Butalbital and Caffeine

•Butalbital

–Pregnancy Category C, can see neonatal withdrawal symptoms with long-term use

–Lactation – not recommended

•Caffeine

–Pregnancy Category B, doses generally lower than that in coffee

–Lactation – compatible

Dichloralphenazone and Isometheptene (Midrin)

•Dichloralphenazone

–Pregnancy Category B

–Lactation – similar agent considered compatible

•Isometheptene

–Pregnancy Category C, extremely limited data

–Lactation – potentially compatible

Questions to Ask:

•Are there alternative therapies?

•Can treatment wait until postpartum?

•Is the disease worse than the therapy?

•What does the available literature say?

Questions to Ask:

•Is this drug used in neonates?

•How old is the infant?

•What is the duration of therapy?

•What are the pharmacokinetics of the agent?

•What is the risk/benefit for the mother?

•Does this medicine cause problems in G6PD deficiency?

Considerations in Breastfeeding:

• Withhold or delay therapy if possible

•Use a drug with poor penetration into milk

•Use an alternate route of administration

•Avoid nursing at peak drug concentrations

•Give drug before infants longest sleep

•Pump and dump milk

•Discontinue breastfeeding

Neuro-humoral system of woman is aimed for keeping uterus’ muscle relaxed during pregnancy. It’s possible because of increasing of blood levels of steroid hormone progesterone which is “pregnancy protector”

Both estrogens and proges-terone are increased during pregnancy but proges-terone prevails

Influence of steroid hormones

Progesterone performs its acton on uterus only in case estrogenes are synthesised enough by corpus luteum

and placenta

In other case, progesterone looses its relaxing action on uterus’ muscle

Progesterone

Increases level of adenosinmonophosphate (AMP) which ties Са2+ ions and blocks actine-myosine contractions

Increases membrane potential of myocyte and particularly blocks impulses between myocytes

Myometrium becomes insensitive to irritatons

Since placenta is formed, progesterone is synthesized by it.

Consequently, placental site is more relaxed than the rest of myometrium

Keeps its relaxing action even in case of retention of the part of the placenta inside of the uterus in puerperium.

It can provoke sub-involution of uterus and post-partum bleeding

Influence of steroid hormones

Before labor level of progesterone decreases and estrogenes are rised

Estrogenes take out myometrium block

Membranes of myocytes become sensitive to:

oxitocine,

prostaglandines,

catheholamines ,

serotonine.

Mechanism of myometrium contractions

Depolarization of membtanes

Releasing of Ca2+

Interaction of calcium ions with contractive proteins.

Myometrium has alpha and beta-adrenoreceptors.

Stimulation of alpha-receptors by catheholamines causes uterus contraction

Stimulation of beta-receptors by catheholamines causes uterus relaxation

Uterus body contains alpha and beta catheholamines receptors

Lower segment contains choline and serotonine receptors

Cervix contains chemo-, baroand mechanoreceptors

Uterotonics and tocolytics drugs

Uterotonics increase uterine contractions (oxytocine, prostaglandines, serotonine, kinines, cathecholamines).

Tocolytics decrease uterine contracions (spasmolytics, beta-receptor-stimulating medications, anti-oxytocin

drugs).

Oxitocine

It’s a hormone of supra-optic and para-ventricular nuclei of hypothalamus

Transported to pituitary by axons

Performs its influence on membranous level

Prostaglandines

Play very big role in preparing to labor and delivery onset.

“Tissue hormones” are made from fatty (lipid) acides

Nowadays synthetic analogues of E2 and F2-alpha prostaglantines are popular because of their high

activity

E2 medications (dinoprostone, prepidil-gel, 1 mg) prepare cervix for labor (makes it “ripe”)

F2-alpha medications (dinoprost, enzaprost, i.v. 5 mg/ml) cause regular uterine contractions

Calcium-chanel-blocking agents:

Corinfar (nifedipine) 10 mg every 20 min until symptoms of threatening of pre-term labor are resolved

Key points of hormonal therapy of mascarriage

Hormonal medications should be strictly indicated;

Risk/benefit shoul be assessed thoroughly;

Individual dosage;

Prescription after 8 weeks of pregnancy should be preferred.

Gestagens

Progesterone 10-25 mg daliy;

Utrogestane 100 mg p.o. per vaginum 2 times per day (till 27 weeks);

Duphastone (didrogesterone) – 40 mg p.o.at once, then 1 pill (10 mg) 2-3 times daily.

Treatment of post-partum hemorrage

Oxitocine 5-20 IU

Methylergometrine — 1 ml i.m.

Prostaglandines

Students must know:

1.The main methods of assessment of fetal well-being in obstetrics

Students should be able:

L To perform an fetal heart tones auscultation.

2.To prescribe an adequate treatment of fetal hypoxia.

3.Ultrasonography assessment.

4.To evaluate of fetal heart tones during electronic fetal monitoring.

Literature:

1.Anderson, PO. Drug use during breastfeeding. Clin Pharm 1991;10:594-624

2.Academy of Pediatrics Committee on Drugs. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89.

3.Boothby LA, Doering PL. FDA labeling system for drugs in pregnancy. Ann Pharmacother 2001;35:1485-9.

4.Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation. 6th ed. Philadelphia, PA: Lippencott, Williams & Wilkins. 2002

5.Hale TW. Medications and Mothers’ Milk. 10th ed. Amarillo, TX: Pharmasoft Publishing 2002.

6.Micromedex, 2007 update, Thomson Healthcare, Inc

7.Medline searches for each agent