)

High risk - ondanestron (5HT3 antagonist) and dexa

What are pre-disposing factors to tumour lysis syndrome ?

Breakdown of tumour cell => releases toxic substances eg urea

Hyperuricamia

Dehydration

Renal impairment

Tx = allupurinol

Do all cytotoxic drugs cause bone marrow suppression?

All EXCEPT vincristine and bleomycin

What is the range for neutropenia ?

• neutrophil count less than 1.06×109/litre

How is neutropenia reduced in patients receiving cytotoxic drugs ?

recombinant human granulocyte-colony stimulating factors G-CSF eg FILGRASTIM, LENOGRASTIM

What meds typically cause SJS?

• lamoTrigine

• Phenytoin

• Fluoroquinolones

• Carbamazepine

• Allopurinol

Effect of giving vinca alkaloids intrathecally rather than IV?

Severe neurotoxicity! Never event !

what are the different groups of chemo/cytotoxic drugs?

Alklayting - cholrambucil, cyclophosphamide

Anthracyclin - doxorubicin, daundorubinc,

Antimetabolites -methotrexate, 5FU, mercaptopurine

Vinca alkoloids - vincristine, vinblastine

Taxanes - paclitaxel

Calcineurin inhibitor - tacrolimus; conc increased by pomelo and pomergrante juice

Others - cisplatin (platinum), carboplatin, Tratuzumab (HER2 positive)

what drug is C/I in Hx of hypersensitivity to macrolides?

• calcineurin inhibitors eg tacrolimus

what drug is preferred for perimenopuase women with breast cancer and why ?

• Tamoxifen is preferred as it directly stops the production of oestrogen from receptors in ovaries

• Letrozole (aromotase inhibitor) only blocks peripheral oestrogen so women still producing oestogen ie perimenopause NOT benefited - better for POST menopause

how long to use contraception for while taking baby harming drugs?

• topiramate - during Tx and 4 weeks after (both)

• isotretinoin - 1 month before starting, during Tx and 1 month after (women)

• sodium valproate - during Tx and 3 months after (both)

• methotrexate - during Tx and for 6 months after (women) AND 3 months after (men)

• MMF - 2 preg tests 8-10 days apart BEFORE starting Tx; contraception during and for 6 weeks after Tx (women) AND 90 days for men

• rituximab - during Tx and 12 months after (both)

• Lefluomide - during Tx and at least 2 years afterwards for women and 3 months for men. Conc of active metabolite must be <20mcg/L in men and women before contraception

how does juice affect the levels of cytotoxic drugs?

• pomelo and grapefruit juice INCREASE levels of cyclosporin AND tacrolimus

• purple grape juice decrease levels

levels of glucocoticoid acitviity in sterioids?

• long acting - dexa, beta

• short acting - pred, methylpred, hydrocort

• intermediate acting - fludro

What medication can cause photosensitivity?

• amiodarone

• Chlorpromazine

• NSAIDs - Naproxen, Piroxicam

• Diuretics - Furosemide, bendro

• Abx - tetracyclines, quinolones, sulphonamides