D4: pH regulation of the stomach

Normal stomach pH: between 1-2 (due to production of HCl by gastric glands) - Part of body’s natural defence against disease-causing microorganisms that enter the digestive system through food (as low pH is not tolerated by majority of microorganisms) - Digestive enzymes require low pH for optimum catalytic activity

• Typically protected by mucous lining • Can be irritated by: 1) Excess stomach acid 2) Drugs that irritate the stomach lining directly 3) Drugs that lower the production of mucous (indirectly making the stomach lining more vulnerable to irritation) • Cause: 1) Indigestion (irritation to stomach lining caused by denaturation of digestive enzymes and excess stomach acid — causing pain to upper abdomen and nausea) 2) Heartburn/acid reflux: acid from the stomach rising up to the esophagus causing a burning sensation 3) Peptic ulcer: erosion of stomach lining

ANTACIDS: weakly basic compounds that are non-specific and do not bind to any specific protein receptor, but relieve symptoms associated with excess stomach acid by neutralising it (acid-base/acid-carbonate reactions) - Eg. Mg(OH)₂, Al(OH)₃, CaCO₃, NaHCO₃ • Mixture of 2 or more antacid ingredients: 1) Mg(OH)₂ is faster-acting, but Al(OH)₃ has a more prolonged effect that can reduce time between dosages 2) Mg(OH)₂ alone also has a laxative effect, counteracted by the constipative effect of Al(OH)₃ • Addition of other substances: 1) Antifoaming agents: relieve bloatedness caused by the CO₂ from acid-carbonate reactions by causing the gas to coalesce and leave as flatulence 2) Alignates: form a protective ‘raft’ layer that floats on top of stomach contents and prevent reflux from acid entering the esophagus

Treatment of peptic ulcers: 1) Stopping acid production 2) Preventing acid secretion RANITADINE/ZANTAC: - Inhibits the production of HCl by binding the histamine-H2 receptor protein on the parietal cell membrane, acting as a H2-antagonist by preventing histamine from binding to the receptor and setting off the chain of events that produce HCl OMEPRZOLE/ESOMEPRAZOLE: - Prevents acid secretion into the stomach by acting as a proton pump inhibitor - Proton pump: pumps protons through cell membranes, as positively-charged H⁺ particles cannot move through non-polar cell membranes) - Non-polar/lipid-soluble drugs can pass through cell-membrane before becoming protonated in the acidic medium of the parietal cell (when structure of the drug becomes changed to its active form to bind to the proton pump permanently and inhibit its function until the cell can produce new proton pumps)

ACTIVE METABOLITE: active form of a drug produced once metabolised by the body, causing the desired action of the drug (Eg. Codeine –> Morphine, Omeprazole –> active form after protonation, Aspirin –> Salicylic acid) 1) Avoid side effects (Eg. Salicylic acid consumed orally can cause extreme stomach lining irritation) 2) To pass through cell membranes (Eg. Active form of omeprazole is charged and will not pass through cell membrane) 3) To increase drug solubility 4) To target drugs to a particular area (Eg. Omeprazole is only converted to active form in highly acidic parietal cell)

BUFFER SOLUTION: solution (consisting of a weak acid HA and its conjugate base A⁻) that resists pH changes when small amounts of acid/alkali are added - Cannot be formed from a strong acid and its conjugate base: strong acid would completely dissociate to form a weak conjugate base that is unlikely to pick up protons when acid is added HA ⇌ H⁺ + A⁻ In acidic conditions: A⁻ + H⁺ –> HA In basic conditions: HA + OH⁻ –> A⁻ + H₂O Eg. Hydrogencarbonate-carbonate buffer in blood H₂CO₃⇌ H⁺+ HCO₃⁻ In acidic conditions: HCO₃⁻ + H⁺ –> H₂CO₃ In basic conditions: H₂CO₃ + OH⁻ –> HCO₃⁻ + H₂O

Measure of dissociation - Lower pKₐ: higher degree of dissociation: stronger acid

pH = pKₐ + log₁₀([base]/[acid])