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 Mechanism of action
 Preparation
 Dose
 Uses
 Side effects
 Immunoglobulin(IgG)
 From the plasma of Rh Neg men and women
sensitized with Rh positive cells
Mechanism of action
 The destruction of Rh antigen by macrophages
Preparation and Dose :
 It is available as 100 and 300µg (300 & 1500 IU)
ANTI-D
USE
 Prevention of Rh D Alloimmunisation
 Idiopathic Thrombocytopenic Purpura
ANTI-D
Prevention of Rh D
Alloimmunisation
 Includes five red cell proteins or antigens- C,c,D,E & e
 Rh negativity is absence of D antigen
 More than 200 D antigen variants exist
 The genes responsible are Rh D and Rh CE located in
the short arm of chromosome 1
 The critical titer is the level at which significant fetal
anemia could potentially develop.
 Generally between 1:8 and 1:32. If the critical titer for
anti-D antibodies is 1:16, a titer ≥1:16 indicates the
possibility of severe hemolytic disease.
Rhesus system
 The Rh D antigen has been reported on
fetal erythrocytes as early as 38 days from
fertilization
 or 7 3/7 weeks of estimated gestational age
FACTS
 Varies according to racial and ethnic origin
 15-17% in American whites and European
 1% in china
 5-10% in India
Incidence
 D-negative individuals may become sensitized
after a single exposure to as little as 0.1 mL of fetal
erythrocytes
Incidence
Causes of fetomaternal
haemorrhage
 Pregnancy loss
 Ectopic pregnancy
 Spontaneous or elective abortions
 Fetal death (any trimester)
Causes of fetomaternal
haemorrhage
 Procedures
 CVS (risk of FMH 14%)
 Amniocentesis (risk of FMH 2-6%)
 Fetal blood sampling/ Cordocentesis
 Evacuation of Molar pregnancy
Causes of fetomaternal
haemorrhage
 Other
 Delivery
 Trauma
 Placental abruption
 Unexplained vaginal bleeding during pregnancy
 ECV (2-6%)
 Manual removal of placenta
Causes of fetomaternal
haemorrhage
 Pregnancy loss
 Ectopic pregnancy
 Spontaneous or elective abortions
 Fetal death (any trimester)
 Procedures
 CVS (risk of FMH 14%)
 Amniocentesis (risk of FMH 2-6%)
 Fetal blood sampling/ Cordocentesis
 Evacuation of Molar pregnancy
 Other
 Delivery
 Trauma
 Placental abruption
 Unexplained vaginal bleeding during pregnancy
 ECV (2-6%)
 Manual removal of placenta
Causes of fetomaternal
haemorrhage
 Anti-D immune globulin should be given to all Rh
D-negative women
 Vaginal bleeding is heavy, repeated, or associated with
abdominal pain
 Particularly if these events around 12 weeks POG
Threatened abortion
 Partial
 Complete ??
Molar
 Alloimmunization has been reported to occur in
24% of women with a ruptured tubal pregnancy
 After 12 weeks of gestation, 300 micrograms Rh D
immune globulin is recommended
Ectopic Pregnancy
 2nd & 3rd trimester
 Yes
IUFD
WHY ALLOIMMUNIZATION IS
UNCOMMON
 Low prevalence of incompatible red cell antigens
 Insufficient trans placental passage of fetal
antigens or maternal antibodies
 ABO incompatibility leads to rapid clearance of
fetal erythrocytes before they elicit an immune
response
 Variable antigenicity : C, c, E, and e antigens
have lower immunogenicity than the D antigen
 Variable maternal immune response to the antigen
WHY ALLOIMMUNIZATION IS
UNCOMMON
 Anti-D immune globulin be withheld from a woman
undergoing postpartum sterilization ???
 NO
 Pregnancies occur despite sterilization procedures
Sterilization
 Initial
 Repeat
ICT
The grandmother theory
 Rh D negative female fetus exposed to Rh D
positive maternal RBCs develop sensitization
 When such individuals reaches adulthood, she
produce anti-D antibodies even before or early in
her first pregnancy
 So the fetus in the first pregnancy is jeopardized
by maternal antibodies –initially provoked by
grandmothers erythrocytes
The grandmother theory
 weak D as Rh D negative for transfusion
 Pregnant women are considered a candidate for
anti-D immune globulin
 Blood donors are interpreted to be Rh D positive
Du or weak D
CORD BLOOD INVESTIGATIONS
 Hb, PCV, Reticulocyte count
 ABO & RH
 Direct Coomb’s Test
 S Bilirubin
CORD BLOOD INVESTIGATIONS
 Half life of Anti D ranges from 16-24 days
 The standard IM dose of Anti D will protect the
average sized mother from fetal haemorrhage of
up to 30ml of fetal whole blood.
 The dose of Rh immunoglobulin calculated is
10 µg for 1 ml of fetal blood when fetomaternal
hemorrhage is > 30 ml
Anti-D Immunoglobulin
 If delivery occurs within 3 weeks of the standard
antenatal anti-D immune globulin administration,
the postnatal dose may be withheld in the absence
of excessive fetal–maternal hemorrhage
 If immune globulin is inadvertently not
administered following delivery, it should be given
as soon as the omission is recognized.
 There may be some protection up to 28 days
postpartum
 Anti D immune globulin may produce a weakly
positive 1:1 to 1:4 ICT titer in the mother.
Anti-D Immunoglobulin
 Immunoprophylaxis with Anti D within 72 hrs of
delivery reduced alloimmunisation rate by 90%
 Additionally provision of Anti D immune globulin
at 28wks gestation reduces 3rd trimester
alloimmunization rate from appx 2% to 0.1%
 Whenever there is doubt whether to give anti D, it
should be given. Even if it is not needed will not
cause any harm.
Anti-D Immunoglobulin
 Without prophylaxis Rh neg woman delivered of
Rh positive ABO compatible infant, has 16% likely
hood of developing alloimmunization
 2% - by the time of delivery
 7% - 6months post partum
 7% - in subsequent pregnancy (Sensibilisation)
 If there is ABO incompatibility Rh
alloimmunisation risk is appx 2% without
prophylaxis
Rh Alloimmunisation Risk
 less than 0.2% with routine antenatal
administration of anti-D immune globulin at 28
weeks of gestation
 Role of 2nd antenatal dose ??????
Rh Alloimmunisation Risk
ADDITIONAL DOSE
 Massive fetomaternal haemorrhage
 Abruptio placentae
 Multiple pregnancy
 Manual removal of placenta
 Trauma
 Placental chorioangioma
ADDITIONAL DOSE
Kleihauer-Betke test
 Kleihauer–Betke acid elution test relies on the
principle that fetal red blood cells contain mostly
fetal hemoglobin F, which is resistant to acid
elution, whereas adult hemoglobin is acid sensitive
 It lacks standardization and precision
 May not be accurate in conditions associated with
red blood cells containing an increased percentage
of hemoglobin F
 Sickle-cell disease
 Thalassemia
 Pregnancies at or near term, when the fetus has already
started to produce hemoglobin A
Kleihauer-Betke test
MAX DOSE Anti-D
Immunoglobulin
 If using an intramuscular preparation of anti-D
immune globulin, no more than five doses may be
given in a 24-hour period
 If using an intravenous preparation, two ampules—
totaling 600 μg—may be given every 8 hours
 Indirect Coombs test may be performed
 A positive result indicates that there is excess
anti–D immunoglobulin in maternal serum
MAX DOSE Anti-D
Immunoglobulin
TOCOLYTICS
TOCOLYTICS
 β-Adrenergic agonists
 Prostaglandin inhibitors
 Calcium channel blockers
 Magnesium sulfate
 Nitric oxide donor
 Oxytocin antagonists
INDICATIONS
INDICATIONS
 Therapeutic
 Preterm labour
 Uterine hyperstimulation caused by oxytocics
 Prophylactic
 ECV
 Intrauterine procedure like IUT
β-Adrenergic agonists
β-Adrenergic agonists
 Isoxsuprine (Duvadilan)
 Ritodrine
 Terbutaline
 Bind to β-adrenoceptors , activate enzyme
Adenylate cyclase , increase in the level of cAMP
reducing intracellular calcium level
Isoxsuprine HCl/ Duvadilan
 Oral 30-60mg/day in 3 doses
 IM 10 mg stat followed by two doses at 3 & 6 hrs
 IV dose
Ritodrine
 Selective β2 receptor agonist used specifically
as a uterine relaxant
 Dose-50mg in 45 ml of NS
 start @3ml/hr(50mcg/min)
 increase 3ml/hr every 10 min till contraction ceases or
 Systolic BP>100mm Hg
 Pulse>110/min
 Basal crepts
 Maximum dose of infusion-21ml/hr(350mcg/min)
 Switch to oral tablets(10mg)
Terbutaline
 Dose-250 mcg subcutaneous
SIDE EFFECTS β-Adrenergic
agonists
SIDE EFFECTS β-Adrenergic agonists
 Maternal
 Tachycardia, palpitations, restlessness, headache,
anxiety
 GI disturbances – nausea , vomiting and constipation
 Hyperglycemia (Ritodrine)
 Hypokalemia
 Myocardial ischemia
 Pulmonary edema
 Neonatal
Hypokalemia, hypoglycemia, hypotension, paralytic
ileus, intracranial hemorrhage
CALCIUM CHANNEL BLOCKERS
 Nifedipine
 Causes relaxation of myometrium
 Markedly inhibits the amplitude of spontaneous and
oxytocin-induced contractions
 10-20 mg 6-8 hrly
 Can be used in diabetics
S/E CALCIUM CHANNEL BLOCKERS
 Headache, dizziness
 Hypotension
 Flushing
 Constipation
 Ankle edema
 Cough
 Wheezing
 Tachycardia
Prostaglandin syntheses inhibitors
 Indomethacin
 The drug is available as 25mg capsules
 50mg loading dose orally or rectally then 25mg
6hrly
 Also used in idiopathic polyhydramnios
 Fetal risks
 Risk of premature closure of ductus arteriosus
leading to pulmonary hypertension
 Avoid use >48hrs and less than 32weeks
Magnesium sulphate
 Compete with calcium for entry into the cell at the
time of depolarization so there is decrease of
intracellular calcium
 4g slow IV then 2g IV per hr until contraction
ceases
 Narrow safety margin
Magnesium sulphate
 Neonatal effects of Magnesium -neuroprotective
a)stabilizes intracranial tone
b)minimizes fluctuations in cerebral blood flow
c)reduce perfusion injury
d)block calcium mediated intracellular damage
OXYTOCIN ANTAGONIST
 Atosiban ( tractocil )
 Nonapeptide
 Competitive antagonist of oxytocin
 Expensive drug
 Bolus 6.75mg over one minute, followed by
18mg/hr infusion for three hour then 6mg/hr
for up to 45 hrs
 Max dose 330mg
NITRIC OXIDE DONORS
 GTN patches
 Maternal headache, hypotension
 Neonatal hypotension
CONTRAINDICATIONS
CONTRAINDICATIONS TO TOCOLYSIS
 Severe Pre-eclampsia
 FGR
 Severe APH
 Fetal anomalies
 Chorioamnionitis
 Maternal heart disease

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Drugs 1.pptx

  • 1.
  • 2.
  • 3.  Mechanism of action  Preparation  Dose  Uses  Side effects
  • 4.  Immunoglobulin(IgG)  From the plasma of Rh Neg men and women sensitized with Rh positive cells Mechanism of action  The destruction of Rh antigen by macrophages Preparation and Dose :  It is available as 100 and 300µg (300 & 1500 IU) ANTI-D
  • 5. USE
  • 6.  Prevention of Rh D Alloimmunisation  Idiopathic Thrombocytopenic Purpura ANTI-D
  • 7. Prevention of Rh D Alloimmunisation
  • 8.  Includes five red cell proteins or antigens- C,c,D,E & e  Rh negativity is absence of D antigen  More than 200 D antigen variants exist  The genes responsible are Rh D and Rh CE located in the short arm of chromosome 1  The critical titer is the level at which significant fetal anemia could potentially develop.  Generally between 1:8 and 1:32. If the critical titer for anti-D antibodies is 1:16, a titer ≥1:16 indicates the possibility of severe hemolytic disease. Rhesus system
  • 9.  The Rh D antigen has been reported on fetal erythrocytes as early as 38 days from fertilization  or 7 3/7 weeks of estimated gestational age FACTS
  • 10.  Varies according to racial and ethnic origin  15-17% in American whites and European  1% in china  5-10% in India Incidence
  • 11.  D-negative individuals may become sensitized after a single exposure to as little as 0.1 mL of fetal erythrocytes Incidence
  • 13.  Pregnancy loss  Ectopic pregnancy  Spontaneous or elective abortions  Fetal death (any trimester) Causes of fetomaternal haemorrhage
  • 14.  Procedures  CVS (risk of FMH 14%)  Amniocentesis (risk of FMH 2-6%)  Fetal blood sampling/ Cordocentesis  Evacuation of Molar pregnancy Causes of fetomaternal haemorrhage
  • 15.  Other  Delivery  Trauma  Placental abruption  Unexplained vaginal bleeding during pregnancy  ECV (2-6%)  Manual removal of placenta Causes of fetomaternal haemorrhage
  • 16.  Pregnancy loss  Ectopic pregnancy  Spontaneous or elective abortions  Fetal death (any trimester)  Procedures  CVS (risk of FMH 14%)  Amniocentesis (risk of FMH 2-6%)  Fetal blood sampling/ Cordocentesis  Evacuation of Molar pregnancy  Other  Delivery  Trauma  Placental abruption  Unexplained vaginal bleeding during pregnancy  ECV (2-6%)  Manual removal of placenta Causes of fetomaternal haemorrhage
  • 17.  Anti-D immune globulin should be given to all Rh D-negative women  Vaginal bleeding is heavy, repeated, or associated with abdominal pain  Particularly if these events around 12 weeks POG Threatened abortion
  • 19.  Alloimmunization has been reported to occur in 24% of women with a ruptured tubal pregnancy  After 12 weeks of gestation, 300 micrograms Rh D immune globulin is recommended Ectopic Pregnancy
  • 20.  2nd & 3rd trimester  Yes IUFD
  • 22.  Low prevalence of incompatible red cell antigens  Insufficient trans placental passage of fetal antigens or maternal antibodies  ABO incompatibility leads to rapid clearance of fetal erythrocytes before they elicit an immune response  Variable antigenicity : C, c, E, and e antigens have lower immunogenicity than the D antigen  Variable maternal immune response to the antigen WHY ALLOIMMUNIZATION IS UNCOMMON
  • 23.  Anti-D immune globulin be withheld from a woman undergoing postpartum sterilization ???  NO  Pregnancies occur despite sterilization procedures Sterilization
  • 26.  Rh D negative female fetus exposed to Rh D positive maternal RBCs develop sensitization  When such individuals reaches adulthood, she produce anti-D antibodies even before or early in her first pregnancy  So the fetus in the first pregnancy is jeopardized by maternal antibodies –initially provoked by grandmothers erythrocytes The grandmother theory
  • 27.  weak D as Rh D negative for transfusion  Pregnant women are considered a candidate for anti-D immune globulin  Blood donors are interpreted to be Rh D positive Du or weak D
  • 29.  Hb, PCV, Reticulocyte count  ABO & RH  Direct Coomb’s Test  S Bilirubin CORD BLOOD INVESTIGATIONS
  • 30.  Half life of Anti D ranges from 16-24 days  The standard IM dose of Anti D will protect the average sized mother from fetal haemorrhage of up to 30ml of fetal whole blood.  The dose of Rh immunoglobulin calculated is 10 µg for 1 ml of fetal blood when fetomaternal hemorrhage is > 30 ml Anti-D Immunoglobulin
  • 31.  If delivery occurs within 3 weeks of the standard antenatal anti-D immune globulin administration, the postnatal dose may be withheld in the absence of excessive fetal–maternal hemorrhage  If immune globulin is inadvertently not administered following delivery, it should be given as soon as the omission is recognized.  There may be some protection up to 28 days postpartum  Anti D immune globulin may produce a weakly positive 1:1 to 1:4 ICT titer in the mother. Anti-D Immunoglobulin
  • 32.  Immunoprophylaxis with Anti D within 72 hrs of delivery reduced alloimmunisation rate by 90%  Additionally provision of Anti D immune globulin at 28wks gestation reduces 3rd trimester alloimmunization rate from appx 2% to 0.1%  Whenever there is doubt whether to give anti D, it should be given. Even if it is not needed will not cause any harm. Anti-D Immunoglobulin
  • 33.  Without prophylaxis Rh neg woman delivered of Rh positive ABO compatible infant, has 16% likely hood of developing alloimmunization  2% - by the time of delivery  7% - 6months post partum  7% - in subsequent pregnancy (Sensibilisation)  If there is ABO incompatibility Rh alloimmunisation risk is appx 2% without prophylaxis Rh Alloimmunisation Risk
  • 34.  less than 0.2% with routine antenatal administration of anti-D immune globulin at 28 weeks of gestation  Role of 2nd antenatal dose ?????? Rh Alloimmunisation Risk
  • 36.  Massive fetomaternal haemorrhage  Abruptio placentae  Multiple pregnancy  Manual removal of placenta  Trauma  Placental chorioangioma ADDITIONAL DOSE
  • 38.  Kleihauer–Betke acid elution test relies on the principle that fetal red blood cells contain mostly fetal hemoglobin F, which is resistant to acid elution, whereas adult hemoglobin is acid sensitive  It lacks standardization and precision  May not be accurate in conditions associated with red blood cells containing an increased percentage of hemoglobin F  Sickle-cell disease  Thalassemia  Pregnancies at or near term, when the fetus has already started to produce hemoglobin A Kleihauer-Betke test
  • 40.  If using an intramuscular preparation of anti-D immune globulin, no more than five doses may be given in a 24-hour period  If using an intravenous preparation, two ampules— totaling 600 μg—may be given every 8 hours  Indirect Coombs test may be performed  A positive result indicates that there is excess anti–D immunoglobulin in maternal serum MAX DOSE Anti-D Immunoglobulin
  • 42. TOCOLYTICS  β-Adrenergic agonists  Prostaglandin inhibitors  Calcium channel blockers  Magnesium sulfate  Nitric oxide donor  Oxytocin antagonists
  • 44. INDICATIONS  Therapeutic  Preterm labour  Uterine hyperstimulation caused by oxytocics  Prophylactic  ECV  Intrauterine procedure like IUT
  • 46. β-Adrenergic agonists  Isoxsuprine (Duvadilan)  Ritodrine  Terbutaline  Bind to β-adrenoceptors , activate enzyme Adenylate cyclase , increase in the level of cAMP reducing intracellular calcium level
  • 47. Isoxsuprine HCl/ Duvadilan  Oral 30-60mg/day in 3 doses  IM 10 mg stat followed by two doses at 3 & 6 hrs  IV dose
  • 48. Ritodrine  Selective β2 receptor agonist used specifically as a uterine relaxant  Dose-50mg in 45 ml of NS  start @3ml/hr(50mcg/min)  increase 3ml/hr every 10 min till contraction ceases or  Systolic BP>100mm Hg  Pulse>110/min  Basal crepts  Maximum dose of infusion-21ml/hr(350mcg/min)  Switch to oral tablets(10mg)
  • 51. SIDE EFFECTS β-Adrenergic agonists  Maternal  Tachycardia, palpitations, restlessness, headache, anxiety  GI disturbances – nausea , vomiting and constipation  Hyperglycemia (Ritodrine)  Hypokalemia  Myocardial ischemia  Pulmonary edema  Neonatal Hypokalemia, hypoglycemia, hypotension, paralytic ileus, intracranial hemorrhage
  • 52. CALCIUM CHANNEL BLOCKERS  Nifedipine  Causes relaxation of myometrium  Markedly inhibits the amplitude of spontaneous and oxytocin-induced contractions  10-20 mg 6-8 hrly  Can be used in diabetics
  • 53. S/E CALCIUM CHANNEL BLOCKERS  Headache, dizziness  Hypotension  Flushing  Constipation  Ankle edema  Cough  Wheezing  Tachycardia
  • 54. Prostaglandin syntheses inhibitors  Indomethacin  The drug is available as 25mg capsules  50mg loading dose orally or rectally then 25mg 6hrly  Also used in idiopathic polyhydramnios  Fetal risks  Risk of premature closure of ductus arteriosus leading to pulmonary hypertension  Avoid use >48hrs and less than 32weeks
  • 55. Magnesium sulphate  Compete with calcium for entry into the cell at the time of depolarization so there is decrease of intracellular calcium  4g slow IV then 2g IV per hr until contraction ceases  Narrow safety margin
  • 56. Magnesium sulphate  Neonatal effects of Magnesium -neuroprotective a)stabilizes intracranial tone b)minimizes fluctuations in cerebral blood flow c)reduce perfusion injury d)block calcium mediated intracellular damage
  • 57. OXYTOCIN ANTAGONIST  Atosiban ( tractocil )  Nonapeptide  Competitive antagonist of oxytocin  Expensive drug  Bolus 6.75mg over one minute, followed by 18mg/hr infusion for three hour then 6mg/hr for up to 45 hrs  Max dose 330mg
  • 58. NITRIC OXIDE DONORS  GTN patches  Maternal headache, hypotension  Neonatal hypotension
  • 60. CONTRAINDICATIONS TO TOCOLYSIS  Severe Pre-eclampsia  FGR  Severe APH  Fetal anomalies  Chorioamnionitis  Maternal heart disease