Nico L Lumbuun, dr.

, SpFK
Faculty of Medicine
UPH

Case
A 22 yo medical student, noted a burning pain in his
upper abdomen since 2 weeks ago. This sensation
occurs 1 to 2 hrs after eating. He is actually in a good
health before, although he smokes approximately 2
packs of cigs & drink 5 cups of coffee a day. He is
currently under stress because of his bachelor exam.
He also been taking 1-2 tabs aspirin daily for the past
2 months because of headache.
The pain frequently awakens him at midnight. His
pain usually relieved by eating and by taking antacid.
What is the most likely problem?
What is the most appropriate treatment?

Anatomy

Meaning of numbers
1. Body of stomach
2. Fundus
3. Anterior wall
4. Greater curvature
5. Lesser curvature
6. Cardia
9. Pyloric sphincter
10. Pyloric antrum
11. Pyloric canal
12. Angular notch
13. Gastric Canal
14. Rugal folds

PGE2

Histamine

ACh
M3

Ranitidine
Gastrin
_
Proglumide
_

Misoprostol

PGE
receptor

Adenyl
cyclase

ATP

Ca++
+

H2

cAMP

Gastrin
receptor

Ca++
+

Protein Kinase
(Activated)
+
+
K
K + H

_
Omeprazole

Proton pump

Gastric acid

Parietal cell
Lumen of stomach

Antacid

Antacids
Weak bases that react with gastric hydrochloric acid

to form a salt and water.

Principal mechanism of action is :

reduction of intragastric acidity.

Acid-neutralization capacity among different
proprietary formulations highly variable, depend on:
rate of dissolution (tablet versus liquid)
water solubility
rate of reaction with acid
rate of gastric emptying.

Antacids cont

Sodium bicarbonate (NaHCO3) reacts rapidly with HCl.

NaHCO3 + HCl CO2 + NaCl + H2O pH gastric .
Formation of CO2 results in gastric distention & belching.
NaCl absorption may exacerbate fluid retention in patients with
heart failure, hypertension, and renal insufficiency.
Unreacted alkali (NaHCO3) is readily absorbed
potentially causing metabolic alkalosis when given in high
doses or to patients with renal insufficiency.
Calcium carbonate (CaCOOH) less soluble, reacts slowly.
CaCOOH + HCL CO2 + CaCl2 + H2O
Also may cause belching or metabolic alkalosis.
Other indications : bone mineralization.
Excessive doses + calcium-containing dairy products can lead
to hypercalcemia, renal insufficiency, and metabolic alkalosis
(milk-alkali syndrome)

Antacids cont
Present

day antacids :
Aluminium Hydroxide
Magnesium Hydroxide
React slowly with HCl magnesium chloride
or aluminum chloride and water.
No gas is generated, belching does not occur.
Metabolic alkalosis is also uncommon
because of the efficiency of the
neutralization reaction.

OTC drug for symptomatic rapid relief of dyspepsia

Antacids cont
Duration of action :
30 min when taken in empty stomach
2 hrs when taken after a meal
Side effects :
Al3+ antacids constipation (As they relax gastric smooth

muscle & delay gastric emptying)

Mg2+ antacids Osmotic diarrhoea .

Both magnesium and aluminum are absorbed and

excreted by the kidneys. Hence, patients with renal

insufficiency should not take these agents long-term.
In renal failure Al3+ antacid Aluminium toxicity &
Encephalopathy

Antacids Common additives

Simethicone Decrease surface tension,

reduce bubble formation

Added to prevent reflux .
Alginates

is a viscous gum that is abundant in the cell walls of

brown algae.

on

Form a layer of foam/gel

top of gastric contents &

reduce reflux
Oxethazaine Surface anaesthetic

(Strocain)

Antacid - Interactions
Adsorb drugs (binding the drug) and form insoluble

complexes that are not absorbed

(ex.tetracycline, quinolone)

Increasing intragastric pH so that the drug's

dissolution or solubility (especially weakly basic or

acidic drugs) is altered.(ketocanazole, iron)

Clinical importance :
Interactions can be avoided by taking antacids
2 hrs before or after ingestion of other drugs .

Is it rational to combine aluminium hydroxide

and magnesium hydroxide in antacid
preparations ?

Combination provides a relatively fast and

sustained neutralising capacity .

(Magnesium Hydroxide Rapidly acting
Aluminium Hydroxide - Slowly acting )
Combination preserves normal bowel function.

(Aluminium Hydroxide constipation

Magnesium hydroxide diarrhoea )

Histamine H2 Receptor
Antagonist
Reversible competitive inhibitors of H2 receptor
Highly selective, No action on H1 or H3 receptors
Very effective in inhibiting nocturnal acid

secretion ( as it depends largely on Histamine )

Modest impact on meal stimulated acid
secretion (As it depends on gastrin, acetyl choline and
histamine)

Cimetidine

Bioavailability

80

Relative Potency 1
Half life (hrs) 1.5 - 2.3
Duration of

Ranitidine

50
5 -10
1.6 - 2.4

1
400

Famotidine

40
32
2.5 - 4

Nizatidine

>90
5 -10
1.1 -1.6

12

0.1

150

20

150

action (hrs)
Inhibition of
CYP 450
Dose mg(bd)

H2 BlockersSide effects & Interactions

Extremely safe drugs
Cimetidine causes gynecomastia,

galactorrhea (as it is antiandrogenic & increases

prolactin level)
Cimetidine inhibits CYP450 (specifically CYP1A2,

& increases
conc. of Warfarin, Theophylline, Phenytoin,
Ethanol.
CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4)

Proton Pump Inhibitors

Most effective drugs in antiulcer therapy
Irreversible inhibitor of H+ K+ ATPase
Prodrugs requiring activation in acid environment
Lipophilic , weakly basic drugs & so accumulate

in canaliculi of parietal cell

Activated in canaliculi & binds covalently to

extracellular domain of H+ K+ ATPase

Acid secretion resumes only after synthesis of

new molecules

Proton Pump Inhibitors

Omeprazole

20 mg o.d. (Once Daily)

Esomeprazole

20 - 40 mg o.d.

Lansoprazole

30 mg o.d.

Pantoprazole

40 mg o.d.

Rabeprazole

20 mg o.d.

Proton Pump Inhibitors Kinetics

PPI are administered as inactive prodrugs.
To protect the acid-labile prodrug from rapid
destruction within the gastric lumen, oral products
are formulated for delayed release as acidresistant, enteric-coated tablet or capsule
formulations.
Esomeprazole, lansoprazole, and pantoprazole

also given intravenously

Half life 1.5 hrs
Since it requires acid for activation - given 1 hr

before meals
Other acid suppressing agents not coadministered

P.P.I. Side effects & Interactions

Extremely safe drugs
Causes hypergastrinemia which leads to

carcinod tumor (ECL cell hyperplasia) in rats,

but no evidence of such tumors in man
Inhibit CYP 450 & hence metabolism of

warfarin, phenytoin, etc

Pantoprazole & Rabeprazole have no significant

interactions

A patient comes to your clinic at midnight

complaining of heart burn. You want to relieve his
pain immediately. What drug will you choose?

Answer :
Antacids
Explanation :
Antacids neutralise the already secreted
acid in the stomach. All other drugs act by
stopping acid secretion and so may not relieve
symptoms at least for 45 min.

Mucosal Protective Agents

Sucralfate
Misoprostol
Colloidal Bismuth compounds

Sucralfate
Salt of sucrose complexed to sulfated aluminium

hydroxide
In acidic pH polymerizes to viscous gel that

adheres to ulcer crater & stimulates mucosal

prostaglandin
Taken on empty stomach 1 hr. before meals
Concurrent antacids, H2 antagonist avoided

( as it needs acid for activation )

Misoprostol
PGE analogue
Modest acid inhibition Stimulate mucus &

bicarbonate secretion
Enhance mucusal blood flow
Approved for prevention of NSAID induced ulcer
Side effect : Diarrhoea & cramping abd. pain 20 %
Not so popular as P.P.I are more effective & better

tolerated

Colloidal Bismuth Compounds

Coats ulcer, stimulates mucus & bicarbonate

secretion
Direct antimicrobial activity against H.pylori
May cause blackening of stools & tongue
Not used for long periods bismuth toxicity

Available compounds :
Bismuth subsalicylate in USA (IndScantoma )
Bismuth subcitrate in Europe
Bismuth dinitrate

A pregnant lady (first trimester) comes to you with

peptic ulcer disease. Which drug will you
prescribe for her ?

Answer :
Antacids or Sucralfate

Explanation ;
H2 antagonists cross placenta and are also
secreted in breast milk. Safety of Proton pump
inhibitors not established in pregnancy.
Misoprostol causes abortion .

Eradication of
H.pylori

Triple Therapy
The BEST among all the Triple therapy regimen is

Omeprazole / Lansoprazole

- 20 / 30 mg bd

Clarithromycin

- 500 mg bd

Amoxycillin / Metronidazole

- 1gm / 500 mg bd

Given for 14 days followed by P.P.I for 4 6 weeks

Short regimens for 7 10 days not very effective??
Newest 7 days

Triple Therapy cont

Some other Triple Therapy Regimens are
Bismuth subsalicylate 2 tab qid

Metronidazole

- 250 mg qid

Tetracycline

- 500 mg qid

Ranitidine /Bismuth citrate

Tetracycline

- 400 mg bd
- 500 mg bd

Clarithromycin / Metronidazole - 500 mg bd

Quadruple Therapy
Given when Triple Therapy fails
Omeprazole / Lansoprazole - 20 / 30 mg bd

Bismuth subsalycilate

- 2 tabs qid

Metronidazole

- 250 mg qid

Tetracycline

- 500 mg qid

Drugs causing peptic ulcer

Non Steroidal Anti Inflammatory Drugs (NSAIDs)
Glucocorticoids
Cytotoxic agents
Stress induced ulceration after head trauma (ICP)

= Cushings ulcer
Stress induced ulceration after severe burns

= Curlings ulcer

Antiemetics

Pathophysiology of Emesis
Cancer chemotherapy
Opioids

Chemoreceptor
Trigger Zone
(CTZ)
Dopamine D2,
5 HT3,Opioid
Receptors

Cerebral cortex
Smell
Sight
Thought

Anticipatory emesis

Vomiting Centre
(medulla)
Muscarinic, 5 HT3 &
Histaminic H1

Motion
sickness

Chemo & radio therapy

Gastroenteritis

Pharynx & GIT

5 HT3 receptors

Vestibular
nuclei

Muscarinic
Histaminic H1

Now answer this question

Which group of drugs can be used as antiemetics ?

Serotonin 5 HT3 Antagonists

Dopamine D2 Antagonist
Anticholinergics
H1 Antihistaminics
Cannabinoids

Serotonin 5 HT3 Antagonist

Potent antiemetics
Even though 5 HT3 receptors are present in

vomiting centre & CTZ, the antiemetic action is

restricted to emesis caused by vagal stimulation.
High first pass metabolism
Excreted by liver & kidney
No dose reduction in renal insufficiency but needed

in hepatic insufficiency
Given once or twice daily orally or intravenously.

Drugs Available
Ondansetron

32 mg / day

Granisetron

10 g / kg / day

Dolasetron

1.8 mg / kg / day

Indications
Chemotherapy induced nausea & vomiting given

30 min. before chemotherapy.

Postoperative & postradiation nausea & vomiting

Adverse Effects
Excellent safety profile
Headache & constipation
All three drugs cause prolongation of QT interval,

but more pronounced with dolasetron.

Dopamine D2 Antagonist
Antagonise D2 receptors in CTZ.
Drugs available

Metoclopramide

10 mg tid

Domperidone

10 mg tid

Both drugs are also prokinetic agents due to their 5

HT4 agonist activity.

Domperidone oral ; Metoclopramide oral & i.v
Metoclopramide crosses BBB but domperidone

cannot.

Now answer this question

Which is a better antiemetic Metoclopramide or
Domperidone ?
As CTZ is outside BBB both have antiemetic

effects.
But as metoclopramide crosses BBB it has

adverse effects like extrapyramidal side effects.

Domperidone is well tolerated.

Phenothiazines & Butyrophenones

Phenothiazines

Prochlorperazine
Promethazine
Phenothiazines are antipsychotics with potent

antiemetic property due to D2 antagonism.

Butyrophenone

Droperidol
Droperidol used for post-op. nausea & vomiting,

but cause QT prolongation.

H1 Antihistaminics
Most effective drugs for motion sickness
Drugs available

Betahistine
Meclizine
Cyclizine
Dimenhydrinate
Diphenydramine
Promethazine Used in pregnancy,
used by NASA for space motion sickness

Anticholinergics
Scopolamine (hyoscine) used as oral or

transdermal patch for motion sickness

Cannabinoids
Dronabinol used as adjuvant in chemotherapy

induced vomiting.It is a psychoactive substance

Nabilone

Now answer this question

A physician prescribed Tab.Ondansetron

for prophylaxis of motion sickness. Even

though ondansetron is a potent antiemetic
it didnt produce any effect in this patient.
Can you explain why ?

Explanation :

Vestibular nuclei has only

muscarinic and H1 histaminic receptors.

GERD (Gastroesophageal Reflux

Disease)
Chronic

symptoms or mucosal damage produced

by the abnormal reflux in the esophagus due to
incompetence of the lower esophageal sphincter
(LES), transient LES relaxation, impaired
expulsion of gastric reflux from the esophagus, or
a hiatal hernia
Symptom :Heartburn,
cough, hoarseness, voice
:
changes, chronic ear ache, burning chest pains,
nausea & vommiting

GERD (Gastroesophageal Reflux

Disease)

Principle Management :
lifestyle modifications
weight loss and elevating the head of the bed
avoiding eating two hours before bed
Certain foods & lifestyle are considered to promote reflux:

Coffee, alcohol, and excessive amounts of Vitamin C supplements

stimulate gastric acid secretion. Taking these before bedtime
especially can cause evening reflux
Foods high in fats and smoking reduce lower esophageal sphincter
competence, so avoiding these tends to help. Fat also delays
stomach emptying
Large meals
Carbonated soft drinks (regular or diet).
Chocolate and peppermint
Acidic foods, such as oranges and tomatoes
Cruciferous vegetables: onions, cabbage, cauliflower, broccoli,
spinach, brussels sprouts
Milk and milk-based products contain calcium and fat, and should
be avoided before bedtime.

GERD (Gastroesophageal Reflux

Disease)
Drug treatment
Proton pump inhibitors are the most effective in reducing gastric
acid secretion. These drugs stop acid secretion at the source of
acid production.
Antacids before meals or symptomatically after symptoms begin
can reduce gastric acidity (increase pH).
Alginic acid may coat the mucosa as well as increase pH and
decrease reflux.
Gastric H2 receptor blockers can reduce gastric secretion of acid.
They relieve complaints in about 50% of all GERD patients.
Prokinetics strengthen the LES and speed up gastric emptying.
Sucralfate is also useful as an adjunct in helping to heal and
prevent esophageal damage caused by GERD, however it must be
taken several times daily and at least 1-2 hours apart from meals
and medications.