Pharmaceutical care when Pharmaceutical care when dispensing OTCdispensing OTC

medications for the medications for the symptomatic treatment ofsymptomatic treatment of

headaches. Pharmaceutical headaches. Pharmaceutical care of patients care of patients

with disorders of local with disorders of local circulationcirculation

HeadachesHeadaches Headache is an almost universal Headache is an almost universal

experience and one of theexperience and one of the most common most common symptoms in medical practice. It varies symptoms in medical practice. It varies fromfrom an infrequent and trivial nuisance to a an infrequent and trivial nuisance to a pointer to seriouspointer to serious disease.disease.

MechanismsMechanismsPain receptors are located at the base of the brain in arteriesPain receptors are located at the base of the brain in arteriesand veins and throughout meninges, extracranial vessels,and veins and throughout meninges, extracranial vessels,scalp, neck and facial muscles, paranasal sinuses, eyes andscalp, neck and facial muscles, paranasal sinuses, eyes andteeth. teeth. Curiously, Curiously, brain substance is almost devoid of painbrain substance is almost devoid of painreceptorsreceptors..Head pain is mediated by mechanical and chemicalHead pain is mediated by mechanical and chemicalreceptors (e.g. stretching of meninges, 5-HT and histaminereceptors (e.g. stretching of meninges, 5-HT and histaminestimulation). Nerve impulses travel centrally via the Vth andstimulation). Nerve impulses travel centrally via the Vth andIXth cranial nerves and upper cervical sensory roots.IXth cranial nerves and upper cervical sensory roots.

Most headaches are benign, but the diagnostic issue –Most headaches are benign, but the diagnostic issue –and usual concern – is the question of serious disease. and usual concern – is the question of serious disease.

Chronic (benign) and recurrent Chronic (benign) and recurrent headachesheadaches

Almost all recurring headaches lasting hours or days –Almost all recurring headaches lasting hours or days –band-like, generalized head painsband-like, generalized head pains, with a history for , with a history for severalseveral years or months – are vaguely ascribed to years or months – are vaguely ascribed to muscle tensionmuscle tension and/or migraine and/or migraine

DepressionDepression is a common is a common accompaniment.accompaniment. In In localized pain of short durationlocalized pain of short duration (minutes to hours), (minutes to hours),

sinusitis, glaucomasinusitis, glaucoma and and migrainous neuralgiamigrainous neuralgia should should be be considered. considered.

Headaches are not caused by essentialHeadaches are not caused by essential hypertension; hypertension; malignant hypertension, with arterial damagemalignant hypertension, with arterial damage and brain and brain swelling, occasionally causes headache.swelling, occasionally causes headache.

Eyestrain from refractive error does not cause headache,Eyestrain from refractive error does not cause headache, though though new prescription lenses sometimes provoke painnew prescription lenses sometimes provoke pain..

Cluster HeadacheCluster Headache

Tension headacheTension headache

The vast majority of chronic daily headaches and recurrentThe vast majority of chronic daily headaches and recurrentheadaches are thought to be generated by neurovascularheadaches are thought to be generated by neurovascularirritation and referred to scalp muscles and soft tissues,irritation and referred to scalp muscles and soft tissues,although the exact pathogenesis remains unclear. although the exact pathogenesis remains unclear.

Tight bandTight band sensations, pressure behind the eyes, throbbing and sensations, pressure behind the eyes, throbbing and burstingbursting sensations are common.sensations are common. What is clear is that almost all What is clear is that almost all

headaches with these features are benign.headaches with these features are benign.There may be obvious precipitating factors such as worry,There may be obvious precipitating factors such as worry,noise, concentrated visual effort or fumes.noise, concentrated visual effort or fumes. Depression is Depression isalso a frequent co-morbid feature. Tension headaches arealso a frequent co-morbid feature. Tension headaches areoften attributed to cervical spondylosis, refractive errorsoften attributed to cervical spondylosis, refractive errorsor high blood pressure: evidence for such associationsor high blood pressure: evidence for such associationsis poor. Headaches also follow even minor head injuries.is poor. Headaches also follow even minor head injuries.Tenderness and tension in neck and scalp muscles are theTenderness and tension in neck and scalp muscles are theonly physical signs.only physical signs. Analgesic overuse is a prominent cause Analgesic overuse is a prominent causeof headache.of headache.

Pressure headachesPressure headaches Intracranial mass lesions displace and stretch meninges Intracranial mass lesions displace and stretch meninges

andand basal vessels. Pain is provoked when these basal vessels. Pain is provoked when these structures arestructures are shifted either by a mass or by changes in shifted either by a mass or by changes in cerebrospinal fluidcerebrospinal fluid (CSF) pressure, e.g. coughing. (CSF) pressure, e.g. coughing. Cerebral oedema aroundCerebral oedema around brain tumours causes further brain tumours causes further shift. These ‘pressure headaches’shift. These ‘pressure headaches’ typically become typically become worse on lying downworse on lying down..

Any headache present on waking and made worse byAny headache present on waking and made worse by coughing, straining or sneezing may be due to a mass coughing, straining or sneezing may be due to a mass lesionlesion..

VomitingVomiting often accompanies pressure headaches. Such often accompanies pressure headaches. Such headaches are caused early, over days or weeks, by headaches are caused early, over days or weeks, by posteriorposterior fossa masses, but over afossa masses, but over a longer time scale – longer time scale – months or years – by hemispheremonths or years – by hemisphere tumours.tumours.

A rare cause of prostrating headache with lower limbA rare cause of prostrating headache with lower limb weakness is an intraventricular tumour causing weakness is an intraventricular tumour causing intermittentintermittent hydrocephalus.hydrocephalus.

Headache of subacute onsetHeadache of subacute onset

The onset and progression of a headache The onset and progression of a headache over days or weeksover days or weeks with or without with or without features of a pressure headache shouldfeatures of a pressure headache should always raise suspicion of always raise suspicion of an intracranial an intracranial mass or seriousmass or serious intracranial disease.intracranial disease.

Encephalitis, viral meningitisEncephalitis, viral meningitis and and chronic chronic meningitismeningitis should also be should also be considered.considered.

Headaches with scalp Headaches with scalp tendernesstenderness

Patches of exquisite tenderness overlying Patches of exquisite tenderness overlying superficial scalpsuperficial scalp arteries are caused by giant cell arteries are caused by giant cell arteritis in patientsarteritis in patients over 50.over 50.

Headache following head injuryHeadache following head injury The majority of post-trauma headaches The majority of post-trauma headaches lasting lasting

days, weeksdays, weeks or months are not caused by any or months are not caused by any serious intracranial pathology.serious intracranial pathology.

However, However, subdural haematomasubdural haematoma must be must be considered.considered.

A single episode of severe A single episode of severe headacheheadache

This common emergency is caused by one of theThis common emergency is caused by one of the following:following:

■ ■ subarachnoid haemorrhage (SAH) and cervical arterialsubarachnoid haemorrhage (SAH) and cervical arterialdissectiondissection■ ■ migraine, or other benign headachesmigraine, or other benign headaches■ ■ meningitismeningitis (occasionally). (occasionally). Particular attention should be paid to Particular attention should be paid to suddenness of onsetsuddenness of onset (suggestive of SAH). (suggestive of SAH). The exact time of onset, The exact time of onset, time to peak,time to peak, duration, duration, associated symptoms and previous headacheassociated symptoms and previous headache history history

should be documented. should be documented. Neck stiffness, vomitingNeck stiffness, vomiting (meningeal irritation) and a rash (meningeal irritation) and a rash

and/or fever suggest bacterialand/or fever suggest bacterial meningitis.meningitis.

ManagementManagement

Headache management involves:Headache management involves:

■ ■ explanation (imaging is often needed)explanation (imaging is often needed)

■ ■ avoiding evident causes, e.g. bright lightsavoiding evident causes, e.g. bright lights

■ ■ physical treatments – massage, ice packs, physical treatments – massage, ice packs, relaxationrelaxation

■ ■ antidepressants – when indicatedantidepressants – when indicated

■ ■ drugs for recurrent headache/migraine.drugs for recurrent headache/migraine.

MigraineMigraine

Migraine is recurrent headache Migraine is recurrent headache

associated with visual andassociated with visual and gastrointestinal gastrointestinal disturbance. disturbance.

The borderland betweenThe borderland between migraine and migraine and tension headaches can be indistinct. Over tension headaches can be indistinct. Over 20%20% of any population world-wide report of any population world-wide report migrainous symptoms;migrainous symptoms; in 90%, these in 90%, these began before 40 years of age.began before 40 years of age.

MigraineMigraine.. Mechanisms Mechanisms Precise mechanisms remain unclear. Genetic factors Precise mechanisms remain unclear. Genetic factors

playplay some part – a rare form of familial migraine is some part – a rare form of familial migraine is associated withassociated with mutation in the alpha-1 subunit of the mutation in the alpha-1 subunit of the P/Q-type voltagegatedP/Q-type voltagegated calcium channel on chromosome calcium channel on chromosome 19.19.

The pathophysiology of migraine is now thought to The pathophysiology of migraine is now thought to involveinvolve changes in the brainstem bloodchanges in the brainstem blood flow which have flow which have been foundbeen found on PET scanning during migraine attacks. on PET scanning during migraine attacks.

This leads to anThis leads to an unstable trigeminal nerve nucleus and unstable trigeminal nerve nucleus and nuclei in the basalnuclei in the basal thalamus. This results in release of thalamus. This results in release of calcitonin-related peptidecalcitonin-related peptide (CGR8), substance P and (CGR8), substance P and other vasoactive peptides, leadingother vasoactive peptides, leading to to neurogenic neurogenic inflammationinflammation, which gives rise to pain, and, which gives rise to pain, and vasodilation vasodilation of cerebral and dural vesselsof cerebral and dural vessels which also contribute which also contribute towards the headache.towards the headache.

Cortical spreading depression is also proposed as aCortical spreading depression is also proposed as a mechanism for the aura.mechanism for the aura.

Some patients recognize Some patients recognize precipitating factorsprecipitating factors::

■ ■ weekend migraine (a time of relaxation)weekend migraine (a time of relaxation)■ ■ chocolate (high in phenylethylamine)chocolate (high in phenylethylamine)■ ■ cheese (high in tyramine)cheese (high in tyramine)■ ■ noise and irritating lightsnoise and irritating lights■ ■ association with premenstrual symptoms.association with premenstrual symptoms.Migraine is common around Migraine is common around pubertypuberty and at the and at the menopausemenopauseand sometimes increases in severity or frequency with and sometimes increases in severity or frequency with

hormonalhormonal contraceptivescontraceptives, in , in pregnancypregnancy and occasionally and occasionally withwith the onset of the onset of hypertensionhypertension or or following minor head following minor head traumatrauma..

Migraine Migraine is not suggestive of any serious intracranial lesionis not suggestive of any serious intracranial lesion..However, since migraine is so common, an intracranial However, since migraine is so common, an intracranial

massmass and migraine sometimes occur together by and migraine sometimes occur together by coincidence.coincidence.

Clinical patternsClinical patterns

Migraine attacks vary from intermittent Migraine attacks vary from intermittent headaches indistinguishableheadaches indistinguishable from tension from tension headaches to discrete episodes thatheadaches to discrete episodes that mimic mimic thromboembolic cerebral ischaemia. thromboembolic cerebral ischaemia.

DistinctionDistinction between variants is somewhat between variants is somewhat artificial. artificial.

Migraine can beseparated into phases:Migraine can beseparated into phases:■ ■ well-being before an attack (occasional)well-being before an attack (occasional)■ ■ prodromal symptomsprodromal symptoms■ ■ the main attack – the main attack – headache, nausea, vomitingheadache, nausea, vomiting■ ■ sleep and feeling drained afterwards.sleep and feeling drained afterwards.

Migraine with aura (Migraine with aura (classical classical migrainemigraine))

Prodromal symptoms are usually visual and related to Prodromal symptoms are usually visual and related to depressiondepression

of visual cortical function or retinal function. of visual cortical function or retinal function. Transient aphasia sometimesTransient aphasia sometimes occurs, with tingling, occurs, with tingling,

numbness, vague weakness of one sidenumbness, vague weakness of one side and nausea. and nausea. The prodrome persists for a few minutes toThe prodrome persists for a few minutes to about an about an

hour. hour. Headache then follows. This is occasionallyHeadache then follows. This is occasionally hemicranial hemicranial

(i.e. splitting the head) but often begins locally(i.e. splitting the head) but often begins locally and and becomes generalized. becomes generalized.

Nausea increases and vomitingNausea increases and vomiting follows. The patient is follows. The patient is irritable and prefers the dark. irritable and prefers the dark.

SuperficialSuperficial scalp arteries are engorged and pulsating. scalp arteries are engorged and pulsating. After severalAfter several hours the migraine settles, sometimes with hours the migraine settles, sometimes with

a diuresis. a diuresis. DeepDeep sleep often ensues.sleep often ensues.

Migraine without aura (Migraine without aura (common common migrainemigraine))

This is the usual variety. Prodromal visual This is the usual variety. Prodromal visual symptoms aresymptoms are vague. vague.

There is a similar headache often accompanied There is a similar headache often accompanied byby nausea and malaise.nausea and malaise.

Basilar migraineBasilar migraine Prodromal symptoms include circumoral and Prodromal symptoms include circumoral and

tongue tingling,tongue tingling, vertigo, diplopia, transient visual vertigo, diplopia, transient visual disturbance,disturbance, syncope, dysarthria and ataxia. syncope, dysarthria and ataxia.

These occur alone orThese occur alone or progress to a typical progress to a typical migraine.migraine.

Hemiparetic migraineHemiparetic migraine

This rarity is classical migraine with hemiparetic This rarity is classical migraine with hemiparetic features,features, i.e. resembling a stroke, but with i.e. resembling a stroke, but with recovery within 24 hours.recovery within 24 hours.

Exceptionally, cerebral infarction occurs.Exceptionally, cerebral infarction occurs.Ophthalmoplegic and facioplegic migraineOphthalmoplegic and facioplegic migraine

These rarities are a IIIrd, VIth or VIIth nerve These rarities are a IIIrd, VIth or VIIth nerve palsy with apalsy with a migraine, and they are difficult to migraine, and they are difficult to diagnose without investigationdiagnose without investigation to exclude other to exclude other conditions.conditions.

Differential diagnosisDifferential diagnosis

A sudden migraine headache may resemble A sudden migraine headache may resemble SAHSAH or or thethe onset of meningitisonset of meningitis. .

Hemiplegic, visual and hemisensoryHemiplegic, visual and hemisensory symptoms must be symptoms must be distinguished from distinguished from thromboembolic TIAsthromboembolic TIAs

In TIAs maximum deficit is present immediately andIn TIAs maximum deficit is present immediately and headache is unusual. headache is unusual.

Unilateral tingling or numbness mayUnilateral tingling or numbness may resemble resemble sensory sensory epilepsyepilepsy (partial seizures). In epilepsy, distinct (partial seizures). In epilepsy, distinct march march (progression) of symptoms is usual.(progression) of symptoms is usual.

ManagementManagementGeneral measures include:General measures include:

■ ■ avoidance of dietary factors – rarely helpful.avoidance of dietary factors – rarely helpful. Patients taking hormonal contraceptives may Patients taking hormonal contraceptives may

benefit from abenefit from a brand change, or trying without. brand change, or trying without. Depot oestrogens are sometimesDepot oestrogens are sometimes used. Severe used. Severe hemiparetic symptoms are a potentialhemiparetic symptoms are a potential reason to reason to stop hormonal contraceptives. stop hormonal contraceptives.

PremenstrualPremenstrual migraine sometimes responds to migraine sometimes responds to diuretics.diuretics.

At the start of an attackAt the start of an attack ParacetamolParacetamol or other or other analgesicsanalgesics should be should be

taken, with an antiemetic such as taken, with an antiemetic such as metoclopramidemetoclopramide if necessary. Repeated use of if necessary. Repeated use of analgesics leads to furtheranalgesics leads to further headaches.headaches.

Triptans Triptans (5HT1 agonists) are also widely used,(5HT1 agonists) are also widely used, sometimes aborting an attack effectively. sometimes aborting an attack effectively. SumatriptanSumatriptan waswas the first marketed; the first marketed; almotriptan, almotriptan, eletriptan, frovatriptan, naratriptan,eletriptan, frovatriptan, naratriptan, rizatriptanrizatriptan and and zolmitriptanzolmitriptan are now available, with are now available, with various various routes of administration. routes of administration.

Triptans should be avoidedTriptans should be avoided when there is when there is vascular disease, and not overused.vascular disease, and not overused.

Ergot DerivativesErgot Derivatives cause constriction of cranial blood vessels and decrease cause constriction of cranial blood vessels and decrease

the pulsation ofthe pulsation of cranial arteries. As a result, they reduce cranial arteries. As a result, they reduce the hyperperfusion of the basilar artery vascular bed.the hyperperfusion of the basilar artery vascular bed.

Because these agents are associated with many Because these agents are associated with many systemic adverse effects, their usefulness issystemic adverse effects, their usefulness is limited in limited in some patients. The ergots are contraindicated during some patients. The ergots are contraindicated during pregnancy because of the potential forpregnancy because of the potential for adverse effects in adverse effects in the mother and fetus.the mother and fetus.

DDihydroergotamine ihydroergotamine ((MigranalMigranal) can be used in the IM or ) can be used in the IM or IV form or as a nasal spray to provide rapid relief from IV form or as a nasal spray to provide rapid relief from migraine headache. This agent is the drug of choice if migraine headache. This agent is the drug of choice if the oral route of administration is not possible. In 2003, the oral route of administration is not possible. In 2003, the parenteral form was approved for the treatment of the parenteral form was approved for the treatment of cluster headaches.cluster headaches.

Ergot DerivativesErgot Derivatives (cont’d) (cont’d)

ErgotamineErgotamine(generic), the prototype drug in (generic), the prototype drug in this class, was the mainstay of migraine this class, was the mainstay of migraine headache treatment before the triptans headache treatment before the triptans became available. This agent is became available. This agent is administered sublingually for rapid administered sublingually for rapid absorption. absorption. CafergotCafergot, the very popular oral , the very popular oral form, combines ergotamine with caffeine form, combines ergotamine with caffeine to increase its absorption from the GI tract.to increase its absorption from the GI tract.

Contraindications and CautionsContraindications and Cautions

Ergot derivatives are contraindicated in the following Ergot derivatives are contraindicated in the following circumstances: presence of allergy to ergotcircumstances: presence of allergy to ergot preparations; preparations; CAD, hypertension, or peripheral vascular disease, CAD, hypertension, or peripheral vascular disease, which could be exacerbated bywhich could be exacerbated by the CV effects of these the CV effects of these drugs; drugs; impaired liver function, impaired liver function, which could alter the which could alter the metabolism andmetabolism and excretion of these drugs; excretion of these drugs; and pregnancy and pregnancy or lactation or lactation because of the potential for adverse effectsbecause of the potential for adverse effects on the fetus and neonate. on the fetus and neonate. Ergotism (vomiting, diarrhea, Ergotism (vomiting, diarrhea, seizures) has been reported in affectedseizures) has been reported in affected infants.infants.

Caution should be used in two instances: with pruritus, Caution should be used in two instances: with pruritus, which could become worse withwhich could become worse with drug-induced vascular drug-induced vascular constrictionconstriction, and with malnutrition , and with malnutrition because ergot because ergot derivatives stimulate thederivatives stimulate the CTZ and can cause severe GI CTZ and can cause severe GI reactions, possibly worsening malnutrition.reactions, possibly worsening malnutrition.

Adverse EffectsAdverse Effects The adverse effects of ergot derivatives can be related to The adverse effects of ergot derivatives can be related to

the drug-induced vascular constriction.the drug-induced vascular constriction. CNS effects include numbness, tingling of extremities, CNS effects include numbness, tingling of extremities,

and muscle pain; and muscle pain; CV effects such asCV effects such as pulselessness, weakness, chest pulselessness, weakness, chest

pain, arrhythmias, localized edema and itching, and MI pain, arrhythmias, localized edema and itching, and MI may alsomay also occur.occur.

the direct stimulation of the CTZ can cause GI upset, the direct stimulation of the CTZ can cause GI upset, nausea, vomiting, andnausea, vomiting, and diarrhea. Ergotism, a syndrome diarrhea. Ergotism, a syndrome associated with the use of these drugs, causes nausea, associated with the use of these drugs, causes nausea, vomiting,vomiting, severe thirst, hypoperfusion, chest pain, blood severe thirst, hypoperfusion, chest pain, blood pressure changes, confusion, drug dependencypressure changes, confusion, drug dependency (with (with prolonged use), and a drug withdrawal syndrome.prolonged use), and a drug withdrawal syndrome.

ProphylaxisProphylaxis The following are used continuously whenThe following are used continuously when attacks are attacks are

frequent:frequent:■ ■ pizotifenpizotifen (5HT antagonist) 0.5 mg at night for several (5HT antagonist) 0.5 mg at night for severaldays, increasing to 1.5 mg (common side-effects aredays, increasing to 1.5 mg (common side-effects areweight gain and drowsiness)weight gain and drowsiness)■ ■ propranololpropranolol 10 mg three times daily, increasing to 40– 10 mg three times daily, increasing to 40–80 mg three times daily80 mg three times daily■ ■ amitriptylineamitriptyline 10 mg (or more) at night. 10 mg (or more) at night. Sodium valproate, methysergide, SSRIs, verapamil, Sodium valproate, methysergide, SSRIs, verapamil,

topiramatetopiramate,, nifedipinenifedipine and and naproxennaproxen are also used. are also used. Gap junctionGap junction blockers are being used in trials.blockers are being used in trials.