This document summarizes the synthesis of thyroid hormone and proton pump inhibitors. It discusses how proton pump inhibitors work by blocking the H+/K ATPase in parietal cells through irreversible inhibition. It also outlines the transport and effects of thyroid hormones, including how thyroid function is tested. Key points covered include the mechanisms of action, pharmacokinetics, medical uses and comparative analysis of pantoprazole with other proton pump inhibitors. References are provided at the end.

1. Synthesis of thyroid hormone & proton pump inhibitors
.

2. Hamdard university Bangladesh
Md omar faruk
BUMS
4TH BARTCH
Id: 934170032
Mobile: 01685990112
01881667925

3. Proton-Pump Inhibitor
They are prodrugs
that activate in acid
environment.
After absorption, the
active metabolite
diffuses into the
parietal cells and
accumulates in the
acidic secretory
canaliculi.

4. Clinically Used PPIs
Omeprazole
Lansoprazole
EsomeprazolePantoprazole
Rabeprazole

5. Mechanism
Of Action

6. Blocking the H+/K ATPase
The consumption of food
stimulates acid secretion
and acid secretion
activates PPIs.
Then activated PPI is converted to a
sulfenamide in the acidic secretory
canaliculi of the parietal cell.
The sulfenamide interacts covalently
with sulfhydryl groups in the proton
pump and make complex, thereby
irreversibly inhibiting its activity.

7. Pharmacokinetics
 The rate of PPIs absorption is decreased by
concomitant food intake.
 The elimination half-life of PPIs ranges from 0.5 to
2.0 hr, but the effect of a single dose on acid secretion
usually persists up to three days.
 Since an acidic pH in the parietal cell acid canaliculi is
required for drug activation, and since food stimulates
acid production, these drugs ideally should be given
about 30 minutes before meals.
 Chronic renal failure does not lead to drug
accumulation with once-a-day dosing of the proton pump
inhibitors. Hepatic disease substantially reduces the
clearance of esomeprazole and lansoprazole.

8. Adverse effects

9. Medical Uses
• Dyspepsia
• Peptic ulcer disease
• Gastro oesophageal reflux disease (GERD)
• Laryngopharyngeal reflux
• Stress gastritis prevention
• Zollinger-Ellison syndrome (often 2-3x the regular dose
is required as compared to the other indications)

10. Comparative
Analysis Of
Pantoprazole
With Other PPIs

11. Reference
q The Health Strategies Consultancy
LLC (March 2005). "Follow The Pill:
Understanding the U.S. Commercial
Pharmaceutical Supply Chain". The
Kaiser Family Foundation.
sacs, G.; Shin, J. M.; Howden, C.W.
(2006). "Review article: The clinical
pharmacology of proton pump
inhibitors". Alimentary Pharmacology
and Therapeutics 23: 2–8.
doi:10.1111/j.1365-2036.2006.02943.x.
PMID 16700898.
Zajac, P; Holbrook, A; Super, ME; Vogt,
M (March–April 2013). "An overview:
Current clinical guidelines for the
evaluation, diagnosis, treatment, and
management of dyspepsia".
Osteopathic Family Physician 5 (2):
79–85. doi:10.1016/j.osfp.2012.10.005.
five Things Physicians and Patients
Should Question". American
Gastroenterological Association.

12. Thyroid Hormone
• Secreted by the
thyroid gland
• Gland secret
major hormone;
– Thyroxine (T4)
–
Triiodothyronine
(T3)
• Controlled by the
primarily TSH (Thyroid
stimulating hormone)
secreted by the ant
Pituitary gland.
• Gland also
secrete calcitonin
(imp hormone in
calcium
metabolism).

13. Transport of thyroid hormone
 • Both T3 & T4 are bound to plasma proteins – Thyroxine binding globin
(TBG) – Transthyretin (TTR – formerly known as Thyroxine binding
prealbumin [TBPA]) – Albumin
 • T4 is secreted 20fold excess over T3.
 • TBG carry 80% of bound hormone (T4>T3), 10% by albumin, 10% TTR
 • Approximately – 99.98% T4 bound – 99.7% T3 bound
 • fT4 is higher conc than fT3.
 • Unbound hormone is available for the biologically action/activity.

14. Iodine metabolism
• Iodine is required
for the formation
of thyroid (150-
200μg/day) (sr 5-
10 μg/dL)
• About 80% is
stored in Thyroid
gland.
• Ingredients which
prevent the
utilization of Iodine
are called as
Goitrogens.

15. Effect of Thyroid Hormones& Thyroid Disorders

16. Thyroid Function test
• Assay of Hormone – T3,
T4, TSH, FT4, FT3,rT3, Anti-
TPO, Anti-Tag – Assay by
ELISA/CLIA/ECLIA – Normal
reference interval
• T3 – 0.8-
2.0ng/ml
• T4 – 5.1-
14.1μg/dl
• fT4 – 0.93-
1.7ng/dl
• fT3 - 3.5-
7.8pmol/L
• TSH – 0.27-
4.1μIU/ml
• Anti-TPO -
<34.0IU/ml

17. Reference
– Vasudevan-Textbook of Biochemistry
– Harper’s-Illustrated Biochemistry
– Gayton-Human Physiology
– KD Tripathi- Essential of medical Pharmacology
– Internet sources