ANTI-ULCER AGENTS:

ANTACIDS

UY1/FMSB/Pharmacology/L3

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 Learning objectives
• Classify anti-ulcer drugs

• Describe the mechanism of action of antacid medications.

• Site the differences in onset and duration of action of various antacid preparations.
• Describe the absorption and systemic actions of various antacid preparations
• List the primary indications of antacids
• Elaborate drug-drug interactions of AA

• Classify cyto-protective drugs for anti-ulcer therapy

• Describe the pharmacological effect of the cyto-protective drugs

• Classify proton pump inhibitors

• Explain the molecular mechanism of proton pump inhibitors
• List drug-drug interactions of proton pump inhibitors
• List specific indications of proton pump inhibitors

• Explain the molecular mechanism of action H2 receptor antagonists

• Describe the primary indication of H2 receptor antagonists
• List drug-drug interactions of H2 receptor antagonists including mechanism

• Describe the use of triple and quadruple therapy regimens used for H. pylori eradication

• Compare the pharmacology of PPI and anti-H2 2

 Antacids
• Mechanism of anti-ulcer effects
– Effects due to chemical action not biological
action
• Directly neutralize stomach acid.
• Best antacids by far are the mixtures of Mg(OH)2
and Al(OH)3
– Topaal®, Maalox®
• Sometimes contain Ca2+ salts are used
• Occasionally bicarbonate is used as the anion.

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 Antacids Physiological effects
• Natural regulatory effects following antacid
administration
– Decreased pepsin activation as pH increases
– Increased acid secretion (Rebound) as pH
increases
– The acid secretion can continue for awhile even
after pH falls to normal level

• Rebound of little consequence with Mg2+ and

Al3+ salts

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Antacids Physiological effects….
• Rebound
– Can be long lasting and large with Ca2+ salts
– Long term use of high Ca2+ antacids
• Increased serum Ca2+, phosphate and other electrolyte
disturbances
• High Na in some antacids may cause
electrolyte disturbances
• Neither Ca2+ nor Na containing antacids are
recommended in treatment of gastric injury

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 Antacids Pharmacokinetics

• Mg2+ salts are rapidly acting

– Fully reacted before clearing from the stomach
• Al3+ salts are slower in neutralizing acids
– May clear from stomach before significant
neutralization occurs
– Food slows stomach emptying and therefore
prolongs action of Al(OH)3 containing agents
• Combinations of Mg2+ and Al3+ containing
antacids reside longer in the stomach
– Provides a rapid and a long-acting component to
acid neutralization

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 Antacids Dosing
• Antacids must be given several times per day
– Best dosing schedule is probably about 1 and 3 hours
after mealtimes and at bedtime
• Gastric acidity has major effects on drug
dissolution in stomach and on absorption
– Decreased acidity alters absorption rate and possibly
bioavailability even in small intestine

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 Antacids: Clinical utility
• Use of antacids in a ulcer therapy
– Not first choice, but a useful adjunct
– Not as effective as H2 blockers and H,K-
ATPase inhibitors
– Not as good for maintenance because they
provide only transient acid neutralization and
no nocturnal protection

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 Antacids Therapeutic utility
• Liquid better than tablets
– May have to take several high-strength tablets
to get an effective dose

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 Antacids Adverse effects
• Al3+ binds and precipitates phosphate and
fluoride
– Prevents absorption
– Chronic use can cause phosphate deficiency
• Laxative effect and bowel movement
– Mg2+ promotes loose stools and in sufficient
dosage, diarrhea
– Al3+ promotes constipation
– So combination cancels out
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 Properties of ideal antacid
• An ideal antacid
– effectively neutralizes large volumes of acid
– has prolonged action
– doesn’t interfere with digestion and absorption
of drugs
– doesn’t interfere with acid-base balance
– is palatable (appetizing)
– inexpensive for long-term use

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END

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