V2ii: Describe the mechanism of action & side effects of 3 classes of drugs that increase uterine tone and 3 classes of drugs which decrease uterine tone

Definitions

Uterus – female reproductive organ responsible for protection of growing fetus, delivery and conception

Tocolytic (Gk. Childbirth stop) – decreases uterine tone; prevents/slows down labour

Oxytocic (Gk. Quick birth) – increases uterine tone; induction, accelerates labour, Tx PPH

Uterine Tone

  • Uterus has smooth muscle with intrinsic PM wh undergoes rhythmic contractions
  • Influenced by:
    • Hormones
      • P – relaxes (prevents child birth occurring throughout pregnancy)
      • O – contracts
    • ANS
      • B2 – relaxes (Adr)
      • A1 – contracts (NA)

Tocolytics

Drug

Effect on Uterine Tone

Other Actions

AE

B agonist

 Salbutamol

B2 agonist

Gs

­↑cAMP

↓intrac Ca++

sm m relaxn

↓uterine tone

Tremor flushing

N+V

Tachycardia

Hyperglycaemia

Hypokalaemia

Calcium antagonist

 Nifedipine

Bind D-binding site of L-type Ca ch

↓intrac Ca

sm m relaxn

↓uterine tone

 

Inhibits amplitude of spontaneous & oxytocin induced contractions

Hypotension

Ankle oedema

HA

Dizziness

Flushing

Cough

wheeze

MgSO4

Inhibits amplitude of spontaneous & oxytocin induced contractions

Flushing

Lethargy

Pulmn oedema

Oxytocics

Drug

Effect on Uterine Tone

Other Actions

AE

Oxytocin

Endogenous hypophyseal hormone produced in hypothalamus → PPG

IV 5-10IU/ml

Use:

Induction labour, PPH, lactation aid

Late preg – O stimulates ­↑oxytocicn R

(so only used at term)

Gq

­↑IP3/DAG

­↑Ca++ release

­↑ampl & freq of smooth m contraction

Low dose – regular co-ordinated contractions with ↑­force

High dose – sustained contractions, incomplete relaxation, impaired uteroplacental BF

Milk let-down

Stimulated myo-epithelial cells

CVS

VD →↓SVR à reflex ­↑CO

↓coronary perfusion

Renal

Mild ADH effect & fluid retention

Fetal

High dose →↓BF → asphyxia

Ergotamine

IV 500mcg/ml

Use: PPH

a/5HT receptor agonist

powerful & prolonged tetanic contractions

uterus contracts as a whole (fundus + cervix)

↓uterine BF

VC of capacitance vessels

­↑CVP & ­BP

CVS

Severe HTN

CA vasospasm

CNS:  Dizzyness, hallucinations, vertigo

PGE/F

Use:

Induction labour

Cervix ripening

Abortion

Endogenous PGIs are produced by the myometrium

PGE – intravaginal injection

PGF – IM injection

Softens cervix

Promotes co-ordinated contractions with ↑­basal ton and cervix relaxation

N+V
Adbm pain

Diarrhoea

Bronchospasm

Uterine rupture

Cardiac arrest