Chapter 26 Drugs Used in Reproductive Endocrinology

I. Drugs That Act on the Uterus (Box 26-1)

A. Oxytocin

1. General considerations

a. Peptide hormone

(1) Synthesized in the hypothalamus

(2) Transported to the posterior pituitary by nerves (neurohypophysis)

(3) Stored in the posterior pituitary

(4) Released as needed

b. Has a facilitatory role in parturition

c. Essential element in the milk-ejection reflex

• Suckling stimulates oxytocin release, which leads to milk “let-down.”

d. Involved in several behaviors

(1) Mating

(2) Parental

(3) Social

(4) Emotional bond between mother and child

e. Oxytocin may have a protective role against stress-related diseases.

Oxytocin is referred to as an anti-stress hormone.

2. Mechanism of action

a. Stimulates contraction of uterine muscle

b. Stimulates smooth muscles of mammary glands

3. Uses

a. Induction of labor (IV infusion)

b. Control of postpartum hemorrhage (IM or IV infusion)

Oxytocin is used to induce labor and to manage postpartum bleeding.

c. Prevent bleeding post D & C (dilation and curettage) procedure (IM or IV infusion)

Oxytocin is used in contraction stress tests.

d. Treatment of incomplete, inevitable, or elective abortion (IV infusion; less common use)

e. Stimulate milk letdown reflex (intranasal)

4. Adverse effects

a. Fetus or neonate

(1) Arrhythmia

(2) Permanent brain damage

c. When vaginal delivery is contraindicated

(1) Abnormal fetal presentation

(2) Cephalopelvic disproportion

(3) Invasive cervical cancer

(4) Active genital herpes

(5) Prolapse of the cord

Don’t use oxytocin if vaginal delivery is contraindicated.

B. Prostaglandins

1. Examples

a. Dinoprostone (PGE₂)

b. Carboprost (PGF_2α)

c. Misoprostol (PGE₁ analogue)

2. Mechanism of action

a. Potent stimulation of uterine contractions

b. PGE₂ plays an important role in cervical ripening.

3. Uses

a. Induction of abortion

(1) Dinoprostone (PGE₂): intravaginal

(2) Carboprost (PGF_2α): IM

(3) Misoprostol (PGE₁ analogue): oral and intravaginal

b. Softening of the cervix (cervical ripening) before induction of labor (administered intravaginally)

Prostaglandins used for cervical ripening

c. Facilitation of delivery of intrauterine fetus (especially immature fetus)

4. Adverse effects

a. Prolonged vaginal bleeding

b. Severe uterine cramps

c. Gastrointestinal (GI) distress (systemic administration)

d. Carboprost is contraindicated in asthma

Carboprost contraindicated in asthma

C. Ergot alkaloids and related compounds

1. Examples

a. Ergonovine

b. Methylergonovine

2. Mechanism of action

a. Increases motor activity of the uterus

b. Results in forceful, prolonged contractions

3. Use to treat

a. Postpartum bleeding

b. Hemorrhage after miscarriage

c. Hemorrhage after D & C procedure

Ergot alkaloids should only be used post partum.

4. Adverse effects

a. Hypertension/hypotension

b. Bradycardia/tachycardia

c. Nausea and vomiting

d. Abdominal pain

e. Prolactin suppression

f. Acute myocardial infarction

5. Contraindication

a. Hypertension

Don’t use ergot alkaloids in hypertensive patients.

b. Toxemia

c. Pregnancy

D. Other drugs that affect the uterus

1. Nonsteroidal anti-inflammatory drugs (NSAIDs)

a. Mechanism of action

• Inhibit prostaglandin synthesis

b. Use

(1) Relief of cramps associated with menstruation (dysmenorrhea)

(2) Blocks endometrial synthesis of prostaglandins during menstruation

• NSAIDs are contraindicated in late second and all of third trimester; close ductus arteriosum necessary for fetal circulation.

Don’t administer NSAIDs during late second or third trimester of pregnancy; premature closure of ductus arteriosus.

2. β₂-Adrenoceptor agonist (see Chapter 5)

a. Examples

(1) Terbutaline (actually used)

(2) Ritodrine (approved by the U.S. Food and Drug Administration [FDA])

b. Mechanism of action

(1) Increases cyclic adenosine monophosphate (cAMP) via activation of β₂-adrenoceptors

(2) Relaxes uterine smooth muscle

c. Uses

(1) Prevention of premature labor (controversial)

(2) Relax hyper-stimulated (tetanic contraction) uterus

Terbutaline blocks hyper-stimulated uterus.

(3) Relax uterus for external version breech (turning of fetus)

3. Magnesium sulfate

a. Mechanism of action

(1) Required for movement of calcium, sodium and potassium out of cells

(2) Relaxes uterine muscle

(3) Reduces transmitter release

b. Uses

(1) Prevention of premature labor (tocolytic agent)

(2) Prevention and treatment of seizures in severe preeclampsia or eclampsia

(3) Treatment and prevention of hypomagnesemia

(4) Treatment of pediatric acute nephritis

(5) Treatment of torsade de pointes

(6) Treatment of cardiac arrhythmias ([VT/VF]) caused by hypomagnesemia

(7) Short-term treatment of constipation

c. Adverse effects (magnesium toxicity)

• Reversed with calcium gluconate

Magnesium toxicity reversed with calcium gluconate

(1) Hypertension

(2) Shock

(3) Myocardial infarction

(4) Nausea and vomiting

(5) Pulmonary edema

(6) Cardiovascular collapse

(7) Hypotonia (muscle weakness)

• Myasthenia gravis is an absolute contraindication

Myasthenia gravis is an absolute contraindication for magnesium sulfate.

4. Nifedipine (see Chapter 14)

a. Mechanism of action

(1) Calcium channel antagonist

(2) Relaxes vascular smooth muscles (e.g., uterus)

b. Use

(1) Prevent preterm labor (IV administration)

Intravenous nifedipine used to prevent preterm labor

(2) Cardiovascular uses (see Chapters 12−14)

(2) Congestive heart failure

(3) Don’t use with magnesium sulfate; masks magnesium toxicity

Don’t use nifedipine with magnesium sulfate.

E. Therapeutic summary of selected uterine drugs (Table 26-1)

II. Estrogens and Related Drugs (Box 26-2)

A. Estrogens

1. Synthesis and secretion (Fig. 26-1)

a. Synthesized in ovarian follicles

• Aromatase conversion of testosterone to estradiol in granulosa cells

b. Controlled by follicle-stimulating hormone (FSH)

• FSH increases aromatase synthesis in granulosa cells.

c. Major secretory product of the ovary is estradiol

2. Physiologic actions

a. Necessary for the normal maturation of females

b. Important for the proliferation of endometrial tissue

c. Required for normal menstrual cycling (Fig. 26-2)

3. Pharmacokinetics

a. Metabolized by the liver

• High first-pass metabolism

b. Enterohepatic cycling contributes to increased protein synthesis responsible for adverse effects.

Table 26-1 Therapeutic Summary of Selected Uterine Drugs

BOX 26-2 Gonadal Hormones and Inhibitors

HRT, hormonal replacement therapy; OC, oral contraceptive; VRC, vaginal ring contraceptive; PC, patch contraceptives

Estrogen Derivatives

Estradiol

Estrogens (conjugated A/synthetic)

Estrogens (conjugated B/synthetic)

Estrogens (conjugated/equine)

Estrogens (esterified)

Estropipate

Selective Estrogen Receptor Modulators (SERMs)

Progestins

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Tags: Rapid Review Pharmacology

Apr 8, 2017 | Posted by admin in PHARMACY | Comments Off

Basicmedical Key

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Drugs Used in Reproductive Endocrinology

Drugs That Cause Contraction

Drugs That Cause Relaxation

Estrogen Derivatives

Estrogen and Progestin Combinations

Selective Estrogen Receptor Modulators (SERMs)

Progestins

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Drugs Used in Reproductive Endocrinology

Drugs That Cause Contraction

Drugs That Cause Relaxation

Estrogen Derivatives

Estrogen and Progestin Combinations

Selective Estrogen Receptor Modulators (SERMs)

Progestins

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