Special Considerations Flashcards
When may dose adjustment be required for thyroid replacement therapy?
if T4 used with other drugs- Rifampin ↑ T4 clearance and Cholestyramine ↓ GI absorption
in pregnancy or elderly
Thioamides- PTU and MMI
If gland suppressed for 2 yrs → permanent remission in some pts but 60-70% relapse
Best drug for hypothyroidism in 1st trimester preg and recommended for nursing mothers
Propylthiouracil
PTU
Best drug for hypothyroidism after 1st trimester preg and recommended for nursing mothers at LOW doses
Methimazole
MMI
Radioactive Iodine
I131
No evidence of cancer risk increase with tx
Metformin
Does NOT induce hypoglycemia
NO weight gain
Often used in combo with oral antidiabetics
Glipizide
Won’t work if beta cells aren’t working well
No effect on insulin sensitivity
Repaglinide
Shorter acting than SU, administer right before a meal
Pioglitazone
NO hypoglycemia risk
Sitagliptin
Weight neutral
Canagliflozin
May facilitate weight loss, improve CV health in patients with CV dz
Can ↑ serum digoxin concentration
Estrogens
Tissue specific effects due to tissue specific receptor expression and dimerization
E2 binds to estrogen receptors (ER-α/ER-β) with greater affinity that E1/E3
Levonorgest
safe for breastfeeding
Estrogen/Progestin Combo Pill
More consistent suppression as combo
Progestins lower dose of estrogen required
Natural family planning
Low effectiveness: about 25% failure rate/yr
Only reliable for women with
consistent 26-32 day cycles
Levonorgestrel
95% effective in first 24hrs ,effectiveness ↓ after 72 hrs
Less effective if obese
Ulipristal
Ella
Maintains very high effectiveness to 120 hr
May not be effective if BMI of ≥ 35
Tamoxifen
Genotyping CYP2D6 no longer FDA recommended
Resistance possibly due to down- regulation of co- repressors, ER- alpha/beta
Avoid combo of tamoxifen and SSRI’s
SSRI’s will inhibit CYP2D6 conversion of tamoxifen to active metabolites endoxifen and 4-hydroxyTAM
Bone sparing effects in post-menopausal women; may cause osteoporosis in pre- menopausal women
Toremifene
Resistance – see tamoxifen
Equal efficacy to tamoxifen in treating breast cancer
Bone sparing effects in post-menopausal women
Leuprolide
Initial administration (first months), prior to GnRH receptor desensitization, can lead to ↑ LH and FSH release, with a transitory ↑ in testosterone and estrogen levels. This may result in an initial worsening of the cancer
Aromatase Inhibitors
Not effective in pre- menopause since fn ovaries in hypothal-pituitary- gonadal axis overcomes AI effects
After menopause, primary source of low estrogen levels is adipose tissue
Trastuzumab
HER2 testing: Detection of HER2 protein overexpression required for patient selection
Pertuzumab
HER2 testing: Detection of HER2 protein overexpression required for patient selection
Resistance of alkylating agents
↑ DNA repair
capacity of tumor cell
↓ transport
of alkylating agent
into cancer cell
↑ glutathione and glutathione ass proteins
↑ glutathione
S-transferase activity
Resistance of Methotrexate
↓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
Resistance of 5-Fluorouracil
Amplification of TS
gene
Resistance of 6-Mercaptopurine
Down-regulation of
HGPRT activity
Resistance of Plant Alkaloids
↑ MDR1
activity
Resistance of Doxorubicin
↑ MDR1
↑
glutathione
peroxidase activity
Resistance rendering
mutations of
topoisomerase II
Resistance of Bleomycin
↑levels of
bleomycin
hydrolase
↑ DNA
repair activity
