SYNTHROID

Jasmie Mong

BPS 201
How Drugs Work
5 December 2013
Final

Abstract
Synthroid is a kind of levothyroxine, which is intended to replace a hormone
that is normally produced by your thyroid gland, to treat hypothyroidism (1). It helps
to increase the metabolic rate of cells of the tissues including bones and the brain
through the control of DNA transcription and the thyroid hormones receptors in the
cytoplasm and nucleus (2). Since Synthroid causes hormonal changes, its side effects
include, weight loss, headache, nervousness, nausea, insomnia, and transient hair loss.
The dosage of Synthroid unique for each patient and it is necessary to avoid the
consequence of overdose or deficiency of treatment. (3)

Introduction
Synthroid is a prescription drug, currently marketed by AbbVie (3).
It is a kind of Levothyroxine, which is a man-made (synthetic) version of
the main thyroid hormone. Thyroid hormone is made and released by the
thyroid gland, and in order to mimic that, Synthroid contains levothyroxine
(T4) sodium. Synthetic T4 is identical to that produced in the human
thyroid gland (1). According to IMS Monthly Prescription, Synthroid is the
number one prescribed brand of levothyroxine medication against
Fig 1. How Synthroid is
three other different kinds of Levothyroxine available in the United
contained
States- Levothroid, Levoxyl and Unithroid (4). The difference
between these three drugs is the deviation in how they are
manufactured (5). Below is the chemical structure of Synthroid.

Fig 2. Chemical Sturcture of Synthroid

Some people believe that Synthroid can be taken as a weight-loss pill or used
to enhance male or female infertility. This concept is actually inaccurate; they are
never recommended as a type of weight-loss drug or fertility solution (6). The main
usage for Synthroid is to treat hypothyroidism, and Pituitary TSH Suppression. (1)

It treats hypothyroidism by replacing the amount of thyroxine the thyroid

doesnt make anymore, helping to restore thyroid hormone balance. In most cases,
thyroid replacement therapy is to be taken for life. The American Association of
Clinical Endocrinologists recommends patients to keep their thyroid-stimulating
hormone level between 0.3 and 3.0 U/L, and each patient has a different dose of
levothyroxine required to stay in that range (7). The most common complication and
the side effect of Synthroid are weight loss, increased appetite, insomnia, anxiety,
heat tolerance, diarrhea or increase in bowel frequency (8). Therefore it is important
to take Synthroid exactly as your doctor prescribed and create a routine so to improve
the way your body absorbs the medicine and the effectiveness of the drug.
Pituitary TSH is any form of treatment of prevention of various types of
euthyroid goiters. Euthyroid goiters are enlarged thyroid caused by insufficient
quantities of iodine in diet triggering compensatory hyperplasia of functionally
normal thyroid tissue, which is usually caused by hormonal imbalances, radiation
treatment, surgery or cancer. (9)
Action
In a human anatomy, thyroid is a butterfly-shaped organ that is located at the
base of ones neck. The endocrine gland secretes hormones into ones body that
control many important functions including the body metabolism. In a normal healthy
body, T3 and T4 are both produced in the thyroid gland through the iodination and
coupling of amino acid tyrosine.
The endocrine system is a set of hormone secreting glands which creates
chemical messages we call hormones, these signals are passed through the blood to
arrive at a target organ, which has cells possessing the appropriate receptor. Most
hormones are made of protein and are secreted by the pituitary, parathyroid, heart,
stomach, liver and kidneys. The pituitary plays an important role in this case, and is
the important link between nervous system and the endocrine system. The pituitary is
located at the base of the brain and is the master gland of the endocrine system.
The pituitary gland controls hormones, which affect growth, sexual development,
metabolism and the system of reproduction. The hypothalamus is a tiny cluster of
brain cells above the pituitary gland, which transmits messages from the body to the
brain. Hypophyseal arteries supply blood to the pituitary gland, releasing different
hormones that affect bone growth and regulate activity in other glands. The pituitary
gland makes hormones to the needs of the body, which are then circulated in the
blood to different body tissues (10).
Synthroid is a form of Levothyroxine, which is a synthetically prepared levo
isomer of thyroxine, the major hormone gland is secreted from the thyroid gland.
Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood.
Thyroxine will then form into T3 which exerts a broad spectrum of stimulatory effects
on cell metabolism. It increases the metabolic rate of cells of the tissues including
bones and the brain (11).

Mechanisms of action (how it causes the effect)

Fig 3. Comparison between the molecule structure of Thyroid and Synthroid.

As mentioned above, Synthroid is intended to replace a hormone that is
normally produced by your thyroid gland, to treat hypothyroidismunderactive
thyroid gland. Synthroid is an orally administered T4, the absorption of
gastrointestinal tract ranges from 40% to 80%(11).
The hypothalamus in the brain produces thyrotropin-releasing hormone, which
acts on the pituitary gland, causing the pituitary gland to produce thyroid-stimulating
hormone. In people with normal thyroid function, the pituitary makes more TSH to
signal the thyroid to make more hormones, when the pituitary recognizes that enough
hormones have been made it stops it production to keep things in balance, however
for people with hypothyroidism, the thyroid does not make enough of thyroxine so the
pituitary responds like its supposed to make more TSH to the thyroid to make more
thyroxine, but fails to do so, the pituitary does not know when to stop making TSH
and causes there to be a high TSH level (12).
The way that Synthroid is transported to different parts of the body is through
the control of DNA transcription and the thyroid hormones receptors in the cytoplasm
and nucleus. Circulating thyroid hormones are greater than 99% bound to plasma
proteins, including thyroxin-binding globulin, thyroxin binding prealbumin, and
albumin, whose capacities and affinities vary for each hormone, which are also
attached to DNA. By attaching to these thyroid hormone proteins, it increases its
solubility (2). From Fig3, we can see the similarity between the molecular structure of
Synthroid and Thyroid. Synthroid will act as a substitute to the lack of thyroxine and
the TSH in the blood will stimulate the thyroid gland to produce thyroxine (T4),
which is not very active. Approximately 80% of the daily does of T4 is deiodinated at
a number of additional sites, including the kidney and in other tissues, to yield equal
amounts of T3 and reverse T3 (1)
The mechanisms by which thyroid hormones exert their physiologic actions
are not completely understood. The control of DNA transcription and protein
synthesis causes their effects. T3 and T4 diffuse into the cell nucleus and binds to
thyroid receptor proteins attached to the DNA.
This hormone nuclear receptor complex activates gene transcription and
synthesis of messenger of RNA and cytoplasmic proteins. (13). Thus by acting as a
replacement for natural thyroxine, symptoms of thyroxine deficiency are relieved.

Adverse effects
Not all doctors recommend Synthroid to patients unless necessary because in
some cases Synthroid worsen your condition as Synthetic T4 may compete with your
bodys natural T4 for cellular receptor sites. Moreover, Synthroid replaces T4, leaving
body to covert them to T3, so oftentimes, taking T4 alone will result in only partial
improvement.
Synthroid is a drug that is hard to prescribe and keep within the optimal
dosage range, taking too little will not help your hypothyroidism and taking too much
will lead to numerous side effects shown below.
Levothyroxine has a narrow therapeutic index. Regardless of the indication for
use, careful dosage titration is necessary to avoid the consequence of overdose or
deficiency of treatment (13). Common side effects include fever, hot flashes,
sensitivity to heat, headache, nervousness, nausea, insomnia, and transient hair loss.
Due to recent research, it was found that TSH suppression was associated with an
increased incidence of premature ventricular beat, an increased left ventricular mass
index and enhanced ventricular systolic function, which causes the above effects (11).
Since it affects hormonal changes, female experience menstrual changes, and
in some cases, maternal hypothyroidism may have an adverse effect on fetal and
childhood growth and development (1).
There are some side effects that are rather rare, but are severe including
pseudotumor cerebri, heart attack, angina, complete stoppage of the heart, abnormal
heart rhythm, chronic heart failure, seizures, fast heartbeat, trouble breathing and
mood changes.
Thyroid hormone is normally produced by ones thyroid gland to regulate the
bodys energy and metabolism, Synthroid is given when the thyroid does not produce
enough hormone on its own, however the main reason why Synthroid causes the side
effects mentioned above is because it speeds up ones metabolism (16). The change of
ones metabolism will cause different bodily reaction.
Conclusion
Synthroid is used to treat an underactive thyroid, and normal doses of it will
not work for weight loss, and large doses or it may cause serious, possibly fatal side
effects, especially with diet pills. It shouldnt be used to treat infertility unless it is
caused by low thyroid hormone levels. Dosage is based on your age, weight, medical
condition laboratory test results and response to treatment. Having enough thyroid
hormone is important for maintaining normal mental and physical activity, and for
children having enough thyroid hormone is important for normal mental and physical
development (3).

List of Reference
1. RxList The Internet Drug Index(2013). Drug Description: Synthroid
(levothyroxine sodium) Tablets, USP, from http://www.rxlist.com/synthroid-drug.htm
2. PubMed Health US National Library of MedicineThe Worlds Largest Medical
Library (June 7, 2013) Hypothyroidism
3. WebMD (2005-2013) Synthroid Oral http://www.webmd.com/drugs/drug-7033Synthroid+Oral.aspx?drugid=7033&drugname=Synthroid+Oral&pagenumber=6
4. Gardiner Harris 2002 Abbott Zealously Markets Synthroid, but Should It?
hsc.usc.edu/~hrkaslow/Teach/Supplementary%20Material/Synthroid/Synthroid-200207-17-WSJ.pdf
5. IMS Monthly Prescription Volume, December 7, 2012.
6. Green WL. New Questions Regarding Bioequivalence of Levothyroxine
Preparations: A Clinicians Response. Journal of the American Association of
Pharmaceutical Scientists. 2005 7:E54-E58. 09 Jul 2008.
7. She Knows Health and Fitness. (Jan 28, 2009) Infertility: Is your thyroid to blame? From
http://www.sheknows.com/health-and-wellness/articles/807574/infertility-is-your-thyroid-to-blame
8. American Thyroid Association. ATA Hypothyroidism Booklet. Falls Church, Va:
American Thyroid Association; 2003.
9.eHow Health. Natural Alternatives for Synthroid by Rebecca Walker
http://www.ehow.com/way_5376027_natural-alternatives-synthroid.html
10. InnerBody(2013) http://www.innerbody.com/image/endo01.html
11. Drugs.com Drug Information Online Data sources include Micromedex
(updated Sep 2nd, 2013), Cerner Multum (updated Sep 16th, 2013), Wolters
Kluwer (updated Sep 1st, 2013) from http://www.drugs.com/sfx/synthroid-sideeffects.html

12. Synthroid (2013) http://www.synthroid.com/hypothyroidism/tshtest.aspx

13. Uchino H, Kanai Y, Kim DK, Wempe MF, Chairoungdua A, Morimoto E, Anders
MW, Endou H: Transport of amino acid-related compounds mediated by L-type
amino acid transporter 1 (LAT1): insights into the mechanisms of substrate
recognition. Mol Pharmacol. 2002 Apr;61(4):729-37.
14. National institutes of Health, Health and Human Sercives (2012) Levothyroxine
sodium tablet http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=9565585129c8-428e-bc5d-f9ec831445d2
15. Mercola.Are Synthetic thyroid drugs like synthroid making your condition
worse(2011)http://articles.mercola.com/sites/articles/archive/2011/08/01/aresynthetic-thyroid-drugs-like-synthroid-actually-making-your-condition-worse.aspx
16. Physicians Desk Reference.
Synthroid(2013)http://www.pdrhealth.com/drugs/synthroid