PROSTAGLANDINS

BY: PHARM.D. INTERN

DEFINITION
• Prostaglandins are hormone like substances that participate in a wide
range of bodily functions such as the contraction and relaxation of
smooth muscles, dilation and contraction of blood vessels, control of
blood pressure and modulation of inflammation. They are derived
from a chemical called arachidonic acid.
BIOSYNTHESIS
TYPES OF PROSTAGLANDINS
• PROSTAGLANDIN- D2
• PROSTAGLANDIN-E2
• PROSTAGLANDIN-F2
• PROSTAGLANDIN-G2
• PROSTAGLANDIN-H2
• PROSTAGLANDIN-I2
 PHYSIOLOGICAL EFFECT
Eicosanoid Biochemical and Physiologic Action
PGD2 Weak inhibitor of platelet aggregation.
PGE1 Bronchial Vasodilation • Inhibitor of lipolysis • Inhibitor of platelet aggregation • Contraction of GI
smooth muscle.
PGE2 Stimulates hyperalgesic response (sensitize to pain) • Renal and bronchial vasodilation • Inhibitor of
platelet aggregation • Stimulates uterine smooth muscle relaxation • Cytoprotection: Protects GI
epithelial cells from acid degradation • Reduces gastric acid secretion • Elevates thermoregulatory set-
point in anterior hypothalamus (fever) • Promotes inflammation

PGF2 Stimulates breakdown on corpus luteum (luteolysis): Animals • Stimulates uterine smooth muscle
contraction • Bronchial constrictor
PGI1 Potent inhibitor of platelet aggregation • Potent transient CV vasodilator, then vasodilator • Bronchial
dilator • Uterine relaxant • Sensitize/amplify nerve pain response
TXA2 Potent inducer of platelet aggregation • Potent vasconstrictor (bronchioles, renal) • Decreases cAMP
levels in platelets • Stimulates the release of ADP and 5-HT from platelets
ROLE OF PROSTAGLANDINS IN PREGNANCY
PGE2:
In-vivo PGE2 contracts both a pregnant and non-pregnant uterus.
In-vitro, PGE2 contracts the pregnant uterus while relaxing the non-
pregnant uterus.
Promotes cervical ripening.
PGF2:
PGF2 is a potent vasoconstrictor
Increases intracellular calcium, thus increasing myometrial contractility.
PGI2 (Prostayclin):
 It is a vasodilator which inhibits uterine contractility.
PROSTAGLANDIN ANALOGUES USED IN
PREGNANCY
Prostaglandin E1(Misoprostol)
• Misoprostol is a synthetic PGE1 analogue approved by FDA 12yrs ago to prevent
ulcers in people under NSAID therapy.

• It increases the secretion of protective mucus that lines the GIT and increases mucosal
integrity by increasing mucosal blood flow.

• Misoprostol has a half life of 20-40 mins and is majorly excreted renally (56-73%)

• It is used for inducing labor at or near term: 0.5mg/ml

• Used for terminating pregnancy: 5µg/ml.

 ADRs
• GI Side effects: abdominal pain(7-20%), diarrhea(13-40%), flatulence

• Other side effects: anemia, cardiac disarrhythmmia, chest pain, hearing loss,
myocardial infarction, thromboembolic disorder.

DRUG INTERACTIONS
• Crofelemer

• Eluxadoline
 TOXICITY
• Acute overdosing is rare but may cause hyperthermia, increased PR and RR. In mild to
moderate toxicity, the overdose effects will be an extension of the adverse effects;
abdominal cramping, diarrhea, headache, dizziness, uterine contractions and bleeding
may occur. In severe toxicities, hypertension, tachycardia, fever, tremors, rabdomyolysis,
renal insufficiency, abnormal LFT can occur.

MANAGEMENT
• Mild to moderate toxicity: Close observation with only symptomatic treatment.

• Severe toxicity: Decontamination with activated charcoal.

 Prostaglandin E2 (Dinoprostone)
• Dinoprostone softens the cervix and facilitates cervical dilation. It stimulates collagenase
secretion, thus reduces collagen network in the cervix.

• Dinoprostone acts directly on the myometrium and stmulates myometrial contractions in

gravid uterus similar to those in term uterus, which is sufficient to cause abortion.

• It is also used for the management of missed abortion or intrauterine fetal death upto 28
weeks gestational age.

• Management of nonmetastatic gestational trophoblastic disease.

• It has a t1/2 ˂ 5min

DOSAGE AND INDICATIONS
• Cervical ripening: 0.5mg into the cervical canal. Max: 1.5mg/24hr

Vaginal insert: 10mg in posterior fornix of vagina.

• Hydatidiform mole, benign: 20mg suppository into the vagina. Repeat every 3-5hr intervals
upto 2 days.

• Termination of pregnancy: 20mg suppository.

ADRs:
Diarrhea(40%); Nausea(33%); vomiting(66%); Headache(10%); abnormal fetal HR(17%),
fetal distress(3.8%); Hypotension; Hyperthermia.
DRUG INTERACTIONS
The activity of oxytocic agents (ergonovine, methylergonovine, oxytocin) may be
augmented by the prostaglandins and thus concomitant use is not recommended.

CONTRAINDICATIONS
In active cardiac, hepatic or pulmonary disease; Acute PID; h/o cesarean

section; Fetal distress; Vaginal bleeding.

Prostaglandin F2α (Carboprost)

MOA: Carboprost tromethamine is an oxytocic. It stimulates myometrial

contractions similar to labor contractions in the gravid uterus at the end of a full
term pregnancy. It also stimulates GI smooth muscles..

DOSAGE AND INDICATION

Postpartum hemorrhage: 250mcg IM every 15-90min as needed upto 2mg.

2nd trimester pregnancy termination: 250mcg IM, followed by 250-500mcg every

1.5-3.5hr. Max: 12mg.
ADRs
The most common adverse effects are vomiting(60%) and diarrhea(60%). Other adverse
effects include Leukocytosis(65%), Headache, Fever(12%), Uterine rupture,
Bronchoconstriction, and Flushing(7%). Large doses of carboprost can elevate blood
pressure(4%), probably by contracting the vascular smooth muscle.

Drug Interactions
The activity of oxytocic agents may be augmented by the prostaglandins and thus
concomitant use is not recommended.

CONTRAINDIICATIONS: PID; Anemia; Asthma; Chorioamnionitis; DM;

Hypertension
OTHER PROSTAGLANDIN ANALOGUES
Prostaglandin Drug General Therapeutic Indication
Gemeprost (PGE1) Abortifacient
Sulprostone (PGE2) Abortifacient
Alprostadil (PGE1) Male sexual dysfunction, Peripheral
vascular disease
Beroprost (PGI2) Peripheral vascular disease
Iloprost; Epoprostenol (PGI2) Peripheral vascular disease
Treprostinil (PGI2) Pulmonary Hypertension
Enoprostil; Ornoprostil (PGE2) Ulcers
Limaprost (PGE1) Buerger’s Disease
Latanoprost; Unoprostone isopropyl; Travoprost Glaucoma
Bimatoprost (PGF2α) Glaucoma
Arthrotec (PGE1) Arthritis
Thank you…