DRUGS USED IN UTERINE MOTILITY

Md. Amran Howlader

Drugs action un Uterus - Cause contraction or relaxation of uterus

-Uterine contractility enhanced by: oxytocin

ergometrine (ergonovine) prostaglandin analogues

-Uterine relaxation enhanced by: B- adrenoceptor agonists

magnesium sulphate prostaglandin synthetase inhibitors

calcium channel blockers

OxytocinPharmacological action 

- Synthesized in the: supraoptic nucleus (SON)

paraventricular nucleus (PVN) of hypothalamus -By axonal transport arrive and stored in the posterior

pituitary -Sensory stimuli from cervix & vagina induce secretion

of oxytocin from posterior pituitary- Stimulation of breast leads to secretion of oxytocin

contraction of myoepithelium milk ejection reflex

On uterus -Stimulates frequency & force of contraction

-Effect dependent on presence of estrogen - Contributes to initiation of labor

- Sensitivity of uterus to oxytocin increase during pregnancy

- Oxytocin induced myometrial contraction inhibited by: B- adrenoceptor agonists

magnesium sulphate inhalational anesthetic agents

On CVS  -Large amounts

marked transient relaxation of vascular smooth muscle

reduction of blood pressure flushing

reflex tachycardia 

Other effects  - Large amounts antidiuretic effect

Mechanism of action : - Specific receptors in myometrium - Elicits prostaglandin production in

endometrial / decidual cells - Alters transmembrane ionic currents in

myometrial smooth muscle cells to produce sustained contraction

 Pharmacokinetics: - Administration IV to induce labor

- Intra-nasal spray – postpartum use to induce lactation

- Inactive when administered orally - T ½ 5 – 12 minutes

- Metabolized by oxytocinase

USES : - To induce labor or augment dysfunction

- Conditions requiring early vaginal delivery Rh problems

maternal diabetes mellitus - Uterine inertia

- Third stage of labor - To control post-partum bleeding

- Milk ejection 

Toxicity : - When properly used toxicity is rare

- Uterine rupture - Water intoxication

- Foetal death - Maternal death from hypertensive episodes

Contraindications : - Foetal distress

- Prematurity - Abnormal presentation

- Cephalo-pelvic disproportion 

Ergot Alkaloids : Ergometrine

• First used as uterine stimulating agent • Ergot – product of fungus • Derevative of 6-methy ergoline • Pure Form – Ergotamine• Ergometrine ( Ergonovine ) water soluble

derivative

ERGOMETRINE ACTIONSUterus :

  - Increase motor activity of uterusDose related increase in frequency & force of

contractionPregnant uterus is more sensitiveUterus at term is more sensitive than early

pregnancy - Combines alpha-agonist , serotonin & other

effects

Ergometrine Ergonovine is more active and less toxic than

ergotamine. Useful for the control of post partum or after labor

bleeding. Should never be given before delivery. Given at the time of delivery of placenta.

 Pharmacokinetics 

- Routs of administration: Parentally OrallyRectally - Extensive first-pass effect- T ½ is 2 hours but effect persist for 24 hours - Metabolized in liver- Excreted in bile

Side effects  -GI upset : diarrhea, nausea, vomiting

- Tingling of fingers and toes- Muscle pain - Overdosage prolonged vasospasm pallor,

anginal pain, gangrene - Contraindicated in : Peripheral vascular disease Coronary heart disease Hypertension Impaired renal & hepatic disease

Prostaglandins Analogues found in uterus are PG-E & PG-F 2-alph  

Actions:  

-On Myometrium: > cause strong uterine contraction

> sensitivity of uterus to prostaglandins increase as gestation progress  

- On Cervix: > local instillation of PG induces ripening, softening and

relaxation of cervix

TOCOLYTIC AGENTSAgents 

-Agents that inhibit uterine contraction 

-Used to delay or prevent premature parturition 

-Slow or arrest delivery for brief periods in order to undertake other therapeutic measures 

Agents: 1. B2-adrenoceptor agonist ( Retodrine & Terbutaline ) 2. Magnesium sulphate 3. Prostaglandins synthetase inhibitor ( Indomethacin ) 4. Calcium Channel Blocker ( Nifedepine & Norcardipine) 

Retodrine  • selective B2-adrenoceptor agonist • developed specifically for use as a uterine

relaxant • relaxes smooth muscles of :• uterus • bronchial tree• arteries• effective 20-36 weeks gestation

Uses  *Mainly used for Rx of premature labor

*Rx initiated with IV infusion and about 30 minutes before the end of IV infusion oral therapy begins

Adverse effects  *Tachycardia

*Increased cardiac output *Fluid overload maternal pulmonary

oedema ( esp. If combined with corticosterioids)

*Hyperglycemia*Hypocalcemia

Prostaglandin synthetase InhibitorsCyclooxygenase inhibitors (NSAIDS esp. Indomethacin) inhibit prostaglandin synthesis – can half pre-term labor

*Concers of foetal and neonatal side effects limit their use

- Premature closure of ductus arteriosis - Increased risk of pulmonary hypertension

- Oligo-hydraminios - Post Maturity

*Used in gestation prior to 34 weeks

Magnesium Sulphate

 *Effective inhibitor of uterine contraction

*Interferes with calcium uptake by myometrial cells which need it to contract

*Generally given IV as an infusion

 Adverse reaction:

- GIT – nausea and vomiting - Hot flushes

- Blurred visionToxicity :

- Decreased respiratory rate - Hypotension

- Extreme muscle Relaxation - Caution

 *Clost monitoring is required