Antacids

ANTACIDS

These are basic substances which neutralize gastric acid and raise pH of gastric contents. Peptic activity is indirectly reduced if the pH rises above 4, because pepsin is secreted as a complex with an inhibitory terminal moiety that dissociates below pH 5: optimum peptic activity is exerted between pH 2 to 4.

Antacids do not decrease acid production; rather, agents that raise the antral pH to > 4 evoke reflex gastrin release → more acid is secreted, especially in patients with hyperacidity and duodenal ulcer; “acid rebound” occurs and gastric motility is increased.

The potency of an antacid is generally expressed in terms of its acid neutralizing capacity (ANC), which is defined as number of mEq of 1N HCl that are brought to pH 3.5 in 15 min (or 60 min in some tests) by a unit dose of the antacid preparation. This takes into consideration the rate at which it dissolves and reacts with HCl. This is important because a single dose of any antacid taken in empty stomach acts for 30– 60 min only, since in this time any gastric content is passed into duodenum. Taken with meals antacids may act for at the most 2–3 hr.

Systemic Antacids

Sodium Bicarbonate

It is water soluble, acts instantaneously, but the duration of action is short. It is a potent neutralizer (1 g → 12 mEq HCl), pH may rise above 7.

However, it has several demerits:

·      Absorbed systemically: large doses will induce alkalosis.

·      Produces CO₂ in stomach → distention, discomfort, belching, risk of ulcer perforation.

·      Acid rebound occurs, but is usually short lasting.

·      Increases Na+ load: may worsen edema and CHF. Use of sod. bicarbonate is restricted to casual treatment of heartburn: provides quick symptomatic relief.

Other uses are to alkalinize urine and to treat acidosis.

Sodium citrate Properties similar to sod. bicarbonate; 1 g neutralizes 10 mEq HCl; CO₂ is not evolved.

Nonsystemic  Antacids

These are insoluble and poorly absorbed basic compounds; react in stomach to form the corresponding chloride salt. The chloride salt again reacts with the intestinal bicarbonate so that HCO₃¯ is not spared for absorption—no acid-base disturbance occurs. However, small amounts that are absorbed have the same alkalinizing effect as NaHCO₃.

Mag. hydroxide has low water solubility: its aqueous suspension (milk of magnesia) has low concentration of OH¯ ions and thus low alkalinity. However, it reacts with HCl promptly and is an efficacious antacid (1 g → 30 mEq HCl). Rebound acidity is mild and brief.

MILK OF MAGNESIA 0.4 g/5 ml suspension: 5 ml neutralizes 12 mEq acid.

Magnesium trisilicate has low solubility and reactivity; 1 g can react with 10 mEq acid, but in clinical use only about 1 mEq is neutralized.

About 5% of administered Mg is absorbed systemically—may cause problem if renal function is inadequate.

All Mg salts have a laxative action—by generating osmotically active MgCl₂ in the stomach and through Mg2+ ion induced cholecystokinin release. Soluble Mg salts are used as osmotic purgatives.

Aluminium Hydroxide Gel

It is a bland, weak and slowly reacting antacid. On keeping it slowly polymerizes to variable extents into still less reactive forms. Thus, the ANC of a preparation gradually declines on storage. Also, the product from different manufacturers may have differing ANCs; usually it varies from 1–2.5 mEq/g. Thus, 5 ml of its suspension may neutralize just 1 mEq HCl. As such, little worthwhile acid neutralization is obtained at conventional doses.

The Al3+ ions relax smooth muscle. Thus, it delays gastric emptying. Alum. hydrox. frequently, causes constipation due to its smooth muscle relaxant and mucosal astringent action.

Alum. hydrox. binds phosphate in the intestine and prevents its absorption—hypophosphatemia occurs on regular use. This may:

·      cause  osteomalacia

·      be used therapeutically in hyperphosphatemia and phosphate stones.

Small amount of Al3+ that is absorbed is excreted by kidney which is not possible in renal failure—aluminium toxicity (encephalopathy, osteoporosis) can occur.

ALUDROX 0.84 g tab, 0.6 g/10 ml susp.

Magaldrate

It is a hydrated complex of hydroxymagnesium aluminate that initially reacts rapidly with acid and releases alum. hydrox. which then reacts more slowly. The freshly released alum. hydrox. is in the unpolymerized more reactive form. Thus, magaldrate cannot be equated to a physical mixture of mag. and alum. hydroxides. It is a good antacid with prompt and sustained neutralizing action. Its ANC is estimated to be 28 mEq HCl/g.

STACID 400 mg tab, 400 mg/5 ml susp.; ULGEL 400 mg with 20 mg simethicone per tab or 5 ml susp.

Calcium Carbonate

It is a potent and rapidly acting acid neutralizer (1 g → 20 mEq HCl), but ANC of commercial preparations is less and variable due to differing particle size and crystal structure. Though it liberates CO₂ in the stomach at a slower rate than NaHCO₃, it can cause distention and discomfort. The Ca2+ ions are partly absorbed.

The greatest drawback of CaCO₃ as an antacid is that Ca2+ ions diffuse into the gastric mucosa—increase HCl production directly by parietal cells as well as by releasing gastrin. Acid rebound is marked. Cal. carbonate is constipating in most individuals, but in some it causes loose motions. The absorbed calcium can be dangerous in renal insufficiency.

Milk Alkali Syndrome

In the past, large quantity of milk was prescribed with CaCO₃ (or NaHCO₃) for peptic ulcer. Such regimen often produced a syndrome characterized by headache, anorexia, weakness, abdominal discomfort, abnormal Ca deposits and renal stones due to concurrent hypercalcaemia and alkalosis. It is rare now.

Antacid Combinations

A combination of two or more antacids is frequently used. These may be superior to any single agent on the following accounts:

·      Fast (Mag. hydrox.) and slow (Alum. hydrox.) acting components yield prompt as well as sustained effect.

·      Mag. salts are laxative, while alum. salts are constipating: combination may annul each other’s action and bowel movement may be least affected.

·      Gastric emptying is least affected; while alum. salts tend to delay it, mag./cal. salts tend to hasten it.

·      Dose of individual components is reduced; systemic toxicity (dependent on fractional absorption) is minimized.

Some available antacid combinations are:

ACIDIN: Mag. carb. 165 mg, dried alum. hydrox. gel 232 mg, cal. carb. 165 mg, sod. bicarb. 82 mg, with kaolin 105 mg and belladonna herb 30 μg per tab.

ALMACARB: Dried alum. hydrox. gel 325 mg, mag. carb. 50 mg, methyl polysilox. 40 mg, deglycyrrhizinated liquorice 380 mg per tab.

ALLUJELDF: Dried alum. hydrox. gel 400 mg, mag.

hydrox. 400 mg, methyl polysilox. 30 mg per 10 ml susp.

DIGENE: Dried alum. hydrox. gel 300 mg, mag. alum. silicate 50 mg, mag. hydrox. 25 mg, methylpolysilox. 10 mg per tab.

DIGENE GEL: Mag. hydrox. 185 mg, alum. hydrox. gel 830 mg, sod. carboxymethyl cellulose 100 mg, methylpolysilox. 25 mg per 10 ml susp.

GELUSIL:  Dried        alum. hydrox. Gel 250 mg, mag. trisilicate 500 mg per tab.

GELUSIL LIQUID: Mag. Trisilicate 625 mg, alum. hydrox. gel 312 mg per 5 ml susp.

MUCAINE: Alum. hydrox. 290 mg, mag. hydrox. 98 mg, oxethazaine 10 mg per 5 ml susp.

TRICAINEMPS: Alum. hydrox. gel 300 mg, mag. hydrox. 150 mg, oxethazaine 10 mg, simethicone 10 mg per 5 ml gel.

MAYLOX: Dried alum. hydrox. gel 225 mg, mag. hydrox. 200 mg, dimethicone 50 mg per tab and 5 ml susp.

POLYCROL FORTE GEL: Mag. hydrox. 100 mg, dried alum. hydrox. gel 425 mg, methylpolysilox. 125 mg per 5 ml susp.

Drug Interactions

By raising gastric pH and by forming complexes, the nonabsorbable antacids decrease the absorption of many drugs, especially tetracyclines, iron salts, fluoroquinolones, ketoconazole, H₂ blockers, diazepam, phenothiazines, indomethacin, phenytoin, isoniazid, ethambutol and nitrofurantoin. Stagger their administration by 2 hours. The efficacy of nitrofurantoin is also reduced by alkalinization of urine.

Uses

Antacids are no longer used for healing peptic ulcer because they are needed in large and frequent doses, are inconvenient, can cause acid rebound and bowel upset, afford little nocturnal protection and have poor patient acceptability. Antacids are now employed only for intercurrent pain relief and acidity, mostly selfprescribed by the patients as over the counter preparations. They continue to be used for nonulcer dyspepsia and minor episodes of heartburn.

Gastroesophageal reflux Antacids afford faster symptom relief than drugs which inhibit acid secretion, but do not provide sustained benefit. May be used off and on for acid eructation and heartburn.