CHAPT.
V
GASTROINTESTINAL AGENTS
Inorganic agents used to treat gastro-intestinal tract disorders:
1. ANTACIDS - Products for altering gastric
2. PROTECTIVES – for intestinal inflammation
3. ADSORBENTS – for intestinal toxins
4. CATHARTICS or LAXATIVES – for constipation
Antacids, protectives, adsorbents – no Rx required
- Responsibility of the pharmacist:
Should know the uses & limitations of these products & all other products
Should be ready to advise his customers
ANTACIDS
NaHCO3
Al(OH)3
Ca containing antacids – Precipitated CaCO 3
Tribasic Ca3(PO4)2
Mg containing antacids – MgCO3 MgO Mg3(PO4)2
Mg(OH)2 Mg trisilicate
ANTACIDS
- Alkali bases used to neutralize the excess HCl which may be causing pain and possible ulceration
- Inactivate the proteolytic enzyme – pepsin
Stomach pH ranges from 1 – 7
- Low acid pH is due to presence of endogenous HCl
For hyperacidity
- Result can range from gastritis (inflammation of gastric mucosa)
To peptic ulcer (circumscribed erosion)
Esophageal ulcer occurs when the esophageal sphincter is defective
- Patients with this condition will frequently suffer from ”heartburn”
People obtain relief from sleeping on a bed elevated at the head to reduce the flow of gastric fluid from
the stomach into the esophagus
There is correlation between the emotions of the individual and peptic ulcer
Tense individual
- Tends to have greater incidence of peptic ulcer than a person who can “release” his tension
Criteria in choosing the appropriate antacid (there is no ideal antacid)
1. It should not be absorbable or cause systemic alkalosis
2. It should not be a laxative or cause constipation
3. Should not exert the effect rapidly and over a long period of time
4. With gastric HCl it should not cause a large evolution of gas
5. Should buffer in the pH 4 – 6 range
6. Should inhibit pepsin
NaHCO3
- One of the electrolyts in acid-base therapy
- Can cause belching and flatulence because of the evolution of CO 2 in the presence of acids
- Found in many effervescent antacid preparations
- Rather used as antacid:
Main function is to react with an acid (citric, tartaric, etc.) with the evolution of CO 2
- Result is a “sparkling flavour
Al(OH)3 (Al containing antacids – constipating effect)
Recognized 2 physical forms by USP:
1. Al(OH)3 gel USP XX
- With pH 5.8-8.0
- Permitted to contain: aromatics like peppermint oil
Sweetening substances (sucrose, glycerine, saccharin or other similar
substances)
0.5% preservative (Na benzoate, benzoic acid, methyl paraben, etc.)
- ideal buffer in the pH 3.5 due to amphoteric character
- problem or disadvantage: loss of antacid properties on aging
2. Dried Al(OH)3 Gel USP
- Also official as Dried Al(OH)3 Gel and Tablets USP
- Both forms are assayed in terms of the Al2O3 content and acid-consuming capacity
AlCl3 (H2O soluble astringent salt)
- Product of the reaction with HCl & Al(OH)3 gel can cause constipation, nausea, vomiting
USES:
Al(OH)3 Gel – gastric antacid
- For the treatment of hyperchlorhydria and peptic ulcer
- For intestinal toxaemia
- Mechanism of action: attributed to its capability of adsorbing HCl, toxins, gases & bacteria
Advantage of the gel – adsorbs pepsin
Ca containing antacids (constipative effect)
- Difference from the Al antacids – their action is dependent upon their basic properties and not
on the amphoteric effect
- In-vitro & in-vivo studies: Ca antacids raised the stomach to nearly 7
- Found in combination with Mg antacids
Precipitated CaCO3
Synonym: Precipitated Chalk
Properties: insoluble in H2O
- Solubility increases by the presence of any NH 4 salt or CO2
- Solubility decreases in the presence of any alkali
USES: popular antacid: fast action
- Found in combination with Mg antacids (laxative effect)
Tribasic Ca3(PO4)2
Synonym: Precipitated Ca3(PO4)2
Occurence: consists of a variable mixture of Ca 3(PO4)2`
- Also found in nature as Ca3(PO4)2. CaF2 as phosphorite or phosphate rock and apatite etc.
USES:
1. Treatment of hyperacidity
-production of primary and secondary PO4 -3 diminishes the H+ conc. of the gastric HCl
Advantage of NaHCO3 or other CO3-2 – no gas produced that may cause flatulence and does not
alkalinized the system
2. Source of Ca for the system
Disadvantage: for its insolubility – very little Ca is absorbed and therefore not valuable in acute
Ca deficiency
Mg Containing Antacids
- There is a large no. Of official antacids containing Mg except Mg trisilicate
As pH of the stomach approaches neutrality, the rate of dissolution of Mg salt slows down and stops the
neutrality therefore the anion rather than Mg cation confers their antacid properties
Mg+2 causes this group of antacid to be laxatives
- Mg found in combination with Al and Ca antacids to equalize the constipative and laxative
actions
MgCO3 [(MgCO3)4.Mg(OH)2.5H2O
Synonym: Heavy MgCO3
USES: antacid properties are due to the OH- and CO3-2 anions reacting with gastric HCl
- Due to its very limited solubility, MgCO3 dissolves only as CO 3-2 and OH- are being consumed
Mg(OH)2
USES: efficient antacid due to its basic character
Laxative – high doses due to the formation of MgCl 2 in the stomach which exerts “salt action” in
the intestinal tract causing a mild laxative action
Milk of Magnesia
- Suspension of Mg(OH)2 containing nlt 7% and nmt 8.5% Mg(OH) 2
- Citric acid (small amount) is added to minimize the interaction of glass containers & Mg(OH) 2
USES: popular antacid
Laxative
MgO
Synonym: Magnesia
Properties: USP recognizes 2 varieties (identical in chem. Composition & in purity):
1. Light MgO
2. Heavy MgO
They differ in density:
LV: 5 g occupy 40 mL to 50mL D = 0.1 – 0.125
5/40 = 0.125 g/mL
5/50 = 0.1 g/mL
HV: 5 g occupy 10 to 20 mL D = 0.25 – 0.5
5/10 = 0.5
5/20 = 0.25
USES: laxative
Diuretic
Antacid
- To prevent formation of gelatinous mass, it should be administered 29x its weight of water
- Magnesia is added to H2O and not the reverse to avoid formation of hard lump
Arsenic antidote
Mg Trisilicate (2MgO.3SiO2.XH2O)
Composition: a compound of MgO & SiO2
Contains nlt 20% MgO and nmt 45% SiO 2
Properties: assayed in terms of SiO2 and MgO and must have a definite MgO:SiO 2 ratio
As amount of SiO2 increases with respect to MgO, there is loss in antacid capability
USES: gastric antacid especially valuable in peptic ulcer
- Its value will depend on this reaction:
2MgO.3SiO2.XH2O + 4H+ → 3SiO2.XH2O + 2Mg+2 + 2H2O
Colloidal silicic acid or hydrous silicon have adsorptive powers
and could protect the ulcer from further acid and peptic attack and possible adsorb the pepsin
Mg3(PO4)2
USE: as antacid
Combination Antacid Preparations:
-several products on the market contain mixtures of antacids since no single antacid meets all the
criteria of an ideal antacid
- most of these combination products will attempt to balance the constipative effect of Ca and Al with
laxative effect of Mg
-some are mixture of an antacid with rapid onset of action and one with supposedly longer duration of
action
a. Al(OH)3 Gel & Mg(OH)2
- Aludrox; Wingel; Maalox and Cremalin
b. Al(OH)3 Gel – Mg trisilicate combination
- Gelusil; Tricreamalate; Triosgel
c. Magaldrate – Al(OH)3 & Mg(OH)2 (Riopan)
d. Simethicone – containing antacids
- Di-Gel; Mylanta
- Simethicone (defoaming agent) is added to some antacids
Because many people with gastric hyperacidity complain of being “gassy”
e. Alginic Acid
- NaHCO3 containing antacids
- Gaviscon; Foamtab
PROTECTIVES & ADSORBENTS
Protectives – for intestinal inflammation
Adsorbent – for intestinal toxin
- Git agents used for the treatment of mild diarrhea
Bi containing products” subCO3 subNO3 Milk of Bismuth
Kaolin
Activated Charcoal
Diarrhea – symptom not a disease
- A serious condition
- There is loss of fluids & electrolytes which can lead to dehydration & electrolyte imbalances
Acute Diarrhea
- Caused by bacterial toxins, chemical poisons, drugs, allergy & disease
Chronic Diarrhea
- Results from git surgery, carcinomas, chronic inflammatory conditions and various adsorptive
defects
Treatment for diarrhea will consist of most products in:
Adsorptive – protective
Antidiarrheal agent
Antibacterial agent
Ideal antidiarrheal agent – acts on the smooth muscle of the gut to produce spasm-like effect which
decreases peristalsis and increases segmentation
The adsorbent-protective should:
- Adsorb toxins, bacteria & viruses
- Provide protective coating in the intestinal mucosa
Bismuth Containing Products
- H2O soluble but a small amount is soluble
- The soluble Bi+3 exerts: mild astringent & antiseptic action
Intestinal H2S + Bi+3 salts → Bi2S3 black stool results from the oral administration of Bi +3 containing
preparations
Bismuth Subnitrate [Bi(OH)2(NO3)4.BiO(OH)
Synonym: White Bismuth
Properties: assayed in terms of Bi2O3
- Incompatible with tragacanth because in the presence of the salt tragacanth precipitates as a
hard mass (overcome by adding Na2HPO4 or Na3PO4
USES: non-irritant intestinal antiseptic
Treatment of gastric ulcer & inflammations – because it lessens gastric secretion & reduce acidity
Treatment of diarrhea
Bismuth Subcarbonate
Property: assayed in terms of its Bi2O3 content
USES; protective & antacid in inflammations of the stomach and bowels
Renders alimentary canal opaque to x-ray – when given in large doses
Astringent and adsorbent
Treatment of diarrhea and dysentery
Milk of Bismuth
Synonym: Bismuth Magma; Bismuth Cream
Composition: Bi(OH)3 & Bi subcarbonate
- Made by: conversion of Bi subnitrate + HNO 3 → Bi(NO3)3
Bi(NO3)3 + (NH4)2CO3 & NH3 solution → Bi(OH)3 & subcarbonate
USES; astringent & antacid
Kaolin [Al2O3.2SiO2.2H2O]
Synonyms: Porcelain Clay; China Clay; Bolus Alba
Occurence: formed by weathering feldspar (KAlSi 3O8)
Properties: has earthly & clay-like taste
- When moistened with H2O, assumes darker color and develops a clay-like color
USES; protective & adsorbent in diarrheal disorders- found with vegetable carbohydrate, PECTIN
(Kaopectate, Kao-Con)
Disadvantage: reported to interfere with the intestinal absorption of Lincomycin
Activated Charcoal
USES: adsorbent in the treatment of diarrhea
Antidote in certain types of poisoning
SALINE CATHARTICS (purgative)
- Quicken and increase evacuation from the bowels
Laxatives – mild cathartics
- Most products are sold even without RX
Criteria to consider when cathartics are properly used as stated in the 1972 AMA Drug Evaluation:
1. Ease defecation – patients with painful haemorrhoids or other rectal disorders
2. avoid hazardous rises in blood pressure – during defecation in patients with hypertension,
cerebral arterial diseases
3. Relieve acute constipation
4. remove solid material from the intestinal tract prior to roentgenographic studies
LAXATIVES- used for short term therapy
Prolonged use – leads to loss of spontaneous bowel rhythm thereby causing the patient to become
dependent on laxatives, the so- called “laxative habit”
4 TYPES OF LAXATIVES
1. Stimulant laxatives
- act by local irritation on the intestinal tract, which increases peristaltic activity
2. Bulk forming
- made from cellulose and other non-digestible polysaccharides which swell when wet and with the
increased bulk stimulates peristalsis
3. Emollient
- act neither as lubricants facilitating the passage of compacted fecal material or as stool
softeners.
- Ex. Mineral Oil
4. Saline Cathartics
- act by increasing the osmotic load of the gastrointestinal tract.
- Salts of poorly absorbable anions and sometimes cations.
The body relieves the hypertonicity of the gut by secreting additional fluids into the intestinal tract.
The resolution increased bulk stimulates peristalsis.
Poorly absorbed anions used as saline cathartics:
Biphosphate SO4-2
Phosphate C4H4O6-2
Soluble Mg salts – cathartics due to the poorly absorbed Mg +2
Saline cathartics – H2O soluble and taken with large amount of H2O, preventing excessive loss of body
fluids & reduces nausea and vomiting if a too hypertonic solution should reach the stomach
MONOBASIC SODIUM PHOSPHATE (NaH2PO4.H2O)
PROPERTIES: acid to litmus and effervesces with Na 2CO3 and this is due to the H2PO4-
USES:
- official category: urinary acidifier in case of cystitis with hexamethylenetetramine
(Methenamine)
with acids → decomposes into formaldehye
- cathartic
DIBASIC SODIUM PHOSPHATE (Na2HPO4.7H2O)
PROPERTIES:alkaline to litmus and phenolphthalein, pH = 9.5
USES: saline cathartic (poor intestinal permeability of the HPO 4-2
CAUTION: should not be confused with commercial tribasic Na 3PO4
KNaC4H4O6.4H2O
SYNONYMS: Rochelle Salt; Seignette Salt
PROPERTIES: coated with white powder since it effloresces in warm, dry air
USES: cathartic
- activity ranging from mild laxative to the more potent hydragogue (watery discharge in the
bowel) depending on the dose administered
- pharmaceutical necessity
- ingredient of Seidlitz powder
form where KNaC4H4O6 is administered as cathartic
effervescent preparation and a palatable product
- one of the component of the useful reagent Fehling’s solution officially used Alk. CuC 4H4O6
(example of chelate complexation)
Chelate Complexation – conc. Of Cu+2 is very little and not precipitated by the NaOH present in the
reagent
MgSO4.7H2O
SYNONYMS: Epsom Salt; Bitter Salt
PREPARATION:
- treating the mineral magnesite (MgCO3) with hot dilute H2SO4
- dissolving the mineral kierserite (MgSO4.H2O) in H2O, heated and concentrating the solution to
crystallization
- heating by calcinations of dolomite (MgCO3.CaCO3) then treating with HCl and evaporating to
dryness
USES:
- active cathartic
chief objection to its use: disagreeable bitter taste lessened by administering the solution in ice-
cold
- anticonvulsant (parenterally)
- antiphlogistic/antiinflammatory (locally) in saturated solution for its anesthetic effect in sprains
and bruises
Mg3C6H5O7
SYNONYMS: Purgative Lemonade
PREPARATION: reacting MgCO3 with citric acid
- should be sterilized or pasteurized
NON-OFFICIAL SALINE CATHARTICS
1. Na2SO4.10H2O – glauber’s salt
2. K2HPO4
3. KHC4H4O6 – cream of tartar
4. Mild Hg2Cl2 – calomel
