PHARM 1 Flashcards
What does larger vs smaller volume of distribution mean
smaller– usually stays in blood larger- usually stays in fat/tissues (lipid soluble)
Drugs that have diff effects on women
CV drugs (higher risk of torsades/ prolonged QT) Zolpedim (ambien) (lower clearance and vol distr) Digoxin- may incr mortality ACEI- incr cough in women Ethanol- higher BAC
What does preganancy do to clearance and Vd
INcreases vd from incr fat (so less in blood) and increases clearance
What does preg do to levels of seizure drugs?
Incr vd decr it in blood, and so does incr in clearance, thus will be less effective and there will be more seizures
What are some teratogens in the first trimester>
Warfarin, Phenytoin, Valproate also thalidomide, lithium, DES (usu not taken in preg)
What can Warfarin, Phenytoin, and Valproate do as teratogens?
warfarin- facial and CNS abnorm, skeletal dysplasia Phenytoin- craniofacial, limb effects, growth def Valproate- spina bifida
What are some teratogens of second or third trimester?
Warfarin again, heparin, ACEI, tetracyclines, aminoglycosides
SxE of later trimester drugs Heparin Warfarin ACEI Tetracycline Aminoglycosides
hep- osteoporosis in mothers warfarin- fetal brain bleed ACeI- oligahydramnios, fetal renal failure and abonormal skull ossif Tetras- stains on teeth aminoglyco- ototox, renal tox (rev)
What are some breast milk sxe drugs?
Phenobarbital (seizure), naldixic acid/sulfonamide/nitrofurantoin(UTIs), lithium, alc ABX
Sxe in breast milk of Phenobarbital Nalidixic acid/nitrofurantoin/Sulfonamide Lithium Ethanol
Pheno- for seizures, but can sedate baby nalidixic/nitros/sulfon- hemolysis risk in G6PDH def kids LIthium- hypothermia, hypotonia, cyanosis (for bipolar) Ethanol- slow met in infants due to them having lower alc dehydrogenase
Category A-X drugs
A- not harmful B-safe if CLINICAL NEED C- safe ONLY if potential benefits outweigh risks D- evidence of risk to fetus X- do not use
How does clearance differ in baby, and what is an example of a drug that is affected by the differing HEPATIC clearance?
-infants have lower hep and renal clearance of drugs, lower gfr -example if Chloramphenicol which is excreted in bile: infants have lower glucoronyl transferase so this prolongs the half life in serum, causing Gray baby syndrome (cardiovascular collapse and death) -kids also have incr Vd (incr fat?)
Drug affected (in infants) by differing renal clearance?
Gentamicin, an aminoglycoside– levels are increased causing hearing loss
How should you change dosing in kids based on differing Vd and renal clearance?
increase loading dose due to Vd increase, and then increase dosing INTERVALS (time in between doses) due to incr in renal clearance (eg in aminoglycosides like gentamycin to avoid ototox)
What can Sulfonamides and Ceftriaxone do to babies and why?
They can cause kernicterus! (brain injury due to accum of bili) This is due to the fact that albumin normally binds free bili, but some drugs like cef and sulf can displace this bind-up causing serum unconj bili to accum
Tetracycline indications in infants?
stains teeth AND inhibits bone growth! -DO NOT GIVE in preganancy or under 8!
quinolones (fluoros like -floxacins) indications in infants?
can damage tendons and growing cartilage, dont give to ANY kids under 18!
Why might drugs affect geriatrics more strongly (what reasons)?
taking more meds, usu women, slower gastric emptying eg on antacids etc, reduced body water so decr Vd of water soluble drugs (need less!) and incr body fat so incr Vd of lipid sol drugs (need more!), renal blood flow and filtration decrease, and so does creat due to loss of muscle mass (unreliable indicator of renal fxn in elderly), decr hepatic blood flow (inhib met), elev in half life can accum to toxic levels
What do combined oral contraceptives contain/generally do?
They have combined estrogen which inhbits rel of FSH from ant pit, decr breakthrough bleeding, incr number of progestin receptors and progestin–thickens cervical mucus so sperm blocked, may inhib LH surge
Adverse effect of combined oral contraceptive on uterus?
polyp formation (in breast, suppresses lactation)
Contraindications of combined oral contraceptives?
THROMBO events (bc can coag), estro-dep neoplasm (obv), p450 drugs reduce efficacy
Serious side effects that are more rare in COCs
DVT, MI/stroke from hypercoagulability (smoking increases this risk, dont use prior to surg)
Timing of combined oral contraceptives?
must be taken at same time every day, can cause breakthrough bleeding, can cause the usual weight gain headache etc
What pop is progestin only contraceptives useful for>
women who cant take estro or are breastfeeding (unlike COC it doesnt reduce breast milk prod), have migraines, have heavy periods causing anemia, or smokers
Timing of POPs?
same time every day! bc it thickens and then thins cerv mucus throughout day
Depo medroxyprogesterone?
high dose progestin injxn that is able to prevent ovulation in all patients from decreasing freq of GnRH pulses from hypothal (preventing LH spike)
Sxe of progestin only contraceptives
breakthrough bleeding, and headache, usual etc -the lower gnrh can decr estro causing osteoporosis -Ca2+ depletion so should only be used for 2 yr max -decr HDL incr LDL, higher likelihood for ectopic preg if occurs
CxI of progestin only contraceptives?
undiagnosed vaginal bleeding, liver disease, BC, p450 -doesnt prevent ovarian cysts as well as COC, very careful timing (may need backup)
Advantages of POP over COC?
fewer sxe than extro, okay for DVT/emoblism/HTN/obesity/DM, safe during lactation, safe for sickle cell, easily reversible bc ovulation starts again after discontinuation
Non oral contraceptive examples?
transdermal patch, ipmlanon (in skin), vaginal nuva ring, injxn like depo, IUD (copper or levon)
Transdermal patch
ethinyl estradiol-norelgestromin -similar to coc, but higher sxe bc more estro plasma, -CxI smoking, preg, estro cancer, hep etc (similar to coc)
Implanon
thin plastic under skin, Progestin only! -sxe irreg bleeding, cxi same as pop, 3 yr
Vaginal nuva ring
similar to coc, incr incidence of vaginitis and vag secr, adv is lower doses of hormones so avoids daily fluctuations seen with pills
IUD
-either copper releasing, or levonorgestrel releasing (mirena) copper toxic to sperm, thickens cerv, sxe cramping and abd bleeding, cxi is anatomical abnormalities and active pelvic infxn, and copper allergy -adv: opper effective for 10 yr, levo for 5, cheap
What are the 3 main types of EC?
oral hormonal pills (COC or POP) copper iud mifepristone
oral pill EC (emergency contraception)? what may make it less effective? which type is best?
-inhibits ov preg etc before implantation, etc etc -should take within 72 hr, less effective if vomit or diarr or if 2nd dose missed -POP better with fewer side effects (PLAN B)
CxI of oral pill EC?
preg, BC/endomet cancer, thrombo, liver dis -usual sxe
What is plan B
progestin only oral EC (levonorgestrel)
Copper IUD EC
effective within 120 hr, prev implantation by changing lining of uterus, etc
Mifepristone EC MOA, Cxi
synthetic steroid that competitively inhibits progesterone receptors and anti-glucocorticoid, abortifacient bc can be fatal to fetus if given after conception, but can also be used as EC if taken after intercourse but before ovulation CxI: contrind with ectopic preg /mass, IUD, adr failure, long term corticosteroid tx, anticoag tx/hemmor disorders, porphyries, after 63 days gestation, after ovlulation as EC
Which EC is most effective?
copper IUD, then plan b, then coc (not always effective), the sooner taken, the better
Estrogens/ gonadotropins/ GnRH agonist drugs?
Estradiol, DES, Leuprolide
Antiestrogens/SERM drugs?
Clomiphene, tamoxifen, raloxifene
Progestin drugs?
Medroxyprogesterone (depo-provera), norethindrone mini pill, and levonorgestrel
Androgen drugs?
Test, Fluoxymesterone, and Danezol
Anti-androgens/ anti-progestins
Mifeprisone, Dutasteride and finesteride
Estradiol/ mestranol uses
act on estro receptor -used in hypogonadism, dysmenorrhea, contraceptive and morning after pill, endometriosis, postmenopause HRT
estradiol and mestranol SxE and CxI?
SxE endometrial carc/BC, MI/stroke, dementia CxI preg, genital bleeding, BC, thrombo, smoking
DES use
same MOA as estradiol, used for prostate carc, previously used to prevent premature death
DES SxE
Clear cell adenocarcinoma in daughter
Leuprolide MOA and use
GnRH agnosit pulsatile (continuous) dose, causes antag effects lowering estro levels -use in endometriosis (growing outside uterus), uterine fibroids -use with weak acting estrogen like estriol to offset menopause sx
Clomiphene MOA and use
-inhib estro R at hypothal and blocks feedback inhib to decr GnRH -use: infertility, induces ovulation
Clomiphene sxe
ovarian hyperstim causing cysts, hot flashes, nervousness, nausea etc
Tamoxifen MOA and use
partial agonist, inhib estro by binding to receptor and preventing estro sensitive tumors, use in ER(+) BC
Sxe Tamox
Uterine cancer and thromboembolism
Raloxifene MOA and Use
Antag, prevents post menopause osteoporosis, prevent BC
sxe of raloxifene
Thrombembolic events
Progesterone MOA and use
similar to estro, contraceptive via negative feedback on GnRH release so no LH surge so no ovulation -use as contraceptive, control of uterine bleeding, endomet, dysmen
sxe progesterone
weight gain, thrombo etc
Medroxyprogesterone (depo-provera) use and moa
inhib GnRH rel to inhib follicle maturation and ovulation -use for contraceptive, injxn
Depo sxe?
bone loss
Mini pill norethindrone moa and uses
thickens cervical mucus, progestin oral contraceptive
Testosterone MOA and uses
binds androgen receptors, cannot be given orally due to hepatic inactivation from first pass effect -use in hypogonadism
side effects of test
increased LDL and decr HDL, aggr/psychosis, hep, cholestatic jaundice, closure of epiphyses, priapism and decr sperm count, masc of women
Danazol (in pharmwiki only) MOA and use
synth test analog, partial agonist to a bunch of receptors, suppr pit-ovarian axis -used for fibrocystic breast dis, endometriosis, hereditary angioedema
danezol sxe and cxi
thromboemb, androgenic effects, intracranial htn cxi: breast feeding, preg
Fluoxymesterone MOA and use
similar to test but more potent, use in mammary cancer in postmen women, hypogonadism in men
Mifepristone MOA and use?
progesterone R antag (and clucocorticoid R antag to tx cushings) -use: termination of intrauterine preg in first 49 days gestation, hyperglycemia of cushings
mifepristone sxe
fetal infxn, prologned vaginal bleeding
Dutasteride and finasteride moa and uses
Inhibits 5-a reductase preventing test from being conv to active DHT, duta inhibits both I and II and fina inhibs type 2 only, takes months -both are for BPH!, fina is for baldness
dutasteride and finasteride sxe and cxi
sxe: importence, decr libido, gynecomastia -cxi: preg, cant donate blood for 6 months
