A Textbook of Clinical Pharmacology and Therapeutics

266 VITAMINS AND TRACE ELEMENTS

Maintenance of

epithelial

cell integrity

Stabilization

of membranes

Component of

rhodopsin

(essential for

normal vision)

VITAMIN A

Cofactor for

microsomal

drug-metabolizing

enzymes

Cofactor in

cholesterol

synthesis

Cofactor in

mucopolysaccharide

synthesis

Normal

soft tissue

growth

Normal

skeletal

growth

Figure 35.1:Functions of vitamin A.

prevent vitamin A deficiency. Regular dietary or parenteral
supplementation of vitamin A may be necessary in patients
with steatorrhoea.

Adverse effects

Long-term ingestion of more than double the recommended
daily intake of vitamin A can lead to toxicity and chronic hyper-
vitaminosis A.
Chronic toxicity includes:

1. anorexia and vomiting;
   2.itching and dry skin;
   3.raised intracranial pressure (benign intracranial
   hypertension), irritability and headache;
   4.tender hyperostoses in the skull and long bones;
   5.hepatotoxicity;
   6.congenital abnormalities.

Acute poisoning causes:

1. headache, vomiting and papilloedema;
   2.desquamation.

Pharmacokinetics

Gastro-intestinal absorption of retinol via a saturable active
transport mechanism is very efficient, but is impaired in patients
with steatorrhoea. Carotene is metabolized to vitamin A in the
intestine. Esterified retinol reaches peak plasma concentrations
four hours after ingestion. Retinol is partly conjugated to a glu-
curonide and undergoes enterohepatic circulation. Clinical evi-
dence of vitamin A deficiency usually appears only months after
reduced intake, when hepatic stores have been depleted.

Contraindications

Excess vitamin A during pregnancy causes birth defects (closely
related compounds are involved in controlling morphogenesis
in the fetus). Therefore pregnant women should not take vita-
min A supplements, and should also avoid liver in their diet.

DERIVATIVES OF VITAMIN A (RETINOIDS)

RETINOIDS AND THE SKIN

Vitamin A derivatives, e.g. etretinate, are discussed in Chapter 51.

RETINOIDS AND CANCER

This is discussed in Chapter 48.

VITAMIN B 1 (THIAMINE)

Physiology

All plant and animal cells require thiamine (in the form of thi-

amine pyrophosphate) for carbohydrate metabolism, as it is a

coenzyme for decarboxylases and transketolases. Thiamine defi-

ciency leads to the various manifestations of beriberi, including

peripheral neuropathy and cardiac failure. Increased carbohy-

drate utilization requires increased intake because thiamine is

consumed during carbohydrate metabolism. It is therefore use-

ful to express thiamine needs in relation to the calorie intake.

Diets associated with beriberi contain less than 0.3 mg thiamine

per 1000 kcal. If the diet provides more than this, the excess is

excreted in the urine. Thus the recommended daily intake of

0.4 mg/1000 kcal provides a considerable safety margin. The

body possesses little ability to store thiamine and with absolutely

deficient intake, beriberi develops within weeks.

Acute thiamine deficiency may be precipitated by a carbo-

hydrate load in patients who have a marginally deficient diet.

This is especially important in alcoholics and thiamine replace-

ment should precede intravenous dextrose in alcoholic patients

with a depressed conscious level. Failure to do this has historic-

ally been associated with worsening encephalopathy and per-

manent sequelae (e.g. Korsakoff’s psychosis). Thiamine is

found in many plant and animal foods (e.g. yeast and pork).

Use

Thiamine is used in the treatment of beriberi and other states of

thiamine deficiency, or in their prevention. Such conditions

include alcoholic neuritis, Wernicke’s encephalopathy and the

neuritis of pregnancy, as well as chronic diarrhoeal states and

after intestinal resection. The parenteral route of administration

is used in confused patients. Once the deficiency state has been

corrected, the oral route is preferred, unless gastrointestinal dis-

ease interferes with ingestion or absorption of the vitamin.

Adverse effects

Anaphylactoid reactions following parenteral thiamine dos-

ing have been reported, so parenteral administration should

be restricted to situations where it is essential.

Pharmacokinetics

Absorption of thiamine following intramuscular injection is

rapid and complete. Thiamine is also well absorbed through

the mucosa of the upper part of the small intestine by both

active and passive mechanisms, and surplus intake is excreted

unchanged in the urine.

VITAMIN B 3 (NIACIN AND NICOTINIC ACID)

Physiology

Niacin is found in yeast, rice, liver and other meats. Its vital

metabolic role is as a component of nicotinamide adenine