Pharmaceutical guidelines of
patients with pathology of CNS
organs. Symptomatic treatment
of HEADACHE
Headaches
• Headache is an almost universal
experience and one of the most common
symptoms in medical practice. It varies
from an infrequent and trivial nuisance to a
pointer to serious disease.
Mechanisms
Pain receptors are located at the base of the brain in arteries
and veins and throughout meninges, extracranial vessels,
scalp, neck and facial muscles, paranasal sinuses, eyes and
teeth.
Curiously, brain substance is almost devoid of pain
receptors.
Head pain is mediated by mechanical and chemical
receptors (e.g. stretching of meninges, 5-HT and histamine
stimulation). Nerve impulses travel centrally via the Vth and
IXth cranial nerves and upper cervical sensory roots.
Most headaches are benign, but the diagnostic issue –
and usual concern – is the question of serious disease.
Chronic (benign) and recurrent
headaches
• Almost all recurring headaches lasting hours or days –
band-like, generalized head pains, with a history for
several years or months – are vaguely ascribed to
muscle tension and/or migraine
• Depression is a common accompaniment.
• In localized pain of short duration (minutes to hours),
sinusitis, glaucoma and migrainous neuralgia should be
considered.
• Headaches are not caused by essential hypertension;
malignant hypertension, with arterial damage and brain
swelling, occasionally causes headache.
• Eyestrain from refractive error does not cause headache,
though new prescription lenses sometimes provoke pain.
Cluster Headache
Tension headache
The vast majority of chronic daily headaches and recurrent
headaches are thought to be generated by neurovascular
irritation and referred to scalp muscles and soft tissues,
although the exact pathogenesis remains unclear.
Tight band sensations, pressure behind the eyes, throbbing and
bursting sensations are common. What is clear is that almost all
headaches with these features are benign.
There may be obvious precipitating factors such as worry,
noise, concentrated visual effort or fumes. Depression is
also a frequent co-morbid feature. Tension headaches are
often attributed to cervical spondylosis, refractive errors
or high blood pressure: evidence for such associations
is poor. Headaches also follow even minor head injuries.
Tenderness and tension in neck and scalp muscles are the
only physical signs. Analgesic overuse is a prominent cause
of headache.
Pressure headaches
• Intracranial mass lesions displace and stretch meninges
and basal vessels. Pain is provoked when these
structures are shifted either by a mass or by changes in
cerebrospinal fluid (CSF) pressure, e.g. coughing.
Cerebral oedema around brain tumours causes further
shift. These ‘pressure headaches’ typically become
worse on lying down.
• Any headache present on waking and made worse by
coughing, straining or sneezing may be due to a mass
lesion.
• Vomiting often accompanies pressure headaches. Such
headaches are caused early, over days or weeks, by
posterior fossa masses, but over a longer time scale –
months or years – by hemisphere tumours.
• A rare cause of prostrating headache with lower limb
weakness is an intraventricular tumour causing
intermittent hydrocephalus.
Headache of subacute onset
• The onset and progression of a headache
over days or weeks with or without
features of a pressure headache should
always raise suspicion of an intracranial
mass or serious intracranial disease.
• Encephalitis, viral meningitis and chronic
meningitis should also be considered.
Headaches with scalp
tenderness
• Patches of exquisite tenderness overlying
superficial scalp arteries are caused by giant cell
arteritis in patients over 50.
Headache following head injury
• The majority of post-trauma headaches lasting
days, weeks or months are not caused by any
serious intracranial pathology.
• However, subdural haematoma must be
considered.
A single episode of severe
headache
• This common emergency is caused by one of the
following:
■ subarachnoid haemorrhage (SAH) and cervical arterial
dissection
■ migraine, or other benign headaches
■ meningitis (occasionally).
• Particular attention should be paid to
• suddenness of onset (suggestive of SAH).
• The exact time of onset,
• time to peak, duration,
• associated symptoms and previous headache history
should be documented.
• Neck stiffness, vomiting (meningeal irritation) and a rash
and/or fever suggest bacterial meningitis.
Management
Headache management involves:
■ explanation (imaging is often needed)
■ avoiding evident causes, e.g. bright lights
■ physical treatments – massage, ice packs,
relaxation
■ antidepressants – when indicated
■ drugs for recurrent headache/migraine.
Migraine
• Migraine is recurrent headache
associated with visual and gastrointestinal
disturbance.
• The borderland between migraine and
tension headaches can be indistinct. Over
20% of any population world-wide report
migrainous symptoms; in 90%, these
began before 40 years of age.
Migraine. Mechanisms
• Precise mechanisms remain unclear. Genetic factors
play some part – a rare form of familial migraine is
associated with mutation in the alpha-1 subunit of the
P/Q-type voltagegated calcium channel on chromosome
19.
• The pathophysiology of migraine is now thought to
involve changes in the brainstem blood flow which have
been found on PET scanning during migraine attacks.
• This leads to an unstable trigeminal nerve nucleus and
nuclei in the basal thalamus. This results in release of
calcitonin-related peptide (CGR8), substance P and
other vasoactive peptides, leading to neurogenic
inflammation, which gives rise to pain, and vasodilation
of cerebral and dural vessels which also contribute
towards the headache.
• Cortical spreading depression is also proposed as a
mechanism for the aura.
Some patients recognize
precipitating factors:
■ weekend migraine (a time of relaxation)
■ chocolate (high in phenylethylamine)
■ cheese (high in tyramine)
■ noise and irritating lights
■ association with premenstrual symptoms.
Migraine is common around puberty and at the menopause
and sometimes increases in severity or frequency with
hormonal contraceptives, in pregnancy and occasionally
with the onset of hypertension or following minor head
trauma.
Migraine is not suggestive of any serious intracranial
lesion.
However, since migraine is so common, an intracranial
mass and migraine sometimes occur together by
coincidence.
Clinical patterns
• Migraine attacks vary from intermittent
headaches indistinguishable from tension
headaches to discrete episodes that mimic
thromboembolic cerebral ischaemia.
• Distinction between variants is somewhat
artificial.
• Migraine can beseparated into phases:
■ well-being before an attack (occasional)
■ prodromal symptoms
■ the main attack – headache, nausea, vomiting
■ sleep and feeling drained afterwards.
Migraine with aura (classical
migraine)
• Prodromal symptoms are usually visual and related to
depression
• of visual cortical function or retinal function.
• Transient aphasia sometimes occurs, with tingling,
numbness, vague weakness of one side and nausea.
• The prodrome persists for a few minutes to about an
hour.
• Headache then follows. This is occasionally hemicranial
(i.e. splitting the head) but often begins locally and
becomes generalized.
• Nausea increases and vomiting follows. The patient is
irritable and prefers the dark.
• Superficial scalp arteries are engorged and pulsating.
• After several hours the migraine settles, sometimes with
a diuresis.
• Deep sleep often ensues.
Migraine without aura (common
migraine)
• This is the usual variety. Prodromal visual
symptoms are vague.
• There is a similar headache often accompanied
by nausea and malaise.
Basilar migraine
• Prodromal symptoms include circumoral and
tongue tingling, vertigo, diplopia, transient visual
disturbance, syncope, dysarthria and ataxia.
• These occur alone or progress to a typical
migraine.
Hemiparetic migraine
• This rarity is classical migraine with hemiparetic
features, i.e. resembling a stroke, but with
recovery within 24 hours.
• Exceptionally, cerebral infarction occurs.
Ophthalmoplegic and facioplegic migraine
• These rarities are a IIIrd, VIth or VIIth nerve
palsy with a migraine, and they are difficult to
diagnose without investigation to exclude other
conditions.
Differential diagnosis
• A sudden migraine headache may resemble SAH or the
onset of meningitis.
• Hemiplegic, visual and hemisensory symptoms must be
distinguished from thromboembolic TIAs
• In TIAs maximum deficit is present immediately and
headache is unusual.
• Unilateral tingling or numbness may resemble sensory
epilepsy (partial seizures). In epilepsy, distinct march
(progression) of symptoms is usual.
Management
General measures include:
■ avoidance of dietary factors – rarely helpful.
• Patients taking hormonal contraceptives may
benefit from a brand change, or trying without.
Depot oestrogens are sometimes used. Severe
hemiparetic symptoms are a potential reason to
stop hormonal contraceptives.
• Premenstrual migraine sometimes responds to
diuretics.
At the start of an attack
• Paracetamol or other analgesics should be
taken, with an antiemetic such as
metoclopramide if necessary. Repeated use of
analgesics leads to further headaches.
• Triptans (5HT1 agonists) are also widely used,
sometimes aborting an attack effectively.
Sumatriptan was the first marketed; almotriptan,
eletriptan, frovatriptan, naratriptan, rizatriptan
and zolmitriptan are now available, with various
routes of administration.
• Triptans should be avoided when there is
vascular disease, and not overused.
Ergot Derivatives
• cause constriction of cranial blood vessels and decrease
the pulsation of cranial arteries. As a result, they reduce
the hyperperfusion of the basilar artery vascular bed.
• Because these agents are associated with many
systemic adverse effects, their usefulness is limited in
some patients. The ergots are contraindicated during
pregnancy because of the potential for adverse effects in
the mother and fetus.
• Dihydroergotamine (Migranal) can be used in the IM or
IV form or as a nasal spray to provide rapid relief from
migraine headache. This agent is the drug of choice if
the oral route of administration is not possible. In 2003,
the parenteral form was approved for the treatment of
cluster headaches.
Ergot Derivatives (cont’d)
• Ergotamine(generic), the prototype drug in
this class, was the mainstay of migraine
headache treatment before the triptans
became available. This agent is
administered sublingually for rapid
absorption. Cafergot, the very popular oral
form, combines ergotamine with caffeine
to increase its absorption from the GI tract.
Contraindications and Cautions
• Ergot derivatives are contraindicated in the following
circumstances: presence of allergy to ergot preparations;
CAD, hypertension, or peripheral vascular disease,
which could be exacerbated by the CV effects of these
drugs; impaired liver function, which could alter the
metabolism and excretion of these drugs; and pregnancy
or lactation because of the potential for adverse effects
on the fetus and neonate. Ergotism (vomiting, diarrhea,
seizures) has been reported in affected infants.
• Caution should be used in two instances: with pruritus,
which could become worse with drug-induced vascular
constriction, and with malnutrition because ergot
derivatives stimulate the CTZ and can cause severe GI
reactions, possibly worsening malnutrition.
Adverse Effects
• The adverse effects of ergot derivatives can be related to
the drug-induced vascular constriction.
• CNS effects include numbness, tingling of extremities,
and muscle pain;
• CV effects such as pulselessness, weakness, chest
pain, arrhythmias, localized edema and itching, and MI
may also occur.
• the direct stimulation of the CTZ can cause GI upset,
nausea, vomiting, and diarrhea. Ergotism, a syndrome
associated with the use of these drugs, causes nausea,
vomiting, severe thirst, hypoperfusion, chest pain, blood
pressure changes, confusion, drug dependency (with
prolonged use), and a drug withdrawal syndrome.
Headaches are distributed in the
general population in a definite
gender-related pattern
• Migraine headaches are three times more likely to occur
in women than men.
• Cluster headaches are more likely to occur in men than
in women.
• Tension headaches are more likely to occur in women
than in men.
• There is some speculation that the female predisposition
to migraine headaches may be related to the vascular
sensitivity to hormones. Some women can directly plot
migraine occurrence to periods of fluctuations in their
menstrual cycle. The introduction of the triptan class of
antimigraine drugs has been beneficial for many of these
women.
Prophylaxis
• The following are used continuously when attacks are
frequent:
■ pizotifen (5HT antagonist) 0.5 mg at night for several
days, increasing to 1.5 mg (common side-effects are
weight gain and drowsiness)
■ propranolol 10 mg three times daily, increasing to 40–
80 mg three times daily
■ amitriptyline 10 mg (or more) at night.
• Sodium valproate, methysergide, SSRIs, verapamil,
topiramate, nifedipine and naproxen are also used.
• Gap junction blockers are being used in trials.
Other benign headaches
■ Ice-cream headache. Sufferers describe intense,
retropharyngeal head pain lasting for a few seconds or
minutes following ice-cream or very cold foods.
■ Primary cough headache is a sudden sharp head pain
on coughing. No underlying cause is found but
intracranial pathology should be excluded. The problem
often resolves spontaneously. Very rarely, for severe
headache, a lumbar puncture with removal of CSF can
help.
■ Primary low CSF volume headaches, seen typically on
standing up, are also well recognized. The patient may
give a history of some event, such as straining or orgasm, but these
headaches sometimes arise spontaneously. Treatment with an
autologous intrathecal blood patch can be helpful.
Secondary low CSF volume can follow lumbar puncture
Other benign headaches (cont’d)
■ Primary sex headache describes varieties of head pain
that typically rise to a crescendo at orgasm, largely in
males. Treatment with propranolol or diltiazem is said to
be helpful, but these pains often resolve spontaneously
after several attacks. Exceptionally, sex headaches
occur with an unruptured intracranial aneurysm.
■ Many other varieties of primary headache are listed in
the international classification, e.g. hemicrania continua,
primary stabbing headache, primary exertional
headache, hypnic headache, and primary thunderclap
headache.
■ Post-traumatic headache is also a common
problem. Headaches do sometimes follow a minor blow
to the head; they tend to resolve, typically within 6–8
weeks. However, when there is third party involvement,
and especially with litigation, these headaches can
persist for long periods. Opinions vary about their
cause.