PHARMACOLOGY OF OBSTETRIC RELEVANT

DRUGSDr.Sreejith.H

Profound physiologic changes in pregnancy involving the mother, placenta and fetus that may alter absorption, distribution and elimination of drugs

Teratogen is an agent , which by acting on the developing embryo or fetus , can cause a structural anomaly

Malformations induced by drugs are important because they are potentially preventable

1st trimester – structural anomaly 2nd trimester- Functional anomaly 3rd trimester- Fetal growth affected

Prevention of gastric aspiration Analgesia Local anaesthetics Drugs which contract the uterus Drugs which relax the uterus

PREVENTION OF GASTRIC ASPIRATION

Antacid used as prophylaxis against aspiration pneumonitis in RSI

30 ml of 0.3 molar solution should be given less than 10 min before starting surgery

Non particulate antacid Efficacy depends on gastric volume & acidity

SODIUM CITRATE

Benzamide dopamine antagonist Prokinetic agent Dopamine receptor antagonism at the chemo

receptor trigger zone Dose: 10 mg oral/ IM /IV Side Effects Crosses Blood Brain Barrier Acute dystonic reactions /extra pyramidal effects Neuroleptic Maliganant Syndrome

METOCLOPROMIDE

Histamine H2 receptor antagonist at parietal cells

Dose : orally 150 mg at onset of labor Or 50 mg im/slow iv 45-60 min before induction Rapid IV – Cardiac arrythmias Oral bioavailability : 50% & 50% excreted

unchanged in urine

RANITIDINE

ANALGESICS

Most commonly used class of drugs for systemic medication

All opioids cross placenta & may cause respiratory depression

Side effects : Respiratory depression Nausea & vomiting Euphoria to excessive sedation

OPIOIDS

Synthetic opioid Dose : 1 mg/kg upto 150 mg IM DOA: 120-150 min Effects in Parturient Confusion Loss of control Sedation Hypoxia Increases gastric volume Decreaes gastric emptying

PETHIDINE(MEPERIDINE)

Effect of Foetus & Neonate highly protien bound high lipid solubility Cross placentaHighest fetal concentration 2-3 hrs after adminstrationProlonged sedationProconvulsant properties

Alternative analgesia option in whom neuraxial anaesthesia is contraindicated

Short half life Iv bolus /patient controlled delivery system Minimal neonatal depression Crosses placenta Usual dose 25-50 mcg iv Peak effect occurs in 3- 5min Duration of action is 30 -60 min Other Routes : subcutaneous, oral or patch S/E : low APGAR SCORE after dose >1mcg/kg Mild maternal sedation after admnistration of 50-100 mcg

FENTANYL

Potent short acting mu agonist Rapid plasma clearance & offset of action Rapid metabolism or redistribution or both Half life 1.3 min 0.4 mcg/kg with a lockout time of 1 min Or Continuous infusion 0.05 mcg/kg/min with a

bolus of 25 mcg

REMIFENTANIL

Opioid agonist- antagonist Structurally related to Oxymorphine & Naloxone Butorphanol k agonist & a mu antagonist Dose 1-2 mg im /iv DOA : 4hrs Nalbuphine partial k agonist & a potent mu antagonist Dose :10 mg im /iv DOA: 6 hrs Ceiling effect : increasing dose doesnot produce

further respiratory depression Rapidly crosses across placenta Sinusoidal FHR pattern

BUTORPHANOL & NALBUPHINE

N20:O2 – 50:50 Takes 30sec to act Most often administered as demand valve for

self administration For optimum effect- inhalation should start

when contraction tightens N2O is a strong analgesic 20% N2O = 15 mg s/c morphine

ENTONOX

LOCAL ANAESTHETICS

Rapid onset of action Minimal risk of toxicity Minimal motor blockade with effective

sensory blockade Minor effect on uterine activity & placental

perfusion

Ideal local anaesthetic

BUPIVACAINE ROPIVACAINE LIDOCAINE CHLOROPROCAINE

Common local anaesthestic Antiarrythmic property Amide group DOA: 45 -90 MIN 70% PROTIEN BOUND Rapid onset of action 90% metabolized in Liver by N-dealkylation(CYP1A2 &

CYP3A4) Elimination half life 1.5- 2 hrs TRANSIENT NEUROLOGICAL SYMPTOMS Readily crosses placenta O.75% to 1.5% for sensory analgesia

LIDOCAINE

Amide group Most commonly used LA for Spinal & epidural Longer duration of action Highly protein bound Route : local infiltration, intrathecal , epidural Metabolised in Liver by N-dealkylation Early labor 0.125% or lower , 0.25% during active phase Lethal dose – 2mg/kg Package – 0.25% & 0.5% For SAB – 0.5% Soln containing 80mg/ml glucose S/E : Cardiotoxicity

BUPIVACAINE

S (-)entanomer of Bupivacaine Crosses placenta Less cardiotoxicity Clinical profile similar to that of Bupivacaine

LEVOBUPIVACAINE

Ester local anaesthetic Rapid onset Lasts only for 45 min Rapid metabolism by ester hydrolysis Donot cross the placenta 3% is used to increase anaesthetic level

quickly in CS or instrumantal delivery S/E - Neurotoxicity

2- CHLOROPROCAINE

Amide Local anaesthetic Homolog of Mepivacaine & Bupivacaine Less potent than Bupivacaine Conc 0.1% to 0.2% are used during Labor Onset duration & sensory block similar to equipotent doses

of Bupivacaine Motor block slightly less than Bupivacaine Less cardiotoxicity Highly plasma protien binding Metabolism by Cytochrome P450 in Liver Costs significantly more than Bupivacaine

ROPIVACAINE

DRUGS WHICH CONTRACT THE UTERUS

Adminstration of uterotonic agent is an integral part of active management of 3 rd stage of labor

Helps to prevent Postpartum Haemorrhage Two most widely used agents Ergometrine – oxytoxin Oxytocin

Posterior pituitary hormone Effective uterine contraction SYNTOCINON- Synthetic oxytocin Uses – Induction & acceleration of labor Missed & complete abortion PPH Immediately after delivery

Oxytocin

Dose : After delivery 5 IU slow iv To prevent PPH is 5IU upto 40IU infused over hrs Action : Act on other vascular smooth muscle (?HYPERTENSION) AntiDiuretic Hormone Side Effect Hypotension & reflex tachycardia May prolong Q-T interval & cause T wave flattening ADH effect on high dose

Amine ergot alkaloid Stimulates contraction of uterus & vascular smooth muscle Dose : 0.2-0.5 mg iv/im Iv route is recommended only for emergencies S/E : peripheral vasoconstriction- hypertension & pulmonary edema Nausea , vomiting , diarrhoea Diziness , hallucination, vertigo & tinnitus CONTRAINDICATIONS: Pre – Eclampsia Eclampsia Pts with Peripheral vascular disease /heart disease Retained placenta

ERGOMETRINE

Ergometrine 0.5mg + Syntocinon 5 IU Routinely adminstered by IM To assist placental seperation& reduction in

PPH

SYNTROMETRINE

Group of endogenous short polypeptides Commonly used to Ripen cervix in induction of

labor May cause Bronchospasm & Hypertension Commonly used Carboprost Misoprostol Dinoprostone Mifipristone (RU486)

PROSTAGLANDINS

PGF2A Potentiates the uterotonic effects of oxytocin Used to treat PPH in pts unresponsive to ergotamine &

oxytocin DOSE: 250mcg by deep im inj Direct intramyometrial inj CAUTIONS: Shouldnot given iv Used cautiously in asthmatics In pts with H/O glaucoma, raised IOP, Uterine scars

CARBOPROST

Synthetic PGE1 analogue Used to treat PPH Used to induce labor for a non viable fetus May be given rectally to facilitate uterine

contraction prior to delivery of placenta Dose : 400-800 mcg Routes : sublingual,oral,rectal,intrauterine S/E: Nausea, vomiting,diarrhoea, abdominal

pain, dyspepsia,hyperpyrexia,shivering

MISOPROSTOL

PGE2 Given as gel,tablet, or pessary intravaginally

to induce labor by ripening cervix

DINOPROSTONE

Prostaglandin antagonist Causes Luteolysis,trophoblastic seperation Given orally with prostaglandin To induce labor after IUD of fetus Labor is induced a nonviable fetus S/E: headache , diziness, GI upset

MIFEPRISTONE(RU486)

DRUG WHICH RELAX THE UTERUS

On rare occassions emergency tocolysis may be requiredEg:Fetal distress with a tonic uterus Uterine inversion Manual removal of placenta For emergency tocolysis during surgery Nitrates Inhalational agents Other classes of drugs NSAIDS (eg:indomethacin) Ca- channel blockers(eg: nifedipine) Magnesium sulphate Beta agonist(eg: Ritrodine)

Prostaglandin synthetase inhibitor May be given orally or rectally To inhibit contractions after cervical circlage Can cause premature closure of fetal ductus

arteriosus Shouldnot be used after 32 weeks of GA

INDOMETHACIN

a direct-acting sympathomimetic with predominantly beta-adrenergic activity and a selective action on beta(2) receptors

Tocolytic agent: decreases uterine contractility arrest premature labor

50mg/5ml/amp

RITODRINE

A recommended initial rate of infusion is 0.05mg/minute increased at intervals of 10 minutes by 0.05 mg increments until there is evidence of patient response, which is usually at a rate of 0.15 to 0.35 mg/min

Contraindicated for use before the 20th week of pregnancy

Pre-existing maternal medical conditions that would be seriously affected by the known pharmacologic properties of a beta-mimetic drug such as hypovolemia, cardiac arrhythmias associated with tachycardia or digitalis intoxication, uncontrolled hypertension, pheochromocytoma, and bronchial asthma already treated by beta-mimetics and/or steroids

Contraindications of tocolytic therapy

Cautions

Tachycardia, arrhythmia, bradycardia, carefully titrate ephedrine

Watch out for fluid overload, the risk for pulmonary edema

Glucose level, electrolyte imbalance( K )

SIDE EFFECTS

Beta 2 agonist Can be given subcutaneously/ im/slow iv

infusion To treat overstimulated contractions

associated with fetal distress In utero fetal resuscitation regimen before

emergency cs

TERBUTALINE

Oxytocin antagonist Used to decrease nuterine contractions Has only few side effects but expensive

ATOSIBAN

LAPROSCOPIC SURGERIES IN PREGNANCY

Risk of misscarriage /preterm labor Risk of damaging gravid uterus Co2 pneumoperitoneumCAPNOGRAPHY is adequate to guide

ventilation during laproscopy in pregnant patients

Pneumoperitoneum pressure should be limited to 15 mm Hg

Etco2 at 32 mm Hg

Laproscopy during pregnancy concerns

1. The operation should occur during the second trimester,ideally before the 23rd week of pregnancy, to minimize therisk of preterm labor and to maintain adequate intraabdominalworking room.

2. Tocolytics are beneficial to arrest preterm labor, but theirprophylactic use is debatable.3. Open laparoscopy should be used for abdominal access toavoid damaging the uterus.4. Fetal monitoring may be performed using transvaginalultrasonography.5. Mechanical ventilation must be adjusted to maintain aphysiologic maternal alkalosis.

The following recommendations are for safe laparoscopy in pregnant

patients: