Pharma

Question 1

Exceptions for dosing drugs by actual body weight

Answer 1

Dose at actual body weight, even in obese patients

Exceptions:
Vincristine: cap at 2mg
Bleomycin for lung toxicity
Carboplatin: cap at 125-150ml/min to limit thrombocytopenia

Question 2

Drugs that should be dosed hepatically

Answer 2

H.E.P.A.T.I.C

HER2 - lapatinib
Etoposide, Estrogen (tamoxifen) 
Paclitaxel, Nab-paclitaxel, Docetaxel, Vinca
Adriamycin - doxorubicin, epirubicin
TKI - sorafenib, sunitinib, imatinib, nilotinib, vemurafenib
Ifosfamide (bili>3)
Cyclophosphamide 
Opioids - morphine

Question 3

Drugs that should be dosed renally

Answer 3

Cisplatin, Carboplatin

Capecitabine*, Cladribine, merCaptupurine, Fludrabrine

Anti-folate - MTX**, pemetrexed

Anthracycline - etoposide, topetecan, irinotecan

Antibiotics - bleomycin, mitomycin

Ifosfamide, Etoposide

Question 4

CYP3A4/5 and CYP2D6 inhibitors

Answer 4

CYP3A4/5 and CYP2D6 break down most chemo drugs and opiates

CYP3A and others inhibitors: grapefruit, HIV drugs, fungal drugs, macrolides (-mycins), fluoroquinolones, antidepressants → will increase chemo and opioid toxicity

Inhibitors increase toxicity (“IIT”)

Question 5

CYP3A4 inducers

Answer 5

CYP3A4 inducers: seizure, TB, PPI, St John’s Wort will decrease concentration and efficacy of chemo

InDucers Decrease efficacy

Question 6

What drugs grapefruit affects

Answer 6

grapefruit alters mechanism of imatinib, erlotinib, lapatinib, sorafenib, sunitinib

Question 7

Regimens with high chance of causing neutropenic fever and require GCSF support

Answer 7

• dose dense ACT for breast cancer
• BEACOPP for HL
• RICE for NHL
• Docetaxel, cisplatin, 5-FU for advanced gastric cancer
• MVAC for bladder cancer

Question 8

Immune checkpoint inhibitor mechanism

Answer 8

T cell activation requires 2 signals
1st signal: T cell receptor binds tumor assoc ag presented by APC by MHC

2nd signal: Main cosimulatory receptor on T cell CD28 binds to B7 ligand subtypes CD80 (B7-1) and CD86 (B7-2) on APC

In response to T cell activation, CTLA-4 upregulated by cancer cells and competes with CD28 for CD80 and CD86 binding to APC. In doing so - APC can downregulate T cell responses and APC function

→ Ipi blocks CTLA4 thereby unleashing immune system