Drugs acting on Genito-Urinary System., by Dr. Baqir Naqvi

1. Drugs Acting on
Genito-Urinary System
(Pharmacology & Therapeutics-1)
Lecture By
Dr. Syed Baqir Raza Naqvi
(BSc, Pharm-D, M. Phil-Pharmacology)
Nazar College of Pharmacy
DAKSON Institute of Health Sciences, Islamabad
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1. Oxytocic drugs
(Uterotonics)

3. 1. Oxytocic drugs
• These are the drugs which have oxytocic activity i.e. have the ability to
stimulate the smooth muscles of uterus.
• Oxytocic's also called Uterotonics have the power to stimulate uterine
contractions.
• These are also called abortificient drugs.
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5. Classification of oxytocic drugs
• Oxytocin
Posterior pituitary
hormones
• Ergometrine, Methyl ergometrine
• Ergotamine, Methyl ergotamine
Ergot Alkaloids
• Prostaglandins E₂ (PG E₂)
• Prostaglandins F₂α (PG F₂α)
Prostaglandins
Miscellaneous
• Quinine, Alcohol
• Emetine, Ethacridine
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6. • Oxytocin is a polypeptide hormone that is released from
posterior pituitary gland.
• Originally it is extracted from posterior pituitary gland of
animals but now it is chemically synthesized.
Synthesis of Oxytocin
• Oxytocin secretion occurs by sensory stimulations from
cervix ,vagina and from suckling at breast.
Oxytocin
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7. Dopamine / Serotonin / Oxytocin
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8. Characteristics
1. Oxytocin acts through G protein-coupled receptors and the
phosphoinositide -calcium second-messenger system to contract
uterine smooth muscle.
2. Oxytocin also stimulates the release of prostaglandins and leukotriene's
that augment uterine contraction.
3. Oxytocin in small doses increases both the frequency and the force of
uterine contractions.
4. At higher doses, it produces sustained contraction.
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9. 5. These contractions resemble the normal physiological contractions of
uterus (contractions followed by relaxation).
6. Immature uterus is resistant to oxytocin.
7. Sensitivity increases to 8 fold in last 9 weeks and 30 times in early labor.
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Characteristics (Cont.)

10. Mode of Action
• The interaction of endogenous or administered oxytocin, with
myometrial cell membrane receptor promotes the influx of Ca++
from extra cellular fluid and from S.R in to the cell, this increase in
cytoplasmic calcium, stimulates uterine contraction .
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Uterine
Contractions

13. Mode of Action
1. Oxytocin alters the trans membrane ionic currents in myometrium
smooth muscle cells to produce sustained uterine contraction.
2. Oxytocin also causes contraction of myo epithelial cells surrounding
the mammary alveoli which leads to milk ejaculation.
• Without oxytocin induced contraction, normal lactation cannot occur.
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14. MOA of Oxytocin
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15. Pharmacokinetics of oxytocin
• R/A: Not effective orally so administered intravenously.
Also available as nasal spray.
• Protein Binding: Not bound to plasma proteins.
• Metabolism: Catabolized by liver & kidneys.
• Half life = 5 minutes.
• D/A: Duration of action is about 20 min.
• Storage: Stored at 2-8 ‘C
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16. Therapeutic Uses of Oxytocin
1. Induction of Labor
• Oxytocin is highly effective to contract the pregnant uterus during or after
35th week of pregnancy. It is given by slow I.V route.
2. Uterine inertia
• Oxytocin is also given in uterine inertia in order to treat partial or complete
cessation of uterine contractility.
3. Post partum bleeding
Also used to check or stop the post partum bleeding.
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17. 4. To decrease systolic/diastolic blood pressure
• When large amounts are administered, oxytocin has marked transient,
direct relaxing effect on vascular smooth muscles.
• Thus decrease in systolic & diastolic pressure and increase in limb blood
flow occurs.
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5. Milk ejaculation
Oxytocin is occasionally employed to promote
milk ejaculation when the lactation appears
to be insufficient in lactating mothers.

18. Adverse effects of Oxytocin
On fetus
• Arrhythmias, hypoxia (low O₂ in blood) & immediate death, Neonatal jaundice
On mothers
• Arrhythmias, convulsions, nausea, vomiting, cerebral hemorrhages.
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Contraindications
• Prematurity.
• Uterine rupture.

19. 2. Ergot Alkaloids
• Ergot is the natural alkaloid of “Claviceps purpurea” that grows on rye, wheat
and other grains.
1. Ergometrine (Ergonovine) 2. Methylergonovine.
• Chemistry: The ergot alkaloids are derivatives of the tetracyclic compound i.e. 6-
methylergoline.
• The first pure ergot alkaloid ergotamine was obtained in 1920, followed by the
isolation of ergometrine in 1932.
• The therapeutically useful natural alkaloids are amide derivatives of d-lysergic
acid.
• Semi-synthetic derivatives are obtained from catalytic hydrogenation of the
natural alkaloids. e.g.- Methergin (methylergonovine).
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20. Pharmacodynamics
Effects on the Uterus
• Alkaloid derivatives induce TETANIC CONTRACTION of uterus without relaxation
in between. These does not resemble the normal physiological contractions.
• It causes contractions of uterus as a whole i.e. fundus and cervix (tend to
compress rather than to expel the fetus).
Vascular effects
• Direct peripheral vasoconstriction In large doses causes damage to capillary
endothelium.
Gastrointestinal effect
• Increased in peristaltic activity.
Miscellaneous effects
5HT partial agonist and 5HT selective antagonist.
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21. Pharmacokinetics
• Absorbed orally from GIT (tablets).
• Usually given I.M.
• Extensively metabolized in liver.
• 90% of metabolites are excreted in bile.
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22. Therapeutic uses of ergometrine
POSTPARTUM HEMORRHAGE:-
• The uterus is extremely sensitive to the stimulant action of ergot and even moderate
doses produce a prolonged and powerful spasm of the muscle quite unlike natural labor.
• Therefore, ergot derivatives should be used only for control of late uterine bleeding and
should never be given before delivery.
• Oxytocin is the preferred agent for control of postpartum hemorrhage but if this is
ineffective, then ERGOMETRINE (0.2 mg ) is given intramuscularly.
• It is usually effective within 1–5 minutes and is less toxic than other ergot derivatives for
this application.
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23. Adverse effects:
• Nausea, vomiting, diarrhea (NVD).
• Hypertension.
• Vasoconstriction of peripheral
blood Vessels (toes & fingers).
• Gangrene.
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Contraindications
a) 1st and 2nd stage of labor.
b) Vascular disease.
c) Impaired hepatic and renal
functions.
Precautions
a) Cardiac diseases.
b) Hypertension.
c) Multiple pregnancy.
Ergometrine

24. MECHANISM OF ACTION
Contract uterine smooth muscle.
Difference between PG’s and Oxytocin
1. PG’s contract uterine smooth muscle not only at term(as with oxytocin),
but throughout pregnancy.
2. PG’s soften the cervix; whereas oxytocin does not.
3. PG’s have longer duration of action than oxytocin.
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3. PROSTAGLANDINS (PGE2 & PGF2α)

25. Therapeutic uses
• Induction of abortion (pathological)**.
• Induction of labor (fetal death in utero).
• Postpartum hemorrhage.
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Side Effects
• Nausea, vomiting, Diarrhea.
• Abdominal pain .
• Bronchospasm (PGF2α), Flushing (PGE2).
Contraindications:
1. Mechanical obstruction of
delivery.
2. Fetal distress.
3. Predisposition to uterine
rupture.
Precautions:
a) Asthma.
b) Multiple pregnancy.
c) Glaucoma.
d) Uterine rupture.

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27. Difference B/w Oxytocin and Prostaglandins
Characteristics Oxytocin Prostaglandins
Contraction Only at term. Contraction throughout
pregnancy.
Cervix Does not soften the cervix. Soften the cervix.
Duration of action Shorter in action. Longer action.
Uses 1. Not used for abortion.
2. Used for induction and
augmentation of labor and post
partum hemorrhage.
1. Used for abortion in 2nd
trimester of pregnancy.
2. Used as vaginal
suppository for induction
of labor.
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2. UTERINE RELAXANTS
(TOCOLYTICS)

29. 2. UTERINE RELAXANTS (TOCOLYTICS)
• These are the drugs which decrease uterine motility.
• Pre mature labor and delivery can be delayed by drugs in order to improve
the perinatal outcome and thus reduce perinatal morbidity and mortality
significantly.
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General Uses of Tocolytics
• Tocolytics are used to delay or postpone labor.
• Arrest abortion Dysmenorrhea and labor suppression to allow fetus to mature.
• Premature labor is done only if cervical dilation is < 4 cm.

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Adrenergic
agonists
• Ritodrine
• Salbutamol
• Terbutaline
• Isoxuprine
Ca+ channel
blockers
• Nifedipine
• Other
dihydro-
pyridines
Miscellaneous
drugs
• Mg. Sulphate
• Progesterone
• Nitrates
• Indomethacin
Classification of Tocolytics

34. Mechanism of Actions of Tocolytics
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36. 1. Adrenergic agonists
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B2 selective agonists
• Suppress premature labor and delay
delivery in exigency.
Dose:
• 50 micrograms/min I.V infusion,
increased with every 10 min.-----(Ceases
uterine contraction.)
• 10mg I.M. 4-6 hourly followed by 10 mg
oral.------ (Delivery postponed).
Adverse effects
Cardiovascular, metabolic
complications, anxiety.
restlessness, headache.
Contraindication
Diabetics, heart diseases.
With steroids or Beta blockers.

37. Nifedipine, Nicadipine, Verapamil
Mechanism of Action
• It blocks the entry of calcium inside the cell.
• Reduces the tone of myometrium and oppose contraction.
• Having smooth muscles relaxant action and Postponed labor.
Dose: 10 mg orally, every 20-30 min, till contraction ceases followed by 10 mg, 6 hourly.
Side effects: Tachycardia, hypotension.
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2. Ca+ Channel Blockers

38. MOA: It acts by competitive inhibition of Ca+ ions inside cell reducing
calcium influx.
• The intracellular Ca+ is displaced by magnesium ion leading to inhibition
of uterine activity.
• Decreases Acetylcholine release and its sensitivity.
• Direct depressant affect on uterine muscles.
Dose:
• Loading dose 4-6g IV (10-20% SOLUTION) over 20-30 min, followed by an
infusion of 1-2g/hr.
Side effects:
• Maternal: Flushing, headache, muscles weakness, pulmonary edema.
• Neonatal: Lethargy, respiratory depression.
Contraindications: in Impaired renal functions.
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3. Magnesium Sulphate (MgSO4)

39. • Indomethacin is a Cyclooxygenase (COX) inhibitor.
• Suldinac another NSAID is also used as it has less placental transfer.
Mechanism of Action
• Decreases synthesis of PG’s, there will be decrease in intracellular free Ca, so
MLCK activation is inhibited that leads to stop uterine contractions.
Dose
• Loading dose 50 mg orally or parenteral followed by 25 mg every 6 hr’s for 48
hrs.
Adverse effects
• Maternal: Heart burn, asthma, GI Bleeding, Thrombocytopenia, renal injury.
• Fetal & neonatal: Neonatal pulmonary hypertension.
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4. NSAIDS (Indomethacin)

40. Rx: Atosiban
Mechanism of Action
• Atosiban Blocks myometrium oxytocin receptors.
• It inhibits intracellular Ca++ release and release of Prostaglandins,
thereby inhibits myometrial contractions.
Doses: IV infusion 300 micrograms/min.
Side effects: Nausea, vomiting, chest pain (rarely).
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5. Oxytocin antagonists

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44. Thank you !
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