A number of widely differing substances are now, for convenience, classed the 'vitamin B complex'. Those used for pharmacotherapy include the following:
Thiamine (Bj) is used orally for nutritional purposes, but is given i.v. in serious emergencies, e.g. Wernicke-Korsakoff syndrome, when it can cause anaphylactic shock; the injection should be given over 10 min (or i.m.).
Cobalamins (B12): see Chapter 29.
Folic acid: see Chapter 29.
Pyridoxine (B6) is a coenzyme (including decarboxylases) for transamination and is concerned with many metabolic processes. Normal adult requirements are about 2 mg/d. As pharmacotherapy, pyridoxine is given to treat certain pyridoxine-dependent inborn errors of metabolism, namely homocystinuria, hereditary sideroblastic anaemia and primary hyperoxaluria. Deficiency may be induced by drugs such as isoniazid, hydralazine and penicillamine; pyridoxine 10 mg/day prevents the development of peripheral neuritis without interfering with therapeutic action.
Pyridoxine has also been used for a variety of conditions including premenstrual tension, vomiting in pregnancy and radiation sickness in doses sometimes exceeding 100 mg/day. Concerns that prolonged exposure to high doses may be harmful, e.g. causing sensory neuropathy, have not been resolved.
Niacin (nicotinic acid, nicotinamide) (B7) is an essential part of codehydrogenases I and II, and so it is present in every living cell. It is used in some hyperlipidaemias, see page 527.
Adverse effects do not occur with standard doses of nicotinamide. Nicotinic acid, which is converted into nicotinamide, causes peripheral vasodilatation accompanied by an unpleasant flushing and itching, and the patient may faint.
Deficiency of ascorbic acid leads to scurvy,3 which is characterised by petechial haemorrhages, haematomas, bleeding gums (if teeth are present) and anaemia. It has a memorable place in the history of therapeutic measurement.
Scurvy had been a scourge for thousands of years, particularly amongst sailors on long voyages. In 1753, Dr James Lind performed a simple controlled therapeutic trial on 12 sailors with advanced scurvy. They were all on the same basic diet and were living in the same quarters on board ship at sea. He divided them into pairs and dosed each pair separately on cider, sulphuric acid, sea-water, vinegar, a concoction of garlic, mustard, balsam and myrrh, and two oranges and a lemon. The pair receiving
3 Only man (and other primates), guinea-pigs, the Indian fruit bat and the red-vented bulbul (a bird) get scurvy; other animals are able to synthesise ascorbic acid for themselves.
the oranges and lemon recovered and were back on duty within a week; of the others, only the pair taking cider was slightly improved. The efficacy of oranges and lemons in the prevention and cure of scurvy was repeatedly confirmed. Eventually the British Navy provided a regular daily allowance of lemon juice, unfortunately later replaced by the cheaper lime4 juice which contained insufficient ascorbic acid to prevent scurvy completely.
Ascorbic acid is required for the synthesis of collagen. It is also a powerful reducing agent (antioxidant) and plays a part in intracellular oxidation-reduction systems, and in mopping up oxidants (free radicals) produced endogenously or in the environment, e.g. cigarette smoke (see Vitamin E).
Indications for ascorbic acid
• The prevention and cure of scurvy
• Urinary acidification (rarely appropriate)
• Methaemoglobinaemia, for its properties as reducing agent (see below)
• Coryza: it is possible that large daily doses (1 g or more/d) of ascorbic acid (daily nutritional requirement 60 mg) may reduce the incidence and severity of coryza (common cold). Reliable trials in this disease are difficult and the results are inconclusive. To justify use of such doses in populations, benefit must be shown to be clinically, as well as statistically, significant; and harm insignificant. This has not been achieved.
High doses may cause sleep disturbances, headaches and gut upsets. Ascorbic acid is partly eliminated in the urine unchanged and partly metabolised to oxalate. Doses above 4 g/d, which have been taken over long periods in the hope of preventing coryza, increase urinary oxalate concentration sufficiently to from oxalate stones. Intravenous ascorbic acid
4 Hence the term 'limey' for British sailors; generally used pejoratively, but obsolete except in Australia.
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