The document discusses drugs that act on the uterus. It describes uterine stimulants/oxytocics like oxytocin, ergot alkaloids, and prostaglandins which increase uterine contraction and are used to induce labor or prevent postpartum hemorrhage. It also discusses uterine relaxants/tocolytics like beta-adrenergic agonists, calcium channel blockers, and magnesium sulfate which decrease uterine motility and are used to delay premature labor. The mechanisms, pharmacokinetics, clinical uses and adverse effects of various oxytocic and tocolytic drugs are provided.
2. Uterus has endometrium & myometrium
Sensitivity of myometrium to drugs affected by hormonal &gestational status
Drugs Acting on uterus
Uterine Stimulants Or Oxytocic
Drugs/ Ecbolics/Abortifacients
Uterine Relaxants
Or
Tocolytics
They ↑uterine contraction
during delivery or at
various stages of labour
↓uterine motility
Relax- uterus
USES-
Induce abortion
Minimize Postpartum hemorrhage (PPH)
Augment abnormal labour
Preventing the early rupture of membrane
USES:-
To delay labour
Arrest threatened abortion
To treat Dysmenorrhoea
6. Synthesis, storage and release of Oxytocin
Para-ventricular nucleus
Hypothalamus
hypothalohypophyseal
Posterior pituitary
Synthesis
Storage
(Stimuli for release)
Persistent distension of cervix
,vagina.suckling,Etc.
Causes contraction of
Pregnant uterus
Causes contraction of
myoepithelial cells of the female
breast
Stored in secretory
granules as
oxytocin-
neurophysin
complex
•Oxytocinase –destroy oxytocin
•Due to pulsatile release –difficult to
measure Cp
Release of oxytocin inhibited by relaxin & alcohol
7. α
Phosphatidyl inositol 4,5 bisphosphate(PIP2)
Inositol-1,4,5-triphisphate(IP3) Diacyl glyceral(DAG)
Sacroplasmic
reticulum
Myosin light
chain kinase
ca
oxy
ßγ
Phospholipase c
Plasma membrane
calmodulin
Mechanism of Action:-
Oxytocin binds to specific GPCR(Gq) on myometrium
8. Pharmacokinetics
Peptide in nature-so destroy by proteolytic enzyme (Gut)
Inactive orally
I.V(I.V.-infusion ), I.M, intranasal spray
Metabolized in kidney and liver
Plasma t ½ ~6min
Destroyed- oxytocinase secreated by pregnant uterus & placenta
Dilution & rate of preparation:-
1IU of oxytocin = 2µg of pure hormone
9. Pharmacodynamic Action-
On UTERUS:-
• ↑ in force and frequency of contractions in pragnancy
• Uterine sensitivity to oxytocin - ↑ by estrogen & ↓by progesterone
• Early pregnancy – high dose of oxytocin is necessary
• Contraction of upper segment & relaxation of lower segment of uterus
→ Expulsion of fetus
• Non-pregnant uterus → resistance to oxytocin
• In human –
Small dose-↑Tone & Amplitude
Large Dose- ↑ Frequency of contraction + Incomplete relaxation
Higher Dose- Sustained contraction without relaxation ↔ resulted in
↓Blood flow to fetal, fetal distress & death (Asphyxial injury)
• During parturition- ↑ Number of Oxytocin receptor (↑ sensitivity )
• Exogenous oxytocin- initiate rhythmic contraction
10. On breast:-
Suckling by infant
↓
Stimulate nipple mechanoreceptors
↓
Hypothalamus
↓
Posterior pituitary
↓
↑Oxytocin release
↓
Contraction of myoepithelial cells of mammary gland
Milk ejection
11. CVS
Normal therapeutic dose= No effect
High doses =vasodilatation
fall in BP ,
Reflex-tachycardia, and flushing
Kidney
-High doses- ADH like effect
In ↓urine output , pulmonary edema etc..
12. Clinical uses of oxytocin
Induction of labor:-(5IU+500 ml of 5% D)
• To induce or augment abnormal labor in pregnant women
• Premature rupture of membranes
• Isoimmunization
• Fetal growth Restriction
• Uteroplacental insufficiency diabetes, preeclampsia, or
eclampsia.
Oxytocin in preferred – IV infusion
Advantages-
1.Plasma t1/2 is short – intensity of action can be controlled
2.At low conc. There is period of complete relaxation between
uterine contraction which prevent fetal asphyxia
3.lower uterine segment is not contracted so, fetal descent is not
compromised
13. Before induction ,rule out:-
Abnormal fetal position
Fetal distress
Placental abnormalities
Previous uterine surgery
OXYTOCIN ( Pitocin or Syntocinon):-
Administered by i.v. infusion
5IU is diluted in 500ml of glucose or saline solution
14. Uterine inertia
absence of effective uterine contractions during labor
Oxytocin can be infused i.v - augment satisfactory
contractions
Oxtocin is the DOC and is preferred over
ergometrine/PGs
• Its short duration of action
• Normal relaxation in b/w contraction
• lower segment is not contracted
• Uterine contractions are consistently augmented
15. Post partum haemorrhage(PPH)-
oxytocin –IV-infusion or IM
Especially useful in hypertensive women where
ergometrine is contraindicated
Action- It acts by forcefully contracting uterine muscle
which compresses the blood vessels passing through it to
arrest hemorrhage.
16. Breast engorgement:-
• Insufficient milk ejection reflex
• Intranasal spray few minute before suckling
• dose not ↑ milk production
Oxytocin challenge test:-
• To assess fetal well-being/utero-placental adequacy
Purpose:- To assess the fetal heart rate response to contractions. The
results of the test may be used to aid the decision making process
regarding mode and timing of delivery
• I.v. infusion in low rate –cont. till uterus contracts about every 4 min
at the same time fetal heart rate is measured.
# if ↑HR=uteroplacental flow is insufficient (fetal hypoxia) need
immediate cesarean delivery
17. Adverse effect -
Non judicious use can leads to serious reaction
i.e. Fetal distress, placental abruption or uterine rupture
High concentration –
excessive fluid retention, or water intoxication :
hyponatremia, heart failure,
seizures, and death.
Bolus injection - hypotension
18. Desamino-oxytocin:-
• Buccal formulation of oxytocin
• Action is similar to oxytocin
Indications-
Induction of labor:-50 IU buccal tabs , every 30 min ,max
10 tabs.
uterine inertia:-25 IU , every 30mis , 25-50 IU 5times for
7days
Breast engorgement:-25-50IU
It is also preferred in hypertensive women in which
ergometrine in contraindicated
19. Ergot Alkaloids
Source:-
Methyl ergometrine is more potent & preferred than ergometrine
They ↑ strength,duration,frequency of uterine contraction
Of both upper & lower segment
• Contraction involve- Fundus,Body,cervical segments
Ergot alkaloids Source
Ergometrine Claviceps purpurea a fungus which infects grasses and
grains (Rey)
Methyl-
ergometrine
Semi-synthetic derivative obtained from lysergic acid
20. Orally absorbed rapidly and completely
Onset of action oral – 15mins
i.m. – 5mins
i.v. – 1 to 2mins
t1/2: 1 – 2 Hrs
Partially metabolized and excreted in urine
Hepatic damage increases toxicity
Mechanism:-
They have agonistic activity on 5-HT2 & α1- adrenergic receptor present
on uterus myometrium
Pharmacokinetics
21. Pharmacological actions
Uterus:
Highly sensitive
Elicits immediate and powerful response
Small dose – ↑FOC + Normal relaxation
High dose – ↑↑ Contractions are powerful,
frequency, resting muscle tone is also
Uterine atony
Risk of fetal distress, compression, asphyxia and death
22. CVS:-
No adrenergic blocking activity
Increase in BP is not seen at doses used in obstetrics (2 mg)
CNS:-
No effects are seen at obstetrics doses
High dose – Interactions with adrenergic, serotonergic
and dopaminergic receptors
Direct stimulating action on emetic center
GIT:
Quite sensitive to ergot alkaloids, increases peristalsis
GI side effects are seen at low doses as it acts on both
emetic center directly and on GI serotonin receptors
23. Uses
In PPH:- Prophylaxis and treatment of PPH
(0.2 to 0.3mg I.M. or 0.2mg i.v.)
Mechanism- cause sustained tonic uterine contraction- uterine BV
are compressed by myometrial meshwork & bleeding stop
Methyl-Ergometrine is preferred over ergometrine because
• Effective orally
• Small doses, less toxic and min adverse effects
• Devoid of adrenergic blocking, vasoconstriction and emetic activity
Management of 3rd stage of labour- Ergometrine (0.2-0.5mg I.M.)
They also prevent uterine atony & control bleeding
24. Adverse Effects
Ergometrine and methyl ergometrine are less toxic than
ergotamine
GI side effects and increase in BP rarely
High doses – Decrease in milk secretion
Over dose of ergometrine causes prolonged vasospasm, gangrene
of finger & toes due to vasoconstriction effect
25. Contraindications
During pregnancy and before 3rd stage of labor
Patients with hypertension, preeclampsia, eclampsia, porphyria,
vascular diseases and collagen diseases
Threatened spontaneous abortions
Liver and kidney diseases
Presence of sepsis may cause gangrene
26. Bromoergocryptine
Bromocryptine is synthetic ergot derivative
Selective D2 receptor agonist
Effective in decreasing the high levels of prolactin
(2.5mg × TDS)
Oxytocic and cardiovascular actions are negligible
27. Prostaglandins
20 carbon containing fatty acids
Lipid derived autacoid
Human seminal fluid, ovary, myometrium and
menstrual fluid
Many PG’s shows inhibitory effect
PGF2 and PGE ↑tone & amplitude of uterine contractions
Sensitize the uterus to oxytocin and also causes oxytocin release
PGF2 helps in process of labor
28. Pharmacological actions:-
Uterine contractions by stimulant effect
Cervical priming:- Cervical ripening at the time of
delivery and abortions
Luteolytic agents :- structural and functional degradation of
the corpus luteum
Inhibits the secretion of progesterone
PG’s are effective in 2nd and 3rd trimesters
Mifepristone is administered priorly as it sensitivity of uterus to
PG’s
29. Adverse effects
Head ache, fever and vasodilatation
Cautiously IOP, hypertension, diabetes, angina and epilepsy
PGF2α has more GI effects than PGE2
Smoking and alcohol consumption is avoided during use and 48hrs
after use
High incidence of adverse effects and delivery complications are
seen when PG’s alone is used
Contraindication:-
Cardiac, renal, pulmonary and hepatic disorders
30. Uses
Therapeutic abortion:
o 2nd trimester pregnancy termination
o Gemeprost administered vaginally as pessaries
o Carboprost analogue of PGF2α given as i.m.
o Misoprostol is give orally or i.v. combined with
mifepristone (T-pill upto 49days)
Cervical priming:
o Dinoprostone
o Endocervical gels, suppositories and oral tablets
31. Post-partum Hemorrhage:
o PG analogue like carbopost is given i.m.
Induction and augmentation of term labor:
o Dinoprostone is preferred - diuretic action
o 0.5mg orally at 30-60mins time interval
(max up to 4 tabs)
o PG’s causes hyperstimulation of uterus
32. Uterine relaxants:-
Action-
Suppress myometrial smooth muscle contraction by
–
↓Intracellular Ca++ conc.& reduce the effect of Ca++
on smooth muscle
Inhibiting the synthesis & release of PG & oxytocin
35. RITODRINE:-
Selective β2 adrenergic agonist
Specifically developed as a uterine relaxant
Route:
i.v infusion,i.m
Side effects:
Pulmonary edema Q
Hypotension
Tachycardia
Hyperglycaemia
Hypokalaemia
36. ISOXSUPRINE:
1.Indicated in premature labour
2.Habitual abortion- three or more consecutive pregnancy
losses
3.Threatened abortion- vaginal bleeding that occurs in the first 20 weeks of
pregnancy
4.Dysmenorrhoea
Route:-i.v, i.m.
SIDE EFFECTS:
Rashes
Nausea
Vomiting
Dizziness
Hypotension
37. SALBUTAMOL:
Used as a primary drug to delay delivery 24-72 hours
Side effects:-
Palpitation
Restlessness
Nervousness
Throat irritation
Ankle edema
38. TERBUTALINE:
It delay births but only during the first 48 hours of
treatment
ADVERSE EFFECTS:
Tachycardia
Hypotension
Pulmonary edema
39. NIFEDIPINE:-
Used for uterine relaxation
Action- It acts via impairing the entry of Ca++ into
myometrial cells via voltage dependent channels & there by
inhibit contractility
It improve fetal outcomes and produce less side effects
Produce few maternal side effects than ritodrine
Side effect-
Hypotension
Tachycardia
CALCIUM CHANNEL BLOCKERS:-
40. MAGNESIUM SULFATE
It suppress uterine contractions
Used to control convulsions
To reduce BP in toxemia of pregnancy
Drug of choice for prevention and treatment of seizures in
pre-elampsia
ROUTE: i.v
This is uesd when β adrenergics are contraindicated
Action- they directly uncoupled EC in myometrial cells &
inhibits cellular Action potential
41. Toxicity-
Life threatening
Lose patellar reflexs – Cp>8-10mEq/L with
Respiratory depression- Cp>10-12mEq/L with
Higher levels cause cardiac arrest
It is monitors by 3 parameter
1.Patellar reflex
2.Respiratory rate
3.Urinary output
42. PROSTAGLANDIN SYNTHESIS INHIBITORS
INDOMETHACIN:
Used to delay preterm labour
Tocolytic effect- inhibiting the PG synthesis
It also can decrease amniotic fluid volume
USE OF INDOMETHACIN IS:
Its unpredictable efficacy-orally or rectally given
Premature closure of fetal ductus arteriosus
Chances of intraventricular hemorrhage in new
born
44. MISCELLANEOUS DRUGS
NITRIC OXIDE DONARS:
Potent vasodilator
Smooth muscle relaxant
Nitroglycerine and other nitrates used to treat Myocardial
ischemia
Used for inhibition of preterm labour
SE-Maternal hypotension
C2H5OH- Not used because of CNS depression, fetal
hypoxia
Progesterone- treatment of threatened abortion
Editor's Notes
Isoimmunization:-the development of antibodies against antigens from the same species, such as anti-Rh antibodies in an Rh-negative person