Uteroplacental Circulation and Transfer of drugs.pptx

Uteroplacental circulation and transfer

1. Uteroplacental Circulation and Transfer of drugs Moderator= Dr Sachreet Presentor = Dr Yashi Gautam

2. Uteroplacental Circulation Consists of two independent circulation system = Maternal circulation(uteroplacental) Fetoplacental circulation

3. FETAL CIRCULATION = Umbilical arteries Chorionic Plate – branches to stem villi- capillaries in terminal villi- return via umbilical vein. ( Fetal blood comes via 2 umbilical arteries and leaves placenta through a single navel vein, vena umbilicalis ) MATERNAL CIRCULATION = Uterine artery- spiral artery – intervillous spaces-uteroplacental arteries-intervillous spac .

4. 3. Bulk Flow Due to hydrostatic or osmotic gradient Water movement depends upon sodium chloride pumping thus ATP dependent 4. BREAKS Delicate villi breaks in intervillous space extruding contents in maternal circulation. eg - alloimmunization and erythroblastosis fetalis

5. PLACENTAL DRUG TRANSFER Maternal and fetal conc. Of drug influenced by drug metabolism in mother, the placenta, the fetus, and also by changes during delivery. Maternal drug administration affect the fetus in 2 ways:- 1. Direct fetal effect via transplacental passage 2. Indirect effect by affecting uteroplacental blood flow THREE TYPES OF TRANSFER ACROSS PLACENTA 1. Complete transfer : Drugs rapidly cross the placenta with conc. Equilibrating in maternal and fetal blood. F/M is 1 eg ; thiopental . 2. Exceeding transfer : Drugs cross the placenta to reach greater conc. In fetal compared with maternal blood. F/M >1 eg ; ketamine. 3. Incomplete transfer : Drugs unable to cross the placenta completely , higher conc in maternal compared to fetal blood F/M <1 eg ; succinylcholine.

6. Factors affecting placental transfer PROTEIN BINDING- Protein bound drugs will not diffuse easily, only free drugs would cross placental barrier easily. DEGREE OF IONIZATION- ionized form will not cross the barrier easily. MOLECULAR WEIGHT- smaller molecular weight drug diffuse easily LIPID SOLUBILITY- higher the lipid solubility higher the transfer of drugs. FETAL-MATERNAL conc. (F:M) is used as an index for transfer of drugs.

7. MATERNAL FACTORS = Drug conc in maternal blood Maternal blood flow ( hypotension , aortocaval compression ) (dec perfusion – dec placental flow – less drug transfer ) Disease alter placental transfer ( pre-eclampsia ) PLACENTAL FACTORS = 1. Gestational Age( placenta is more permeable in early pregnancy )

8. LOCAL ANESTHESIA LA- weak bases, low degree of ionization, bound to alpha 1 acid glycoprotein. BUPIVACAINE AND ROPIVACAINE = highly soluble but have high degree of protein binding . LIDOCAINE= less lipid soluble than bupivacaine , low degree of protein binding – will cross placenta . CHLOROPROCAINE = least placental transfer because rapidly broken down by plasma cholinesterase.

9. INDUCTION AGENTS PROPOFOL = Highly lipid soluble and able to cross placenta easily. Associated with transient depression of APGAR score. THIOPENTOL= Highly lipid soluble , weakly acidic, 75% protein bound nd <50% ionized at physiological pH – crosses placenta easily. Doses >8mg/kg produce neonatal depression, whereas lower doses produce no significant neonatal effects providing induction to delivery time is <5 minutes. KETAMINE = Rapidly cross placenta Does not cause neonatal depression Higher doses- cause respiratory depression and muscular hypertonicity BENZODIAZEPINES= cross placenta easily (highly lipid soluble and non ionized )

10. INHALATIONAL AGENTS Volatile anaesthetic agents readily cross the placenta – highly lipid soluble, low molecular weight. Inhalational agent produces less fetal depression when MAC<1 and delivery occurs within 10 min Volatile agents dec blood pressure and uteroplacental blood flow. Depression of contractility of uterus caused by enflurane, halothane, and isoflurane – dose dependent. Higher dose – uterine atony and increase blood loss at delivery.

11. Nitrous oxide Crosses placenta rapidly. Diffusion HYPOXIA – occur in neonates exposed to nitrous oxide immediately before delivery- supplement oxygen required.

12. OPIOIDS : All opioid cross placenta . They are weak bases, bound to alpha -1 glycoprotein. PETHIDINE = Longer half life is due to its active metabolite norpethidine (may lead to resp depression ) MORPHINE = Poor lipid soluble but readily cross placenta due to low protein binding and increased free drug . FENTANYL = Highly lipid soluble and albumin bound, so cross placenta easily.

13. MUSCLE RELAXANT Quaternary ammonium compounds and fully ionized. Low lipid solubility Hence they donot cross the placenta except gallamine.

14. ANTICHOLINERGICS Transfer of anticholinergic drugs across the placenta mimics the transfer of these drugs across the blood –brain barrier. GLYCOPYROLATE= Quaternary ammonium compound which is fully ionized- poor transfer across placenta ATROPINE = Lipid soluble tertiary amine – cross placenta.

15. VASOPRESSORS Uterine vasculature has both alpha and beta adrenergic receptors. Alpha-1 receptor –uterine contraction, Beta-2 receptor- uterine relaxation Phenylephrine – drug of choice for maternal hypotension associated with less fetal acidosis than ephedrine