Drugs Acting On The Uterus

Question 1

Classes of drugs causing uterine relaxation

Answer 1

• Beta adrenergic agonists, eg salbutamol, ritodrine, terbutaline
• Oxytocin competitive receptor antagonists, eg atosiban
• Prostaglandin synthesis inhibitors, eg indomethacin, meloxicam
• Ca-channel blockers, eg nifedipine
• Magnesium sulphate
• Progesterone

Question 2

Classes of drugs causing uterine contraction

Answer 2

• Oxytocin
• Prostaglandins
• Ergot alkaloids, eg Ergometrine, Methlyergometrine

Question 3

Uterine contraction occurs when…

Answer 3

…myosin and actin crosslink due to the activation of myosin light chain kinase.

Question 4

Myosin light chain kinase is stimulated by

Answer 4

• calcium-calmodulin complex when there is an increase in intracellular calcium
• Reduced levels of cAMP.

Question 5

Types of drugs causing contraction based on MOA

Answer 5

• Drugs that stimulate G protein oxytocin coupled receptors increases uterine contraction, for example oxytocin and prostaglandins.
• Drugs stimulating alpha 1 receptors – stimulates uterine contractions – ergometrine, methylergometrine.

Question 6

Types of drugs causing relaxation based on MOA

Answer 6

• Drugs stimulating beta 2 receptors – blocks uterine contractions ie. salbutamol, terbutaline, ritodrine
• Drugs blocking calcium entry into the cell – calcium channel blockers (Nifedipine) -
• Drugs blocking prostaglandin production (PGs not available to act at receptors) - Cyclooxygenase inhibitors
• Drugs blocking oxytocin receptors – e.g atibosan

Question 7

Examples of PGs

Answer 7

Prostaglandins – PGE2 , PGF2α

Question 8

Oxytocin MOA

Answer 8

Activates G protein – coupled receptor – IP3 – increase intracellular calcium, increases local prostaglandin production

Question 9

Actions of oxytocin

Answer 9

• Stimulates myoepithelial cells in the mammary gland to contract – milk let down
• Vasodilator
• Antidiuretic – large doses

Question 10

Clinical uses of oxytocin

Answer 10

• Labour induction or augmentation
• 3rd stage of labour and post partum haemorrhage
• Abortifacient in incomplete abortion

Question 11

Actions of ergometrine

Answer 11

• Initiates strong contraction on the flaccid/non-contracted uterus; little effect on contracted uterus
• Moderate vasoconstriction

Question 12

Ergometrine MOA

Answer 12

MOA – Alpha adrenoceptor agonist

Question 13

Ergometrine PK

Answer 13

Route of administration – oral, im. Iv

Question 14

Ergometrine side effects

Answer 14

• vomiting, nausea
• Hypertension
• Headaches
• Angina
• Ergotism

Question 15

Ergotism is characterised by

Answer 15

Cramps
Spasm
Hallucination
Severe GI upset
Dry gangrene
Burning pains

Question 16

Oxytocin metabolism and RODA

Answer 16

Intravenous or Intramuscular routes

Inactivated in the liver and kidneys circulating oxytocinase

Question 17

Oxytocin side effects

Answer 17

• Dose related hypotension – reflex tachycardia
• Fetal distress
• Water retention and dilutional hyponatraemia

Question 18

Actions of PGs

Answer 18

PGE and PGF – contracts the non pregnant and pregnant uterus, relaxes cervix

PGF 2α – Ischaemic necrosis of the myometrium preceding menstrual flow. Has a little vasoconstrictor effect.

PGE2, PGF2 - Vasodilators

Question 19

Disorders of PGs

Answer 19

Dysmenorrhea – increased production of PGE2 and PGF2α

Menorrhagia – increased vasodilation and reduced haemostasis. Due to PGE2 and PGI2 increase, compared to PGF2α.

Question 20

Examples of exogenous PGs

Answer 20

Dinoprostone PGE2

Carboprost 15-Methyl PGF2α

Misoprostol PGE1 analogue

Question 21

Side effects of PGs

Answer 21

• Uterine pain
• Nausea
• Vomiting