Pharmacology Nursing 3703 By Linda Self

   Pregnancy is dynamic state with legion of physiologic changes Maternal-placental-fetal circulation— drugs readily cross placenta Placental transfer occurs by fifth week of gestation

    Drugs enter fetal circulation, are active as fetus has low levels of albumin, thus low drug binding Drugs to liver slowly metabolized due to immaturity of liver Drugs excreted by kidney into amniotic fluid where fetus swallows Blood-brain barrier poorly developed so many drugs readily cross

  Can use knowledge of maternal-fetal circulation to deliver meds to fetus Examples include: digoxin for fetal tachycardia, Synthroid for hypothyroidism, PCN for exposure to syphilis, corticosteroids to accelerate surfactant production in preemies

    Give meds only when absolutely necessary Drugs chosen should be based on stage of pregnancy and known information Any drugs used should be in the lowest possible dosages Live viral vaccines should be avoided due to possible harm to fetus

  Drug teratogenicity likely to occur 1 st trimester 2 nd and 3 rd trimester effects vary. May result in growth retardation, respiratory problems, infection, bleeding or congenital heart problems

 Drugs taken at any time during pregnancy can affect baby’s brain because brain development continues throughout pregnancy and after birth

    Folic acid supplementation important to prevent neural tube defects All women of childbearing potential should ingest 440-600 mcg of folic acid from food +/or supplement Pregnancy, need 800mcg Ginger is ok for nausea

     A—studies in pregnant women reveal no risk B—animal studies reveal no risk to fetus C—risk unknown D—positive evidence harm X—contraindicated, risks outweigh benefits

  Coumadin—spontaneous abortion, congenital anomalies. Heparin is anticoagulant of choice in pregnancy.

Anticonvulsants-high rate of abnormalities. Dilantin, Tegretol, Depakote are category D.

    NSAIDs can cause congenital heart abnormalities. Cat. D.

ASA associated with bleeding. Cat. D.

Cautious use of antihypertensives. Methyldopa for hypertension in pregnancy.

May see hydralazine or labetalol in acute situations.

  ACE inhibitors and ARBs contraindicated. Can cause renal defects, craniofacial abnormalities, fetal limb abnormalities. Ex. Enalapril, captopril, amlodipine.

Antibiotics considered acceptable: azithromycin, cephalosporins, penicillins, clindamycin, erythromycin

    TCAs Cat. D Some SSRIs Cat. C but studies reveal relationship w/heart defects, craniosynostosis, anencephaly Insulin is treatment of choice for diabetics in pregnancy. Not aspart or glargine.

Lithium—cardiac defects, thyroid abnormalities

   Anemias: iron deficiency, physiologic and megaloblastic Iron supplements may be appropriate if iron deficiency anemia Folic acid supplementation in megaloblastic anemia

  Constipation secondary to decreased peristalsis, increasing uterine weight on intestines Treat with psyllium, docusate or MOM

  GERD-increased abdominal pressure, relaxed esophageal sphincter. Small meals, avoid caffeine, may give Zantac if necessary. Avoid PPIs.

No Pepto-Bismol

   Gestational diabetes-tested weeks 24-28 Tx with nutrition and exercise If needed, best to use insulin or acarbose (decreases digestion of CHO in gut)

   Nausea and vomiting—crackers when awakening Vitamin B6 may help Zofran and Reglan both Category B

    Grp B streptococcus-do vaginal culture at 35-37 weeks. If positive, tx with antibiotics at onset of labor until delivery.

HIV-HAART. Goal is to achieve RNA load <400 copies/ml.

Tx reduces transmission to fetus by 2/3s. During labor, treat with IV zidovudine.

   Treat infant of HIV+ mother with zidovudine for 6 weeks Children with HIV infection, treat with Bactrim by 4-6 weeks UTIs—treat asymptomatic bacteriuria to prevent preterm deliveries, cystitis and pyelonephritis. Macrodantin, possibly cephalosporin or pcn.

   Abortion is termination of pregnancy before 20 weeks gestation Prostaglandins stimulate uterine contractions—can be used to induce abortion Cytotec (misoprostal) often used to tx gastric ulcers. PO or intravaginally to induce parturition

     Drugs used to inhibit labor and maintain pregnancy Uterine contractions between <37 weeks with cervical changes are considered premature Tocolytics may prolong pregnancy in order to provide steroids (resp. develop.) Can use nifedipine, terbutaline, Indocin Magnesium sulfate under debate but still used

   Oxytocin stimulates uterine contraction and “let-down” Pitocin is synthetic form of oxytocin May be used to induce labor and/or control uterine bleeding after delivery or to complete incomplete abortion

      Parenteral opioids used to control pain during labor and delivery Morphine, meperidine, fentanyl Meperidine less neonatal resp. depression Stadol (butorphanol) Epidural analgesics—Duramorph, fentanyl, morphine Epidural anesthetics-bupivacaine

  Ophthalmia neonatorum can cause blindness. Chlamydia trachomatis. EES to each eye at birth. Also useful for GC.

Vitamin K is administered to prevent hemorrhagic disease. Infant has immature liver, lack intestinal bacteria (synthesize vitamin K). One dose of phytonadione 0.5 to 1mg.

  Most systemic drugs taken by mother reach infant in breast milk Women with HIV should not breast feed

   Endogenous estrogens and progesterone synthesized from cholesterol Estrogen synthesis in adipose tissue may be significant source of estrogen. Requires a minimum body weight and fat content (16-24%) Interrelationship of estrogens and progesterone on each others receptors

    Composed of three types Estradiol major estrogen Purpose—promotes growth in tissues r/t reproduction and sexual characteristics in women Menstrual cycle—1 st half, increasing levels of estrogens, 2 nd half, estrogen and progesterone continue to rise then stop abruptly. Endometrium then sloughs.

  Placenta produces large amounts of estrogen during pregnancy Causes enlargement of uterus, growth of glandular tissue in the breasts, broaden pelvis

   Secreted by corpus luteum Cause changes in second half of cycle which provide for implantation and nourishment of a fertilized ovum If ovum is fertilized, progesterone acts to maintain pregnancy

    Corpus luteum produces progesterone during first weeks of gestation Placenta then takes over Progesterone prepares breasts for lactation by promoting development of milk-producing cells Synthetic progestins affect LDL and HDL and may decrease glucose tolerance

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Act by: Inhibit hypothalamic secretion of gonadotropin releasing hormone, in turn inhibits FSH and LH. No ovulation thus no conception.

Produce cervical mucous that resists penetration of sperm into reproductive tract Affect endometrial maturation and reception of ova

       Component of birth control pills and other preparations for women 12-45 Contraindicated in pregnancy Relieve vasomotor symptoms r/t estrogen deficiency===ERT HRT—no unopposed estrogen For delayed sexual development DUB

Debate is on whether benefits outweigh risks

   Oppose estrogen Suppress ovarian function in dysmenorrhea, endometriosis, endometrial cancer and DUB

Debate on whether therapeutic or too many risks

   Control fertility and prevent pregnancy Contraception after “unprotected” sex Menstrual disorders (amenorrhea, dysmenorrhea)

       Known or suspected pregnancy— teratogenic Thromboembolic disorders Cancers of breast or genital tissues Undiagnosed vaginal or uterine bleeding Fibroid tumors Altered liver function Gallbladder disease

   History of cerebrovascular disease, coronary artery disease, thrombophlebitis, hypertension Women over 35 yo who smoke Family history of breast or reproductive system cancer

      Conjugated estrogens (synthetic) Cenestin Conjugated estrogens –Premarin Estradiol-Estrace Estradiol hemihydrate—Vagifem Estradiol transdermal—Estraderm, Climara, Vivelle Estrone—injection weekly

  Palliative in metastatic breast cancer (when anti-estrogens become less effective) Black box warning: estrogen w or w/o progestins increase lipids, coagulation and possibly promotion of cancer

   With minimal androgenic effects include: desogestrel, norgestimate Intermediate androgenic activity: norethindrone and ethynodiol High androgenic activity : norgestrel

   Depo-Provera and Provera (medroxyprogesterone) Megace (megestrol acetate) Aygestin (norethindrone acetate)

    Micronized for oral use Does not have the negative lipid panel effects For amenorrhea, DUB Oppose estrogens in women with intact uterus

    Usually contain a synthetic estrogen and a synthetic progestin Monophasic—fixed amounts of estrogen and progestins Biphasics—fixed amounts of estrogen with varying doses of progestins Triphasics—varied amounts of both estrogen and progestins

     Monophasics—Alesse, Loestrin, Ortho Novum, Yasmin, Yaz, Zovia, many more Biphasics—Mircette, Ortho-Novum Triphasics—Estrostep, Tri-Levlen, Triphasil *(with varying levels of hormones, fewer side effects) Progestin Only—Depo-Provera, Ortho Evra, others

  Implanon—progestin only, 3 years, single rod Mirena—IUD impregnated with levonogestrol, 5 years

     Reason for use Desired route Duration of action Transdermal estradiol –decreases dosage needed, more like natural level Progestin component can cause acne, weight gain, lipid levels

    Anti-seizure medications and antibiotics can decrease effectiveness of the OCP Estrogens can decrease effectiveness of sulfonylurea antidiabetic drugs (increase their metabolism) Warfarin effectiveness decreased Decreased Dilantin (phenytoin) effectiveness

     Plan B (levonorgestrel) Only product on market for avoidance of pregnancy after unprotected intercourse Most effective within 24h and <72h Inhibits ovulation No effect on pregnancy after implantation

    Vasomotor s/s ? Memory Bone health GU health

   Inability to conceive after 12 months of contraceptive-free intercourse 1 in 10 couples degree of infertility May opt for ovulation induction by use of Ovid (HCG choriogonadotropin alpha— like LH) used with Pergonal (menotropins—contains both FSH and LH)

   Clomid (clomiphene) is nonsteroidal estrogen receptor modulator Inhibits negative feedback mechanism of hypothalamus by competition with receptors Signals hypothalamus to release gonadotropin releasing hormone>>>increases FSH and LF>>promotes follicular maturation and ovulation

   Preparation of human gonadotropins FSH and LH. Once follicles ripen, hCG is administered.

Use this drug when gonadotropin secretion is insufficient Adverse effects: ovarian enlargement, multiple births, spontaneous abortion

   Usually produced by placenta Similar in action to LH Exogenous use induces ovulation in owmne who have ovulatory failure

   Testosterone primary male sex hormone Secreted by Leydig’s cells Instrumental in development of male sexual characteristics, reproduction, and metabolism

     Male sexual characteristics Promotes stimulus for descent of testes into the scrotum—usually after 7 th month of pregnancy 11-13 years, surge of testosterone Consistent secretion until about 50 Skin thickens, body hair, bones thicken, laryngeal enlargement, skeletal muscle (slows loss of N+ and amino acids)

    Synthetic drugs with increased anabolic activity and decreased androgenic activity in relation to testosterone Used for tissue building and growth stimulating effects For cryptorchidism Schedule III

      Indications: Low testosterone levels in males (see text) Muscle wasting as seen in HIV/AIDS Delayed puberty For growth stimulation To increase libido

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Serious side effects: Fluid retention hyperglycemia Decreased testicular function and impotence Liver disorders—neoplasms, cholestatic hepatitis HTN, elevated LDL, decreased HDL Heart damage Aggression, hostility, combativeness May cause premature baldness

     Depo-testosterone Androgel (testosterone gel) Android (methyltestosterone) cryptorchidism Androderm (testosterone transdermal) Danazol endometriosis

   During pregnancy Liver disease Prostate disease

  In up to 42% of men ages 40-70 yo Multi-causation

   With stimulation, acetylcholine enhances production of nitric oxide Nitric oxide activates activity of enzymes>>cGMP (vasodilatory) Inflow of blood increases secondary to this relaxation Also with secondary effect on cAMP which contributes to an erection

  Cause decreased catabolism of cGMP (concentrated in genital tissue) Cause increasing cAMP which results in an increase of arterial blood flow to corpora

   DM, HTN, depression History of dysfunction Use of testosterone is indicated for decreased libido

   Concurrent use of nitrates Concurrent use of alpha adrenergic blocking agents like Flomax (tamsulosin), Hytrin (terazosin) Cautin in those with cavernosal fibrosis, Peyronie’s

   Viagra (sildenafil) Cialis (tadalafil) Levitra (vardenafil)

   Adjust doses in those over 65, in those with renal or hepatic disease or those taking EES, ketoconazole, cimetadine, antiretrovirals SE—HA, blue vision, nasal congestion, dyspepsia, dizziness Ensure is cardiovascularly fit to take med

   Yohimbe—psychoactive, aphrodisiac Ginseng—increases energy and resistance Multiple herbals