Prescribing in practice

Leg cramps: the underlying

causes and available treatments
Abdelrazig Salih MD, FRCP (Edinburgh), FRCP (London)
Leg cramps are a painful and
VM

common complaint, especially in older patients and

pregnant women. Here the
author describes the various
causes and the range of
physical and drug therapies
available.

Figure 1. Physical measures to relieve leg cramps include immediately massaging

and flexing the affected muscles

eg cramps are involuntar y,

painful contractions of whole
muscles or muscle groups, which
usually occur in the calf or small
muscles of the foot but can affect
other parts of the leg. The severity
of the pain is variable and each
attack can last up to a few minutes.
Cramps may occur intermittently
during one day, or they may persist
over several weeks. While the majority will resolve spontaneously some
cases may require treatment, and

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leg cramps are an important cause

of insomnia among older people.
Leg cramps can affect both
young and older people. In a survey of 233 people aged 60 years and
over on a general practice register,
about a third reported cramps during the previous two months, and
in those aged 80 years or over the
proportion rose to half.1 Cramps
are also common among pregnant
women (45 per cent)2 and in 7 per
cent of children.3

Pathogenesis of leg cramps

It has been suggested that muscle
cramps occur as a result of stimulation of the reflex arc and possibly through hyperextension of the
motor neurones in any leg nerve
or in the spinal cord.4
It has also been proposed that
leg cramps occur when a maximally contracted muscle is stimulated, thus shortening the
muscle beyond physiological tolerance.5
Prescriber 5 September 2007

31

Prescribing in practice

Idiopathic
common cramps
Metabolic
thyroid disease
diabetes mellitus
hypoglycaemia
hyponatraemia
hypocalcaemia
hypomagnesaemia
hyper- and hypokalaemia
metabolic myopathy
Drugs
nifedipine
raloxifene
phenothiazines
morphine (withdrawal)
diuretics
penicillamine
ethanol
terbutaline
nicotinic acid
Occupational
writers
miners
musicians
Toxins
lead
tetanus
strychnine
Congenital
McArdles disease
Neoplasm
neoplastic peripheral nerve
infiltration
Miscellaneous
liver cirrhosis
sarcoidosis
lumbar spondylosis
Peripheral vascular or
neurological disease
Table 1. Conditions associated with
muscle cramps
32

Prescriber 5 September 2007

Visible fasciculations may precede and follow the cramp, indicating excessive excitability of the
terminal branches of motor neurones supplying the muscle. It is
unclear why cramps are painful,
but this is probably because the
demands of the overactive muscle
exceed metabolic supply, causing a
relative ischaemia and accumulation of metabolites.
Clinical evaluation

It is important to take a careful

histor y as medical conditions,
drugs and occupational factors
(see Table 1) may give a clue as to
the cause of the cramps. Careful
attention should be paid to the
time of onset and duration of
attacks.
The physical examination
should include a search for signs of
the conditions mentioned in Table
1, and particularly for signs of
peripheral neuropathy, vascular
insufficiency and underlying conditions such as diabetes and hyperthyroidism.
Investigations may include
analyses of thyroid-stimulating hormone, urea and electrolytes, heavy
metals and a glucose tolerance test.
Analyses of lactate and creatine
kinase levels and an electromyogram are useful if a muscle disorder is suspected.
Treating muscle cramps

The underlying cause of the leg

cramps must be addressed first.
Once this has been discovered, various methods can be used to treat
the cramps including physical measures and quinine sulphate, among
others.
Physical therapy
Placing a pillow to prop up the feet
at the end of the bed has been suggested, or lying in the prone position, possibly with the feet hanging
over the end of the bed.5

exclude all treatable secondary

causes
treat mild symptoms with
stretching exercises
resistant symptoms may be
treated with quinine sulphate at
200mg daily; this can be
increased to 300mg daily
if there is no response to
quinine within four weeks,
withdrawal should be considered
if benefit is obtained, then
quinine can be stopped
temporarily every three to four
months to see if it is still needed
patients should be counselled
on side-effects
Table 2. Practical approach to the
management of leg cramps

Others advise that, when

cramps occur, the patient should
immediately massage and flex the
affected muscles, and the pain will
be relieved in a few minutes.
Alternatively, stretching the calf
muscles before going to bed by performing simple exercises can also
be effective.6
Quinine sulphate
Although earlier studies7 failed to
show any benefit from taking quinine sulphate, later trials 8 have
found it to be superior to placebo
in alleviating leg cramps.
A meta-analysis has demonstrated the effectiveness of 200300mg quinine sulphate at
bedtime taken for up to four weeks
over placebo in preventing cramps
and reducing the number of nights
with cramps by over a quarter.9 In
this study, quinine had no effect on
the duration or severity of cramps
once they had started.
Although the mode of action of
quinine in leg cramps is not well
understood, the drug is thought to
decrease the susceptibility of the
muscle end-plate to nerve stimulation and increase the muscle
refractory period.
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Prescribing in practice

Quinine is metabolised mainly

by the liver, with peak blood levels
occurring one to three hours
after oral intake. The half-life
may be prolonged in older
patients who are receiving other
medications.
One of the side-effects of quinine is cinchonism, which results
in nausea, vomiting, tinnitus and
disturbed vision. This may progress
to deafness, optic atrophy, renal
failure, cardiac arrhythmia and
death.
Visual toxicity occurs when the
blood concentration of quinine
exceeds 10mg per litre, and this
may lead to permanent blindness.
Other side-effects include hypoglycaemia, thrombocytopenia,
hepatitis and hypersensitivity reactions. Quinine is contraindicated
during pregnancy and can lead to
digoxin toxicity.
In the USA, the Food and Drug
Administration (FDA) has abandoned quinine in the treatment of
leg cramps because of potentially
fatal immune-allergic reactions.
A therapeutic trial of quinine in
patients with leg cramps should be
considered only if physical measures have failed and there are significant symptoms, but the
treatment should be stopped if it
has not produced any benefits.

Prescriber 5 September 2007

Naftidrofuryl oxalate
Naftidrofuryl oxalate 30mg, given
as a slow-release preparation twice
daily in a double-blind, placebocontrolled study of 14 patients, was
more effective than placebo in
increasing the number of crampfree days by 34 per cent.10
Vitamin E
The role of vitamin E (alpha-tocopher yl) in the treatment of leg
cramps is controversial. Some studies11 based on a small number of
patients have shown benefit
among dialysis-induced leg
cramps, while a comparative
study 12 with quinine has not
demonstrated any superior effect
of vitamin E over placebo.
Conclusion

Leg cramps is a common condition

that can potentially cause disabling
symptoms. Precipitating factors
should be identified and treatment
is directed at those with significant
symptoms.
References

1. Naylor JR, Young JB. A general population sur vey of rest cramps. Age
Ageing 1994;23:418-20.
2. Valob A, Bohmer T. Leg cramps in
pregnancy how common are they?
Tidsskr Nor Laegforen 1999;119(11):
1589-90.

3. Leung AK, Wong Be, Chan PY, et al.

Nocturnal leg cramps in children: incidence and clinical characteristics. J Natl
Med Assoc 1999;91(6):329-32.
4. Layzer RB, Rowland LP. Cramps. N
Engl J Med 1971;285:31-40.
5. Weiner IH, Weiner HL. Nocturnal
leg muscle cramps. JAMA 1980;244:
2332-3.
6. Daniell HW. Simple cure for nocturnal leg cramps [letter]. N Engl J Med
1979;301:216.
7. Warburton A, Royston JP, ONeill CJ,
et al. A quinine a day keeps the leg
cramps away? Br J Clin Pharmacol
1987;23:459-65.
8. Fung Mc, Holbrook JH. Placebo-controlled trial of quinine therapy for nocturnal leg cramps. West J Med 1989;
151:42-4.
9. Man-Son-Hing M, Wells G. Metaanalysis of efficacy of quinine for treatment of nocturnal leg cramps in
elderly people. BMJ 1995;310:13-7.
10. Young JB, Connolly MJ. Naftidrofuryl treatment for rest cramp. Postgrad
Med J 1993;69:624-6.
11. Roca AO, Jarjoura D, Blend D, et al.
Dialysis leg cramps. Efficacy of quinine
versus vitamin E. ASAIO J 1992;38:481-5.
12. Connolly PS, Shirley EA, Wasson
JH, et al. Treatment of nocturnal leg
cramps. A cross over trial of quinine vs
vitamin E. Arch Intern Med 1992;
152:1877-80.

Dr Salih is a consultant rheumatologist at Warrington General Hospital,

Cheshire

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