OXYTOCICS PDF

# Oxytocics Prepared by: Mirza Anwar Baig M.Pharm (Pharmacology) Anjuman I Islam's Kalsekar Technical Campus, School of Pharmacy. New Panvel, Navi Mumbai ## Definition - Oxytocics are the drugs of varying chemical nature that have the power to stimulate the contraction of uterine muscles. -...

# Oxytocics Prepared by: Mirza Anwar Baig M.Pharm (Pharmacology) Anjuman I Islam's Kalsekar Technical Campus, School of Pharmacy. New Panvel, Navi Mumbai ## Definition - Oxytocics are the drugs of varying chemical nature that have the power to stimulate the contraction of uterine muscles. - Also called Uterotonics - The introduction of oxytocic drugs for the treatment of Post Partum Hemorrhage (PPH) has been regarded as "one of the enduring achievements of modern science". ## Drugs Producing Uterine Contractions (Oxytocic Drugs) 1. **Oxytocin** 2. **Ergot Alkaloids** * Ergometrine (Ergonovine) 3. **Prostaglandins** * PGE2 * PGF2α 4. **Miscellaneous** * Quinine * Emetine * Alcohol * Ethacridine ## Oxytocin ### Synthesis - Is a posterior pituitary hormone secreted by the posterior pituitary gland. - Oxytocin secretion occurs by sensory stimulation from cervix, vagina, and from suckling at breast. ### Secretion A diagram showing the secretion of oxytocin. - Oxytocin is synthesized in the hypothalamus - Oxytocin moves down to the posterior pituitary gland - From the posterior pituitary, oxytocin is released into the bloodstream  ### Pharmacodynamics - Oxytocin acts through **G protein-coupled receptors** and the phosphoinositide-calcium second-messenger system to contract uterine smooth muscle. - Oxytocin also stimulates the release of **prostaglandins** and leukotrienes that augment the contraction. - Oxytocin in small doses increases both the frequency and the force of uterine contractions. - At higher doses, it produces sustained contraction. ### Mechanism of Action A diagram showing the mechanism of action of oxytocin. - The interaction of endogenous or administered oxytocin with myometrial cell membrane receptor promotes the influx of Ca⁺⁺ from extracellular fluid and from SR into the cell. - This increase in cytoplasmic calcium stimulates uterine contraction.  ### Uterus - These contractions resemble the normal physiological contractions of uterus (contractions followed by relaxation). - Immature uterus is resistant to oxytocin. - Contracts uterine smooth muscle only at term. - Sensitivity increases to 8 fold in last 9 weeks and 30 times in early labor. ### Breast - Oxytocin also causes contraction of myoepithelial cells surrounding mammary alveoli, which leads to milk ejection. - Used in breast engorgement ### Kidneys - At high concentrations, oxytocin has weak antidiuretic and pressor activity due to activation of vasopressin receptors. ### Pharmacokinetics - Not effective orally - Administered intravenously - Also as nasal spray - Not bound to plasma proteins - Catabolized by liver & kidneys - Half life = 5 minutes - Duration of action-20min - Stored at 2-8 °C ### Therapeutic Uses 1. **Induction & augmentation of labor** (slow I.V infusion) * Uterine inertia * Incomplete abortion * Post maturity 2. **Post partum uterine hemorrhage** (I.V drip). 3. **Impaired milk ejection** - One puff in each nostril 2-3 min before nursing. ### Side Effects: - Hypertension - Uterine rupture - Fetal death (ischaemia) - Water intoxication - Neonatal jaundice ## Ergots ### Chemistry - Ergot is the natural alkaloid of _Claviceps purpurea_ that grows on rye, wheat and other grains. * Ergometrine (Ergonovine) * Methylergonovine - The ergot alkaloids are derivatives of the tetracyclic compound **6-methylergoline**. - The first pure ergot alkaloid ergotamine was obtained in 1920, followed by the isolation of ergometrine/ergonovine in 1932. - The therapeutically useful natural alkaloids are amide derivatives of _d-lysergic acid_. - Semi-synthetic derivatives are obtained from catalytic hydrogenation of the natural alkaloids. * e.g.- Methergin (methylergonovine) ### Pharmacodynamics #### Effects on the Uterus - Alkaloid derivatives induce **TETANIC CONTRACTION** of uterus without relaxation in between. These do not resemble the normal physiological contractions. - It causes contractions of uterus as a whole, i.e. fundus and cervix (tend to compress rather than to expel the fetus). (Difference between oxytocin & ergots) #### Vascular Effects - **Direct peripheral vasoconstriction**, in large doses causes damage to capillary endothelium. - Example: Ergotamine and DHE #### Gastrointestinal Effect - Increased in peristaltic activity. #### Miscellaneous - 5HT partial agonist - 5HT selective antagonist ### Pharmacokinetics - Absorbed orally from GIT (tablets). - Usually given I.M. - Extensively metabolized in liver. - 90% of metabolites are excreted in bile ### Therapeutic Uses - **Postpartum Hemorrhage**. * The uterus at term is extremely sensitive to the stimulant action of ergot and even moderate doses produce a prolonged and powerful spasm of the muscle quite unlike natural labor. * Therefore, ergot derivatives should be used only for control of late uterine bleeding and should never be given before delivery. * Oxytocin is the **preferred agent** for control of postpartum hemorrhage, but if this is ineffective, **ERGOMETRINE** (0.2 mg) is given intramuscularly. * It is usually effective within 1-5 minutes and is less toxic than other ergot derivatives for this application. ### Side Effects - Nausea, vomiting, diarrhea - Hypertension - Vasoconstriction of peripheral blood Vessels (toes & fingers) - Gangrene ### Contraindications - 1st and 2nd stage of labor - Vascular disease - Impaired hepatic and renal functions ### Precautions - Cardiac diseases - Hypertension - Multiple pregnancy ## Prostaglandins ### Mechanism of Action - Contract uterine smooth muscle ### Difference Between PGS and Oxytocin - PGS contract uterine smooth muscle not only at term (as with oxytocin) but throughout pregnancy. - PGS soften the cervix; whereas oxytocin does not. - PGS have a longer duration of action than oxytocin. ### Analogues & Common Preparations | Analogues | Preparations | | ------------- | ------------- | | PGE1 (methyl ester) | MISOPROSTOL | | PGE2 | DINOPROSTONE | | | (NOTE: less toxic, more effective so widely used.) | | PGF2α | DINOPROSTONE TROMETHAMINE | | PGF2α (methyl analogue) | CARBOPROST | **Preparations** - Tablet: 0.5mg dinoprostone (prostinE₂). - Vaginal suppository: 20mg PGE₂/50mg PGF_2α lipid base. - Vaginal pessary: 3mg PGE₂. - ProstinE₂ gel: 500µg into cervical canal, below internal OS/1-2mg in the posterior fornix. - Parenteral: * PGE₂ - ProstineE₂ 1mg/ml. * PGF_2α-ProstinF_2α (Dinoprost tromethamine) 5mg/ml. * Methyl analogue of PGF_2α- Carboprost 2.5mg/10ml vial. ### Therapeutic Uses 1. Induction of abortion (pathological) 2. Induction of labor (fetal death in utero). 3. Postpartum hemorrhage ### Side Effects - Nausea, vomiting - Abdominal pain - Diarrhea - Bronchospasm (PGF2α) - Flushing (PGE2) ### Contraindications - Mechanical obstruction of delivery - Fetal distress - Predisposition to uterine rupture ### Precautions - Asthma - Multiple pregnancy - Glaucoma - Uterine rupture ## Difference between Oxytocin and Ergometrine | Character | Ergometrine | Oxytocin | |---|---|---| | Contractions | Tetanic contraction; doesn't resemble normal physiological contractions | Resembles normal physiological contractions | | Uses | Only in P.partum hemorrhage | * To induce & augment labor. *Post partum hemorrhage | | Onset and Duration | Moderate onset Long duration of action | Rapid onset Shorter duration of action | ## Difference Between Oxytocin and Prostaglandins | Character | Prostaglandins | Oxytocin | |---|---|---| | Contraction | Contraction throughout pregnancy | Only at term | | Cervix | Soften the cervix | Does not soften the cervix | | Duration of action | Longer | Shorter | | | i. Used for abortion in 2nd trimester of pregnancy. ii. Used as vaginal suppository for induction of labor | i. Not used for abortion ii. Used for induction and augmentation of labor and postpartum hemorrhage | ## Thank you Compiled by: Prof. Anwar Baig