2018B13 List the drugs which affect uterine tone and outline the adverse effects of these agents.

Mechanism of action (MoA) and adverse effects (AE)

Oxytocin

·   Bind oxytocin receptor, a G_q G protein coupled receptor (GPCR)

·   ↑IP₃ -> ↑ICF [Ca²⁺] (also ↑DAG)

·   At low dose: intermittent contraction

·   At high dose: tonic contraction

·   Receptors upregulated from from 36/40

·   AE: N&V, vasodilatation, slightly ADH effect on kidney (V₂) -> H₂O reabsorption, hyponatraemia

Carbetocin

·   Synthetic analogue of oxytocin

Ergometrine

·   Oxytocic mechanism unclear

·   Causes tonic contraction at any dose cf. oxytocin

·   Known receptor effects:

o α₁: ↑SVR, ↑BP, risk of APO (contra-indicated in pre-eclampsia)

o 5HT₂ agonist: N&V

o DA agonist: N&V

Misoprostol

·   PGE₁ analogue

·   Binds PGE₂-R -> multiple G protein-coupled receptor subtypes

·   AE: diarrhoea

PGF_2α

·   MoA: binds G_q protein-coupled receptor -> ↑ICF Ca²⁺

·   AE: bronchoconstriction, hypertension, nausea

Mechanism of action and adverse effects:

Terbutaline

·   β₂ agonist / G_s GPCR -> ↑cAMP -> ↑inhibition of MLCK

·   AE: ↑HR (cardiac B2) ↓K⁺ (↑Na⁺K⁺ATPase activity), lactic acidosis (β² liver and skeletal muscle), tremor (β₂ skeletal muscle)

Nifedipine

·   Inhibit L-Ca²⁺ -> ↓ICF [Ca²⁺]

·   AE: reflex ↑HR, peripheral oedema

GTN

·   Prodrug

·   Reacts with endothelial ICF sulfhydryl groups -> NO -> activate GC -> ↑cGMP -> ↑MLCP activity, ↑Ca²⁺ reuptake, ↑K⁺ efflux

·   AE: ↓BP (vascular SM), reflex HR, flushing, headache, metHbaemia (bad in foetus)

·   Note tachyphylaxis (depletion of sulfhydryl groups)

Atosiban

·   Nonapeptide

·   Competitive antagonist at oxytocin receptor

·   AE: headache, nausea&vomiting

Volatile anaesthetics

·   Inhibit L-Ca²⁺ -> ↓ICF [Ca²⁺]

·   Note ↑risk sedated neonate

·   ↑Risk PPH if GA Caesarean

·   Supplement with N₂O

·   AE: maternal and foetal anaesthesia, respiratory and cardiovascular depression, nausea and vomiting