Alkalinisation

Potassium citrate alkalinises the urine and increases its volume. They are used to change the pH of urine. 

Alkalinisation of urine (alkaline diuresis) is effective for salicylates and phenoxyacetate herbicides. 

Ionisation determines the partitioning of drugs across membranes. Unionised molecules can easily cross and reach an equilibrium across a membrane, while the ionised form cannot cross. When the pH is different in the compartments separated by the membrane the total (ionised + unionised) concentration will be different on each side. An acidic drug will become concentrated in a compartment with a high pH and a basic drug in one with a low pH. This is known as ion-trapping, and occurs in the stomach, kidneys, and across the placenta. Urinary acidification accelerates the excretion of weak bases, such as pethidine, while alkalinisation increases the excretion of acidic drugs, such as aspirin. As an example consider pethidine (pKa 8.6) with an unbound plasma concentration of 100 (arbitrary units). At pH 7.4 only 6% of the pethidine will be unionised so that at equilibrium the concentration of unionised pethidine in the urine will be 6 units. In urine at pH 6.5 only 0.8% of the pethidine will be unionised so that the total concentration in the urine will be 744 units. 

Alkalinisation of local anaesthetic solution with sodium bicarbonate (NaHC03) increases the pH of the solution to a value near its pKa. This results in an increased proportion of unionised drug available for neural penetration and thereby reduces the onset time. Carbonation is a term used to describe the acidification of a local anaesthetic solution with carbon dioxide. Following injection, the carbon dioxide diffuses into the axoplasm causing a decrease in the pH. This results in a higher proportion of ionised drug within the cell. In theory this should enhance the Na-i- channel block but in practice the results are disappointing. 

Aspirin (acetylsalicylic acid, Figure 7.9) is a derivative of salicyclic acid, which was first used in 1875 as an antipyretic and antirheumatic. The usual dose for mild pain is 300-600 mg orally. In the treatment of rheumatic diseases, larger doses, 5-8 g daily, are often required. Aspirin is rapidly hydrolysed in the plasma, liver and eiythrocytes to salicylate, which is responsible for some, but not all, of the analgesic activity. Both aspirin and salicylate are excreted in the urine. Excretion is facilitated by alkalinisation of the urine. Metabolism is normally very rapid, but the liver enzymes responsible for metabolism are easily saturated and after multiple doses the terminal half-life may increase from the normal 2-3 h to 10 h. A soluble salt, lysine acetylsalicylic acid, with similar pharmacological properties to aspirin, has been used by parenteral administration for postoperative pain. Aspirin in low doses (80-160 mg daily) is widely used in patients with cardiovascular disease to reduce the incidence of myocardial infarction and strokes. The prophylaxis against thromboembolic disease by low-dose aspirin is due to inhibition of COX-1-generated thromboxane A2 production. Because platelets do not form new enzymes, and COX-1 is irreversibly inhibited by aspirin, inhibition of platelet function lasts for the lifetime of a platelet (8-10 days). 

Two main effects occur here. First, change in the pH of urine—weak bases, such as pethidine, are more easily excreted in an acid urine while alkalinisation promotes excretion of weak acids, such as salicylates and phenobarbital. Second, drugs that compete for an active excretion mechanism will reduce each other s elimination—probenecid was used in the early days of penicillin to conserve the drug, while less desirable interactions also occur, e.g. chlorpropamide and phenylbutazone interact to give increased levels of chlorpropamide and a danger of hypoglycaemia. 

Urinary pH significantly affects the activity of nitrofurantoin, with loss of potency as the urine becomes more alkaline. For this reason, women with lower UTI who are prescribed nitrofurantoin should be advised not to take alkalinising agents such as potassium citrate (Effercitrate). 

Alkalinising the urine may provide symptomatic relief but has no antibacterial effect. 

SYMPATHOMIMETICS ANTACIDS-SODIUM BICARBONATE Possibly t ephedrine/ pseudoephedrine levels Alkalinising urine 1 excretion of these sympathomimetics Watch for early features of toxicity... 

Rhabdomyolysis may result from prolonged pressure on muscles, from agents that cause muscle spasm or convulsions (phencyclidine, theophylline) or be aggravated by hyperthermia due to muscle contraction, e.g. with MDMA ( ecstasy ). Aggressive volume repletion and correction of acid-base abnormality may be needed, and urine alkalinisation may prevent acute tubular necrosis. 

Phenoxy herbicides (2,4-D, mecoprop, dichlorprop) are used to control broad-leaved weeds. Ingestion causes nausea, vomiting, p5rrexia (due to uncoupling of oxidative phosphorylation), hyperventilation, hypoxia and coma. Their elimination is enhanced by urine alkalinisation. Organochlorine pesticides, e.g. dicophane (DDT), may cause convulsions in acute overdose. Treat as for status epilepticus. 

Acid-base disturbance. Alkalosis or mixed alkalosis/ acidosis need no specific treatment. Metabolic acidosis is treated with sodium bicarbonate, which alkalinises the urine and accelerates the removal of salicylate in the urine (see p. 97). 

Potassium citrate, which alkalinises the urine, should be given to prevent formation of pure uric acid stones. 

Lassen, N. A. Treatment of severe acute barbiturate poisoning by forced diuresis and alkalinisation of the urine. The LancetII, 338 (1960). 

Aluminium and magnesium antacid salts are included in reflux-suppressant formulations because they help to neutralise stomach contents and any material that is refluxed through the LOS. Gastric alkalinisation is also thought... 

Alkalinising agents are the only treatments available specifically for cystitis without prescription. 

A young woman is referred to you by your medicines counter assistant, as she has picked up a General Sales List alkalinising treatment for cystitis but she tells your assistant she has not used such a product before. The client says that she thinks she has cystitis, but when you ask her if she has had cystitis before she says no, but she has talked about her symptoms to a friend who has had cystitis, and her friend thinks that this is what it is. In response to your questions, the symptoms she describes are urine not being passed more frequently than normal, but dark with an unpleasant smell pain about halfway up her back on both sides, and she has been feeling feverish since she woke up this morning. 

Would you sell the alkalinising treatment to the woman If not, what would you do or recommend ... 

First statement Alkalinising agents containing sodium or potassium salts should not be sold to patients taking drugs for hypertension. 

Sulphur dioxide (free and total) Wines Pervaporation UV—Vis 1.2 gg mL 1 (both analytes) Flow injection system p-rosaniline plus formaldehyde solution as the acceptor stream sample alkalinisation prior to injection for total sulphur dioxide determination [551]... 

---