Pharm E2- OBGYN

What is the MC OTC med that women use during pregnancy?

Acetaminophen

What is any significant postnatal change in function or form in an offspring after prenatal treatment?

Teratogenesis

What are examples of known teratogens?

ACEi, androgenic hormones, Isotretinoin, warfarin, lithium, phenytoin, thalidomide, VPA, cigarettes, cocaine

Which is the most critical period for fetal development?

14-56 days post conception (organogenesis)

What particles cross the placenta easier?

Uncharged & smaller mw (250-500)

What is ion trapping?

fetal pH lower than mother → change in pH affects charge of drug, can cross but can’t get back out

(can happen in placenta or breast milk)

Which category shows low fetal harm through controlled studies which fail to demonstrate risk in the fetus during the first trimester (very safe in pregnant women)?

A

Which pregnancy category consists animal studies showing no risk to fetus with no controlled human studies OR animal studies have indicted risk but human studies did not (safe to use in pregnant women)?

B

What pregnancy category consists of animal studies that indicated risk but there are no human studies (majority of drugs; not enough evidence; weigh risk vs benefits)?

C

What pregnancy category consists of positive evidence for fetal risk but there may be certain situations where the benefits outweigh the risk?

D

What pregnancy category is absolutely contraindicated; there is a definite fetal risk and no risk outweighs any benefit in pregnant women?

X

What is the pH of breast milk?

6.35-7.67 (ion trapping can occur)

When do maternal physiologic changes occur during pregnancy?

begin 1st trimester & peak in 2nd

Albumin ______ during pregnancy, which increases the Vd for highly protein bound medications (higher free fraction → higher drug levels)?

Decreases

How does weight gain during pregnancy affect fat soluble medications?

Increased Vd (higher levels)

What are treatment options for nausea and vomiting in pregnancy?

Dietary changes, Pyridoxine (B6), Doxylamine (first gen antihistamine), Diclegis, Metoclopramide, Promethazine, 5-HT3 antagonists

Which medications used to treat N/V in pregnancy are more likely to cause sedation & have risk for extrapyramidal / Parkinsonian effects?

Metoclopramide & Promethazine

Which 5-HT3 antagonists can be used to treat N/V in pregnancy?

Ondansetron, Granisetron, Dolasetron (B)

Which treatment options for N/V are more expensive, can prolong QT, & are more likely to pass into breast milk (Mw- 400) but not expected to harm infant?

5-HT3 antagonists

When choosing a treatment option for heartburn in pregnancy, what should be avoided because it can worsen BP & edema?

Sodium bicarbonate & magnesium trisilicate

What are treatment options for heartburn in pregnancy?

Sucralfate, antacids in moderation (use low Na)

If no resolution → H2RAs then PPIs

What is the 1st step in managing constipation in pregnancy?

Inc fiber & water & moderate exercise

What is the drug of choice for constipation in pregnancy because they are not absorbed (no exposure to fetus)?

Bulk forming laxatives - Methylcellulose, Psyllium husk

What are other treatment options for constipation in pregnancy?

Surfactants / stool softeners (Docusate sodium - C),

Osmotic laxatives short term (Miralax, Lactulose, Sorbitol, Magnesium salts)

Stimulants short term (Senna, Bisacodyl)

What constipation treatment should be avoided in pregnancy due to decreased fat soluble vitamins absorption?

Mineral oil

Drugs affecting which vitamins should be avoided in pregnancy?

Fat soluble vitamins (ex Warfarin - vit K, Tretinoin- vit A)

What is the best preventative option for hemorrhoids in pregnancy?

Try to avoid constipation

Why are external topical products preferred for treatment of hemorrhoids?

Lower rate of systemic absorption compared to internal products

What are other treatment options for hemorrhoids in pregnancy?

Preparation H (hydrocortisone or phenylephrine), Tucks (witch hazel), Sitz baths

What is the drug of choice for diarrhea in pregnancy?

Stool bulking agents

What drug is category B and can be used to treat diarrhea by working peripherally on GI opioid receptors?

Loperamide

What condition is BP > 140/90 in the absence of proteinuria after 20 weeks gestation?

Gestational hypertension

What hypertension is preexisting or developed prior to 20 weeks gestation?

Chronic

What is hypertension accompanied by proteinuria (≥300 mg/24hr)?

Mild pre-eclampsia

What condition is characterized by elevated BP 160/110, proteinuria exceeds 5g/24hr or persistent dipstick of 3+, and or severe HA / visual disturbances / epigastric pain?

Severe pre-eclampsia

What condition consists of generalized tonic clonic seizures in a patient with pregnancy induced HTN?

Eclampsia

What is the non pharmacological management for HTN during pregnancy?

Activity restriction (but risk for VTE), stress reduction, exercise

*also daily Ca reduces risk (but can cause constipation)

What is the drug of choice for severe preeclampsia / eclamptic seizures?

Magnesium sulfate

What should be avoided in the treatment of eclamptic seizures (teratogenic)?

Benzodiazepines & phenytoin

What drug was the previous DOC for chronic HTN management during pregnancy that acts as a false neurotransmitter after metabolism by stimulating alpha 2 receptors & decreasing sympathetic outflow?

Methyldopa

What drug is a 3rd gen BB that is first line for chronic HTN management in pregnancy, available orally or IV?

Labetalol

What other agents are used to treat HTN in pregnancy?

DHP (2nd go to), nitroprusside or nitroglycerin for rapid IV tx

What is gestational diabetes (GDM)?

Any degree of glucose intolerance w/ onset or first recognition during pregnancy that usually resolves after delivery but puts pt at higher risk for T2DM

What is the drug of choice for GDM during pregnancy and lactation because it does not cross the placenta (category B)?

Insulin

What drug can be used to treat GDM by stimulating the pancreas to release insulin & minimally crosses the placenta?

Glyburide (Sulfonylurea)

What drug is an insulin sensitizer at the liver & skeletal muscle (tries to reverse insulin resistance) that can be used to treat GDM and lacks teratogenicity?

Metformin

What is the drug of choice for acute thromboembolism in pregnancy and has a longer ½ life?

LMWH (Enoxaparin)

How long should Enoxaparin be used for VTE treatment in pregnancy?

Minimum 3 months (continue throughout pregnancy & 6 weeks after delivery)

When should a UTI be treated in pregnancy?

Always, even if asymptomatic

What drugs can be used to treat UTIs in pregnancy?

*(all category B and safe for breastfeeding)

Nitrofurantoin (MC), amoxicillin, cephalosporin

What drug inhibits bacterial carbohydrate metabolism and disrupts bacterial cell wall formation (most frequently used in UTI tx)?

Nitrofurantoin (Macrocrystal)

What is the drug of choice for pain in pregnancy (cat B)?

Acetaminophen

What drug is cat B during 1st & 2nd trimester & cat D in 3rd trimester (premature closure of ductus arteriosus)?

NSAIDs

What drug is cat B during 1st & 2nd trimester for short intervals, but cat D if prolonged use or high doses at term?

Morphine

What is the safest/best option for treatment of postpartum depression (just 1 MOA)?

SSRIs

What are examples of SSRIs that can be used to treat postpartum?

Citalopram, Escitalopram, Paroxetine, Fluoxetine

What is a possible SE of SSRIs?

Potential for withdrawal SE (mom & baby)

Which SSRI has a 1.2-2 fold increased risk of cardiac malformations in the first trimester?

Paroxetine (Paxil)

What is the 2nd line option for postpartum depression (no adverse effects reported but gets excreted into breastmilk in low concentrations)?

TCAs - Amitriptyline, Nortriptyline, Desipramine

Who should take 400 mcg of folic acid daily?

All women capable of becoming pregnant (prevent NTDs)

Who should consume 4mg (higher dose) of folic acid beginning atleast 1 month prior to conception?

Women who’ve given birth to infant w/ NTD

What is the purpose of tocolytic therapy?

Postpone delivery (used when there’s regular contractions w/ cervical changes → relaxes uterine smooth muscle to delay)

What are the 4 classes of tocolytic therapy?

Beta antagonists, magnesium, CCBs, NSAIDs (Indomethacin)

What drug is a beta agonist (B2 selective) with similar effects to albuterol that is given IV or PO to delay delivery?

Terbutaline (Brethine)

What CCB appears to be more effective in postponing delivery than other gents (esp if HTN also present) & has fewer ADRs?

Nifedipine

What tocolytic option is preferred if hypotension is a concern?

Indomethacin

What tocolytic therapy option is given IM weekly from 16-36 weeks to high risk women with a history of preterm birth?

Progesterone (17-a-hydroxyprogesterone)

What drug is a PGE2 analog given vaginally to induce labor and removed when labor begins or after 12 hours?

(*must monitor fetal HR)

Dinoprostone (Cervidil)

What drug is a PGE1 analog that is used to induce labor, pregnancy termination, & treatment of NSAID induced ulcers?

Misoprostol (Cytotek)

What is the most commonly used agent to facilitate uterine contractions & induce labor?

Oxytocin (Pitocin)

What are possible ADRs of Oxytocin that can be seen in mother and baby?

Arrhythmia (PVC), bleeding due to depletion of fibrinogen

What is the most common epidural infusion for labor pain management?

Fentanyl + Bupivacaine

The following SEs are seen with what drug?

• hypotension, pruritus, inability to void

• prolonged 1st&2nd stages of labor (can’t feel contractions/urge to push)

• spinal HA due to puncture of subarachnoid space

• *no affect on fetus - stays in moms spinal column

Fentanyl/bupivacaine epidural

A patient is in their 3rd trimester and has a headache. What do you give them?

(*example test Q from lecture)

Acetaminophen

A patient is interested in becoming pregnant. They currently take Labetalol, Insulin, Captopril, and a flinstone prenatal gummy vitamin. Which of these is contraindicated in pregnancy?

(*example test Q)

Captopril

What is the major secretory product of the ovary?

Estradiol (converted to estrone & estriol in the liver or periphery)

What drug is made from estrogens (equilenin and equilin) made from horse pee (lol)?

Premarin

What are examples of synthetic estrogens?

Ethinyl estradiol (MC), micronized estradiol, estradiol cypionate, estradiol validate, estropipate

What drug?

• highly protein bound - alpha2 globulin & albumin

• metabolized in liver & excreted in bile → hydrolyzed in intestine to active re-absorbable compounds (colonic bacteria blocks off conjugated molecule & frees estrogen to be reabsorbed)

  • enterohepatic recycling ; extends half life

• high ratio of hepatic to peripheral effects dictated by dosage form

Estrogen

How would a 3A4 inducer (like Rifampin) affect estrogen?

Shorten half life & decrease levels

What is the MOA of estrogen?

Bound estrogens disassociate from SHBG → cross cell membrane → enter nucleus & bind receptors → forms dimers (Era & Erb) & binds to EREs → regulates various genes and transcription

*different actions in different tissues

What drug/hormone has the following clinical effects?

• stimulates development of secondary sex characteristics

• can cause long bone epiphyseal closure & stop growth phase

• develops endometrial lining

  • interaction w/ progesterone encourages regular bleeding & shedding

Estrogens

Why is progesterone needed along with estrogen (if intact uterus)?

Continuous exposure to estrogen leads to hyperplasia and abnormal bleeding

What metabolic effects does estrogen have?

dec bone resorption (stimulate apoptosis of osteoclasts & antagonize PTH), stimulate adipose development, higher serum protein, inc HDL & TG, reduce cholesterol

How does estrogen affect coagulation?

enhances → inc clotting factors & dec antithrombin III

Estrogen ____ edema & fluid retention

produces

How can estrogen treat primary hypogonadism?

replaces deficiency → can begin at 11-13 y/o, given on days 1-21 of each month

*progestin added after first uterine bleeding

What are clinical uses for estrogen?

Primary hypogonadism, postmenopausal hormonal therapy- sx mgmt, osteoporosis prevention/tx, intractable dysmenorrhea & excessive androgen secretion

What patient can receive estrogens alone?
(*test Q)

Patient with hysterectomy

Which patient needs progestin along with estrogen to reduce endometrial hyperplasia and cancer risk?

(*test Q)

Patient with intact uterus

What dosage form should be used for atopic vaginitis / vaginal symptoms alone?

Topical / Intravaginal

What are adverse effects of estrogen?

uterine bleeding (screen for cancer), inc breast cancer risk, adenocarcinoma, endometrial carcinoma (give progestin), N/V, breast tenderness, hyperpigmentation, migraines, cholestasis, HTN

What has the maternal use of diethylstilbestrol (DES) been linked to?

Adenocarcinoma

What are contraindications to estrogens?

Estrogen dependent neoplasms, undiagnosed genital bleeding, liver disease, thromboembolic disorder, heavy smokers

What hormone is most important to humans, produced in ovary, testis & adrenal cortex and is the precursor to estrogens, androgens, and adrenocrotical steroids?

Progesterone

What drugs are progestins?

Norgestrel

Levonorgestrel

Norethindrone

Norgestimate

Desogestrel

Drospirenone

What receptors do progestins also act at?

androgen receptors (AR) and mineralocorticoid receptors (AR, MR)

**masculizing SEs, swelling, HTN

How is progesterone metabolized?

rapidly absorbed, high first pass effect, excreted into urine

What is the MOA of progestin?

Works similarly to estrogen; binds to progesterone response element (PRE)

What drug/hormone has the following effects?

• inc basal insulin levels & insulin response to glucose

• competes w/ aldosterone in kidney → inc release of aldosterone

• maturation & secretory changes in endometrium

Progestin