Drugs acting on uterus - drdhriti


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A power point presentation on the Drugs acting on Uterus suitable for undergraduate MBBS level medical students.

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  • Each mL of sterile nonpyrogenic solution prepared by synthesis contains: oxytocin activity 10 IU (10 USP Posterior Pituitary Units), sodium acetate 2 mg, sodium chloride 5.1 mg and chlorobutanol 5 mg (as preservative) in water for injection. pH adjusted with acetic acid to approximately 3.9. Single-dose ampuls of 0.5, 1 and 5 mL. Sleeves of 5 or 10. Use only if solution is clear. Discard unused portion. Store at room temperature (15 to 30°C). Protect from freezing.
  • Amino acid alkaloids – partial agonist and antagonist of alpha receptor, serotonergic and dopeminergic, Amine alkaloides – no alpha blocking action, hydrogenation – produces more alpha blocking but no vasoconstriction
  • Drugs acting on uterus - drdhriti

    1. 1. Drugs acting on UterusDr. D. K. BrahmaDepartment of PharmacologyNEIGRIHMS, Shillong
    2. 2. Uterine stimulants (oxytotics orabortifacients) Posterior Pituitary hormones: Oxytocin,Desamino oxytocin Ergot alkaloids: Ergometrine,methylergometrine Prostaglandins: PGE2, PGF2α,misoprostol Miscellaneous: ethacridine and quinine
    3. 3. Oxytocin Hormone of Posterior pituitary. Theother hormone is vasopressin
    4. 4. Biosynthesis - Physiology Synthesized as cell bodies ofpraventricular nucleus andsupraoptic nucleus ofhypothalumus as prohormone Precursor broken down toactive hormone andneurophysin complex Packaged into the secretorgranules by oxytocin-neurophysin complex Secreted from nerve endingsin posterior pituitary gland(neurohypophysis)
    5. 5. Oxytocin - Physiological Role1. Labour2. Milk ejection reflex3. Neurotransmission
    6. 6. Oxytocin secretion Sensory stimuli from cervix, vagina andbreast suckling Expulsive phase is triggered by sustaineddistension of uterine cervix and vagina Oestrogen increases its secretion Ovarian polypeptide relaxin inhibits itsrelease ADH: Pain, haemorrhage and dehydrationincreases secretion
    7. 7. Actions of Oxytocin –Uterus Increase in force and frequency of contractions Low doses: Full relaxation occurs between the contractions, buthigh doses – basal tone increases Mechanism - High electrical activity of myometrium cellmembrane – burst of discharges Very low level of motor activity in the first two trimesters - 3rdtrimester onwards – spontaneous motor activity progressivelyincreases and sharp rise initiates labor Uterine sensitivity - 8 fold increase in in last 9 weeks and 30 fold increasein number of oxytocin receptors between early pregnancy and early labour –estrogen No. of receptors and myometrium sensitivity increases late in pregnancy –labour initiation and postpartum involution Increase in contraction is restricted to fundus and the body Non pregnant uterus are resistant to its action Oxytocin antagonist ATOSIBAN suppresses preterm labor
    8. 8. … Actions – contd.Breast Role in milk ejection Breast suckling and manipulation induces oxytocin release Mechanism: Contractions of myoepithelial surrounding alveolarchannels in mammary gland forces milk into large collectingsinuses – milk ejection reflex
    9. 9. Oxytocin – other effectsCVS No effect in low dose but at higher dosesfall in BP, reflex tachycardia and flushingKidney ADH like effect in high doses – decreasedurine output, pulmonary oedema etc.
    10. 10. Oxytocin – Mechanism ofaction (OXTR) Specific G protein-coupled membrane receptorsrelated to Vasopressin (V1 and V2) receptors Depolarization of muscle fibres and Ca++ influx Human myometrium – receptors coupled to Gqactivation leads to generation of IP3 – release of Ca++ ions Increase in local prostaglandin concentration –uterine contraction Kinetics: Being a peptide not effective orally Short half life – 3 to 6 minutes Available as injections for IM and IV use – 0.5 ml, 1 ml and 5ml etc.
    11. 11. Clinical uses ofoxytocin1. Induction of labour To induce or augment labor inpregnant women Indications:Premature rupture of membranesPre and post maturityIntra uterine growth retardation (IUGR)Placental insufficiency – diabetes, preeclampsia or eclampsia Before induction, rule out:Abnormal fetal positionCephalopelvic disproportionEvidence of fetal distressPlacental abnormalitiesPrevious uterine surgeryOxytocin is the drug of choice for induction of labor
    12. 12. Clinical uses of oxytocin (Pitocinor syntocinon) – contd. 5 IU is diluted in 500 ml of5% glucose or 0.9% saline– 5 milli IU/ml Start at low doseprogressively increase0.2 – 2 ml/min Induces labour within 2 – 4IU If no induction after givingupto 30 – 40 mU/min –higher doses areunsuccessful If labour – reduce the doseprogressively Unitage: 1 IU of Oxytocin= 2 mcg of pure hormone
    13. 13. Oxytocin infusion Monitoring Presence of Physician Mother and fetus monitoring – fetal andmaternal heart rate, maternal BP and strengthof contractions If uterine hyper stimulation – discontinueinfusion Higher dose (more than 20 mu/min) mayreduce water clearance – leading to waterintoxication, coma and death
    14. 14. Clinical uses of oxytocin – contd.2. Augmentation of labour In hypotonic contractions in dysfunctional labour(nulliparous) – administer as above But be careful, normal progression of labor shouldnever be tried to hasten, because over stimulationmay cause Uterine rupture Trauma of mother Trauma of fetus Compromised fetal oxygenation Useful in prolong latent phase of cervical dilation or arrest ofdilation
    15. 15. Clinical uses of oxytocin –contd3. Post partum haemorrhage, cesarean section: 5 IU IM or slow IV for immediate response Especially useful in hypertensive women whereergometrine cannot be used Also to maintain normal tone of uterine muscle4. Breast engorgement: Inefficient milk ejection reflex Intranasal spray before suckling
    16. 16. Ergometrine Natural ergot alkaloid alsocalled ergonovine andmethylergometrine is itsderivative - an aminealkaloid Recall ergots: amino acid,amine and semisyntheticderivatives Amino acid alkaloids –ergotamine, ergotoxin etc. Amines – ergometrine Semisynthetic derivatives -DHE Claviceps purpurea
    17. 17. Pharmacological Actions -ergometrine Uterus: Increases force, frequency and duration of contractions At low dose contraction is phasic in nature with normal relaxation inbetween But moderate increase in dose – sustained contraction occurs More sensitive - Gravid uterus and at puerperium Contractions involve lower segment also CVS: Weaker vasoconstrictors than their amino acid counterparts - less chance ofdeveloping endothelial damage No significant rise in BP CNS: Interacts partially with dopaminergic, adrenergic and serotonergic receptors No significant effect in usual doses GIT: High doses cause increased peristalsis
    18. 18. Ergometrine – contd. Methylergometrine is preferred over ergometrine - higherpotency and less marked other effects Pharmacokinetics: Near complete absorption form GIT Immediate onset of action with IV route Metabolized in liver and excreted in urine Half life – 1 to 2 hrs Adverse effects: No complication in usual doses - Nausea, vomiting and rise in BPmay occur Decrease in milk secretion (dopaminergic) Contraindications: Pregnancy before 3rdstage of labour, vasculardisease, hypertension, liver and kidney diseases
    19. 19. Ergometrine - Uses Postpartum haemorrhage: to prevent Used the dose of 0.2 to 0.3 mg IM immediatelyafter delivery Continued for 4 - 7 days post partum If already PPH, use higher dose 0.5 mg IV Cesarean section and instrumental delivery –to prevent uterine atony For normal involution: 0.125 mg orally tds for4 – 7 days postpartum
    20. 20. Prostaglandins PGE2 and PGF2α – tocolytics Uses: AbortionIn early termination with antiprogesterone (Mifepristone)Midtrimester abortion – extra-amniotic injection followed byoxytocin (1o mg/ml available) Induction/augmentation of labour – intravaginalroute is preferred Cervical priming – intravaginal gel (cerviprime) Post-partum haemorrhage
    21. 21. Uterine relaxantsTocolytics
    22. 22. Tocolytics - drugs These are drugs that inhibit uterinecontractions Beta-sympathomimetics (beta-2)Ritodrine, isoxsuprine, terbutaline and salbutamol Calcium channel blockers: Nifedepine Magnesium sulfate Prostaglandin inhibiting agents: Indomethacin Oxytocin antagonist: Atosiban Ethyl alcohol
    23. 23. Tocolytics Therapeutic uses: Delay or postpone labor – to allow fetus tomature and transfer of mother to ahealthcare centre Threatened abortion Dysmenorrhoea
    24. 24. Ritodrine MOA: Relaxation of uterine smooth muscle bystimulation of beta-2 receptors Doses: 50 mg of ritodrine in 500 ml of 5% glucosesolution. Start by 10 drops per minute and increaseby 5 drops every 10 minutes until uterine contractionscease Infusion should be continued for 12-48 Hrs after cessation ofcontractions Oral therapy should be continued every 8 Hrs after food Monitor maternal pulse, BP and FHS Adverse effects: CVS effects like hypertension, tachycardia,arrhythmia etc. & metabolic effects like hyperglycemia,hyperinsulinemia and hypokalaemia – also foetalhypoglycaemia and paralytic ileus
    25. 25. Ritodrine – contd. Contraindications: Heart disease - Hypertension or hypotension   Hyperthyroidism and diabetes Antepartum haemorrhage (dilatation of the uterinearteries may increase the bleeding) Rupture of membrane Preparations: available as Ritodie/yutopar Tablet 10 mg / tablet or injections 10 mg/ml – 1mlor 5 ml Isoxsuprine (duvadilan) is available asoral and injections (10, 20, 40 mg tablets) 
    26. 26. Magnesium sulfate andCalcium channel blockers Magsulf: Action: The intracellular calcium is displaced by magnesiumion leading to inhibition of the uterine activity Dosage: The initial dose is 40 cc of 10% solution givenslowly IV. The subsequent doses depend upon the responseand the development of MgSO4 toxicity so reflexes andrespiratory rate should be observed Uses: Used for prevention of seizures in eclampsia, notused for arrest of preterm labor for its toxicites Nifedepine: equal efficacy with beta-2 agonists Dose: 10 mg every 30 minutes and followed by 10 mg every6 hrly Problems: tachycardia, hypotension and foetal hypoxia
    27. 27. Summary – must know Drugs used as uterine stimulants -Classification Oxytocin – Mechanism of action o uterus andits therapeutic uses Ergometrine – Pharmacological actions inuterus and therapeutic uses Drugs used as Tocolytics – role of ritodrine(beta-2 agonists) in arrest of labor
    28. 28. Thank you