PHARM - Reproduction Flashcards

Question

Drugs to INDUCE labor?

Answer 1

OXYTOCIN --> works particularly well at the LATER STAGES of pregnancy when receptors are upregulated When oxytocin binds, it causes STRONG UTERINE CONTRACTION through cAMP-dependent release of Ca2+ in smooth muscle GIVEN IV or with PGE1/MISOPROSTOL... PGE1 (MISOPROSTOL) --> Intravaginally given to cause CERVICAL RIPENING and UTERINE CONTRACTIONS, also through an upregulation of Ca2+ in the myometrium Should probably be used sparingly (can close ductus arteriosus)

Answer 2

CLOMIPHENE -- SERM (estrogen antagonist - no neg feedback, increased LH and FSH) BROMOCRIPTINE if patient is producing too much prolactin!!!

Answer 3

RITRODINE and TERBUTALINE (beta receptor agonists) - increase cAMP within uterine smooth muscle --> lower MLCK, lower MLC, relaxation

Answer 4

OXYTOCIN --> strong uterine contractions/influx of calcium; given IV PGE1(MISOPROSTOL) --> cervical ripening and uterine contractions, increases Ca2+ --> contraction! intravaginally Often given together

Answer 5

Giving HIGH LEVELS OF ESTROGEN and PROGESTERONE will potentiate NEGATIVE FEEDBACK in the HYPO and PITUITARY, thus INHIBITING THE RELEASE OF FSH and LH Effects --> Suppresses follicle development (no FSH), Prevents OVULATION (no LH surge), Endometrium stays secretory (high P, prevents implantation), Cervical secretions maintain ANTI-SPERM properties (high P), interferes with normal fallopian tube movement (high E)

Answer 6

Give estradiol continuously and it will BLOCK OVULATION, and thus pregnancy Problem is that it has a HUGE FIRST PASS and can only be given effectively IM ETHINYL ESTRADIOL --> eventually found that adding ethinyl group will INCREASE BIOAVAILABILITY to 40-50% and achieve high enough levels for 1x/day dosing MESTRANOL --> Metabolized in the liver to ethynil estradiol

Answer 7

First try were drugs similar to PROGESTERONE and then we switched to 19-norestrone --> SIGNIFICANT ANDROGENIC EFFECTS (weight gain, hair growth, acne) Newer drugs DECREASE ANDROGENIC SIDE EFFECTS DROSPIERNONE (yaz, yasmin) --> ANALOG OF SPIRONOLACTONE --> hypotension is a relatively severe side effect!

Answer 8

These include a SYNTHETIC ESTROGEN with slow metabolism and a PROGESTIN Work because ESTROGEN maintains proliferative endometrial state until withdrawal bleeds, and PROGESTIN maintains anti-sperm cervical secretions At first, HIGH DOSE 21/7 preps (21 days on, 7 off for bleeding) The doses were 3-4x bigger than what women were used to!!! Caused FSH and LH to be COMPLETELY SUPPRESSED and BLOCK FOLLICLE DEVELOPMENT BUT, such high doses can be stored in ADIPOSE TISSUE, allowing for CONTINUOUS RELEASE of hormone and preventing withdrawal periods!!! patients wouldn't always restore normal fertility probably due to some atrophy of the HPA

Answer 9

Now we use a MUCH LOWER DOSE --> 0.02-0.1 mg synthetic E and 1-2 ug P This is still VERY EFFECTIVE, though we see some abnormal LH surges once in a while (constant E should block it) We can also see BREAKTHROUGH BLEEDS if we cannot sustain endometrium whole 21 days, give more E if this happens COMBO preps can be MONO or BIPHASIC Mono - E and P constant throughout Biphasic -- vary the E dose throughout to try and maintain a relatively normal cycle (for the sake of other organs like breast and bone that receive the stimulation too) BUT since the whole point of BC is to interrupt the normal cycle and prevent ovulation, Biphasic seems pretty unnecessary

Answer 10

PROGESTIN ONLY --> eliminates some of the severe side effects of excess E 35-75 ug doses --> primarily works by PREVENTING FERTILIZATION via maintenance of the anti-sperm secretions Not as effective, but good for those who cannot use E Breakthrough bleeds, irregular menses

Answer 11

Depoprovera (Progestin) 150 mg IM dose EVERY 3 MONTHS Side effects --> decreased bone density, possible infertility in future

Answer 12

Work for 3 years!!!! Arm implants (filled with levornegestrel-progestin) Both have good restoration of fertility after the drug is ceased

Answer 13

Regulated cycles, decreased blood loss with menstruation, decreased cramps, correction of anemia, decreased tension, increased libido, decreased ovarian cysts, decreased acne, decreased ovarian and endometrial gain

Answer 14

N/V, headache, tension, breast discomfort, anxiety, fatigue, depression, weight gain, adenitis, amenorrhea, cholasma (brown spots) Very bad effects --> decreased GLUCOSE TOLERANCE, reversible HTN, benign hepatomas, cervical cancer (HPV+ patients), breast cancer (giving lots of E!), venous thrombotic events (increased clotting factors, aggregation, etc) < 35 --> HYPERCOAGUABILITY is worse in PREGNANCY than on the pill > 35 --> CONTRAINDICATED because the hypercoaguability of taking it outweighs pregnancy

Answer 15

Morning After Pill! Can be used after HIGH RISK SEX and REDUCE ODDS OF PREGGO by 60-80% Super high dose of PROGESTERONE which stops ovulation if it has not yet occurred --> inhibits sperm with ANTI-SPERM SECRETIONS, fallopian tube motility and blastocyst implantation if it has already occurred ULIPROSTOL --> single 30 mg dose can be given within 5 days LEVONOGESTRAL (progestin) --> Plan B --> can be a single 1.5 mg dose or two 0.75 mg doses and must be taken within 72 hours; OTC for women over 17; more side effects N/V, H/A, abdominal pain, dysmenorrhea, dizziness

Answer 16

Anti-Progesterone ABORTIFICANT that can be taken AT ANY POINT IN FIRST TRIMESTER to terminate a pregnancy When pregnant, P is required for MAINTENANCE of the endometrium early --> BLOCK P's EFFECTS at its receptor --> Causes DETACHMENT OF UTERINE LINING --> fetus detaches too MUST BE GIVEN WITH MISOPROSTOL IN ORDER TO FACILITATE CONTRACTIONS (remember?!?!) and EXPEL THE LINING

Answer 17

MAINLY DUE TO LOW ESTROGEN Hot flashes Vasomotor effects Osteoporosis Urogenital Atrophy

Answer 18

ESTROGEN REPLACEMENT (no uterus) COMBO THERAPY (uterus - P protects endometrium from E!) These therapies given in E doses less than 25% that of normal OCPs Can be conjugated equine estrogen, estrone sulfate, estradiol transdermal patch, vaginal cream (cream for women on aromatase inhibitors because it stays more LOCAL) ERT and HRT both VERY EFFECTIVE at decreasing menopausal symptoms, get more effective at high doses WHI study no increase of breast cancer risk, DECREASE colon cancer risk!

Answer 19

CV effects -- stroke, MI, VTE --> because of this, only recommended for patients who have DEBILITATING menopausal symptoms; could be worse in elderly Increased DEMENTIA, cognitive loss Increase ENDOMETRIAL CANCER RISK only on HRT which is approved for patients with a uterus only Estrogen proliferation in the UTERUS so there is an increased risk of uterine cancer

Answer 20

TERATOGENS

Answer 21

50% of US pregnancies are UNPLANNED Women may be taking drugs that are fine for them but teratogenic to their unborn baby if they don't know they are pregnant A lot of detrimental effects occur in the FIRST TRIMESTER (critical period of organogenesis) so this is a significant problem

Answer 22

A good alternative to the categories --> Super blunt and says "this drug will harm your baby" or "this drug increases risk of cardiac malformations" --> will also say WE DONT KNOW (better than category C or D) Let's us know what it's based on (animal studies, human studies) and where to ACCESS data Clinical considerations too --> risk of inadvertent exposure, risk of untreated comorbidities, dosage changes for medications already taken

Answer 23

Marketed as a NON-BARBITUATE sedative Used for nausea, available without prescription; FDA never approved its use here in the US, so most cases were in Europe Epidemic of infants born with ABNORMAL LIMBS (PHOCOMELIA) 20-30% of the babies were affected, but this just shows that NOT EVERYONE IS SUSCEPTIBLE TO TERATOGENS PLACENTA was thought to be protective, but THALIDOMIDE PROVED THIS WRONG

Answer 24

Was tested in animals, but it just precipitated, never really getting into the system This DOES NOT MEAN that animal studies aren't relevant MOST DRUGS THAT ARE TERATOGENIC IN HUMANS ARE TERATOGENIC IN ANIMALS TOO --> Misoprostol is an exception BUT, the reverse is not always true --> A drug that is NOT teratogenic in animals doesn't mean it won't be in humans Nowadays, also very important to prove that drugs are not only non-teratogenic, but GOOD FOR THEIR INDICATED USE TOO

Answer 25

3-4% are born with birth defects while 4-5% of those are due to drugs/chemicals

Answer 26

GENETICS - fetus' susceptibility depends on the genotype and the way it interacts with environment; not all thalidomide embryos had problems; CYP enzymes differ in racial groups, may be SPECTRUM of effects TIMING - Susceptibility to teratogens varies; depends on the developmental stage at time of exposure SPECIFICITY - Some drugs act in specific ways on developing cells and tissues, causing characteristic malformations (Thalidomide - limbs, Topiramate - cleft lip, Valpro - Neural tube defects) DOSE EFFECT - Manifestations of abnormal development increase in degree as the dose increases --> from no effect to totally lethal; more drug more seal babies

Answer 27

Animal studies - generally use HIGHER DOSES for animals; also the same effects don't occur in animals/humans (they have TAILS for example) Case Reports - important for thalidomide, but WE DONT KNOW THE DENOMINATOR (3/3000? 3/300? 3/50?) Case-Control - Generally better than case reports; RETROSPECTIVE (start with outcome, work back to exposure); relies on RECOLLECTION; good for moderate risk teratogens Cohort - Tend to be PROSPECTIVE and start with exposure; takes out recollection aspect; but the limit is that we are EXPOSING a woman to find a trend!!! Human studies also only consider LIVE BIRTHS - don't talk about babies killed in utero! Some teratogenic effects may be very long term, like cognitive or cancers, and we won't be able to trace it back to being teratogenic in nature

Answer 28

Causes CNS effects, facial changes; 30-50% risk in chronic binge drinkers Most common cause of drug-induced birth defects and a leading cause of intellectual/developmental disability FAS -- flat midface, indistinct philtrum, low set ears, think upper lip, low nasal bridge

Answer 29

Can all cause CV malformations in the FIRST TRIMESTER, prolonged renal failure, decreased skull ossification, renal tubular dysgensis in 2nd/3rd EQUALLY AS BAD (all Anti-HTN) --> they are CATEGORY D in the 2nd or 3rd, and CATEGORY C in the 1st

Answer 30

PROPYLTHIOURACIL, METHIMAZOLE Fetal/neonatal goiters and hypothyroidism HYPERthyroid MUST be treated during pregnancy!! But these drugs may cause adverse effects, oh well Recommended to use PROPYLthiouracil in the FIRST TRIMESTER and then switch to METHIMAZOLE

Answer 31

Neural tube defects!

Answer 32

Small for gestational age!

Answer 33

Vaginal CARCINOMA for girls exposed in utero!!!! GU defects in female and male offspring 50% females

Answer 34

Neonatal hypoglycemia NEED TO KNOW DM status of mother Was it BEFORE preggo? If so --> Type I are kept on normal insulin If type II -- oral hypoglycemic are SWITCHED TO INSULIN during pregnancy --> insulin has been shown to CONTROL BLOOD SUGAR better and we want to have VERY TIGHT CONTROL as high blood sugar is bad for the baby) Maternal diabetes can cause CAUDAL REGRESSION SYNDROME, congenital heart defects, neural tube defects

Answer 35

EBSTEINS ABNORMALITY --> atrialized right ventricle

Answer 36

Folic acid inhibitor --> CNS and Limb malformations!!!!

Answer 37

Constriction of the DUCTUS ARTERIOSUS Also INHIBIT prostaglandins which can SLOW LABOR (PGs can be used to induce labor) --> this can increase bleeding risk

Answer 38

Facial and CNS defects; 10% full blown, 30% partial

Answer 39

Neonatal WITHDRAWAL syndrome if taken late Withdrawal from alcohol/barbs can be fatal!

Answer 40

Small for gestational age Causes vasoconstriction --> OXYGEN DEPRIVATION IN FETUS Nicotine ALONE IS NOT TERATOGENIC --> have them on the patch during pregnancy!!! Spontaneous abortion, perinatal death, premature birth, general pregnancy complications, intrauterine growth retardation, congenital malformations ***FASTEST GROWING SET OF NEW SMOKERS IS ADOLESCENT GIRLS***

Answer 41

CNS, craniofacial, CV or other defects 25% have anomalies 40% miscarriage rate CATEGORY X!!!!! No safe dose ever justified when pregnant; need to take pregnancy tests when taking it to make sure you aren't pregnant/reduce risk of inadvertent exposure

Answer 42

Neural tube defects (spina bifida) --> 1% risk Inhibits folate absorption

Answer 43

Skeletal and CNS defects; DANDY WALKER syndrme 17-30% USE LOW MOLECULAR WEIGHT HEPARIN

Answer 44

Can cause OCP FAILURE (carbamezapine, Valpro, Phenytoin, Phenobarb) Be advised to use TWO FORMS OF BIRTH CONTROL or to INCREASE ESTROGEN in OCP --> these drugs INDUCE CYP450 THAT METABOLIZES ESTROGEN!!!!

Answer 45

Seem to have a "class effect" like ANTI-HTN May be a very small increase in CV abnormalities when using PAROXETINE during 1st trimester SERTRALINE may cause pulmonary HTN during 3rd When it comes to depression and the terrible effects it could have, then the benefit probably outweighs the risk

Answer 46

Antithyroid Enzyme inducers Drugs producing dependence Oral hypoglycemics Anticoagulants CNS depressants Ototoxic agents

Answer 47

HORMONE THERAPY OF CANCER

Answer 48

Seeks to manipulate the production and/or action of specific, endogenous hormones that typically promote malignancy MAINLY FOR BREAST AND PROSTATE CANCER Goal is to PREVENT PROLIFERATION OF PRIMARY TUMORS or METASTASIS in response to ESTROGENS (Breast) or ANDROGENS (Prostate) Drugs designed to either BLOCK their action or PREVENT their synthesis Found when women with breast cancer started showing smaller tumors when their OVARIES were removed!!! In 60-70% of breast cancers, malignant cells express ESTROGEN RECEPTORS!!!!!!!

Answer 49

GnRH released from HYPOTHALAMUS (pulsatile fashion!) GnRH travels to ANTERIOR PITUITARY and acts on GONADOTROPIC RECEPTORS LH and FSH ARE STIMULATED and these ACT ON THE OVARIES OR TESTES Stimulates the PRODUCTION OF ESTROGEN and PROGESTERONE or ANDROGENS These steroids have secondary actions on BREAST TISSUE (mammary glands) OR THE PROSTATE

Answer 50

BLOCK STEROID ACTION All roids exhibit a flat, planar structure; after they are produced, they FREELY DIFFUSE ACROSS MEMBRANES and enter the cytoplasm of nucleus Sometimes they are converted to HIGHER AFFINITY HORMONES (T --> DHT via 5-a-reductase) These then bind a SPECIFIC RECEPTOR --> conformational change that transports the complex to the nucleus and BINDS THE DNA SO! Steroids can act as DNA ENHANCERS!!! Increasing transcription/translation Since a large majority of steroid-targeted genes are involved in tissue-specific proliferation, excess hormones can ultimately promote TUMOR GROWTH --> THIS IS WHY WE BLOCK STEROID ACTION

Answer 51

All steroids come from a COMMON CHOLESTEROL PRECURSOR --> this includes sex hormones We generally tend to target the END STAGE STEPS to prevent side effects of having no steroids at all, as long as we still block SEX STEROIDS then all is good! 3 ENZYMES TARGETED AROMATASE: Androgens --> Estrogen 5-ALPHA-REDUCTASE: T --> DHT 17-ALPHA HYDROXYLASE (earlier step)

Answer 52

Selective Estrogen Response Modulators TAMOXIFEN!!!!! RALOXIFENE (less side effects)!!!! FULVESTRANT --> estrogen antagonist!

Answer 53

Selectively targets estrogen receptors in the mammillary epithelial tissue PREVENTS A CONFORMATIONAL CHANGE SO NO COACTIVATORS CAN BIND --> HALTS TRANSCRIPTION!!!!!! Blocks ALL ESTROGEN STIMULATED PROTEINS FROM BEING TRANSLATED Indicated as FIRST LINE ADJUVANT (usually with aromatase inhibitors) following resection of an estrogen sensitive tumor to prevent residual disease and metastasis; 5-10 year course Metastatic Breast Cancer CHEMOPREVENTATIVE agent in those predisposed!!

Answer 54

CYP450 metabolizes Tamoxifen extensively (6 metabolites) MAJOR = N-desmethyltamoxifen MINOR = 4-hydroxytamoxifen N-des is then broken to ENDOXIFEN WHICH IS THE ACTIVE METABOLITE CYP2D6 mediates Tamox --> 4hydroxy and N-des --> Endoxifen steps: Patients may have polymorphism that determines the efficacy! HIGH ACTIVITY CYP2D6 IS BETTER (more metabolism to the active metabolite) SSRI may BLOCK CYP2D6 so that there is POOR CONVERSION VERY LONG HALF LIFE!!! Parent = 7 days, N des = 14 days (can "forget" to take the drug and it won't matter for a couple days"

Answer 55

Positive *besides treating breast cancer* = DECREASES LDL and LIPOPROTEINS SLOWS DEVELOPMENT OF OSTEO Side effects --> systemic estrogen receptor binding will cause: INCREASED INCIDENCE of ENDOMETRIAL CANCER (pro-estrogen in uterus!!!!); eye diseases, frequent HOT FLASHES, thrombocytopenia, CV problems After 5-10 years, most tumors DEVELOP RESISTANCE TO TAMOXIFEN

Answer 56

Oral SERM with less side effects than Tamoxifen Binds to BOTH ALPHA AND BETA ESTROGEN RECEPTORS WITH HIGH AFFINITY In the breast tissue, it is an ESTROGEN ANTAGONIST, preventing proliferation Estrogen agonist in BONE!!! Good! Prevents osteoporosis!!!!! Used for INVASIVE BREAST CANCER, PREVENTION IN HIGH RISK, AND OSTEOPOROSIS!!!

Answer 57

Extremely effective ESTROGEN ANTAGONIST Indicated for POST-MENOPAUSAL WOMEN who have progressed to METASTATIC WHILE ON TAMOXIFEN Simultaneously causes DEGRADATION OF RECEPTORS WHILE ALSO ANTAGONIZING IT!!!! Side Effects --> GI effects, headache, back pain, hot flashes IM once/month

Answer 58

Aromatase is involved in the synthesis of estrogen and converts ANDROSTENIDIONE --> ESTRONE and TESTOSTERONE to ESTRADIOL Inhibit this, so ESTROGENS ARE NOT PRODUCED ANASTRAZOLE, LETROZOLE (non-steroidals) EXEMESTANE (steroidal) Steroidals (EX) --> substrate analogs that act as "suicide" inhibitors, IRREVERSIBLY INACTIVATING AROMATASE Non-steroidals --> interact REVERSIBLE with the heme group of CYP enzymes VERY EFFECTIVE! After one week serum estrogen is brought BELOW DETECTABLE LEVELS (and does not affect cholesterol or aldosterone) Shown to INCREASE DISEASE FREE & OVERALL SURVIVAL and decrease risk of CONTRALATERAL TUMORS! ***FIRST LINE TREATMENT FOR ESTROGEN POSITIVE BREAST CANCERS (60-70%)*** Used instead of or AFTER tamoxifen EXEMESTANE good for PREVENTION

Answer 59

***POST MENOPAUSAL WOMEN ONLY!!!!!!! If given to PRE menopausal women, the estrogen reduction would be SO SIGNIFICANT that the anterior pituitary would give out MASSIVE LH AND FSH!!! This would stimulate the ovary to abnormally hyperproliferate and hyperovulate, potentially RUPTURE

Answer 60

Generally well tolerated Minor effects due to the significant drops in estrogen, closely resemble MENOPAUSAL symptoms Enhanced osteoporosis and joint pain Long term use associated with RESISTANCE

Answer 61

FLUTAMIDE BICALUTAMIDE Non-steroidal, oral, FIRST LINE FOR ADVANCED METASTATIC Side effects - both metabolized by the liver to active compound, thus they can cause HEPATIC TOXICITY and LIVER FAILURE GYNECOMASTIA (larger amounts of estrogen relative to T --> alters mammary tissue) Loss of LIBIDO GI effects Bicalutamide has less side effects

Answer 62

Bind to androgen receptors in the prostate and seminal vesicles --> competitively inhibit the actions of T and DHT Blocks the proliferation/DNA enhancement Also block androgen-regulated NEGATIVE feedback on the anterior pituitary --> Massive LH and FSH surge that can target the testes and secrete a LOT of Testosterone in the peripheral circulation; could theoretically wash out the inhibition GIVE WITH GnRH ANALOGS to PREVENT THIS (downregulates the HPA)

Answer 63

GOSERELIN LEUPROLIDE Persistent elevation of GnRH --> Gonadotrope receptors in anterior pituitary DOWNREGULATE so that FSH and LH production DECREASES --> has a DOWNSTREATM EFFECT on the PRIMARY SEX ORGANS --> Limits Steroid Hormone Production 80-100x more potent than GnRH itself! Essentially acts as a chemical oophorectomy or orchidectomy in patients with breast/prostate cancer Initially, may have a BRIEF STIMULATION before the downregulation/inhibition sets in --> TUMOR FLARES can be painful, especially in metastatic bone disease; so give with HORMONE ANTAGONISTS TO SHUT IT OFF AT ONCE Side Effects --> Hypogonadism, loss of libido, hot flashes, dryness, vaginal atrophy

Answer 64

FINASTERIDE Orally administered steroid Alternative to surgery for BPH Targets receptors in HAIR FOLLICLES so it can cause baldness!! Could potentially PREVENT BPH --> but the tumors that DID emerge (even though there were less overall) were MORE aggressive Competitively inhibits 5-ALPHA REDUCTASE in selective target tissue; this will PREVENT T-->DHT Decreasing DHT HALTS EXCESSIVE PROLIFERATION --> improves urinary outflow, shrinks the prostate

Answer 65

Glucocorticoids in cancer Indicated at EXTREMELY HIGH DOSES in combo therapy for: ALL, CLL, MYELOMA, HODGKINS/NHL Complete remissions with chemo are SIGNIFICANTLY improved when prednisone is added Metabolism --> Immediately comverted to PRENISOLONE --> acts directly on lymphocytes, stimulating receptor-mediated apoptosis Side effects --> extensive, affects almost every organ; continuous administration --> RESISTANCE

Answer 66

SERMS - TAMOXIFEN, RALOXIFENE (estrogen antagonists) FULVESTRANT -- extremely effecting estrogen antagonist

Answer 67

ANASTRAZOLE LETROZOLE EXEMSTANE Prevent T --> estradiol conversion POST MENOPAUSAL WOMEN ONLY!!!!!! in premenopausal, no inhibition, massive LH/FSH, hyperstimulated ovaries!

Answer 68

FLUTAMIDE and BICALUTAMIDE (anti-androgens!!!!)

Answer 69

GnRH analogs (DOWNREGULATE SYSTEM) GOSERELIN LEUPROLIDE

Answer 70

FINASTERIDE (inhibits 5-alpha reductase -- so no conversion of T --> DHT)

Answer 71

GLUCOCORTICOID --> ORAL PREDNISONE

PHARM - Reproduction Flashcards

(95 cards)