6. Heartburn
a painful burning sensation in the chest and throat
along with a sour or bitter taste in the throat and
mouth
Symptoms are often worsened after heavy meals,
leaning forward, or lying flat
The feeling can last for a few minutes or a few hours.
10. WHAT IS GERD ???
A chronic condition in which the stomach
contents leak backwards from the stomach
into the esophagus.
This can irritate the esophagus and cause
heartburn and other symptoms.
This can leads to many chronic and acute
symptoms.
14. How does acid reflux occur?
When eating, food passes from the throat through
the esophagus and into the stomach.
A fibrous muscular ring in the lower esophagus
called lower esophageal sphincter (LES) prevents
the food from returning back to the esophagus.
LES become weak/ loosen in GERD patients
This allows digestive juices to leak back into the
esophagus which irritates the esophageal lining.
15. Prolonged Exposure May
Cause Esophagus to:
Become inflamed, with risk of having
esophagitis.
Become narrow
Develop an open sore (ulceration).
18. Factors that Weaken or Loosen
Esophageal Sphincter:
Smoking
Alcohol
Increased abdominal pressure caused by obesity or
pregnancy
A bulge in the stomach (hiatal hernia) that
protrudes above the diaphragm
Certain food (spicy, chocolate, peppermint,
caffeine).
Drug- drug interactions
21. Proton Pump Inhibitors
They are prodrug (inactive form) which is
neutrally charged (lipophilic) with pKa 4-5
They readily across stomach cell membranes
with acidic environments
It is protonated and rearranges into its active
form in acid
It covalently and irreversibly bind to the gastric
proton pump, deactivating the acid production
22. Example of PPIs
Omeprazole
Lansoprazole
Pantoprazole
Rabeprazole
Esomeprazole
Dexlansoprazole
Extended Release
Immediate Release
25. • Prodrug PPI is taken orally
and enters in stomach.
• Inactivated PPI is
protonated with presence
of H+ into activated form.
• Sulphenamide
intermediate (SN) is
formed which is very
reactive and readily to
bind covalently with
sulfhydryl groups (SH) in
proton pumps
• This binding inhibits acid
secretion by proton pump
– no exchange of H+ and
K+
26.
27. Pharmacokinetics of PPI - Omeprazole
Peak plasma levels: 0.5 – 3.0 hrs
Bioavailability: decreased by 50% with meal
taken.
Recommend take it 30 minutes before having
meal
Distribution: Protein binding Is 95%
Undergo rapid first pass metabolism
Elimination half life : 0.5 – 2.0 hrs
Duration of action : 24 hrs
28. Drug-drug Interactions
Hepatic CYP-mediated oxidative metabolism. Alter drug
metabolism by induction or inhibition of the cytochrome
P450 enzymes.
Gastric acid secretion decreased by PPIs can influence the
absorption of other.
Greater potential: Omeprazole, esomeprazole and
lansoprazole.
Lower potential: Pantoprazole.
34. Common Effects of PPs
1. Headache
2. Stomach Pain
3. Nausea
4. Diarrhea
5. Vomiting
6. Constipation
35. Long Term Effects of PPIs
Deficiency of Vitamin B12
Deficiency of iron
Decreased calcium absorption
Osteoporosis
Pneumonia
Clostridium difficile colitis
Hypomagnesemia
Acute Interstitial nephritis
36. Deficiency of Vitamin B12
VB12 is found in wide variety of animal foods
Keep body nerve & body cell healthy, aid in the
production of DNA, formation of RBC
Gastric acid secretion required for the body to
absorb VB12.
PPI reduce secretion of gastric acid, reduce
absorption of VB12.
Lack of VB12 causes weakness in body , anaemia
and loss of balance
38. Heme-iron directly absorb via heme transporter to
the duodenum
Non heme-iron convert from (Fe3+) to (Fe2+) for
absorption into duodenum
Conversion happen in acidic environment
Gastric acid enhance the solubility and prevent
precipitation of insoluble Fe3+
PPI drug increase the pH of stomach
Resulting gastric environment to be more alkaline
39. In alkaline environment, promotes the oxidation of
(Fe2+) to (Fe3+)
When pass through the duodenum, iron will not be
absorb
Precipitation of ferric iron happens
Lack of iron causes fatigue, dizziness, lowered
immunity and anaemia
40. Associated with hypomagnesaemia
Abnormally low level of magnesium in blood
Due to PPI affects the gastrointestinal
absorption of magnesium
Increased Ach release (PNS)
May cause cardiac complications,
arrhythmias
Associated with hypocalcaemia
41. Increased the risk of C. difficile
A type of infection in the colon
caused by Clostridium difficile
bacteria
Produce toxins that damage the
lining of colon
42. Increased risk of having AIN
Acute Interstitial Nephritis
Kidney tubules become swollen (inflamed) that occur
suddenly for a temporary period.
Mostly occurred during drug-drug interaction, i.e. with
antibiotics (penicillin) that leads to AIN or long term
used PPI
43. Current Research
“Common Heartburn Drugs Linked to Kidney Disease in Study: MedlinePlus.” Accessed May 29, 2016.
https://www.nlm.nih.gov/medlineplus/news/fullstory_158313.html.
47. Antireflux Surgery
Hiatal Hernia problem
Tightening the opening
in diaphragm to keep
stomach
Wrap the upper part of
stomach with stitches.
The stitches helps prevent
stomach acid and food from
flowing back into the esophagus.
48.
49. Is the PPIs the best treatment?
PPIs really worked in treatment of GERD, but many
people have trouble discontinuing because the amount
of acid in their digestive system surges when they stop
taking the drug.
Clinicians, pharmacists and patients have to weight
the benefits against the potential side effects.
Future studies will help to better inform these
decisions.
51. 1. What is the real causes of gastroesophageal reflux disease (GERD) ?
(i) Heartburn
(ii) Histal Hernia
(iii) Weak Lower Esophageal Sphincter (LES)
(iv) Too less acid
A. I , ii, iii
B. I . Iii .iv
C. Ii , iii , iv
D. All of above
52. 2. What is the correct sequences of mechanism action of PPIs ?
P – Sulfoxide group in PPI is converted into activated form
of sulfonamide intermediate
Q –PPI which is prodrug are activated by acid in stomach
R –Enzyme-inhibitor complex is formed by binding to sulfhydryl
residue in proton pump
S – Their inhibition effect on acid secretion is exerted
A. P,Q,R,S
B. Q,P,R,S
C. S,P,R,Q
D. Q,R,S,P
53. 3. Which one of the following are the latest
medication on treating GERD ?
(i) GABAB receptor agonists
(ii) Cannabinoid receptor agonists
(iii) Potassium-competitive acid blockers
(iv) CCK (cholecytokinin) antagonists
A. I, ii, iii
B. ii, iii, iv
C. I, iii, iv
D. All of above
54. 4. Which one of the following is the common side effect of
having PPIs for long term use?
(I) hypomagnesaemia
(II) Acute Interstitial Nepritis
(III) Deficiency of Vitamin B12
(IV) Dementia
A. I, II, III
B. I,III,IV
C. II, III, IV
D. All of above
Editor's Notes
When you eat, food passes from the throat to the stomach through the esophagus. A ring of muscle fibers in the lower esophagus prevents swallowed food from moving back up. These muscle fibers are called the lower esophageal sphincter (LES).
When this ring of muscle does not close all the way, stomach contents can leak back into the esophagus. This is called reflux or gastroesophageal reflux. Reflux may cause symptoms. Harsh stomach acids can also damage the lining of the esophagus.
SH group also knowns as cysteine residue
S=O sulfoxide group
The study is in JAMA Neurology
Chronic or acute condition, specific and monitoring in drug usage is recommending.
patients who require a PPI for appropriate indications, at the lowest dose, and for the shortest time possible care
1-For complicated acid-peptic disease, dose
reduction or cessation of PPI therapy may not
be possible.
2-If the PPI was prescribed only for symptom
relief, as in cases of dyspepsia or no erosive
gastroesophageal reflux disease, reduce the
dose of PPI to as low as possible to maintain
symptom control.
Several directions in drug development have been pursued in patients who failed PPI treatment. These include more early and profound acid suppression, reduction in the rate of TLESRs, improving esophageal and/or gastric motility, attenuation of esophageal pain and mucosal coating of the esophagus.
