Drugs used in obstetric emergenciesVasanthakumari,Msc (N)

Lecturer(pediatrics)Sri manakula vinayagar nursing

clg,pudhucherry.

Drugs in Pregnancy

FIRST TRIMESTER :

congenital malformations (teratogenesis)

SECOND & THIRD TRIMESTER :

affect growth & fetal development or

toxic effects on fetal tissues

NEAR TERM :

adverse effects on Labour or

neonate after delivery

Drug categories

Category –A - practically Not harmful during any trimester of pregnancy. eg- antibiotics( penicillin, ampicillin, amoxicillin, cloxacillin,

erythromycin stearate, cephalosporin)

vitamin and mineral in standard doses Thyroxin and humanized insulin

Conti….

Category B - used in pregnancy with out adverse effect eg- metronidazole, tinidazole,

azithromycin,nystatin, paracetamol, ranitidine, ritodrine,

Conti…..

• Category – C - Shown adverse fetal effects in the animal model, but no adequate studies in pregnant women

• - immediate benefits have to be weighed against the potential risks of drug used

• Eg- trimethoprim, anti tuberculosis drugs, norfloxacin, ciprofloxcin,lfloxacin,– aminophylline, quinine, acyclovir, zidovudine,heparin,– hydralazine, Beta blockers, MAO- inhibitors,

lorazepam etc.

Conti..

• Category –D - known to be potentially harmful. Evidence of positive fetal risks. Certain situation maternal benefits may outweigh the potential fetal risks.

• Eg – Tetracycline's, streptomycin, kanamycin, phenytoin,phenobarbitone, valproicacid, alprazolam,chlordiazepoxide,lithium, tricyclic depressants, ACE inhibitors,

spironolactone, propyl thiouracil, corticosteroids,tobacco, iodine, warfarin, thiazides, alcohol,

etc.

Conti…….

• Category- X - proven to exert harmful effects on the fetus in both animal and humans.

• Fetal risks outweigh any possible benefits to mother • Hence should be avoided.Eg.

Aminoptterin.,androgens,clomphene,diethylstilboestrol,oestrogens,antimalignancy drugs,substance abuse, such as heroin,opium,lysergic acid diethylamide,etc used by drug addicts.

Definition of Obstetric Emergencies:

• An emergency is an occurrence of

serious and dangerous nature,

developing suddenly and

unexpectedly, demanding

immediate attention.

Obstetric emergencies related

directly to pregnancy include, for

instance1.Pre-eclampsia

2.Eclampsia

3.Antepartum Haemorrhage

4.Postpartum Haemorrhage

5.Amniotic Fluid Embolism

6.Congenital Heart Disease

7.Epilepsy

Uterotonics and tocolytics drugs

• Uterotonics increase uterine contractions (oxytocine, prostaglandines, serotonine, kinines, cathecholamines).

• Tocolytics decrease uterine contracions (spasmolytics, beta-receptor-stimulating medications, anti-oxytocin drugs).

METHERGINE

“Speedy”OXYTOCIN

“The Champ”

CytotecInexpensive (?) Effective

Medications for Uterine AtonyMedications for Uterine Atony

Mechanism of myometrium contractions

• Myometrium has alpha and beta-adrenoreceptors.

• Stimulation of alpha-receptors by catheholamines causes uterus contraction

• Stimulation of beta-receptors by catheholamines causes uterus relaxation

Mechanism of myometrium contractions

• Uterus body contains alpha and beta catheholamines receptors

• Lower segment contains choline and serotonine receptors• Cervix contains chemo-, baro- and

mechanoreceptors

Severe Pre eclampsia / HTN

• IV Labetolol (ß blocker): - Side effects: headache, nausea, vomiting, postural

hypotension & liver damage - Contraindication: Asthma, marked bradycardia• IV hydralazine (vasodilator) : - Side effects: headache,nausea, vomitting, dizziness,

flushing, tachycardia, palpitation & hypotension - Because of hypotension preload with gelofusin adv. - Contraindication- SLE, severe tachycardia & MI

Nifedipine• Calcium Channel blocker

• Clinical use: • Mild to moderate- 5-20 mg TDS/PO• Severe HTN- 10 mg Retard/PO • Tocolytic- Incremental doses every 20 min until

contraction stop, then 20 mg TDS/PO

• Side effects: Headache,dizziness,palpitation, tachycardia, hypotension,sweating & syncope.

Magnesium Sulphate• Clinical use: Prevention & treatment of seizure in

eclampsia / severe pre eclampsia

• Dose: 4g IV stat then 1g/hr to be continued 24hr after last seizure

• Side effects: nausea,vomiting,flushing, drowsiness,confusion,loss of tendon reflexes, hypotension, decrease U/O, respiratory depression, arrhythmias,cardiac arrest

• Because of toxicity, Mg levels monitored

Magnesium Sulfate

• • Mech of action is unclear• – Impedes acetylcholine release?• – Decr sens of the motor end plate?• – Central anticonvulsant effect?• • 4 g iv bolus(20 cc of 20% soln) over 10‐

15min• • Maintenance is 1 3 g/h(alt 10 g im)‐

MgSo4

• First line treatment of eclampsia• • Recommended as prophylaxis against• eclampsia in severe pre eclampsia

MgSo4

• • Cochrane reviews: MgSo4 safer and more• effective than diazepam or phenytoin for• prevention of recurrent seizures• • SE: Mg toxicity• – Loss of DTRs @ 8 10 mEq/L‐• – Respiratory paralysis @10 15 mEq/L‐• – Cardiac arrest @ 20 25 mEq/L‐

MgSo4•• Monitor:•– RR hourly•– Patellar reflexes hourly•– U/O <20cc/hr decrease dose‐‐•– Serum Mg levels q 4 hrs 94 8mEq/L)‐•• Crosses the placenta freely rarely NN‐‐•depression• Calcium gluconate 1g iv over 3 5 min(10cc of‐‐ ‐ 10% soln) antidote!

Post partum hemorrhage

• Postpartum Haemorrhage- uterotonics- oxcyticin

• 0.2 mg IM/IV q2-4hr PRN; not to exceed 5 doses, THEN 0.2-0.4 mg PO q6-8hr PRN for 2-7 days

• Administer IV only in emergency because of potential for Hypertension & CVA

• Administer over >1 minute and monitor BP• Refractory Cluster Headache (Off-label)• 0.2 mg PO q6-8hr, not to exceed 6 months

OXYTOCIN

• The common medication used to achieve uterine contraction

• First-line agent to prevent and treat PPH

OXYTOCIN“The Champ”

Oxytocin Mechanism of action:• Acts through oxytocin receptors present in

smooth muscles of myometrium.• Stimulates the amniotic and decidual

prostaglandin production.• Mobilization of bound intracellular calcium from

sarcoplasmic reticulum to activate the contractile protein.

• There is increase in frequency and force of uterine contractions, similar to physiological uterine contractions

Oxytocin Duration of action: approximately 20 minutes. In non pregnant

women, half life (t1/2) is 10-15 minutes and the removal from circulation is due mainly to kidneys and liver, but t1/2 in pregnant women is only 3 minutes, because of presence of enzyme oxytocinase in placenta, uterine tissue and plasma which inactivates it.

• Given orally it is ineffective as it is inactivated rapidly in the Gastro-intestinal tract by enzyme, trypsin, needs to be administered by parenteral, nasal or buccal routes.

Unitage and Preparation: 1 international unit (i.u.) of oxytocin is equivalent to 2 microgram of pure hormone.

• Commercially available preparation is produced synthetically. Oxytocin injections are available in concentration of 5 i.u. / ml (Syntocinon) , 5 i.u/ 0.5ml. (pitocin) or 2 i.u./ 2ml. (oxytocin).

• Oxytocin nasal spray contains 40 units/ ml.

Oxytocin

Indications for stopping the infusion Abnormal uterine contractions • occurring too frequently ( less than every 2 minutes), • lasting more than 60 seconds ( hyper stimulation) • and increased tonus in between the contraction Evidence of Foetal distress Appearance of untoward maternal signs and symptoms

Oxytocin Dangers of Oxytocin Maternal • Uterine hyper stimulation; increased frequency and duration

of uterine contractions & / or increased tonus, is often associated with abnormal foetal heart rate pattern

• Urine rupture; high risk in grand multipara, malpresentation, contracted pelvis, prior uterine scar and excessive dosages.

• Water intoxication; due to its ADH like antidiuretic action, when used in high dosages i.e. 30 – 40 i.u. / min., manifested by hyponatremia, confusion, convulsions, coma, CHF and even death. Can be prevented by strict intake output record, use of salt solutions, and by avoiding high doses oxytocin for a longer time.

• Hypotension; it is seen with bolus i.v. injection especially when the patient is hypovolemic or in patients with heart disease. Occasionally may produce anginal pain.

• Anti- diuresis; especially with higher dosages Foetal • Foetal distress, foetal hypoxia or even foetal death

may occur due to reduced placental blood flow due to uterine hyper stimulation.

Oxytocin (Syntocinon)• Octapeptide• Strong rhythmical contraction of myometrium• Large doses- sustained contraction(↓ placental blood

flow & fetal hypoxia/death)• Clinical use: - IOL (IVI 3U syntocinon+50 ml of saline) - Augment slow labour (IVI same as above) -3rd stage of labour- 5 U IM for HTN ,cardiac disease - IVI 40 U in 500ml saline ( PPH) -Surgical termination of preg./ERPC- 5U slow IV

uterotonics- methylergonovin

• Postpartum Haemorrhage• 0.2 mg IM/IV q2-4hr PRN; not to exceed 5 doses,

THEN 0.2-0.4 mg PO q6-8hr PRN for 2-7 days• Administer IV only in emergency because of

potential for Hypertension & CVA• Administer over >1 minute and monitor BP• Refractory Cluster Headache (Off-label)• 0.2 mg PO q6-8hr, not to exceed 6 months

• carboprost tromethamine (Rx) - Hemabate• Refractory Postpartum Uterine Bleeding• Initial 250 mcg IM, repeat PRN q15-90min• No more than 2000 mcg or 8 doses

• misoprostol (Rx) - Cytotec• Postpartum Hemorrhage (Off-label)• Prophylaxis: 600 mcg PO within 1 minute of

delivery• Treatment: 800 mcg PO once; use caution if

prophylactic dose already given and adverse effects present or observed

• Use only in settings where oxytocin not available

• ergonovine (Discontinued) - ergometrine, Ergotrate• Pospartum or Postabortion Hemorrhage• 0.2 mg IM; may repeat in 2-4hr; not to exceed 5 doses

total• Give IV only in emergency because of potential for

HTN & CVA• Alternatively, 0.2-0.4 mg PO q6-12hr PRN for 48 hr or

until danger of uterine atony has passed; no more than 1 week

• Give over >1 minute & monitor BP

Dinoprostone ( prostin E2)

• Vaginal pessary/gel• Clinical use: IOL – 3mg 6hrs apart ( no more than

2 pessaries in 24hrs and max. 3 doses)• Side effect: Nausea ,vomiting, diarrhoea, fever, Uterine hyperstimulation , HTN, bronchospasm• Advantages : - Mobile patient -Reduce need for syntocinon

Carboprost ( Hemabate)

• Dose ; 250µg deep IM repeated every 15 min max 8 doses.

(OR Intra-myometrial use at C/S)

• Side effects: Nausea ,vomiting, diarrhoea, fever, bronchospasm, dyspnoea, pulmonary oedema,

HTN, cardiovascular collapse

• Clinical use: Postpartum haemorrhage

Atosiban(Tractocile)• Oxytocin receptor antagonist• Inhibition of uncomplicated preterm labour

between 24-33 weeks ( Tocolytic)• Contraindication: severe PET, eclampsia, IUGR,

IUD, placenta previa, placental abruption, abnormal CTG, SROM after 30/40

• Side effects: Nausea,vomiting,headache, hot flushes, tachycardia, hypotension & hyperglycemia

• Dose- Stat IVI then continue infusion until no contraction for 6 hrs.

Other tocolytics

• Salbutamol inhaler- 100 mcg x 2 puffs stat• Terbutaline- 250 mcg subcutaneous

• Clinical use: both drugs are used for short term. (i) relaxing uterus at C/S (ii) ECV procedure

• Side effects: Headache, palpitation, tachycardia, MI ,arrhythmias, hypotension & collapse

Mild /Moderate HTN/PET

• Methyldopa: -Dose: 250mg BD/TDS , PO max dose 3g /day -Side effects: Headache,dizziness,dry mouth , postural

hypotension,nightmares, mild psychosis, depression,hepatitis & jaundice

- Important to stop drug in postnatal period

• Labetolol 100-200mg BD/TDS PO max 2.4g/24hr

• ACE inhibitors are contraindicated in pregnancy

Don’t forget analgesia & anaesthesia for labour & delivery!!

Commonly used drugs that should be avoided in pregnancy and safer alternatives

Drug class Drugs to avoid in pregnancy

Associated problems

Drugs considered safer alternatives

analgesics Non steroidal anti inflammatory

Increased risk of spontaneous abortion

Paracetamol,opiates

antibiotics trimethoprim Causes structural defects-cleft palate

Penicillin and cephalosporin

anticoagulants Warfarin(1st

&3rd trimester)CNS defects,hemorrhage, stillbirth, spontaneous abortion, prematurity.

Low molecular weight heparin

anticonvulsants' phenytoin Congenital facial anomalies

carbamazepine

Cardio vascular drugs

amiodarone Cardiac arrhythmias and growth restriction

digoxin

Antibiotics categorized according to their safety profile

Name of the drugs category remarks

Ampicillin, cephalexin,amoxycillin,erythromycin,chloramphenicol,clindamycin.

A May be prescribed safely

Tinidazole, trimethoprim + sulphonamides

C Preferably avoided

Tetracycline, aminoglycosides,doxycycline

D Should always be avoided

Drugs in early pregnancy• Mifepristone- 200mg PO• Mechanism: Antiprogestogenic steroid Sensitizes myometrium to prostaglandin-induced

contractions & ripens the cervix• Clinical use: Medical termination of pregnancy Medical management of miscarriage/IUD• Side effects: Gastro intestinal cramps, rash, urticaria,

headache,dizziness,• Contraindication: severe asthma

Misoprostol• Synthetic prostaglandin• PO/PV route• Clinical use: - Medical TOP - Medical management of miscarriage/ IUD ( For 1st trimester single dose of 400mcg From 12- 34 weeks 400mcg 3hrly ,max 5 doses) - Postpartum hemorrhage- 800mcg PR/PV• Side effects: nausea,vomiting, diarrhoea, abdominal pain

Methotrexate

• Cinical use: Medical management of ectopic pregnancy

• Dose 50mg per kg/m2• Criteria- adenexal mass, non viable pregnancy

hCG< 3000U, haemoperitonuem < 150ml• Side effects: • Disadvantage : repeated hCG levels, emergency

surgery• Advantage: Avoid surgery, tube preserved

Menorrhagia / dysmenorrhea• Mefenamic acid: - NSAID, reduces bleeding by 25% - Dose: 250-500mgx TDS D1-3 of cycle or PRN - Side effects: Gastro-intestinal discomfort nausea,

diarrhoea, bleeding/ulceration• Tranexamic acid: - Antifibrinolytic,reduces bleeding by 50% - Dose: 1g TDS/QDS D1-4 of cycle - Contraindication: thromboembolic disease - Side effects: nausea,vomiting,diarrhoea, thrombo

embolic event

Progestogens• Dysfunctional uterine bleeding/menorrhagia-

Norethisterone 5mg TDS D5-25 (3ks on/1wk off) • Endometriosis- same dose contin. 9 months• Menorrhagia- Depoprovera, Mirena• Contraception- Mini pill, Mirena• Induce withdrawal bleeding eg. PCOS ( 10 days Rx)• Endometrial hyperplasia ( except atypical variety)- Depo

provera, Mirena• HRT • Women with previous preterm labours -cyclogest pessary

200mg PV/PR daily till 36 weeks• Following IVF/ICSI- Gestone inj + cyclogest pessary

Progesterone• Increases membrane potential of myocyte and particularly

blocks impulses between myocytes• Myometrium becomes insensitive to irritatons

myometrium

Estrogen

• Contraceptive - COC• DUB/menorrhagia-COC • Endometriosis- COC continued for 9 months• PCOS/Hirsutism - Dianette• PMS- E2 patches + Mirena• HRT• Hypogonadism- cyclical therapy initially oestogen

then combined oestrogen & progesterone

Gonadorelin analogue• Mechanism- Initial stimulation then down regulation

of GnRH receptors reducing the release of gonadotrophins and in-turn release of estrogen & androgen production

• Side effects:menopausal symptoms, headache, hypersensitivity( rash,asthma, anaphylaxis), palpitation,hypertension,breast tenderness & GI symptoms, irritation of nasal mucosa (spray)

• E.g Prostap, Zoladex & Buserelin spray• S/C /IM inj. Monthly or nasal spray TDS for 6/12• Maximum treatment no more than 6 months

Gonadorelin analogue- clinical use

• Endometriosis• Chronic pelvic pain • Prior to myomectomy- size & bleeding• Prior to hysterectomy for fibroids• Infertility- pituitary desensitisation before induction

of ovulation by gonadotrophin for IVF• Menorrhagia in perimenopausal women• Precocious puberty

Danazol• Mechanism: Inhibits pituitary gonadotrophin -antioestrogenic & antiprogestogenic - androgenic activity• Dose : 200-800mg 4 divided dose for 3-6 month

• Clinical use: - Endometriosis - Benign fibrocystic disease(breast tenderness)

• Side effects: Nausea, headache,dizziness, weight gain, libido changes, androgenic side effects ( acne, oily skin, hair loss,voice changes)

HRT• Benefits: - Systemic therapy- improves vasomotor symp. - prevents osteoporosis- Vaginal cream/ pessary - atrophic vaginitis/ urinary symptoms• Risk of HRT: - Breast Ca(6 additional cases in 50-59 old , 5 yr use)- Ovarian Ca (1)- Endometrial Ca(unopposed E2)- VTE (7)- Stroke (1)- Coronary heart disease(15 ,70-79yr)

HRT• Route-Tab,gel,patches,implant,vaginal pessary/cream

• Conventional HRT prep: E2 +12 days P : Combined E+P• Sequential HRT: - Indication: Perimenopausal women with uterus - Regular withdrawal bleeding• Continuous combined: - Indication: Postmenopausal (>1yr) with uterus - Bleed free

Other HRT• Raloxifene: SERMs - Post menopausal women>1 yr - Prevents osteoporosis - less risk of breast Ca - Not effective for vasomotor symptoms - Same risk of VTE as other HRT

• Tibolone - Synthetic prep with oestogenic,progestogenic &

androgenic effect - Same benefits & risks as HRT - Improves libido

Management of vasomotor symptoms of menopause

• Systemic HRT• Tibolone• Clonidine• Venlafaxine• Fluoxetine• Not recommended- ginseng,Kosh,Soya prep( ?

safety)

Anticholenergics for Urge incontinence

• Preparations: - Tolterodine (Detrusitol XL) 4mg/OD - Solifenacin(Vesicare) 5-10mg OD - Trospium chloride(Regurin) 20mgBd - Oxybutynin- tab 2.5 mg OD - patches 36mg twice weekly

• Side effects: dry mouth,constipation,blurred vision,dry eyes,drowsiness,dizziness & palpitation

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