Uterotonic drugs during caesarean section Dr S Parthasarathy MD DA DNB Dip Diab DCA Dip Software statistics PhD physiology IDRA FICA Why do we need uterotonics 1 induce ID: 764237
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Uterotonic drugs during caesarean section Dr. S. Parthasarathy MD., DA., DNB, Dip. Diab ., DCA, Dip. Software statistics- PhD ( physiology) IDRA, FICA
Why do we need uterotonics 1. induce labour 2. prevent PPH 3. treat PPH ‘‘It did not take her very long to die’’ Ernest Hemingway
Why should we know ? Every year 166 000 women die of obstetric haemorrhage ,These drugs are used routinely They have narrow therapeutic safety margin
Three classes Oxytocin Ergots Prostaglandins
Oxytocin Pictures modified from the internet for closed academic purpose only
Why in pregnancy ( late ?? ) The concentration of myometrial receptors and myometrial gap junctions increase as gestation advances increasing sensitivity to oxytocin
Pharmacodynamics it causes contraction, followed by relaxation of the uterus, and at pharmacological doses can cause an increased frequency and incomplete relaxation of uterine musculature desensitization of oxytocin receptors in myometrium after prolonged exposure to oxytocin during labor.
Innumerable regimens 5 units intravenous bolus - followed by oxytocin 40 IU diluted in 500 mL saline for four hours15 IU of oxytocin in 1 L saline and infuse this solution in 1 h . 20-40 Unit/min by IM Upto 3 units is OK
Extrauterine actions Hugging ! Oxytocin creates a sense of pleasure and hence prompts us to repeat the act again. The release of Oxytocin tends to alter the brain signals which produce facial expressions, perhaps changing the firing for amygdala , which is very important for the processing of emotional stimuli
Oxytocin – others “let down reflex” Nipple to hypothalamus Breast milk – expression Relationships and bonding !
CVS Oxytocin is a vasodilator Predominant hypotension Reflex tachycardia 10 units Vs 2.5 units in preeclampsia May be dangerous in mitral and aortic stenosis or hypovolumia !! Increased PAP Use phenylephrine – effects are blunted more than ephedrine
Psychiatric common manifestation of Oxytocin deficiency would be generalised depression and anxiety, sleep disturbances, isolation and panic attacksRelationship to autism Schizophrenia
Pharmacokinetics Uterine contractions are seen after 3-5 minutes and approx 1 minute of administration through intramuscular and intravenous routes respectively. Metabolized and excreted in liver and kidneys 15 minutes – action over !
Side effects Excess contraction and possible rupture Hypotension , tachycardia Nausea or vomiting Memory problems or confusion Runny nose, sore throat, or coughing severe headaches hallucinations, confusion Seizures and severe hypertension, arrhythmias
Side effects ADH-like response if given in high doses with risk of water intoxication should be given in electrolyte-containing solutions, not dextrose in waterIf infusion at 10 IU.h−1 is indicated beyond 4 h, serum electrolyte concentrations must be checked to guide correction of hyponatraemia
carbetocin Carbetocin , a synthetic analog of oxytocin, has the same affinity as oxytocin for myometrial receptors, but differs for having a much longer plasma half-life than oxytocin (40 min vs. 15 min, respectively 5 IU of carbetocin
Ergot alkaloids Ergot, derived from the fungus Claviceps purpurea , was the first effective oxytocic drug pulvis ad partum’’ (the powder of birth), to ‘‘ pulvis ad mortem ’’ (the powder of death), due to the associated titanic uterine contractions, leading to fetal asphyxia, stillbirth and uterine rupture
Dosage The RCOG guideline recommends an intravenous injection of 0.5 mg slowly for the management of uterine atony , World Health Organisation (WHO) stipulates 0.2 mg intravenously or intramuscularly, to be repeated as necessary every 15 min to a maximum of 1 mg. Prophylactic oral ergometrine – no role I prefer subcutaneous Second line
Where it acts ? Ergometrine is also a partial agonist at adrenergic, 5HT-1, and dopamine receptors Not established wellHalf life is 120 minutes
Side effects Hypertony and rupture Vasoconstriction and hypertension Coronary and renal artery spasm CVA , retinal detachment Possible infarction in 8 cases reported so far 9 % incidence of vomiting after oxytocin may be upto 45 % with IV ergometrine
No to ergometrine Ergometrine is contraindicated in eclampsia, preeclampsia or a history of hypertension and in patients with peripheral vascular disease or heart disease. It is also contraindicated if there is any suspicion of retained placenta If at all , use after expulsion of placenta
Syntometrine Syntometrine is a combination preparation, rarely used during LSCS, containing 5 IU oxytocin and 0.5 mg ergometrine . Following intramuscular administration, the time to onset of the uterine response is considerably shorter than after ergometrine alone, and the duration of action is several hours
Prostaglandins First isolated in seminal fluid – hence the name prostaglandins increase intramyometrial calcium concentrations and enhance uterine contraction.Their effects are mediated via G-proteins and the activation of calcium channels Other roles – PDA , gastric ulcers , inflammmation etc.
Cyclopentanone nucleus Where is the hydroxyl substitution – A,B Number of double bonds – 2 or 1
Carboprost – PGF2α IM or Intra myometrial 125 250 Rarely 500 µg Used – repeated every 15 minutes to a maximum of 2 mg NO intravenous
misoprostol Prostaglandin E1 ( misoprostol ) is a cheap and widely available uterine stimulant.Less effective than oxytocin 200 µg tablets sublingual , rectal Methyl ester , hence first pass metabolism is high In preeclampsia , second line drug
Side effects of prostaglandins Bronchospasm Hypertension Nausea and vomiting Diarhoea Shivering and fever Beware in glaucoma More in PG E1
Summary Stimulants Oxytocin Ergots Prostaglandins