A Textbook of Clinical Pharmacology and Therapeutics

dinucleotide (NAD) and nicotinamide adenine dinucleotide
phosphate (NADP). Niacin can be generated in the body in
small amounts from tryptophan. Deficiency of niacin causes
pellagra, that can manifest clinically as a syndrome complex
which includes dementia, dermatitis and diarrhoea.

Uses

1. Niacin is used to treat and prevent pellagra. If oral
   treatment is not possible, intravenous injections are
   available.
   2.Nicotinic acid (or nicotinic acid analogues, e.g. acipomox)
   may be used to treat dyslipidaemia (Chapter 27), but
   hypolipidaemic dosing is limited by
   vasodilatation/flushing.

Adverse effects

In replacement therapy for pellagra, adverse effects are
uncommon. High doses (as used for hyperlipidaemia) cause
the following:

1. vasodilatation due to prostaglandin D 2 – this can be
   reduced by premedication with aspirin;
   2.nausea, vomiting and itching;
   3.hyperglycaemia;
   4.exacerbation of hyperuricaemia.

Pharmacokinetics

Both niacin and nicotinamide are well absorbed via the intestine
and are widely distributed to tissues. When the usual dietary
amounts are administered, a high proportion is excreted as
N-methyl nicotinamide and other metabolites. When increased
doses are administered, a higher proportion is excreted
unchanged in the urine.

VITAMIN B 6 (PYRIDOXINE)

Physiology

Vitamin B 6 occurs naturally in three forms, namely pyridox-
ine, pyridoxal and pyridoxamine. All three forms are con-
verted in the body into pyridoxal phosphate, which is an
essential cofactor in several metabolic reactions, including
decarboxylation, transamination and other steps in amino
acid metabolism. Pyridoxine is present in wheatgerm, yeast,
bran, rice and liver. Deficiency causes glossitis, seborrhoea, fits,
peripheral neuropathy and sideroblastic anaemia. Isoniazid
prevents the activation of pyridoxal to pyridoxal phosphate
by inhibiting the enzyme pyridoxal kinase, and slow acetyla-
tors of isoniazidare at increased risk of developing peripheral
neuropathy for this reason (Chapters 14 and 44).

Use

Pyridoxine hydrochloride is given to patients at risk (e.g. alco-
holics) during long-term therapy with isoniazidto prevent
peripheral neuropathy, and in deficiency states. Large doses

are used in sideroblastic anaemia. Pyridoxineis also used to

treat certain uncommon inborn errors of metabolism, includ-

ing primary hyperoxaluria. Large doses are sometimes used

to treat premenstrual syndrome, and there is a lobby of enthu-

siasts for this, despite a paucity of evidence.

Adverse effects

There have been reports of ataxia and sensory neuropathy fol-

lowing administration of large doses (2 g/day) of pyridoxine

for more than two months.

VITAMIN C (ASCORBIC ACID)

Physiology

Ascorbic acid is present in large quantities in citrus fruits,

tomatoes and green vegetables. Vitamin C is essential to

humans, monkeys and guinea pigs which, unlike other mam-

mals, cannot synthesize it from glucose. Dietary lack of vita-

min C causes scurvy, which is characterized by bleeding gums

and perifollicular purpura. Ascorbic acid is involved in sev-

eral metabolic processes (Figure 35.2). It is a potent water-

soluble anti-oxidant. The nutritional status of vitamin C can

be assessed by measuring the intracellular leukocyte concen-

tration, but this is not routinely performed or available.

Uses

1. Ascorbic acidis used in the prophylaxis and treatment of
   scurvy. (Perhaps the first recorded clinical trial involved
   the distribution of citrus fruit to some, but not all, British
   naval vessels and observation of the incidence of scurvy.
   The Admiralty were (after some prevarication) convinced
   and British sailors were subsequently provided with
   limes – whence the term ‘limeys’.)
   2.Ascorbic acidincreases the absorption of orally
   administered iron.
   3.The reducing properties of ascorbate may be used in the
   treatment of methaemoglobinaemia.
   4.In scorbutic patients, wound healing is delayed and this is
   restored to normal by administration of ascorbic acid.

Adverse effects

Ascorbic acidis non-toxic in low doses. However, administra-

tion of 4 g daily raises the urinary excretion of oxalate. Large

VITAMINC(ASCORBICACID) 267

Anti-oxidant

Collagen

biosynthesis

Steroid

metabolism

VITAMIN C

Folic acid

activation

CYP450

drug-metabolizing

enzyme function

Mitochondrial

electron transport

chain function

Figure 35.2:Functions of vitamin C.