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.

1. Drugs Acting on Uterus

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

3. Drugs Acting on uterus
Uterine stimulants
Posterior pituitary hormones
Oxytocin,
Desamino oxytocin
Ergot alkaloids
Ergometrine
Methylergometrine
Prostaglandins
PGE2 ,
PGF2α
15-methyl PGF2α
Misoprostol
Miscellaneous agents
 Ethacridine, Quinine
Tocolytics
Adrenergic Agonists-
Ritodrine, Isoxsuprine,
Salbutamol,Terbutaline
CCB’s - Nifedipine
Oxytocin blockers- Atosiban
MgSo4
Miscellaneous drugs

4. Introduction
Oxys+ tokos="quick" + "birth
Oxytocin is a nonapeptide freely water soluble & acid stable –
posterior pituitary hormone (Para ventricular nuclei)
1911-used child birth contractions
Oxytocin

5. Chemistry
phe Arg
Ile Leu
Both are 8-amino
acid peptide
Octapeptide.
But differ in 2
amino acids at
Position 3 & 8
12

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

33. 1. β -agonist-
Mechanism- Bind to β2 receptor on myometrium
↓
Activate adenyle cyclase activity
↓
↑cAMP levels – activate cAMP dependent protein
kinase
↓
↓intracellular Ca++ conc..
(Muscle relaxation )

34. β2 adrenergic agonists
Drugs:-
Ritodrine
Isoxsuprine
Salbutamol
Terbutaline

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

43. OXYTOCIN RECEPTOR ANTAGONIST
ATOSIBAN :
Oxytocin receptor blocker
↑uterine relaxation by competitively blocks the oxytocin
receptor
Route-IV-infusion
SE-Nausea, vomiting, Hypotension, skin rashes

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