THYROXINE AND OXYTOCIN

(OVERVIEW )
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 CHAPTER#1: THYROXINE
INTRODUCTION:
 Thyroxine is the primary hormone which is secreted by the thyroid gland.

 It is the inactive form and most of it is converted to an active form called

triiodothyronine by organs such as the liver and kidneys.

 It is also known as 3,3’,5,5’- tetra iodothyronine (T4).

 Thyroxine plays an important role in controlling body metabolism and

regulates the functions of the heart and the digestive tract.
HISTORY:

 In 1856 Schiff recognizes, that the thyroid gland during animal researches
causes heavy damage of the nervous system.

 Thyroxine was 1st isolated in pure form in 1914, at the Mayo Clinic by
Edward Calvin Kendall from extracts of hog thyroid glands.

 The hormone was Synthesize in 1927 by British chemist Charles Robert

Harrington and George Barger.
BIOCHEMISTRY:

 Thyroid hormones are constructed by adding iodine residues to the amino

acid tyrosine, which is the major component of protein thyroglobulin.

 Thyroglobulin is produced in the endoplasmic reticulum of the thyroid

follicular cells and excreted into the colloid follicles.

 Within the follicles Iodination (the addition of iodine) to tyrosine occur.

 Initially, the compound that is formed is Monoiodotyrosine (MIT), which is a

single iodine added to tyrosine through the action of enzyme
Thyroperoxidase (TPO).
 Diiodotyrosine (DIT)

(Monoiodotyrosine (MIT)

• A second iodine is added to MIT through the TPO enzyme, forming

Diiodotyrosine (DIT).

Diiodotyrosine (DIT)
 
• When two DIT molecules combine through the action of TPO, the hormone
tetra iodothyronine is formed, which is more commonly called thyroxine or T4.
STRUCTURE OF THYROXINE:

Physical Characterization:
 Molecular formula: C15H11I4NO4
 Molar mass: 776.87 g/mol
 pKa-data: Carboxyl group: pKa = 2.4
Phenol group: pKa = 6.87
Amino group: pKa = 10.1
BIOSYNTHESIS OF THYROXINE:
 Iodine and tyrosine are essential for the formation of hormone.
 Iodine is consumed through diet.
 It is converted into iodide and absorbed from GI tract.
 For the synthesis of thyroxine hormone in normal quantities, approximately
1mg of iodine is required per week or about 50mg per year.
Stages of Synthesis of Thyroxine Hormone

 Synthesis of thyroxine hormone is a complex multi-step process which

possesses steps that occur within the follicular epithelial cells and also within
the cellular follicular lumen. Synthesis occurs in 5 stages:

 Thyroglobulin synthesis
 Iodide trapping
 Oxidation of iodide
 Transport of iodine into follicular cavity
 Iodination of tyrosine
 Coupling reactions
1. Thyroglobulin Synthesis:
 Endoplasmic reticulum and Golgi apparatus in the follicular cells of thyroid
gland synthesize and secrete thyroglobulin continuously.
 Thyroglobulin molecule is a large glycoprotein containing 140 molecules of
amino acid tyrosine.
 After synthesis, it is stored in the follicle.
2. Iodide Trapping:
 Iodide is actively transported from blood into follicular cells, against
electrochemical gradient.
 This process is called iodide trapping.
 Iodide is transported into follicular cell along with sodium by sodium-iodide
symporter pump, which is also called iodide pump.
 Normally, iodide is 30 times more concentrated in the thyroid gland than in
the blood.
 However, during hyperactivity of the thyroid gland, the concentration of
iodide increases 200 times more.
3. Oxidation of iodide:
 Once inside gland iodide is taken into lumen by transporter-Pendrin
 Then iodide is oxidized to iodine by enzyme peroxidase
 

4.Transport Of Iodine Into Follicular Cavity:

 From the follicular cells, iodide is transported into the follicular cavity by an
iodide –chloride pump called pendrin.
5. Iodination Of Tyrosine:
 Combination of iodine and tyrosine is known as iodination.
 It takes place in thyroglobulin.
 First, iodine is transported from follicular cells into the follicular cavity, where
it binds with thyroglobulin.
 This process is called organification of thyroglobulin.
 Then, iodine (I) combines with tyrosine, already present in thyroglobulin.
 Iodination of tyrosine occurs in several stages.
 Tyrosine is iodized first into monoiodotyrosine (MIT) and later into di-
iodotyrosine(DIT).
 MIT and DIT are called the iodotyrosine residues.
Coupling Reactions:
 Iodotyrosine residues get coupled with one another.
 The coupling occurs in different configurations, to give rise to different thyroid
hormones.
 Coupling reactions are:
 one molecule of DIT and one molecule of MIT combine to form tri-
iodothyronine (T3)
 sometimes one molecule of MIT and one molecule of DIT combine to
produce another form of T3 called reverse T3 or rT3. rT3 is only 1% of
thyroid output.
 Two molecules of DIT combine to form tetra iodothyronine (T4), which
isthyroxine.
 Tyrosine + I = Monoiodotyrosine (MIT)
 MIT + I = Di-iodotyrosine (DIT)
 DIT + MIT = Tri-iodothyronine (T3)
 MIT + DIT = Reverse T3
 DIT + MIT = Tetra iodothyronine or thyroxine (T4)
Storage:
 Once thyroxine hormone is synthesized it is stored in follicles.
 In the form of TG (30 T4).
 Stored hormone can meet body requirements for 1-3 months.

Secretion:
 Peroxidase-processed thyroglobulin is then endocytosis by follicular
epithelial cells on a regulated basis whenever the thyroid gland is stimulated
to release thyroid hormone into circulation.
Release and Transport of hormone:
 Once endocytosed into follicular epithelial cell, the thyroglobulin is broken
down by lysosomes, thus releasing attached MIT, DIT, T3, and T4.
 T3 and T4 are then transported out of the follicular epithelial cells into the
circulation.
 The iodine atoms of MIT and DIT are salvaged and transported back into
follicular lumen ac I-.
Metabolism of T4:
 De-iodination:
About 40% T4 de-iodinated into T3 by enzyme 5’de-iodinase.

 Decarboxylation:
Very few decaroxylated to form tetra-iodothyroacetic acid and tri-
iodothyroacetic acid.
 
 Conjugation:

 T4 along with T3 conjugate in the liver to form sulphate and glucuronide.

 These conjugates enter the bile and to the intestine.
 Thyroid hormone conjugates are hydrolyzed and reabsorbed from the
intestine (Enterohepatic circulation) and some are excreted in stool.
 Regulatory Control of T4 Hormone:
Hypothalamic-Pituitary-Thyroid-Axis:
 
 Hypothalamus produces TRH + Somatotropin
 stimulate the pituitary gland to produce TSH.
 TSH act on thyroid gland stimulate secretion
 of T4 and T3
 + iodine trapping + new hormone synthesis
 + stimulate thyroid cell hypertrophy.
 T4 + T3 = negative feedback mechanism on
 pituitary gland + hypothalamus.
 Wolff-Chaikoff Effect:

 Autoregulation by food Iodine.

 Iodine content in diet and iodine trapping are inversely proportional. (2,3)

Normal values of T4 total:

 1 to 15 Years: 7.3 to 11.7 µg/dL
 Adult: Male = 4.6 to 10.5 µg/dL
 Female = 5.5 to 11.0 µg/dL
 Greater than 60 years: 5.0 to 10.7 µg/dL (3)
PHARMACOKINETICS OF T4

99% of T4 are bound to plasma proteins (TBG: thyroid-binding globulin)

T4 has a half-life of 6 – 7 days (long)
Some of the circulating T4 is de iodinated to T3, the more potent and rapidly acting form.
Enzyme inducers (rifampin, phenytoin, phenobarbital, carbamazepine) increase the
metabolism of T4.
Excreted in bile and urine and feces.
 
Oral T4 (Thyroxine):

When T4 is taken orally, up to 80% of it is absorbed.

Peak serum concentration is reached two to four hours after ingestion.
Serum concentration then rises by 20 to 40%.
Half-life of T4 is relatively long, at 190 hours.
A fatty meal lowers its absorption by 40% and even drinking coffee lowers its absorption
by 27-36%.
Consequently, oral T4 thyroid hormone must be taken in the fasting state, with water, 30
to 60 minutes before breakfast.
80% excreted in kidney (urine) and 20% in feces. (4,5)
Mechanism of action of thyroxine (T4)
Levothyroxine ( T4) is a synthetic version of one of the
body’s natural thyroid hormone. Normally the hypothalamus
secrets thyrotropin releasing hormone (TRH), which then
stimulates anterior pituatry to secrete thyroid stimulating
hormone (TSH), which subsequently stimulate the thyroid to
secrete 80% of thyroxine (T4) . 50% of thyroxine (T4) then gets
converted into active metabolite L-triiodothyronine (T3). The
thyroid hormone then works by binding to thyroid receptor
proteins contained within the cell nucleus.

Once inside the nucleus, thyroid hormone works by directly

influencing DNA transcription to increase body metabolism by
increasing gluconeogenesis, protein synthesis, the mobilization of
glycogen stores, and other more functions.
Physiological effects of Thyroxine (T4):
 Thyroxine have profound effect on many physiologic process such as
growth,development and metabolism.
 It plays vital role in digestion, heart and muscle
function.
 It stimulates protein synthesis.
 Promotes intestinal absorption of glucose and
may cause hyperglycemia.
 Increase the rate of depth of respiration.
 Have tendency to lower the serum cholesterol.
 It also promotes vasodilation which leads to
enhanced blood flow to many organs.
Clinical significance:

When thyroxine is administered, the proteins are mobilised and diuresis continues until
the puffiness (myxoedema) is cleared.
If your body releases too much thyroxine it can lead to a condition named thyrotoxicosis.
This cam cause GOITER (which is the swelling of the neck because of enlargement of
thyroid gland).
If the body produces too little thyroxine it can lead to Hypothyroidism.
It can cause headache which may lead to migraine.
Maintain level of thyroxine can maintain the level of iodine in the body.
 
Medicinal uses:

Levothyroxine (T4) is used to treat an underactive thyroid (hyperthyroidism).

Thyroxine medication can also used to treat certain thyroid problems like goiter and
thyroid cancer.
It helps to maintain mental and physical health.
It replaces or provide more thyroid hormone, which is normally produces by the thyroid
gland.
Transport of Thyroxine hormone:

 Within the plasma, T4 are mostly transported almost entirely in association

with two proteins called THYROXINE-BINDING PROTEIN. Which acts as
specific carrier agents for the hormones.
 Two main carrier proteins are:
 Thyroxin-binding globulin (TBG)
 Thyroxine binding prealbumin (TBGA)
 When large amount of T4 are present and the binding capacities of the
above two specific carrier proteins are saturated, the hormones can be
bound to “Serum albumin”. Approximately 0.05% of the circulating thyroxine
is in the free unbound form. Free T4 are the metabolically “active” hormones
in the plasma.
CONVERSION OF T4 IN TO T3:

About 94 percent of the hormone made in the thyroid gland is T4. The remaining 6 percent is
triiodothyronine (T3).
Although the thyroid gland secretes only a little T3, it is most active form of the body can use.
T4 must be converted into T3 before the body can use it.
Most of its conversion happens in the liver, but also take place in cells of the heart, muscle,
gut and nerves.
These cells convert T4 into T3 with an enzyme called tetraidothyronine 5’ deiodinase, which
removes one molecule of iodine.
In the end, only about 60 percent of T4 is converted into usable T3. Twenty percent becomes
reverse T3 (rT3), an inactive form the body cannot use.
Level of rT3 can become too high in times of major trauma, surgery, or severe chronic
illness.
Another 20 percent of T4 can be converted to T3 by healthy gut bacteria in the digestive
tract.

If the conversion of T4 to T3 is poor, then you may experience some of the common
hypothyroid symptoms like fatigue, depression, sensitivity to cold temperature, difficulty in
concentrating and more.
THYROXINE DEFICIENCY OR HYPOTHYROIDISM:

Too little production of thyroxine by the thyroid gland is known as hypothyroidism.

When your thyroid doesn’t produce enough thyroxine hormone, the balance of
chemical reactions in our body can be upset and causes hypothyroidism
It may also be caused by autoimmune diseases, poor iodine intake or caused by the
use of certain drugs, radiation therapy, thyroid surgery. Sometimes the cause is
unknown.
Thyroid hormone are essential for physical and mental development so untreated
hypothyroidism before birth or during childhood can cause mental impairment and
reduced growth.
Hypothyroidism in adults causes reduced metabolism. It can result in symptoms such
as fatigue, intolerance of cold temperatures, low heart rate, weight gain, reduced
appetite, poor memory, depression, stiffness of the muscle and reduced fertility.
In general, children and teens who develop hypothyroidism have the same sign and
symptoms as adults do, but they may also experience poor growth, delayed puberty,
delayed development of permanent teeth.
Untreated hypothyroidism can lead to number of health problems such as goiter,
heart problems, myxedema, peripheral neuropathy.
 
THYROTOXICOSIS:

The release of too much thyroxin in the blood stream is known as thyrotoxicosis.
This may be caused by overactivity of the thyroid gland (hyperthyroidism) as in Graves'
disease, inflammation of the thyroid or a benign tumor.
Thyrotoxicosis can be recognized by a goitre, which is a swelling of the neck due to
enlargement of the thyroid gland.
A single nodule or multiple nodules in the thyroid gland which can produce excessive
thyroxine also can cause hyperthyroidism.
Thyrotoxicosis can also come from inflammation of the gland (thyroiditis) or from taking too
much thyroid medication. In these cases the thyroid gland itself is not overactive, but there
is still too much thyroid hormone in the blood.
Untreated thyrotoxicosis can lead to serious medical complications such as heart rhythm
disturbances and osteoporosis caused from the long-term effects of hormone
overproduction.
Mild thyrotoxicosis may not cause any symptoms to begin with. Symptoms associated with
more severe cases include nervousness, irritability, fatigue, hair loss, intolerance to heat,
increased perspiration and decreased menstrual flow.
Treatment for thyrotoxicosis will depend upon the age, the cause and severity of the illness
and other medical conditions.
HOW IS THYROXINE CONTROLLED:

 The production and release of thyroid hormones, thyroxine and

triiodothyronine, is controlled by a feedback loop system that involves
the hypothalamus in the brain and pituitary and thyroid glands.
 The hypothalamus secretes thyrotropin-releasing hormone which, in
turn, the stimulates the pituitary gland and to produce thyroid stimulating
hormone.
 This hormone stimulates the production of the thyroid hormones,
thyroxine and triiodothyronine, by the thyroid gland.
 This hormone production system is regulated by a feedback loop so that
when the levels of the thyroid hormones (thyroxine and triiodothyronine)
increase, they prevent the release of both thyrotropin-releasing
hormone.
 This system allows the body to maintain a constant level of thyroid
hormones in the body
Anti-thyroid drugs:

Anti-thyroid drugs are also called thyroid inhibitors. These interfere directly or indirectly with the synthesis of
thyroid hormones. The major inhibitors may be classified in to four categories:
Anti-thyroid which interfere directly with the synthesis of thyroid hormones.
Ionic inhibitors which block the iodide transport mechanism.
Iodide itself which in higher concentrations suppress the thyroid hormones.
Radioactive iodine which damages the gland with ionizing radiations.

THERAPEUTIC EFFECTS OF ANTI-THYROID DRUGS:

The anti-thyroid drugs are used in the treatment of hyperthyroidism in the following three ways:
As definitive treatment, to control the disorder in anticipation of a spontaneous remission
In conjunction with radioiodine, to hasten recovery while awaiting the effects of radiation
To control the disorder in preparation for surgical treatment. 

MECHANISM OF ACTION OF ANTI-THYROID DRUGS:

Anti-thyroid drugs inhibit the formation of thyroid hormones by interfering with the incorporation of
iodine into tyrosyl residues of thyroglobulin; they also inhibit the coupling of these iodotyrosyl
residues to form iodothyronines. This indicates that they interfere with the oxidation of iodide ion
iodotyrosyl groups.
CLASSIFICATION OF ANTI-THYROID DRUGS:

The anti-thyroid drugs which have clinical utility includes:

 Thioureylenes
 Aniline derivatives
 Polyhydric phenols

 Thioureylenes:
Thiourea and its simpler aliphatic derivatives and heterocyclic
compounds containing a Thioureylene group make up the majority of the
known anti thyroid agents. These include compounds Propylthiouracil,
Methimazole and Carbimazole.
Propylthiouracil Methimazole

Carbimazole
ANILINE DERIVATIVES:

 Sulfonamides make up the largest number that have been found to inhibit
human thyroid. Optimal anti-thyroid activity is associated with para-
substituted amino benzene grouping with or without aliphatic substitution on
the amino nitrogen.

POLYHYDRIC PHENOLS:

 It includes resorcinol which caused hypothyroidism and goiter in the form of

an ointment for the treatment of leg ulcers.
DOSAGE AND OVER DOSAGE OF ANTI-THYROID DRUGS:
PROPYLTHIOURACIL:

  It is available in the form of 50-mg tablets. The usual dose for the
treatment of hyperthyroidism is 75-100 mg Q8H. Over dosage may be
required up to 1200 mg daily. Improper spacing of doses with 300mg daily
causes failure of response as the drug is fully effective for only a few
hours. This delay or failure of response is also caused by unusually large
thyroid gland and when iodine in any form is given beforehand. When
doses larger than 300 mg daily are needed, further subdivision of the time
of administration of daily dose into 4- or 6-hour intervals is advised.
 
Methimazole and Carbimazole:
 
These are available in 5- and 10-mg tablets. Carbimazole is a carbethoxy
derivative of Methimazole. Initial dose is 5 or 10 mg Q8H.
Due to the half-life of Methimazole which is 6-13 hours, dosage regimen
should produce uninterrupted suppression of thyroid gland.
SIDE EFFECTS OF ANTI-THYROID DRUGS:
 
Agranulocytosis
Sore throat or fever
Mild granulocytopenia
Thyrotoxicosis
Purpuric, papular rash
Pain and stiffness in the joints
Paresthesia
Head ache, nausea
Depigmentation of hair
Rare reactions include hepatitis and nephritis

CONCLUSION:
Hyper thyroidism may be of two kinds:
Grave’sdisease
Hyperthyroidism caused by one or more over functioning nodules.

Hyperthyroidism respond to anti-thyroid drugs in a latent period of a few days to two or more weeks before
improvement is seen. Particularly, when the hyperthyroidism is severe, definite improvement may be seen in one or
two days. Patients suffering from enlargement of goiters particularly nodular, the response may be slower. In most
cases, treatment with an anti-thyroid drug requires medical attention only at monthly or bimonthly intervals and
adjustment of doses is based entirely on symptoms or simple clinical signs. Anti-thyroid drugs are most importantly
used in the preparation of hyperthyroid patient for subtotal thyroidectomy.
REFERENCE:
The pharmacological basis of therapeutics/Goodman and Gilman’s
https://www.labce.com/spg864492_the_biochemistry_of_thyroid_hormones.aspx
https://www.pharmaceutical-journal.com/news-and-analysis/news/levothyroxine-from
-sheep-thyroid-injections-to-synthetic-formulations/11123454.article?firstPass=false
Chemistry of thyroxine; isolation of thyroxine from the thyroid gland by Charles Robert
Harington.
Thyroid hormone synthesis, Editor Steven L. Jones, Lippincott Williams and Wilkin’s
2001.
Synthesis of thyroid hormones; bioscience notes, Vol 3, Edited by B.M Trost and I.
Fleming, Oxford. 1991. pg. 659-703.
The American society of Health-System Pharmacist, retrieved 8 December 2016.
Levothyroxine – Drug usage statistics, ClinClac 23 December 2019.
Cooper Ds, Halpern R, wood LC, levin AA, Ridgway EC, L-thyroxine therapy in
subclinical hypothyroidism.
Ono Y, Ono S, Yasunaga H, Matsui H, Fushimi K, Tanaka Y, clinical characteristics and
Outcomes of myoxedema coma.
MN Chatterjea Rana Shinde Textbook of medical biochemistry Eight edition.
https://www.yourhormones.info/hormones/thyroxine/
https://drknews.com/conversion-t4-t3-important-consideration-low-thyroid-fun
ction/
 CHAPTER#2: OXYTOCIN

INTRODUCTION:

Oxytocin is a harmone that acts on organs in the body (including the

breast and uterus) and as a chemical messenger in the
brain,controlling key aspects of the reproductive system, including
child birth and lactation, and aspects of human behaviour.
ALTERNATIVE NAME OF OXYTOCIN ARE:
Alpha-hypophamine.

Manufactured Versions: Carbetocin, Syntocinon , Pitocin.

 
Oxytocin is produced in the hypothalamus and is secreted into the bloodstream by the posterior pituitary

gland. Secretion depends in the electrical activity of the neurons in the hypothalamus, it is released into the
blood when the cells are excited.
 
The two main actions of the oxytocin in the body are contraction of the womb (uterus) during child birth and
lactation. Oxytocin stimulates the uterine muscles to contract and also increase production prostaglandins,
Which increase the contraction further.
 
Manufactured Oxytocin is sometimes given to induce labour if it has not started naturally or it can be used to
strengthen contractions to aid child birth.
 
In addition, manufactured oxytocin is given to speed up delivery of the placenta and reduce the risk of heavy
bleeding by contracting the uterus.
 
During breast feeding, oxytocin promotes the movement of milk into the breast, allowing it to be excerted by
nipple.Oxytoxin is also present in men, playing a role in sperm movement and production of testosterone by
the testes.
 
In the brain,oxytocin acts as a chemical messenger and has been shown to be important in human
behaviours including sexsualarousal,recognition,trust,anxiety and mother-infant bonding.As a result, Oxytocin
has been called “Love harmone” or “Cuddle chemical”.
DISCOVERY OF OXYTOCIN:

Oxytocin was descovered by Henry Dale in 1906.Its molecular structure was

determined in 1952.

SOURCE OF OXYTOCIN:
In the hypothalamus,oxytocin is made in magnocellular neurosecretory
cells of the supraoptic and paraventricular nuclei, and is stored in Herring
bodies at the axon terminals in the posterior pituitary.It is then released
into the blood from the posterior lobe (neurohypophysis) of the pituitary
gland.

CHEMICAL FORMULA:
C43H66N12O12S2
 
STRUCTURE:
• BIOSYNTHESIS OF OXYTOCIN:
Oxytocin is a cyclic non peptide that differ from vasopressin by only two
amino acids. It is synthesize as larger precursor molecule in cell bodies of a
paraventricular nucleus ,and to a lesser extent, the supraoptic nucleus in the
hypothalamus.
The precursor is rapidly converted by proteolysis to the active hormone and
its neurophysin ,packaged into secretory granules as an oxytocin-
neurophysin complex and secreted from nerve endings that terminate
primarily in the posterior pituitary gland(neurohypophysis)

• ACTION ON PREGNANT UTERUS (MILK EJECTION REFLEX):

The two main actions of oxytocin in the body contraction of the womb
(uterus) during childbirth and lactation. Oxytocin stimulates the uterine
muscles to contract and also increase production of prostaglandins, which
increase contraction further.
• ACTION ON NON PREGNANT UTERUS:

The action of of oxytocin on non pregnant uterus is to facilitate the

transport of sperms through female genital tract up to fallopian tube by
producing the uterine contraction during the sexual intercourse.
During the sexual intercourse, the receptors in the vagina are
stimulated. The vaginal receptor generate the impulses, which are
transmitted by somatic afferent nerves to the paraventricular and
supraoptic nuclei of hypothalamus. When these two nuclei are
stimulated ,oxytocin is released and transported by blood .While
reaching the female genital tract, the hormone causes contraction of
uterus towards the fallopian tube .It is also a neuroendocrine reflex.
The senstivity of uterus to oxytocin is accelerated by estrogen and
decreased by progesterone.
Brand Name:
 Pitocin
 Syntocinon
 American Oxytocin
 European Oxytocin

 
High and Low level of Oxytocin:
 
 High level of oxytocin causes benign prostatic hyperplasia, a condition
which affects the prostate in more than half of men over the age of fifty. This
may cause difficulty in passing urine.
 Low level of oxytocin causes autism and autistic spectrum disorders (e.g.
Asperger syndrome) – a key element of these disorders being poor social
functioning.
 Low oxytocin causes depressive symptoms.
 Lack of oxytocin can prevent the milk let down reflex and make breast
feeding difficult.
Dosage:

 Injectable solution –10 units per ml

 Postpartum Hemorrhage-10 units IM after delivery of placenta, add 10-40
units; no to exceed 40 units; to 1000 ml of nonhydrating IV solution and
infuse at necessary rate to control uterine atony.
 Labor induction-0.5-1 mUnit /min IV, titrate 1-2 mUnit/min q15-60min until
contraction pattern reached that is similar to normal labor ( usually
6mUnit/min); may decrease dose after desired frequency of contraction
reached and labor has progressed to 5-6 cm dilation.
Side Effects:
Common side effects of Oxytocin:
 
Slow heart rate.
Fast heart rate.
Pre mature ventricular complexes and other irregular heartbeats (arrhythmias).
Permanent central nervous system or brain damage and death secondary to suffocation.
Neonatal seizure.
Neonatal yellowing of skin or eyes (jaundice).
Fetal death.

Low Apgar score(5 minutes).

Uteroplacental hypoperfusion and variable deceleration of fetal heart rate.
Inadequate fetal oxygen levels (hypoxia).
Perinatal hepatic necrosis.
Fetal hypercapnia.
Severe decreases in maternal systolic and diastolic blood pressure increases in heart
rate, systemic venous return and cardiac output and arrhythmia.
Toxicity:
An inappropriate dosage of oxytocin can lead to dangerous tachycardia,
arrhythmias, and myocardial ischemia.
High dosages of oxytocin can cause uterine rupture, hypertonicity, and
spasms.
 
PHARMACOKINETICS OF OXYTOCIN:
Absorption: Uterine response after IV administration is immediate and subside
after 1 hour. Uterine contraction occurs 3-5 mins after IM administration and
decreased within 2 -3 hours. When 100-200 milliunits is administered IV,
Contractions of the myoepithelial tissues surrounding the alveoli of the breasts
occur within minutes and lasts for about 20 mins.
Distribution: It distributed throughout the extracellular fluid and crosses the
placenta.
Route of elimination: Biliary and renal
Metabolism: Oxytocin is rapidly metabolized in the liver and also in plasma by
oxycocinases. It is also metabolized to a smaller degree by the mammary gland.
Excretion: Only small amount is excreted in the urine as oxytocin.
PHYSIOLOGICAL FUNCTIONS:

The pituitary gland secretions are responsible for the peripheral functions of the hormone. The secretions from
centrally projecting Oxytocin neurons that differ from those that enter posterior pituitary or that are collaterals
from them are responsible for its behavioural effects. It is believed so because the Oxytocin secreted from
pituitary gland cannot re-enter brain as it cannot cross the blood brain barrier.
Parturition and uterine contraction: Oxytocin causes the contraction of uterine muscles and is commonly
used to induce labor in clinical practice. Oxytocin acts on uterus already primed by oxytocin, at the time of
parturition. Due to increased plasma level of oxytocin and increased sensitivity of uterus to oxytocin, uterus
contracts vigorously leading to expulsion of foetus. Thus oxytocin initiates and completes parturition.

Milk ejection: Discharge or expulsion of milk from breast of mother into mouth of baby during breast feeding
is called milk ejection reflex or milk let down reflex. Action of oxytocin at the mammary gland causes ejection
of milk into the sub areolar sinuses from where it is excreted. As the baby suckles, an impulse is generated
and is transmitted to the hypothalamus via spinal nerves. This nerve signal causes oxytocin secretion.
Oxytocin is also believed to cause an indirect effect on milking through the hormone, prolactin.

Sexual behavior: The amount of plasma oxytocin is found to increase during sexual arousal, and also
orgasm can markedly raise the plasma levels of the hormone in men. The primary aim of oxytocin treatment
in women is to induce labor as it aids in the contraction of uterus.

Role in Reproduction: Oxytocin has been found to modulate contractility of male reproductive tract in order
to modulate sperm transportation and maturation and also the process of spermiation. The action of
oxytocin on muscle contractibility may accelerate sperm and egg transport.
 Role in Social functioning: Oxytocin has a role in regulating the social behavior of many species

and so can also influence the social behaviors in human. Oxytocin helps in the emotional bonding
between human and dogs. Oxytocin is necessary in modulating the formation of social memories
and also expression of aggressive and affiliative behavior.

Social memory and social recognition: Central oxytocin administration enhances social memory in

males whereas an oxytocin receptor antagonist blocks social memory in female and male rats. Data
from clinical studies reveal that oxytocin promotes face recognition in human.
 
Anxiety: Oxytocin can also function as an anxiolytic agent as it decreases stress hormone release

in both humans and rats. Animal research has demonstrated relationships between oxytocin’s role
in anxiety and social behaviors. The acute and chronic anxiolytic effects of oxytocin have been
demonstrated in a number of rodent study. Oxytocin in humans can work to reduce anxiety by
increasing recognition and feelings of affiliation. Lower oxytocin levels of plasma reported in
humans with depression. Oxytocin released from brain also appears to reduce stress responses,
including anxiety. Oxytocin has the ability to evoke feelings of contentment, causes a reduction in
anxiety and feeling of calmness and security around mate.
 
Love and trust: Oxytocin increases trust and decreases fear. The oxytocin amounts in blood rises

during hugging and orgasm. People in their first stage of romantic attachment had increased level
of oxytocin, compared with those of non-attached single people. Thus, this hormone is sometimes
referred to as “love hormone”. Oxytocin also enhances feelings of generosity, trust and may help in
the recognition and understanding of other’s feelings.
 
PSYCHOLOGICAL FUNCTIONS:
Autism: The positive correlation between oxytocin and formation of social bonds in
animal studies has made many to believe that oxytocin abnormalities may play a
role in autism. Actually, various studies indicate that single nucleotide
polymorphisms (SNPs) in oxytocin is linked with ASD. Infusion of oxytocin
intravenously into adults with autism markedly reduces both number and severity
of repetitive behaviors and also can enhance memory. Administration of Oxytocin
was found to increase emotion recognition and improvement of social behavior.
 
Schizophrenia: People with schizophrenia may be like that they have lost their
ideas with reality. It is one of the most disabling type of a psychiatric disorder, with
a small proportion of patients troubled with this disorder possible to maintain
independent function. Several early reports indicate that treatments with oxytocin
induced sudden therapeutic results and was stayed away from hospitalization in
patients with schizophrenia, where its potential action was by working as a
“psychic energizer” thereby revising energy, apathy and depression. Oxytocin
produced importantly greater therapeutic actions across a broad spectrum of
symptoms that included both positive and negative symptom groups that were
based upon changes in the positive and negative syndrome scale (PANSS).
Clinical Global Impression (CGI) scores also were significantly found improved
with oxytocin.
Pain perception: Oxytocin causes analgesia for acute or chronic pain in humans.
Oxytocin lowers pain threshold in rats. Oxytocin has been recognized recently as
a significant mediator of endogenous analgesia and it can reduce frequency of
headache and pain in chronic migraine. It has also been reported that oxytocin
decreases thoracic cancer pain. Decreased concentrations of oxytocin seems to
be markedly associated with pain, stress, and depression in fibromyalgia patients.

INDICATIONS:
In pregnancy:
Second trimester abortion.
Induction of labor.
To facilitate cervical ripening for effective induction.
In Labor:
Augmentation of labor.
Active management of third stage of labor given after separation of placenta for
promoting uterine contraction and stoppage of bleeding.
In Puerperium:
To minimize blood loss.
Control of post-partum haemorrhage.
 References:

 PubMed.gov
 Drugbank.ca
 www.drug.com
 https://www.rxlist.com/pitocin-side-effects-drug-center.htm
 https://reference.medscape.com/drug/pitocin-oxytocin-343132