Drugs Used in

Gastrointestinal Disorders
Drugs influence contraction
activity of Uterus

Lecture 14

PhD Oksana Bondar

Scientific and Educational Center of

Pharmacology
The gastrointestinal tract serves many important functions:
digestive, excretory, endocrine, exocrine
Acid-peptic disease - a group of disorders involving erosion or ulceration of the
mucosal lining of the GIT; includes GERD, gastric and duodenal ulcers, nonulcer
dyspepsia, and stress-related gastritis.
Gastroesophageal reflux disease (GERD) - esophageal irritation or inflammation due
to reflux of stomach acid; also known as heartburn
Gastroparesis - paralysis of the muscles of the stomach and possibly other parts of the
GIT due to damage to GI nerves or muscle; common in advanced diabetes and
advanced Parkinson’s disease
Inflammatory bowel disease (IBD) - Inflammatory disorder involving irritation and
ulceration of the colon and rectum (ulcerative colitis) or the colon plus more proximal
parts of the GIT (Crohn’s disease)
Irritable bowel syndrome (IBS) - disease of unknown origin characterized by episodes
of abdominal discomfort and abnormal bowel function (diarrhea, constipation, or both)

A. Drugs Used in Acid-Peptic Diseases

Goal - reduce intragastric acidity, promote mucosal defense or, eradicate the
bacterium Helicobacter pylori (80% of patients with duodenal ulcers).
1. Antacids are weak bases that neutralize stomach acid by reacting with protons in
the lumen of the gut. When used regularly in the large doses, antacids reduce the
recurrence rate of peptic ulcers.
• Magnesium hydroxide (Mg[OH]2) and Aluminum hydroxide (Al[OH]3)
NO absorption from the bowel.
Magnesium hydroxide has a strong laxative effect, whereas aluminum hydroxide
has a constipating action! → used alone or in combined preparations (Almagel®).
• Calcium carbonate (CaCO3) and Sodium bicarbonate (NaHCO3) (Alka Seltzer)
are also weak bases, but absorbed from the gut! → produce systemic effects →less
popular as antacids. May cause belching (because of CO2) or metabolic alkalosis.

2. H2(Histamine)-receptor antagonists
Cimetidine, Ranitidine, Famotidine, and Nizatidine
H2 receptor of parietal cell competitive inhibition → suppress basal and meal-
stimulated acid secretion (60–70% inhibition of total 24-hour acid)!
Direct stimulation of the parietal cell by gastrin or acetylcholine also blocked in the
presence of H2-receptor blockade!
Selective (do not block H1 histamine receptors (sedation))
Especially effective at inhibiting nocturnal acid secretion! but have a modest impact
on meal-stimulated acid secretion.
Half lives from 1.1 to 4 hours, fist pass metabolism, 50% bioavailability, eliminate by
glomerular filtration, and renal tubular secretion (renal insufficiency needs dose
reduction), commonly given twice daily.
FIGURE 1 Schematic model of physiologic control of hydrogen ion (acid) secretion by the gastric
parietal cells, which are stimulated by gastrin (acting on gastrin/CCK-B receptors), acetylcholine
(ACh; M3 receptor), and histamine (H2 receptor). ECL - enterochromaffin-like cells.
From 1970s until the early 1990s (discovery of proton pump inhibitors) were the most
commonly prescribed drugs in the world!
Over-the-counter preparations of the H2 antagonists are heavily used by the public.
Effective against:
• Gastroesophageal Reflux Disease GERD (intermittent drug twice daily)
• Peptic ulcer disease (once daily at bedtime, produce effective ulcer healing of
uncomplicated ulcers)
• Nonulcer dyspepsia (over-the-counter agents)
• Prevention of stress-related gastritis and bleeding in seriously ill patients
(intravenous H2 antagonists are preferable over proton pump inhibitors)

Adverse Effects: H2 antagonists are extremely safe drugs!

Adverse effects in less than 3% of patients and include diarrhea, headache, fatigue,
myalgias, and constipation.
Intravenous H2 antagonists may increase the risk of nosocomial pneumonia and
enteric infections in critically ill patients.
FIGURE 2. Twenty-four-hour median intragastric acidity pretreatment (red) and after 1
month of treatment with either ranitidine, 150 mg twice daily (blue, H2 block), or
omeprazole, 20 mg once daily (green, PPI).
3. Proton pump inhibitors
Omeprazole (S-isomer Esomeprazole)
Lansoprazole (R-isomer Dexlansoprazole)
Pantoprazole
Rabeprazole
Lipophilic weak bases, oral formulations are enteric coated to prevent acid inactivation
in the stomach.
Absorbed in alkaline intestinal lumen → infuse into the parietal cell → become
protonated and concentrated more than 1000-fold in acidified compartments →
conversion to active drug → forms a covalent disulfide bond with H+/K+ ATPase and
irreversibly inactivate it.
Pharmacokinetics: proton pump inhibitors are ideal drugs, they are concentrated and
activated near their site of action.
Rapidly metabolized in the liver, have negligible renal clearance, half-lives 1–2 h,
durations of action 24 h, require 3–4 d of treatment to achieve full effectiveness.
Application: Inhibit both fasting and meal-stimulated secretion because they block
the final common pathway of acid secretion.
Once-daily dosing - effective in 85–90% of patients; up to 15% require twice-daily
dosing!
First-line therapy for patients with symptomatic GERD!
More effective than H2 antagonists for GERD and peptic ulcer and equally effective in
the treatment of nonulcer dyspepsia and the prevention of stress-related mucosal
bleeding!
Adverse effects: occur infrequently, diarrhea, abdominal pain, headache, chronic
treatment cause hypergastrinemia, may decrease the oral bioavailability of vitamin
B12 and certain drugs, small increase in the risk of respiratory and enteric infections.

4. Treatment of H. pylori-associated Ulcers

There are two therapeutic goals: to heal the ulcer and to eradicate the infection.
Treatment: combinations of two antibiotics and a proton pump inhibitor.
The best treatment regimen: 14-day regimen of “triple therapy” with proton pump
inhibitor twice daily; clarithromycin (inhibit ribosomal protein synthesis), 500 mg twice
daily; and either amoxicillin (cell wall inhibitor), 1 g twice daily, or metronidazole
(block nucleic acid synthesis), 500 mg twice daily.
After completion of triple therapy: the proton pump inhibitor once daily for a total of
4–6 weeks to ensure complete ulcer healing.
5. Mucosal Protective Agents
Sucralfate - an aluminum sucrose sulfate, poorly soluble molecule that polymerizes
in the acid environment of the stomach → polymer binds to injured tissue and forms a
protective coating over ulcer beds.
Accelerates the healing of peptic ulcers and reduces the recurrence rate.
Sucralfate must be taken 4 times daily , toxicity is very low .
Colloidal bismuth – form a protective coating on ulcerated tissue, has direct
antimicrobial effects, stimulate mucosal protective mechanisms, eliminates
enterotoxins.
Reduces stool frequency and liquidity in infectious diarrhea.
Nonprescription bismuth compounds are widely used by patients for the nonspecific
treatment of dyspepsia and acute diarrhea.
Misoprostol
The human GI mucosa synthesizes a number of prostaglandins; the primary ones are
prostaglandins E and F.
Misoprostol, a methyl analog of PGE1.
Misoprostol increases mucosal protection and inhibits acid secretion.
It is effective in reducing the risk of ulcers produced by NSAIDs
Multiple daily dosing and poorly tolerated adverse effects (GI upset and diarrhea) 
B. Drugs That Promote Upper Gastrointestinal Motility
• Gastroparesis
• Postsurgical gastric emptying delay
• GERD (esophageal sphincter pressures↓)
Prokinetic drugs stimulate upper GI motility
1. In the past cholinomimetic agonists (Bethanechol) were used.
The acetylcholinesterase inhibitor (Neostigmine) is used for acute large
bowel distention.
2. In the enteric nervous system, Dopamine inhibits cholinergic stimulation
of smooth muscle contraction → D2 dopamine receptor antagonists
(Metoclopramide, Domperidone) promote GI motility!
Metoclopramide (like antipsychotic drugs) have useful antiemetic properties,
but produse extrapyramidal effects, and hyperprolactinemia!
Domperidone do not cross the blood-brain barrier → no CNS toxicity!
3. The macrolide antibiotic (Erythromycin) promotes motility by stimulating
motilin receptors (stimulate migrating motor complex).
C. Laxatives
Increase bowel movement and prevent constipation by several mechanisms:
• an irritant or stimulant action on the bowel wall;
• a bulk-forming action on the stool that evokes reflex contraction of the bowel;
• a softening action on hard or impacted stool;
• a lubricating action that eases passage of stool through the rectum.

Lubiproston: chloride-rich fluid secretion into the intestine ↑ → intestinal motility stimulation
and shortens intestinal transit time.
D. Antidiarrheal Agents
Only if diarrhea is mild to moderate!
Opioids and derivatives of opioids are most effective !
Activate presynaptic mu opioid receptors in the enteric nervous system
→ acetylcholine release ↓ and peristalsis ↓.
At the usual doses, they lack analgesic effects.
Have been selected for maximal antidiarrheal and minimal CNS effect.
• Diphenoxylate (schedule II alone, in combination - schedule V)
• Loperamide (not abused, not controlled)
Diphenoxylate + antimuscarinic alkaloids (Atropine to prevent drug abuse)
It should not be used in children due to the risk of respiratory depression!
It should not be used for people with diarrhea caused by an infection!
Slowing of peristalsis can prevent clearing of the infectious organism !
Adsorbents:
Adsorb intestinal toxins and microorganisms + coating or protecting the intestinal
mucosa.
Activated carbon, Aluminum hydroxide, Methylcellulose, Bismuth subsalicylate,
Kaolin (white clay, silicates) + Pectin from apples = popular nonprescription
preparation that absorbs bacterial toxins and fluid → decreased stool liquidity.
FIGURE 3 Release of serotonin (5-HT) by
enterochromaffin (EC) cells from gut distention
stimulates submucosal intrinsic primary
afferent neurons (IPANs) via 5-HT1P receptors
and extrinsic primary afferent neurons via 5-
HT3 receptors. Submucosal IPANs activate the
enteric neurons responsible for peristaltic and
secretory reflex activity. Stimulation of 5-HT4
receptors (5-HT4R) on presynaptic terminals of
IPANs enhances release of acetylcholine
(ACh) and calcitonin gene-related peptide
(CGRP), promoting reflex activity.
ENS - enteric nervous system
E. Drugs Used for Irritable Bowel Syndrome (IBS)
IBS - recurrent episodes of abdominal discomfort + diarrhea or constipation (or
both).
Treatment is symptomatic: if diarrhea → antidiarrheal agents and antispasmodics
to relieve abdominal pain (anticholinergic drugs Dicyclomine and Hyoscyamine
(one of Atropine isomer))
If constipation → laxatives
+ low doses of tricyclic antidepressants.

Alosetron, a potent 5-HT3 antagonist, treatment of women (preferential efficacy) with

severe IBS with diarrhea (risk of severe constipation → restricted only to chronic
diarrhea not responding to conventional therapy).

Lubiprostone and Linaclotide are laxatives that activates the type 2 chloride
channels in the small intestine, treatment of women with IBS with predominant
constipation, also effective against chronic idiopathic constipation.
 There are four important
sources of afferent input to the
vomiting center:
1. Chemoreceptor trigger zone
is accessible to emetogenic
stimuli in the blood or
cerebrospinal fluid.
2. The vestibular system is
important in motion sickness
via cranial nerve VIII.
3. Vagal and spinal afferent
nerves from the
gastrointestinal tract
are rich in 5-HT3 receptors.
4. The central nervous system
plays a role in vomiting due to
psychiatric disorders, stress.

FIGURE 4 Neurologic pathways involved in pathogenesis of nausea and vomiting.

Irritation of the GI mucosa by chemotherapy, radiation therapy, distention, or acute

infectious gastroenteritis → release of mucosal serotonin and activation of these
receptors → vomiting center and chemoreceptor trigger zone stimulation.
F. Drugs With Antiemetic Actions
Especially valuable in cancer chemotherapy-induced vomiting!
• The 5-HT3 antagonists (Ondansetron, Granisetron, Dolasetron, Palonosetron)
Blockade of 5-HT3-receptor in the vomiting center and chemoreceptor trigger zone
but mainly through blockade of peripheral 5-HT3 receptors on extrinsic intestinal vagal
and spinal afferent nerves.
Treatment of emesis attributable only to vagal stimulation (postoperative) and
chemotherapy.
• Corticosteroids (Dexamethasone)
The basis for these effects is unknown!
During chemotherapy used in combination with 5-HT3-receptor antagonists.
• Antagonist of the neurokinin 1 (NK1) receptor (Aprepitant)
Aprepitant (an oral formulation) is a highly selective NK1-receptor antagonist that
crosses the blood-brain barrier and occupies brain NK1 receptors, used in
combination with 5-HT3-receptor antagonists against highly emetogenic
chemotherapeutic regimens.
• Phenothiazines § Butyrophenones (Prochlorperazine, Promethazine,
Droperidol, Haloperidol) Phenothiazines and Butyrophenones are antipsychotic
agents that can be used for their potent antiemetic (dopamine and muscarinic
receptors block) and sedative properties (antihistamine activity).
Treatment of postoperative nausea and vomiting, in combination with opiates and
benzodiazepines for sedation during surgical and endoscopic procedures, for
induction and maintenance of general anesthesia.
• D2 dopamine receptor antagonists, Substituted benzamides (Metoclopramide,
Trimethobenzamide)
Metoclopramide promote GIT motility but does not increase gastric acid secretion!
Mechanism of action - dopamine-receptor blockade + sedation (antihistamine effect)
Adverse effects are extrapyramidal: restlessness, dystonias, and parkinsonian
symptoms
• H1 histamine blockers (Diphenhydramine, Dimenhydrinate, Meclizine)
Weak antiemetic activity, treatment of motion sickness, cause sedation, treatment of
emesis due to chemotherapy
• Antimuscarinic drugs (Scopolamine)
One of the best agents for the prevention of motion sickness ! Better tolerated as a
transdermal patch than oral formulation (high incidence of anticholinergic effects)
• Cannabinoid receptor agonists (Dronabinol and Nabilone)
Tetrahydrocannabinol can be used as appetite stimulant and as an antiemetic
But the mechanisms for these effects are not understood!
G. Drugs Used in Inflammatory Bowel Disease (IBD)
1. Aminosalicylates - drugs containing 5-aminosalicylic acid (5-ASA, Mesalamine) are
used as topical therapy for IBD.
Mechanism of action - inhibiting the synthesis of prostaglandins, inflammatory
leukotrienes, cytokines.
Proprietary coated formulations of 5-ASA (Pentasa, Asacol, Lialda) deliver 5-ASA to
different segments of the small and large intestine.
Balsalazide, Olsalazine, and Sulfasalazine contain 5-ASA bound by an azo (N=N)
bond to an inert compound, another 5-ASA molecule, or sulfapyridine.
Sulfasalazine (containe sulfapyridine) has a higher incidence of adverse effects than
the other drugs.
Releasing sulfapyridine (folate antagonist from sulfonamide group) is responsible
for antibacterial action of sulfasalazine (treatment of urinary tract infection).
Delayed-release tablets of sulfasalazine are used to treat rheumatoid arthritis.

2. Other agents for the treatment of Ulcerative colitis and Crohn’s disease.
• Antibiotics
• Glucocorticoids (Budesonide)
• Immunosuppressive antimetabolites (Azathioprine, 6-mercaptopurine,
Methotrexate), doses lover than for chemotherapy
• Anti-tumor necrosis factor [TNF] drugs, TNF stimulates T-cells presented in
inflammatory bowel (Infliximab, Adalimumab, Golimumab)
• Natalizumab is a humanized monoclonal antibody that blocks integrins on
circulating leukocytes.

FIGURE 5 Sites of 5-
aminosalicylic acid (5-ASA)
release from different
formulations in the small
and large intestines.

H. Pancreatic Enzyme Replacements

Steatorrhea, a condition of decreased fat absorption together with an increase in stool
fat excretion, results from inadequate pancreatic secretion of lipase.
Oral administration of pancreatic lipase (Pancrelipase or Pancreatin) obtained from
pigs can help. The enzyme should be taken as enteric-coated capsules
I. Drugs That Inhibit the Formation of Gallstones
The formation of cholesterol gallstones can be inhibited by the bile acid derivative.
Ursodiol decreases hepatic cholesterol secretion and has other effects on hepatocyte
canalicular membranes. Toxicity due to the drug is uncommon.

Drugs acting on Uterus

Drugs acting on uterus can primarily affect the endometrium or the myometrium!
Endometrium ← Estrogens, Progestins and their antagonists.
Myometrium ← Sympathetic and Parasympathetic innervation (Autonomic drugs),
Uterin stimulants, Uterin Relaxants.

Uterine Stimulants (Oxytocins, Abortifacients):

These drugs increase uterine motility
• Posterior pituitary hormone – Oxytocin, Desamino Oxytocin, Carbetocin
• Ergot alkaloids – Ergometrine (Ergonovine), Methylergometrine
• Prostaglandins – PGE2, PGF2α, 15-methyl PGF2α, Misoprostol
• Miscellaneous – Ethacridine, Quinine

Oxytocin is a 9-amino-acid peptide, precursor synthesized in hypothalamus, active

hormone secreted from posterior pituitary gland.
The number of oxytocin receptors increases markedly during later part of pregnancy.
Oxytocin increases PG synthesis and release by the endometrium which may
contribute to the contractile response.

Stimuli for oxytocin secretion:

• Dilation of the cervix and vagina
• Suckling at the breast
• Estradiol stimulates oxytocin secretion
• Relaxin inhibits its release
Oxytocin inhibit free water clearance by the kidney through action on vasopressin V2
receptors.
High doses of oxytocin cause fall in BP (due to vasodilation) resulting in reflex
tachycardia.
Plasma t1/2 of oxytocin is about 13 min.
Oxytocin action on Uterus:
• With low doses increase frequency and force of uterine contractions
• Basal tone increases only with high doses
• Increased contractility is due to heightened electrical activity of the myometrial cell
membrane
• Increased contractility is restricted to the fundus, body is relaxed
Oxytocin action on Breast:
Oxytocin contracts the myoepithelium of mammary alveoli → milk ejection reflex
Initiated by suckling so that it may be easily sucked by the infant
These cells in breast are more sensitive than myometrium to oxytocin
Uses of oxytocin to induce labor
Induction of labor in case of:
• Postmaturity
• Prematurely in toxaemia of pregnancy, diabetic mother, erythroblastosis, ruptured
membranes or placental insufficiency.
Dosage – slow IV infusion started at a low rate and progressively accelerated.

Before starting infusion, confirm that:

• Presentation is correct
• Fetal lungs are adequately mature
• There is no cephalopelvic disproportion
• No placenta previa
• No fetal distress
• No uterine scar (due to previous surgery)

Other uses of oxytocin: inefficient milk ejection reflex.

An intranasal spray may be given few minutes before suckling
Why oxytocin preferred for induction and augmentation of labor
Oxytocin is the drug of choice and is preferred over ergometrine/PGs for the above
three purposes:
• Because of its short t½ and slow IV infusion, intensity of action can be controlled
and action can be quickly terminated
• Low concentrations allow normal relaxation in between contractions — fetal
oxygenation does not suffer
• Lower segment is not contracted: fetal descent is not compromised

Desamino-oxytocin
Developed as a buccal formulation;
Action is similar to injected oxytocin.
Its indications are:
• Induction of labor: 50 IU buccal tablet repeated every 30 min, max 10 tabs
• Uterine inertia during childbirth: 25 IU every 30 min
• Promotion of uterine involution (from pregnant to non-pregnant state) 25–50 IU 5
times daily for 7 days
• Breast engorgement 25–50 IU just before breast feeding
Carbetocin
It is a long-acting analogue of oxytocin that has been introduced recently
Uses - prevention of uterine atony after caesarean section
Toxicity of Uterine Stimulants:
Due to excessive stimulation of uterine contractions:
• fetal distress
• placental abruption
• uterine rupture
These complications can be detected early by standard fetal monitoring.
Due to inadvertent activation of vasopressin receptors:
• excessive fluid retention, or water intoxication, leading to hyponatremia
• heart failure, seizures, and death
• bolus injections of oxytocin can cause hypotension
To avoid hypotension, oxytocin is administered intravenously as dilute solutions at a
controlled rate.

Ergot alkaloids
The stimulant action of ergot alkaloids on the uterus is due to α agonist and serotonin
agonist actions.
Sensitivity of the uterus to the stimulant effects of ergot increases during pregnancy
because of increasing dominance of α1 receptors.
In small doses, ergot evokes rhythmic contraction and relaxation of the uterus
At higher doses, they induce powerful and prolonged contractions.
These drugs produce sustained tonic uterine contraction, bleeding stops!
Only the amine ergot alkaloid Ergometrine (Ergonovine) and its derivative
Methylergometrine are used in obstetrics.
Methylergometrine is 1.5 times more potent than Ergometrine on the uterus, but other
actions are less marked.
Adverse effects and contraindications:
Nausea, vomiting and rise in BP
Decrease milk secretion if higher doses are used for many days.
Ergometrine should be avoided in vascular disease, hypertension, toxaemia,
sepsis—may cause gangrene, liver and kidney disease
Contraindicated in pregnancy and before 3rd stage of labor
Uses:
• Control and prevent postpartum haemorrhage (PPH) – 0.2–0.3 mg IM. At delivery
of anterior shoulder.
• Treatment of PPH – 0.5 mg IV
• After caesarean section - to prevent uterine atony
• To ensure normal involution, prophylactically
• Diagnosis of variant angina (A small dose of ergometrine injected IV during
coronary angiography causes prompt constriction of reactive segments of coronary
artery that are responsible for variant angina)
Prostaglandin Analogs
PGE2, PGF2α and 15-methyl PGF2α are potent uterine stimulants, especially in the
later part of pregnancy.
Cause ripening of cervix.
Since Misoprostol (a PG analogue used for peptic ulcer) produces less side effects, it is
being used for obstetric indications as well.
Action of PGs on Uterus:
PGE2 and PGF2α uniformly contract uterus
The sensitivity is higher during pregnancy
There is progressive modest increase with the advance of pregnancy.
However, even during early stages, uterus is quite sensitive to PGs but not to
oxytocin.
PGs increase basal tone as well as amplitude of uterine contractions.
When tested in vitro, PGF2α consistently produces contraction while PGE2 relaxes
nonpregnant but contracts pregnant human uterine strips.
At term, PGs soften the cervix at low doses and make it more compliant.
Role of PGs in pregnancy:
Foetal tissues produce PGs.
At term PGF2α has been detected in maternal blood.
It is postulated that PGs mediate initiation and progression of labor.
Aspirin has been found to delay the initiation of labor and also prolong its duration.
Uterine relaxants [Tocolytics]
• Adrenergic agonists [β2 agonists]
• Ca2+ channel blockers
• Magnesium sulfate
• Atosiban
• Progesterone

● Adrenergic agonists:
Ritodrine is a Beta-2 agonist
Use: To delay labor
IV infusion 50 μg/min → rate increased every 10 min till uterine relaxes → 10 mg oral
or IV 4-6 mg hourly → Labor delay till hours to few weeks
But cardiovascular complications (Hypotention, Tachycardia) !
CI: heart disease, diabetes, on beta blockers.
Others: Isoxsuprine (also a vasodilator), Terbutaline (oral, SC, IV)

● Magnesium sulfate:
Magnesium affects uterine activity by decreasing the release of acetylcholine at the
neuromuscular junction, also increase cAMP and competes with calcium on Ca-rec.
To delay preterm labor, 4g IV bolus then infusion 2g/hour → 24-48 h labor delay
IV infusion to reduce toxemia of pregnancy
Drug of choice in treatment of seizures in preeclampsia and eclampsia!
Similar effect than β2
Toxicity: flushing, nausea, drowsiness, blurry vision are common.
CNS and respiratory depression, arrhythmias, muscular paralysis in overdose.
the use of magnesium for the treatment of preterm labor is decreasing in recent years
in favor of other tocolytic agents.

● Ca2+ channel blockers:

Reduced Ca entry → Reduced tone
Nifedipine – oral 10mg every 20-30 min till uterine relaxes → 10 mg 6 hourly
But Tachycardia and Hypotension! Fetal Hypoxia! (but in comparison with β2 fewer
side effects)

● Atosiban: peptide analog of oxytocin, antagonist of oxytocin receptors

Fewer cardiovascular complications than β2 and Ca2+ blockers
Help to delay labor but do not reduce mortality and morbidity!

● Progesterone
Anti inflammatory action (inflammation induces labor) + action on progesterone
receptor → transcriptional activation
Natural progesterone should be used, not synthetic
Oral, IV, vaginal suppositories
T ½ - 13 h → daily treatment
17P – a natural progesterone conjugate with longer T1/2 – 7 days, IM 1 pill per week
Meta analysis: progesterone significantly reduce risk of preterm birth < 34 weeks and
<36 weeks, reduce perinatal death → recommended prophylactically to women's
with a history of preterm labor and to women's with short cervix

Others: Ethyl alcohol, Nitrates, Halothane etc.*

Indications & Contraindications for Tocolytics:

Ind: Delay Preterm Labour
CI:
• More than 37 weeks gestation
• Fetus >2500g
• Fetus in distress
• Cx dilation > 4 cm
• Ruptured membrane
• Toxemia
• Cardiac diseases
• PPH
 Drugs acting on Uterus

Uterine Stimulants Uterine Relaxants

• Posterior pituitary hormone - • Adrenergic agonists(β2) –

Oxytocin, Desamino oxytocin Ritodrine, Isoxsuprine
• Ergot alkaloids - Ergometrine, • Ca++ channel blockers -
Methylergometrine Nifedipine
• Prostaglandins - Misoprostol • Magnesium sulfate
• Ethacridine, Quinine • Oxytocin antagonist – Atosiban
• Progesterone