Special Considerations

Question 1

When is the peak plasma conc of sidenafil?

What is it metabolized by?

Answer 1

Peak plasma conc at 1 hr so pts instructed to take 1 hr before intercourse

HL 4 hr (effective duration)

Metabolized by CYP3A4

Question 2

Sildenafil

Viagra

Answer 2

Large ↓ in BP, syncope, lower cardiac perfusion and MI if used with nitrates

Question 3

Calcium

Answer 3

Combine with vit D supp when osteoporosis meds are taken

Question 4

Calcium Gluconate (IV)

Answer 4

Safer SC infiltration than CaCl

Question 5

Calcium Chloride (IV)

Answer 5

Necrosis can occur if spills from blood to tissues so cannot use SC or IM

Question 6

Calcitriol

1,25 -OH D3

Answer 6

May cause more hypercalcemia than either paricalcitol or doxercalciferol

Question 7

What happens if PTH is active 3-5 hr/day

Answer 7

osteoblast activity ↑ more than osteoclast

Question 8

What happens if PTH is active 24 hr/day

Answer 8

osteoclast activity ↑ more than osteoblast → bone loss and ↑ serum Ca2+

Question 9

Teriparatide

hPTH 1-34

Answer 9

In rodents, LT use causes osteosclerosis and osteosarcomas

Question 10

Raloxifen

Answer 10

↓ risk of breast ca and endometrial ca but not stroke or embolism

Question 11

Biphosphonates

Answer 11

Poor intestinal absorption so must take in the AM after overnight fast with nothing but water for the first 30-60 mins after taking

Can cause esophageal erosion so take w/ 8 oz water and do not lay down for 1 hr

Drug holidays after 5 yrs due to atypical femur fx (even tho rare)

Question 12

Ibandronate

oral or IV

Answer 12

Lack of hip fx reduction data so not considered first line like other biphosphonates

Question 13

Denosumab

Answer 13

Similar to biphosphonates but more expensive

Inj subcutaneously q6mo (osteoporosis), or q1mo (malignancy)

Question 14

Salmon Calcitonin

Answer 14

Longer HL than human’s

Question 15

Cortisol/Glucocorticoids

Answer 15

Diabetogenic when combined with calcineurin inhibitors (must monitor glucose levels closely)

Question 16

Azathioprine

Answer 16

Avoid combining with ACE
inhibitors – drug interaction → potentiated myelosuppression

ACE inhibitors suppress
erythropoietin

PMT metabolizes 6-MP
FDA
recommends genotyping patient’s for inactive allele of TPMT (bc will accumulate 6-MP)

Patients with inactive allele → ↓ dosage of azathioprine

Question 17

Mycophenolate Mofetil

Answer 17

Selectively targets lymphocyte population (B- and T-cells) due to:
Lymphocyte population
dependent on de novo purine synthesis pathway (containing IMPDH) for synthesis of guanine nucleotides.

Other cell types can alternatively use purine salvage pathway for synthesis of guanine nucleotides

Mycophenolate preferentially inhibits type II isoform of IMPDH, which is primarily expressed in lymphocytes

This selectivity is thought to make MM less toxic overall compared to azathioprine, methotrexate & glucocorticoids

Question 18

Calcineurin Inhibitor

Answer 18

Diabetogenic when combined with glucocorticosteriods

Combined with glucocorticosteriods to lower effective/therapeutic dose of cyclosporine

Must closely monitor blood levels

Question 19

Sirolimus

Answer 19

Thought to be associated with less renal toxicity compared to calcineurin inhibitors

Question 20

Adalimumab

Humira

Answer 20

Often combined with other traditional DMARD’s (e.g. methotrexate, azathioprine, cyclosporine)

Concurrent therapy with methotrexate to prevent antibody formation against adalimumab

Question 21

Etanercept

Enbrel

Answer 21

Less immunogenic than other TNF-alpha blocking agents

Often combined with other traditional DMARD’s (e.g. methotrexate, azathioprine, cyclosporine)

Question 22

Infliximab

Remicade

Answer 22

Often combined with other traditional DMARD’s (e.g. methotrexate, azathioprine, cyclosporine)

Concurrent therapy with methotrexate to prevent antibody formation against infliximab

Question 23

Rituximab

Answer 23

Often given in conjunction with methotrexate to prevent Ab formation against Rituximab

Question 24

Tocilizumab

Answer 24

Suppression of IL-6 receptor can lead to induction of CYP2C9, 2C19, 2D6 and 3A4
→
Plasma levels of drugs metabolized by these enzymes are typically decreased by tocilizumab

Question 25

Methotrexate

Answer 25

Given to patients to decrease antibody formation against biologic therapies

Question 26

Resistance to ALKYLATING AGENTS

Answer 26

↑ DNA repair
capacity of tumor cell

↓ transport
of alkylating agent
into cancer cell

↑ glutathione and glutathione ass proteins

↑ glutathione
S-transferase activity

Question 27

Resistance to Methotrexate

Answer 27

↓transport
via down-reg of
reduced folate carrier
protein (MTX transporter)

↓ FPGS activity

Amplification of DHFR

Mutation of DHFR w/ ↓ affinity for MTX

MDR1 expression

Question 28

Resistance to 5-Fluorouracil

Answer 28

Amplification of TS

gene

Question 29

Resistance to 6-Mercaptopurine

Answer 29

Down-regulation of

HGPRT activity

Question 30

Resistance to Vinca Alkaloids (vinblastine and vincristine)

Answer 30

↑ MDR1

activity

Question 31

Resistance to Paclitaxel

Answer 31

↑ MDR1

activity

Question 32

Resistance to Etoposide

Answer 32

↑ MDR1

activity

Question 33

Resistance to Irinotecan

Answer 33

↑ MDR1

activity

Question 34

Resistance to Doxorubicin

Answer 34

↑ MDR1

↑
glutathione
peroxidase activity

Resistance rendering
mutations of
topoisomerase II

Question 35

Resistance to Bleomycin

Answer 35

↑levels of
bleomycin
hydrolase

↑ DNA
repair activity