Carboprost
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Carboprost is a synthetic prostaglandin analogue of PGF2α that is used to induce abortion between 13-20 weeks of pregnancy and in postpartum hemorrhage. It works by binding to FP receptors in the uterus and myometrium, causing powerful contractions that expel the products of conception. Common side effects include diarrhea, nausea, vomiting, and uterine cramping pain. It is administered as a single intramuscular injection of 250 mcg that can be repeated if needed. Carboprost has a short duration of action of 3-6 hours and is metabolized and excreted primarily in the kidneys.
Carboprost
- 2. Introduction • Carboprost is a synthetic prostaglandin analogue of PGF2ά (specifically, it is 15- methyl-PGF2ά) with oxytocic properties.
- 4. • 20-Carbon carboxylic acids with Cyclopentane ring • Formed by PUFA Prostaglandins types Prostanoic acid 2468 10 12 14 16 18 20 PGE2 PGF2ά COOH PGE1
- 5. EICOSANOIDS Cyclooxygenase pathway Arachidonic Acid Cyclooxygenase PGG Prostacyclin synthetase Thromboxane synthetase PGI2 PGH2 TXA2 PGE2 PGD2 PGF2
- 6. Structure
- 7. Chemical data Formula C20H34O5 Mol. mass 354.48 g/mol
- 8. Systematic (IUPAC) name • (5Z,9a,11a,13E,15S)-9,11,15-trihydroxy-15- methylprosta-5,13-dien-1-oic acid
- 9. Preparation • 1ml ampule containing 250 mcg of carboprost
- 10. Mode of Action • G : ↑IP3, DAG, activity of this receptor mediated by G protein which activate a phosphatidylinositol-calcium second messenger system initiate luteolysis in corpus luteum Carboprost is a uterine stimulant which results in expulsion of the products of conception. It is also used to induce abortion between 13-20 wk of pregnancy. It produces myometrial contractions responsible for placental hemostasis.
- 11. Pharmakokinetics • Metabolism : • T ½ : • Onset of action : • Duration of action : • Excretion :
- 12. • Metabolism of prostaglandin PG-F2 alpha occur rapidly in most tissue but fastest in lung by alveolar type II cells from lungs of adult male
- 13. T ½ : half life of PGF2 vary from few second to few minute .Average half life is 1 minute. 3 to 6 hours in amniotic fluid, less than 1 minute in blood plasma
- 14. • The peak plasma level of the drug is reached about 30 minutes after injection. A successful clinical response is expected after a single injection in about 75% of cases. In refractory cases, additional dosing at 15-90 minute intervals may be beneficial. The total amount of drug given should not exceed 2 mg (8 doses). The clinical response may be enhanced with concomitant use of oxytocin. It may be less effective when used in the setting of chorioamnionitis. Onset of action :
- 15. • Mainly through kidney •Excretion
- 16. Type Receptor Function PGI2 IP •vasodilation •inhibit platelet aggregation •bronchodilatation EP1 •bronchoconstriction •GI tract smooth muscle contraction EP2 •bronchodilatation •GI tract smooth muscle relaxation •vasodilatation comparison of different types of prostaglandin, prostacyclin I2 (PGI2), prostaglandin E2 (PGE2), and prostaglandin F2α (PGF2α).
- 17. PGE2 EP3 •↓ gastric acid secretion •↑ gastric mucus secretion •uterus contraction (when pregnant) •GI tract smooth muscle contraction •lipolysis inhibition •↑ autonomic neurotransmitters •↑ platelet response to their agonists and ↑ atherothrombosis Unspecified •hyperalgesia •pyrogenic
- 18. PGF2α • Act on FP receptor cause • Uterus contraction • Bronchocontriction
- 19. Uses ABORTION • Carboprost -15 methyl PGF2α analogue, for midterm abortion and missed abortion. • (It is also used for PPH.)
- 20. • This drug, carboprost (15-methyl-PGF2) is used to induce second-trimester abortions • ; not responding to conventional methods of Methotrexate. • The success rate is approx. 80%. It is administered as a single 250-mcg intramuscular injection, repeated if necessary. • S/E- Vomiting and diarrhea.
- 21. FACILITATION OF LABOR • PGE2, PGF2 , and their analogs effectively initiate and stimulate labor, but PGF2 is 1/10th as potent as PGE2. • There appears to be no difference in the efficacy of PGE2 and PGF2 when they are administered intravenously; • however, they may be of more use locally to promote labor through ripening of the cervix.
- 22. Used in postpartum hemorrhage caused by uterine atony not controlled by other methods. Unlabeled use: • Hemorrhagic Cystitis • PID
- 23. Contraindications • Hypersensitivity. • Acute pelvic inflammatory disease. • Patients with acute cardiac, pulmonary, renal or hepatic disease. • History of caesarian, major uterine surgery. Pregnancy.
- 24. Precautions • asthma • anemia • jaundice • diabetes mellitus • seizure disorders • past uterine surgery • Cardiopulmonary disorders, • glaucoma, • severe hepatic or renal dysfunction, • labour.
- 25. Doses Pregnancy termination in the 2nd trimester: Intramuscular • Adult: As tromethamine: 250 mcg deep IM, repeated at 1.5 to 3.5-hr intervals depending on uterine response. May be increased to 500 mcg if necessary. Max: 12 mg. Postpartum haemorrhage: Intramuscular • Adult: As tromethamine: 250 mcg deep IM at 15- to 90-min intervals. • Max Dosage: 2 mg.
- 26. Drug interaction • Action enhanced by prior inj of hyperosmolar urea. Potentially Fatal: Enhances action of oxytocin hence both drugs should be used sequentially and carefully monitored.
- 27. Side effects Adverse Effects • diarrhea (most common, may be sudden in onset) • fever • chills • Nausea & vomiting, • uterine cramping pain, • vaginal bleeding
- 28. Adverse Drug Reactions • Nausea, • vomiting, • diarrhoea • abdominal pain • flushing, shivering • headache, dizziness • and hypotension, temporary pyrexia, dyspnoea, pulmonary oedema. • Potentially Fatal: Severe CVS disorders including fatal hypotension, tachypnea, pyrexia and MI (in patients with high risk factors) following intra-amniotic or intravaginal admin. Convulsions and ECG changes, amniotic fluid embolism and uterine rupture, foetal distress and rarely foetal death during induction of labour.
- 29. Pregnency • Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.
- 30. Pediatric Use • Safety and effectiveness in pediatric patients have not been established.
- 31. Systemic effects • CVS : • vasodilatation • inotropic effect • it also constricts many larger vein including pulmonary vein &arteries it has little effect on BP • Uterus : • contraction, • softening of cervix
- 32. • Bronchoconstriction • More potent than histamine • Asthma may be due to imbalance between constrictor PG and dilator Respiratory system
- 33. • Spasmogenic • Increase fluid &electrolyte secretion • Longitudinal & circular muscles of gut are contracted • Colic& watery diarrhoea are important side effect due to increase propulsive activity G.I.T.
- 35. THANKS