chapter v gastrointestinal agents

8/20/2019 Chapter v Gastrointestinal Agents

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Pharmaceutical Chemistry 1: Gastrointestinal Agents | Suzette Pamela G. Santos | 1FPharmacy

CHAPTER V: GASTROINTESTINAL AGENTS

1.

Antacids – alters gastric pH

2.

Protectives - for intestinal inflammation

3.

Adsorbents - for intestinal toxins

4.

Cathartics or laxatives - for constipation

ANTACIDS-

alkaline bases that neutralizes excess hydrochloric acid which causes pain and ulceration

-

to inactivate the proteolytic enzyme, pepsin

pH 1 – empty stomach, excessive endogenous HCl

pH 7 – food is present

Gastritis – general inflammation of the gastric mucosa

Peptic Ulcer – a general circumscribed erosion

o

Esophageal ulcer – lower end of the esophagus

- esophageal sphincter is defective, heartburn

o

Gastric ulcer – stomach

- malignancy and hemorrhage are common

- bleeding

o

Duodenal Ulcer – duodenum

- perforation

Criterias for Ideal Antacid:

1.

not absorbable/cause systemic alkalosis

2.

not a laxative nor cause constipation

3.

exerts the effect rapidly and over a long period of time

4.

not cause a large evolution of gas, flatulence

5.

buffers in pH 4-6 range6.

inhibits pepsin

SODIUM BICARBONATE-

drug of choice for metabolic acidosis

-

rapid action but short duration

-

causes belching and flatulence

-

function is to react with an acid

- to mask the salinity of the drug, “sparkling” flavor

ALUMINUM HYDROXIDE [Al(OH)3]

- “Amphogel” -

treatment of hyperchlorhydria, peptic ulcer and intestinal toxemia

Physical Forms:

1.

Suspension - Aluminum Hydroxide Gel – white viscous suspension, pH 5.5-8.0

- includes sweetening agents, aromatics and preservatives

2.

Powder - Dried Aluminum Hydroxide Gel – amorphous powder, made into tablet

advantage of the gel is its large surface area and thus, great adsorption

but loses its antacid properties upon aging

causes constipation, nausea and vomiting




Calcium-Containing Antacids

-

causes constipation

CALCIUM CARBONATE [CaCO3]

-

“Precipitated Chalk”

-

microcrystalline powder, fast action

-

causes flatulence and constipation[Ca

+2

] -

found in combination with Magnesium antacids

- Lozenges and Oral Suspension

− −+ − −→ +

*hyperacidity *flatulence

TRIBASIC CALCIUM PHOSPHATE Ca3(PO4)2

- “Precipitated Calcium Phosphate”

-

after ignition at 800oC, 90% Tribasic calcium phosphate

-

found in nature as phosphorite/phosphate rock and apatite(Ca3(PO4)2●CaF2

-

there is NO GAS PRODUCED and does not alkalinize the system

Magnesium-Containing Antacids

-

antacid property depends on the anion/basic property

-

Mg ion causes it to be laxative

o

combination with Al and Ca antacids to equalize constipative and laxative action

MAGNESIUM CARBONATE [Mg(CO3)4●Mg(OH)2●5H2O

-

antacid property are due to hydroxide and carbonate ions reacting with the gastric HCl

MAGNESIUM HYDROXIDE-

laxative in high doses

-

exerts salt action (MgCl2) -> laxative action

MILK OF MAGNESIA – suspension of Mg(OH)2

MAGNESIUM OXIDE-

“Magnesia”

-

laxative and diuretic

o

Light Variety – occupies 40-50mL

o

Heavy Variety – occupies 10-20mL

-

arsenic antidote

-

prepared by adding Magnesia to water (1:20)

MAGNESIUM TRISILICATE 2MgO●3SiO2●xH2O

-

compound of MAGNESIUM OXIDE + SILICON DIOXIDE

-

silicic acid or hydrous silica has absorptive properties

MAGNESIUM PHOSPHATE Mg3(PO4)2●5H2O

Combination Antacid Preparations

-

most of these combination are an attempt to balance the constipative effect of calcium and

aluminum with laxative effect of magnesium

a.

Aluminum Hydroxide Gel – Magnesium Hydroxide

Aludrox, WinGel, Maalox, Cramlin

b.

Aluminum Hydroxide Gel – Magnesium Trisilicate

Gelusil, Tricreamalate, Triosgel

c.

Magaldrate – combination of aluminum hydroxide and magnesium hydroxide

d.

Simethicone – defoaming agent

e.

Alginic acid – sodium Bicarbonate

- for reflux espophagitis




PROTECTIVES AND ADSORBENTS-

for the treatment of mild diarrhea

Acute diarrhea – caused by bacterial toxins, chemical poisons, drugs, allergy (easily treated)

Chronic – GI surgery carcinoma (over a long period of time)

Antidiarrheal – decreases peristalsis*slows down the movement of intestinal tract

1. Adsorptive-protective – adsorbs toxins, bacteria and viruses, and provides protective coating of the

intestinal mucosa

2. Antidiarrheal – should act directly on smooth muscle of the gut, producing spasm-like effect, which

decreases peristalsis and increases segmentation

3. Antibacterial agent – only effective if there is an actual infection caused by microorganisms

Bismuth-containing Products

bismuth ion – exerts a mild astringent and antiseptic action

o

astringent – causes constriction of the mucosa, destroying the bacteria

BISMUTH SUBNITRATE Bi(OH)2(NO3)4●BiO(OH)

-

“White Bismuth”

-

hygroscopic powder, acidic with litmus paper

-

assayed in terms of bismuth trioxide (Bi2O3)

-

incompatible with tragacanth (precipitates as a hard mass)

o

remedy is the addition of sodium biphosphate or trisodium phosphate

USES

-

non-irritant intestinal antiseptic

-

lessens gastric secretions, and reduces acidity

-

remedy against diarrhea

BISMUTH SUBCARBONATE BiO2(CO3)2 ●H2O

-

yellowish white, affected by light

-

protective and antacid effect in the inflammations of the stomach and bowels

-

60 grams dose – rendering the alimentary canal opaque to x-ray

-

astringent and adsorbent in the treatment of diarrhea and dysentery

MILK OF BISMUTH-

“Bismuth Magma/Bismuth Cream”

-

Bismuth hydroxide + Bismuth subcarbonate (suspension)

o

prepared through the conversion of bismuth subnitrate nitrate by adding HNO3 o

then by treating it with ammonium carbonate and ammonia solution

-

used as ASTRINGENT and ANTACID

KAOLIN-

“Porcelain Cay/China Clay/Bolus Alba”

-

native hydrated aluminum silicate

o

elutriation – powdered and freed from gritty particles

-

contains 20.9% aluminum

-

formed by the weathering of FELDSPAR (KAlSi3O8)

-

has an earthly and clay-like taste, turns darker when moistened with water

-

found together with pectin (Kaopectate)

-

ADSORBENT and PROTECTIVE in diarrheal conditions

-

interferes with intestinal absorption of lincomycin

ACTIVATED CHARCOAL-

adsorbent in the treatment of diarrhea

-

antidote to some types of poisoning




SALINE CATHARTICS-

purgatives

-

agents that quicken and increase evacuation from the bowels

o

Laxatives – mild cathartics

“laxative habit” – loss of bowel rhythm, and becoming dependent on laxatives

4 Types of Laxatives

1.

Stimulant Laxatives – act by local irritation on the intestinal tract, increasing the peristaltic

activity

2.

Bulk-forming laxatives – made from cellulose and polysaccharides, which swell when wet, and

this increased bulk stimulates peristalsis

3.

Emollient Laxatives – acts as lubricants or stool softeners

4. Saline Cathartics – increases osmotic load of GI tract

Poorly absorbable ions used as saline cathartics:

biphosphate

phosphate

sulfate

tartrate

magnesium

They are water soluble and should be taken with large amounts of water to prevent excessive

loss of body fluids.

MONOBASIC SODIUM PHOSPHATE NaH2PO4●H2O

-

slightly deliquescent

-

acidic to litmus, effervesces with sodium carbonate

-

URINARY ACIDIFIER

o

in case of cystitis, with hexamethylenetramine* (Methenamine)

decomposes into formaldehyde in the presence of acids

-

CATHARTIC

DIBASIC SODIUM PHOSPHATE Na2HPO4●7H2O

-

white granular salt, effervesces in warm dry air

-

alkaline to litmus and phenolphthalein (pH 9.5)

-

1, 2, 7, 12 H2O (official)

- SALINE CATHARTIC

-

should never be confused with tribasic sodium phosphate, which is very alkaline and caustic,

and should be used for intestinal purpose

POTASSIUM SODIUM TARTRATE KNaC4H4O6●4H2O

- Rochelle Salt, Seignette Salt

-

colorless crystals with a cooling saline taste

-

often coated with white powder as it effloresces in warm dry air

-

CATHARTIC – MILD LAXATIVE HYDRAGOGUE

o

producing watery discharges from bowel

-

an ingredient of Seidlitz Powder

o

form in which it is administered as cathartic

-

effervescent and palatable

-

component of Fehling’s solution ( Alkaline Cupric Tartrate)

o

an example of chelate complexation




MAGNESIUM SULFATE MgSO4●7H2O

-

Epsom salt, Bitter Salt

-

small colorless needle-like crystals with a cooling saline bitter taste

-

effloresces in air, neutral to litmus

-

active cathartic with little pain or nausea and produces watery stools -

must be administered in ice-cold condition to avoid bitter taste

-

used parenterally as anticonvulsant

-

anesthetic effect in sprains and bruises

-

antiphlogistic action

Preparation

1.

Magnesite (MgCO3) with hot dilute sulfuric acid

2.

Kierserite (MgSO4●H2O) in water, heating then, crystallization

3.

Dolomite(MgCO3 ●CaCO3) – heating by calcinations, treating with HCl

dissolved in sulfuric acid, boiled and filtered

MAGNESIUM CITRATE- Purgative Lemonade

-

MgCO3 + citric acid

-

sodium or potassium bicarbonate reacting with citric acid producing a lemon-flavored solution

-

must be sterilized or pasteurized

NON-OFFICIAL SALINE CATHARTICS

1. SODIUM SULFATE – Glauber’s Salt

2.

POTASSIUM PHOSPHATE – Dibasic Potassium Phosphate, DKP, Dipotassium HydrogenPhosphate

3.

POTASSIUM BITRATE – Cream of Tartar

4.

CALOMEL – Mercurous chloride, Mild Mercury Chloride

chapter v gastrointestinal agents

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