Lecture 8 - Nov 11 Flashcards
(31 cards)
Smooth muscle contraction:
-at term the myometrium is one large smooth muscle
-motor neuron releases ach to cause action potential as muscle membrane
-action potential releases calcium from sarcoplasmic reticulum
-calcium binds to troponin which exposing binding sites on actin for myosin
-myosin pulls past the actin (power stroke)
-mlck is activated when it binds with a calcium-calmodulin complex
-due to need for calcium to activate mlck the force of smooth muscle contraction is regulated by the amount of ca in the cytoplasm
-increases in intracellular Ca are due to release from either the sarcoplasmic reticulum or extracellular sources
-can inhibit smooth muscle contraction by either having low intracellular calcium or by stimulating the phospho kinase a PKA
-pka modifies mlck so that it can’t bind to the calcium-calmodulin complex
Increasing cellular Ca:
-an increase in the 2nd messengers inositol triphosphate IP3 and diacylglycerol DAG
-IP3 binds into the sarcoplasmic reticulum, allowing the release of Ca
-DAG opens the Ca channels on the cell membrane
-IP3 can also activate voltage gated CA channels on the cell surface
-letting more extracellular Ca into cell
Induction/Augmentation of Labour:
-agents that cause uterine contractions are called oxytocics (from greek - oxy = sift, tokos = childbirth)
-includes both prostaglandins and oxytocin
-should not be offered in the context of an unripe crevice (bishop score less than 7)
-perform cervical ripening first = the use of mechanical or pharmacologic means to soften, efface, and dilate the cervix prior to the induction of labour
-cervical ripening may be time consuming and may require more than 1 method
-ballon catheter, membrane sweeping, prostaglandinE (misoprostol), prostandlindE2 (dinoprostone)
Prostaglandins for Cervical Ripening:
-mostly given per vagina:
-misoprostol PGE1 - various doses and routes (SL, PV, most effective)
-dinoprostone PGE2 supplied at pristine E2, vaginal gel, 1mg or 2mg place in posterior vaginal fornix and may be repeated 6 hrs later
-prepidil (0.5mg dinoprostone) gel form used for intracervical use
-cervidil (control-released dinoprostone vaginal insert): polymer base with 10mg dinoprostone attached to retrieval string; releases 0.3mg PGE2 per hours in vagina for 12hr
-due to longer t1/2 of prostaglandins should be used with caution if there is an increased likelihood of uterine tachysystole, foetal compromise or uterine rupture
slide 9
pge1 is more efficous than pge2
Oxytocin: iol or augmentation
-nonapeptide produced by the hypothalamus and released by posterior pituitary
-synthetic oxytocin sold as a clear aqueous solution for IM injection or IV infusion (pitocin)
-receptors for oxytocin exist in the myometrium, myoepithelial cells of breast ducts, glandular cells of breast alveoli, brain
-oxytocin receptors in the myometrium increase greatly in number in 2rd trimester (partially because of effects of oestrogen)
-contractions of the uterus are largely the result of prostaglandins and oxytocin produced during a posterior feedback loop
-doses of oxytocin can be given to induce or augment labour - stimulates positive feedback loop, associated with the cervical stretch induced by the initial uterine contractions
-oxytocin also has an affinity for the antidiuretic hormone receptor
-uterus may also be hypersensitive to oxytocin, leading to tachysystole
slide 13
in 2019 midwives became able to use oxytcoin in pp period
Prostaglandins
-PGE1, PGE2, PGF2a and their analogues (ex misoprostol) may stimulate uterine contractions
-main receptors in the uterus for the PAGE fault are EP1 and EP3, misoprostol is synthetic PGE1, dinoprostone is PGE2
-FP receptors for PGF2a ex carboprost HEMABATE)
Misoprostol:
-used for treatments for ulcers since it reduces gastric acid secretion (binds to prostaglandin receptors on surface of gastric cells; trade name cytotec)
-misoprostol PO or PR for labour induction has not been in Canada because of risks associated with uterine rupture and hypertonic (can lead to foetal distress)
-becoming more common in some centres
-added to last SOGC CPG in 2023
-prostanoids are tend not used for cervical ripening or IOL in people with previous caesarean delivery, uterine surgery or ruptured membranes
-absolute contraindications: previous full thickness uterine surgery and known foetal compromise
-common off-label uses include medical abortion, cervical ripening before surgical abortion, induction after intrauterine foetal death (its use for PPH will be discussed later in this lecture)
slide 15
Herbal Oxytocin - Castor Bean:
-castor oil is made from cold pressing the seeds (beans) of the ripe fruit of ricinus communis
-active oxytocin component appears to be ricinoleic acid
-taken PO, ricinoleic acid acts as a uterine stimulant but the mechanism is unclear
-shown to bind to EP3 receptor in uterus and bowel
-effects in part thought to be due to increased stimulation of the bowel therefore the uterus is stimulated by an irritant effect
-adverse effects: nausea, vomiting and subsequent dehydration
Tocolytics for labour:
-greek, tokos = childbirth, lysis = loosening
-used in attempts to prevent preterm labour or relieve uterine tachysystole (sometimes used for ECV)
-none of the clinically used tocolytic agents will be able to suppress myometrial contractions in the presence of strong stimulation of myometrium
Nifedipine (ADALAT):
- a Ca channel blocker
-works by blocking entry of extracellular Ca into myometrial cells (slow/stop uterine contractions)
-sometimes used in hypertensive disorders of pregnancy as well as it dilates blood vessels
-few undesirable side-effects (commonly reported = headache and hypotension 10-20% of cases)
Nitroglycerin:
-glyceryl trinitrate, NITROL
-primarily a heart medication for treatment of angina
-used off-label for tocolysis in cases of uterine tachysystole (either as a skin patch or a sublingual spray)
-mechanism = production of nitric oxide from nitroglycerine
-NO travels to smooth muscle cells, activates guanylyl cyclase
-GS converts GTP to cGMP
-cGMP causes a sequestration of CA
-smooth muscle cells relax
-relaxes smooth muscle both in in blood vessels and the myometrium
Postpartum haemorrhage PPH:
-defined as blood loss of more than 500ml following a vaginal delivery or more than 1000 ml after a caesarean delivery
-clinically, any amount of blood loss that results in S Sx of hypovolemic shock or hemodynamic instability should be considered a PPH
-primary PPH occurs in 2-6% of births worldwide, secondary or delayed PPH in 1-3%
slide 22 - the 4 t’s of pph
Uterine contraction:
-usually normal uterine contractions after delivery prevent PPH
-special helical arrangement of myosin and actin in the uterus allow for contraction of the entire organ
-uterine contraction compresses the spiral arteries enough to slow blood flow and allow clot formation
-active management of the 3rd stage is thought to reduce the likelihood of PPH
Oxytocics for the treatment of PPH:
-first line treatment = oxytocin
-2nd/3rd line = ergonovine maleate, carboprost tromethamine, misoprostol
-3rd line = carbetocin
slide 24
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Oxytocin side effects:
-very common:
-vascular effects: feeling of warmth, flushing, hypotension
-gastrointestinal: nausea, abdominal pain
-common:
-nervous system disorders: headache, dizziness, tremor
-GI: vomiting, metallic taste
-rare:
-cardiac disorders: tachycardia
-structurally related to ADH, theoretical potential for water retention and water intoxication (hyponatremia)
-oxytocin and carbetocin can get into milk but its a tiny amount and will be degraded by peptidases in infant GI tract
-may cause milk let-down
-allergic reactions are highly unlikely
slide 27
slide 28
ergonovine side effects
-nausea vomiting
-stimulates alpha 1 adrenoceptors found in blood vessels which leads to an increase in blood pressure
-headache
-contraindications - pregnancy and hypertension
