HEALING ULCERS

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HEALING ULCERS
Liquorice extract (licorice) for gt 2000 years in
China .... helps ulcers heal
Prostaglandins are natural hormones that help
heal holes in the stomach wall, but an enzyme
(15-hydroxyprosta-glandin dehydrogenase) stops
the prostaglandins from working. Licorice
blocks this enzyme, and so the prostaglandins
stick around longer, make ulcers heal.
HOWEVER chemistry always has a price, licorice
causes cortisol to bind to a protein causing
sodium to be retained, increases BP, water
retention, () head aches, lethargy,....
() Addisons disease is caused by a deficiency
of cortisol, so liquorice helps that
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The active ingredient was found in 1960 (a
triterpenoid derived from glycyrrhizic acid)
and was sold as CARBENOXOLONE the market leader
for ulcer treatment for 10 yrs, but had the
side effects above.
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BISMUTH COMPOUNDS (1786 on) PEPTOBISMOL today
1920's surge in use because also a syphilis
treatment Use rebounded in 1980's Peptic ulcer
patients have larger than normal amounts of
BACTERIUM Helicobacter pylori (H. pylori),
especially type O blood, where bacterium links to
stomach wall via a sugar.
Bismuth salts() inhibit this linking, and so
with Amoxicillin (a penicillin) which kills the
bacteria, have been used to treat ulcers since
about 1990.
()Bismuth salicylate, carbonate or basic nitrate.
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THE ANTI-HISTAMINES In late 60's found that
HISTAMINE is a signaling compound, which causes
release of stomach acid.
an AMINE
In 1972, the receptor (H-2), was recognized
different from the H-1 receptor that causes
allergies. Eating, stress,.... causes histamine
to be released, which on triggering the H-2
receptor starts acid secretion.
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RECEPTORs are like LOCKS, if an appropriate KEY
(CHEMICAL) is inserted, the LOCK will OPEN (the
RECEPTOR will TURN ON) AGONIST chemical that
binds to a receptor and turns it on (a key that
goes in the lock and turns) ANTAGONIST chemical
that binds the receptor but does not turn it on
(like a key that fits but jams the lock)
Thus an H-2 receptor ANTAGONIST was needed which
would bind to the receptor stronger than
histamine itself, but not promote the release,
i.e. block the receptor an AGONIST binds and
promotes the effect
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H-2 receptor ANTAGONIST
SMITH-KLINE-FRENCH launched TAGAMET (chemical
name cimetidine) in Nov 1976
fits lock and blocks it
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By 1983 Tagamet world-wide sales were 1B (7000
ulcer related deaths in US in 1982) Heals ca.
70-80 ulcers in 4 weeks requires 3 doses per
day of 150-300 mg LD50 mice (rats) 2.6 (5) g/kg
orally (lethal dose to kill 50 of population)
essentially non-toxic cf. aspirin 0.4
g/kg in people Generic cimetidine available in
90s and now as an OTC over-the-counter drug,
usually in lower doses, eg. 100mg Tagamet-HB
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An improvement was ZANTAC (ranitidine) 150mg
twice per day
and then PEPCID-AC and MAALOX-H2 (famitidine)
OTC drugs now in 75mg or 100 mg doses
Few side effects mild diarrhea, skin rash
4 to 9x more effective than cimetidine
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Also in Canada Nizatidine (2006)
Need to find out more about a drug?
The CPS (Canadian Compendium of
Pharmaceuticals and Specialties) 2005 version in
ELL 305 especially good on approved usages,
doses, side effects eg. Nizatidine is on page 162
The MERCK Index 13th Ed. in ELL 305 good for
a quick overview of almost all chemicals eg.
Nizatidine is on page 1192 updates thru
http//www.pharmacists.ca/content/hcp/tools/drugne
ws/drugs.asp?SrchALL
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Using the Merck Index
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TURNING OFF THE ACID PUMP Histamine is one of
the signals that starts acid secretion, however
acid is not stored but generated by passage of
protons across a membrane (H one way, K the
other). This is caused by an ATP-ase enzyme
blocking this enzyme, reduces the amount of acid
pumped ASTRA ZENECA were the first to patent
Omeprazole for this purpose, and in 1989 launched
as PRILOSEC (USA), LOSEC (Canada)
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PRILOSEC (USA), LOSEC (Canada)
Advantage One 20 mg pill per day self limiting
- does not stop acid, reduces it STOPS acid
reflux into esophagus (Zollinger-Ellison
syndrome), very low (4g/kg) toxicity, few side
effects. Disadvantage 2 per pill
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By 2001, (PRI)LOSEC was THE 2 DRUG overall, with
sales of 6.1B but it has now dropped out of the
top 10 due to competition from generics eg.
apo-omeprazole in Canada (2003)(APOApotex) And
from NEXIUM (Mg salt of the S-enantiomer) The
Purple Pill has captured gt40 of US market
thanks to heavy advertising (this does protect
AZs patents!). 2008 Nexium 7.7B (No. 3
prescribed drug in US)
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Several new prazoles are now on the
market PREVACID lansoprazole PEPTAZOL /
PROTIUM pantoprazole PARIET / ACIPHEX
rabeprazole
Starting June 2003 BC Pharmacare changed
coverage of PPI (proton pump inhibitors) for GERD
(gastroesophageal reflux disease) LOSEC had to be
approved by Pharmacare once per year forced to
try PARIET ACIPHEX(USA) rabeprazole, (Japan)
is 40 cheaper than LOSEC but approval waived