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These clinical cause of headache criteria are not enough to make a definite diagnosis of cervi- C generic malegra fxt plus 160 mg free shipping impotent rage. Evidence that the pain can be attributed to the neck disor- cogenic headache malegra fxt plus 160 mg line erectile dysfunction doctor toronto, as it is sometimes difficult to differentiate der or lesion based on at least one of the following: clinically between cervicogenic headache safe 160mg malegra fxt plus erectile dysfunction 18-25, migraine, and 1. Demonstration of clinical signs that implicate a source tension-type headache [6, 7]. Abolition of headache following diagnostic block of a articular injection of local anesthetic into the affected joint is cervical structure or its nerve supply using placebo or now considered a major criterion in the diagnosis of cervico- other adequate controls. Pain resolves within 3 months after successful treatment hospital-based) and the criteria used. Sjaastad, in 2008, of the causative disorder or lesion reported a cervicogenic headache prevalence of 4. Nuchal onset of pain was a characteristic trait as pain exacerbations began in the neck/ Diagnostic Criteria by the International occipital region in 97 % of the cases [8 ]. Clinical, laboratory, and/or imaging evidence of a disor- der or lesion within the cervical spine or soft tissues of the neck, known to be able to cause headache C. Cervical range of motion is reduced and headache is Neuroanatomy and Neurophysiology made significantly worse by provocative maneuvers. Headache is abolished following diagnostic blockade to the outer lamina of the dorsal horn of the upper three to of a cervical structure or its nerve supply. Convergence between these afferents accounts for side-locked pain, provocation of typical headache by digital the trigeminocervical pain referral. Therefore, pain originat- pressure on neck muscles and by head movement, and ing from cervical structures supplied by the upper cervical posterior-to-anterior radiation of pain. However, although spinal nerves could be perceived in areas innervated by the these may be features of cervicogenic headache, they are not trigeminal nerves such as the orbit and the frontotemporopa- unique to it, and they do not necessarily define causal rietal region (see Fig. Bartsch and Goadsby [ 13] showed that noxious stimula- Migrainous features such as nausea, vomiting, and tion of the greater occipital nerve induces increased central photo-/phonophobia may be present with cervicogenic excitability of supratentorial afferents and vice versa; stimu- headache, although to a generally lesser degree than in lation of the dura mater increases trigeminocervical neurons’ migraine, and may differentiate some cases from tension- responsiveness to cervical input [14]. Common Sources of Cervicogenic Headache Etiology Atlantoaxial Joint Cervicogenic headache is referred pain from cervical structures innervated by the upper three cervical spinal The lateral atlantoaxial joint, which is innervated by the C2 nerves. Thus, possible sources of cervicogenic headache ventral ramus, is not an uncommon cause of cervicogenic are the atlantooccipital joint, atlantoaxial joints, C2–3 headache. It may account for 16 % of patients with occipital intervertebral disk, C2–3 zygapophyseal joint, upper pos- headache [15]. Other sources include the trapezius and the sternocleidomastoid muscles, posterior cranial fossa dura mater, and upper cervical C2–3 Zygapophyseal Joint and Third spinal nerve roots [11]. Occipital Headache The Quebec Headache Study group in 1993 stated that cervical facet dysfunction is probably the most important The C2–3 zygapophyseal joint is innervated by the third clinical source [12 ]: occipital nerve, which is the superficial medial branch of the • Tumors, fractures, infections, and rheumatoid arthritis dorsal ramus of C3 [16]. Pain stemming from this joint of the upper cervical spine have not been validated for- (named third occipital headache) is seen in 27 % of patients mally as causes of headache, but are nevertheless presenting with cervicogenic headache after whiplash injury accepted as such when demonstrated to be so in indi- [17]. Occipital neuralgia is defined as unilateral or bilateral • Headache caused by upper cervical radiculopathy is now paroxysmal, shooting or stabbing pain in the posterior part of coded in the Appendix as A11. Cervical Radiculopathy) Occipital neuralgia must be distinguished from occipital referral of pain from the atlantoaxial or upper zygapophyseal C2 neuralgia is a distinctive type of occipital neuralgia, and joints or from tender trigger points in neck muscles or their it is caused by lesions affecting the C2 nerve root or dorsal insertions [10 ]. The C2 root lies posterior to the lateral atlan- dorsal ramus of C2 with contribution from C3. The lesser toaxial joint; thus, disorders or inflammation of this joint occipital nerve is one of the terminal branches of the superfi- may lead to irritation or entrapment of the nerve root [26 ]. It arises from the lateral branch of the C2 neuralgia manifests as intermittent lancinating occipital ventral ramus of C2 with contributions from C3. Segmental pain that is associated with lacrimation, ciliary injection, nerve blocks at C2 and C3 may be necessary to make the and rhinorrhea. C2 neuralgia Cryoneurolysis, radiofrequency ablation, and more per- that responds poorly to pharmacotherapy and thermoco- manent neuroablative approaches as dorsal rhizotomy at agulation, decompression, or C2 ganglionectomy may be C1–3 and partial posterior rhizotomy at C1–3 showed vari- indicated [11]. Occipital nerve stimulation is Headache caused by upper cervical radiculopathy has becoming now the most attractive, reversible neuromodula- been postulated, considering the now well-understood tion approach for intractable occipital neuralgia [23 ]. Assessment of any tender points over the occipital nerves, to Cervical Myofascial Pain) suboccipital muscles, trapezius, and cervical paraspinal muscles Trigger points in the posterior neck muscles specially the tra- 2. Cervical spine range of movements: flexion, extension, pezius, sternocleidomastoid, and the splenius capitis have lateral flexion, and rotation been proposed as a cause of headache [27, 28]. The exception is migraine without aura and, to a associated with pericranial tenderness [10]. This diag- ache from migraine and tension-type headache include nosis is suggested till there is more evidence that this type of side-locked pain, provocation of typical headache by headache is more closely related to other cervicogenic head- digital pressure on neck muscles and by head move- aches than to tension-type headache. Moreover these tender points usually overlie the zyg- • Cervical spine x-rays are helpful in identifying apophyseal joints, so it is difficult to be distinguished from degenerative and arthritic changes and to exclude other underlying painful joints [11]. Flexion/exten- management of myofascial pain showed no efficacy beyond sion films are important to assess any instability. The use of botulinum toxin is controver- attention to the craniocervical junction is essential. Tender points over the suboccipital muscles, trape- relief for a few months in one study [34]. However, cervical zius, and cervical paraspinal muscles; consider trig- disk interventions are not commonly performed because of ger point injections. Botox injections may be the potential for serious complications mainly infection and indicated in resistant cases. Tenderness to palpation over the C2–3 joint, espe- Practical Approach to the Management cially in patients with whiplash injury; consider of Cervicogenic Headache third occipital nerve block and neurolysis. Tenderness to palpation over the lower cervical Cervicogenic headache is one of the most debatable and facet (C3–6) with increased pain on extension and challenging areas in headache medicine. Patients usually lateral rotation; consider cervical facet nerve benefit the most from a multidisciplinary approach (medial branch) block and neurolysis. Tenderness to palpation over the atlantoaxial therapy (biofeedback and relaxation therapy), and the (C1–2) joint with increased pain on rotation of C1 judicious utilization of interventional pain management over C2 while the neck is flexed; consider atlanto- modalities (Fig. Patients with clinical picture of C2 or C3 neuralgia, genic headache is to make an accurate diagnosis and to or patients who do not respond to the above pinpoint the source of pain. Painful intervertebral dys- function: Robert maigne’s original contribution to headache of cervical origin. Entrapment of the C2 root and ganglion pain [corrected] with botulinum toxin-A: a pilot study. Postgrad prospective pilot study of botulinum toxin injection for refractory, Med. Atlantoaxial Joint: Atlantoaxial Joint 1 1 Injection and Radiofrequency Ablation Samer N. Narouze Cervicogenic headache is referred pain from cervical Clinical Presentation and Physical structures innervated by the upper three cervical spinal Examination nerves. It is a fairly common cause of cervicogenic Clinical presentations suggestive of pain originating from headache as it may account for up to 16 % of patients with the lateral atlantoaxial joint include occipital or suboccipital occipital headache [1]. Distending the lateral atlantoaxial pain with little radiation, focal tenderness over the suboccipi- joint with contrast agent in human volunteers produces tal area or over the transverse process of C1, restricted pain- occipital pain, and injection of local anesthetic into the joint ful rotation of C1 on C2, and pain provocation by passive relieves the headache [1, 2 ]. These clinical signs have a positive predictive value the C1–C2 facet joint and is the main focus of this chapter.

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Tere is no evi- In comparison with other antiemetic agents such as dence that use of droperidol at the doses routinely droperidol (1 buy 160mg malegra fxt plus visa erectile dysfunction pills images. A new agent malegra fxt plus 160 mg cheap erectile dysfunction medication otc, risk of sudden cardiac death in the perioperative palonosetron (Aloxi) order malegra fxt plus 160mg online erectile dysfunction treatment washington dc, has an extended duration of population. It may cause extrapyrami- to cause sedation, extrapyramidal signs, or respi- dal and anticholinergic side efects. The most commonly reported (Phenergan) works primarily as an anticholinergic side efect is headache. As with other agents of this class, Tis efect may be more frequent with dolasetron, anticholinergic efects (sedation, delirium, confu- although it has not been associated with any adverse sion, vision changes) can complicate the postop- arrhythmias. The recommended intrave- opposed to the end of surgery, and its mechanism nous dose is 12. Tey may be most benefcial in patients at increased risk for postoperative respiratory depression or emesis. Patients with tifying patients at greatest risk so that prophylaxis, asthma have an increased incidence of aspirin sensi- ofen with multiple agents, may be initiated. Elderly patients clear ketorolac Mechanism of Action more slowly and should receive reduced doses. Aspirin decreases the protein binding of ketoro- lac, increasing the amount of active unbound drug. Clinical Uses Ketorolac does not afect minimum alveolar con- centration of inhalation anesthetic agents, and its Ketorolac is indicated for the short-term (<5 days) administration does not alter the hemodynamics of management of pain, and appears to be particularly anesthetized patients. In anesthesia, clonidine is used increased risk of cardiovascular thromboembolic as an adjunct for epidural, caudal, and peripheral events. When given epidurally, the analgesic efect recently become available for perioperative use in of clonidine is segmental, being localized to the level the United States. A peripheral nerve block, clonidine will markedly pro- maximal adult (>50 kg weight) dose of 1 g is infused long both the anesthetic and analgesic efects. Patients weigh- Unlabeled/investigational uses of clonidine ing 50 kg or less should receive a maximal dose of include serving as an adjunct in premedication, 15 mg/kg and a maximal total dose of 75 mg/kg/d. Less commonly, bradycardia, Clonidine (Catapres, Duraclon) is an imidazoline orthostatic hypotension, nausea, and diarrhea may derivative with predominantly α -adrenergic ago- be observed. It is highly lipid soluble and readily following long-term administration (>1 mo) can penetrates the blood–brain barrier and the placenta. The overall efect is to decrease sympathetic Epidural clonidine is usually started at 30 mcg/h in activity, enhance parasympathetic tone, and reduce a mixture with an opioid or a local anesthetic. Tere is also evidence clonidine is readily absorbed, has a 30–60 min onset, that much of clonidine’s antihypertensive action and lasts 6–12 h. In the treatment of acute hyperten- occurs via binding to a nonadrenergic (imidazo- sion, 0. In contrast, its analgesic efects, par- blood pressure is controlled, or up to a maximum of ticularly in the spinal cord, are mediated entirely via 0. Transdermal preparations of clonidine can also tors that block nociceptive transmission. Dosages should be reduced for dine has a rapid onset and terminal half-life of 2 h. The drug is metabolized in the liver and its metab- olites are eliminated in the urine. Dosage should Drug Interactions be reduced in patients with renal insufciency or Clonidine enhances and prolongs sensory and hepatic impairment. Additive efects with hypnotic agents, general anesthetics, and Drug Interactions sedatives can potentiate sedation, hypotension, and Caution should be used when dexmedetomidine is bradycardia. The drug should be used cautiously, if administered with vasodilators, cardiac depressants, at all, in patients who take β-adrenergic blockers and and drugs that decrease heart rate. Reduced require- in those with signifcant cardiac conduction system ments of hypnotics/anesthetic agents should prevent abnormalities. It of carotid chemoreceptors by low doses of appears to be more selective for the α2 receptor than doxapram stimulates hypoxic drive, producing an clonidine. At higher doses it loses its selectivity and increase in tidal volume and a slight increase in also stimulates α1-adrenergic receptors. Clinical Uses Dexmedetomidine causes dose-dependent sedation Clinical Uses anxiolysis and some analgesia and blunts the sym- Because doxapram mimics a low Pao , it may be 2 pathetic response to surgery and other stress. Most useful in patients with chronic obstructive pulmo- importantly, it has an opioid-sparing efect and does nary disease who are dependent on hypoxic drive not signifcantly depress respiratory drive; excessive yet require supplemental oxygen. Doxapram is not a specifc Discontinuation afer more prolonged use can reversal agent, however, and should not replace stan- potentially cause a withdrawal phenomenon simi- dard supportive therapy (mechanical ventilation). It has also been used for For example, doxapram will not reverse paralysis intraoperative sedation and as an adjunct to general caused by muscle relaxants, although it may tran- anesthetics. The most common cause of postoperative hypoventilation—airway Side Effects obstruction—will not be alleviated by doxapram. The principal side efects are bradycardia, heart For these reasons, many anesthesiologists believe block, and hypotension. Doxapram should not be used in patients Side Effects with a history of epilepsy, cerebrovascular disease, acute head injury, coronary artery disease, hyperten- Abrupt reversal of opioid analgesia can result in sion, or bronchial asthma. Continuous intravenous infusions (1–3 mg/min) provide longer-lasting efects (the Dosage maximum dose is 4 mg/kg). In postoperative patients experiencing respira- tory depression from excessive opioid administra- Drug Interactions tion, intravenous naloxone (0. The awakening from halothane anesthesia, as halothane brief duration of action of intravenous naloxone sensitizes the myocardium to catecholamines. Terefore, intramuscular naloxone (twice the Mechanism of Action required intravenous dose) or a continuous infu- Naloxone (Narcan) is a competitive opioid receptor sion (4–5 mcg/kg/h) is recommended. Its afnity for opioid µ receptors appears respiratory depression resulting from maternal to be much greater than for opioid κ or δ receptors opioid administration is treated with 10 mcg/kg, Naloxone has no signifcant agonist activity. Neonates of opioid- dependent mothers will exhibit withdrawal symp- toms if given naloxone. The primary treatment of Clinical Uses respiratory depression is always establishment of an N a l o x o n e r e v e r s e s t h e a g o n i s t a c t i v i t y a s s o - adequate airway to permit spontaneous, assisted, or 9 ciated with endogenous (enkephalins, controlled ventilation. A dramatic example is the reversal of unconsciousness that occurs in a patient with opioid overdose who Drug Interactions has received naloxone. Perioperative respiratory The efect of naloxone on nonopioid anesthetic depression caused by excessive opioid administra- agents such as nitrous oxide is insignifcant. Some degree Naloxone may antagonize the antihypertensive of opioid analgesia can ofen be spared if the dose efect of clonidine. The reversal efect of fumazenil is based on its strong antagonist afnity for benzodiazepine Naltrexone is also a pure opioid antagonist with a receptors.

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Prior irradiation for retinoblastoma is one circumstance where sebaceous gland carcinoma can occur in children purchase malegra fxt plus 160 mg on line impotence. It has also occurred in adulthood among patients who had irradiation for acne during childhood buy cheapest malegra fxt plus erectile dysfunction over 50. Chapter 3 Eyelid Sebaceous Gland Tumors 55 ■ Eyelid Sebaceous Carcinoma: Diffuse Neoplasm Masquerading as Inflammation Sebaceous carcinoma can invade the epidermis of the eyelid or the epithelium of the conjunctiva and exhibit diffuse Pagetoid spread order malegra fxt plus discount erectile dysfunction treatment old age. This can result in a clinical appearance that simulates an inflammatory process such as blepharoconjunctivitis. Histopathology of diffuse epidermal involvement by seba- carcinoma in a 75-year-old woman. Histopathology of diffuse conjunctival epithelial involve- noma with early corneal epithelial invasion. Note the intact basement membrane and chronic inflammatory cells in the conjunctival stroma. Chapter 3 Eyelid Sebaceous Gland Tumors 55 ■ Eyelid Sebaceous Carcinoma: Diffuse Neoplasm Masquerading as Inflammation Sebaceous carcinoma can invade the epidermis of the eyelid or the epithelium of the conjunctiva and exhibit diffuse Pagetoid spread. This can result in a clinical appearance that simulates an inflammatory process such as blepharoconjunctivitis. Histopathology of diffuse epidermal involvement by seba- carcinoma in a 75-year-old woman. Histopathology of diffuse conjunctival epithelial involve- noma with early corneal epithelial invasion. Note the intact basement membrane and chronic inflammatory cells in the conjunctival stroma. Appearance of everted eyelid showing area where lesion arose from the tarsal conjunctiva. Histopathology, showing lobules of malignant sebaceous cells with extensive necrosis. However, most cases can be diagnosed readily by experienced pathologists who have had experi- ence with this neoplasm. Section showing normal sebaceous glands (below) and mal (Pagetoid) invasion by tumor cells. Comedo pattern in sebaceous carcinoma, representing pagetoid growth pattern in epidermis. Sebaceous gland tumors of the eyelids and conjunctiva in the Muir-Torre syndrome: a clinicopathologic study of five cases and literature review. Pedunculated mass with intrinsic vascularization in medial strating lobules of moderately differentiated sebaceous carcinoma cells. Orbital exenteration specimen showing wide removal of ing anterior portion of orbit. She had been treated for 2 years for blepharoconjunc- ricular lymph node metastasis, not well seen in photograph, at the time tivitis with a poor response to treatment and sebaceous carcinoma was of referral for the eyelid neoplasm. In spite of lymph node dissection and irradia- tion, the patient died from tumor dissemination. Chapter 3 Eyelid Sebaceous Gland Tumors 61 ■ Eyelid Sebaceous Carcinoma: Pentagonal Full-Thickness Eyelid Resection Results are shown of a resection of sebaceous carcinoma of the upper eyelid. The tarsus the eyelid is tighThat the end of the procedure, it resumed its normal posi- was closed with interrupted absorbable sutures. A plastic shell has been placed temporarily on the cornea ing of the semicircular flap. A semicircular flap (Tenzel flap) has been outlined, extending from lateral canthus. Chapter 3 Eyelid Sebaceous Gland Tumors 63 ■ Eyelid Sebaceous Carcinoma: Large Tumor and Rotational Forehead Flap After removal of larger tumors near the medial aspect of the eyelid, a rotational forehead flap may be required to achieve satisfactory closure of the wound. A clinicopathologic correlation of a tumor managed by this technique is presented. A semicircular incision is outlined to rotate normal skin Post-treatment photographs are not available. Histopathology showing diffuse invasion of tumor cells center (comedocarcinoma pattern. The technique of map biopsies for diffuse sebaceous carcinoma is shown and can be used for surgical planning. Resection one entire upper eyelid posterior lamella, includ- some of the map biopsy specimens being placed on squares of paper. C 4 Eyelid Sweat Gland Tumors 66 Part 1 Tumors of the Eyelids Eyelid Syringoma General Considerations Selected References Simple cysts of eccrine or apocrine sweat glands are called 1. Cutaneous Abnormalities of the Eyelid from sweat gland epithelium, beginning with syringoma. Eyelid tumors of apocrine, eccrine, more common and is often bilateral, symmetric, and most pro- and pilar origins. Benign ocular adnexal tumours of syringomas are usually not associated with other conditions. Treatment of multiple facial syringomas with the coidosis, and other conditions (2). Syringoma: removal by electrodessication and is composed of cords and nests of solid cells with ducts curettage. Numerous cystic dilations of the ducts can result in keratin cysts that can suggest the diagnosis of milium, trichoepithe- lioma, or squamous cell carcinoma. The keratin cysts can rup- ture and incite a granulomatous inflammatory reaction (3). Concerning pathogenesis, human papillomavirus types have been detected in solitary eyelid syringoma, suggesting a viral etiology (13). Other methods of management include electrodessication and curettage, dermabrasion, and carbon dioxide laser resurfacing (14–19). Some authors have advocated combination of carbon dioxide laser and trichloroacetic acid (16). Although solitary syringoma is cyto- logically benign, it can recur after incomplete excision and exhibit aggressive behavior. Chapter 4 Eyelid Sweat Gland Tumors 67 ■ Eyelid Syringoma Syringoma can be multiple or solitary. Although syringoma is almost always benign, low-grade malignant behavior can rarely occur. Recurrent solitary, larger syringoma of lower eyelid of a 20- ducts and tubules of epithelial cells, with lightly eosinophilic material in year-old woman. Ophthal- eccrine hydradenoma, and porosyringoma) is a tumor that mology 1991;98:347. Lever’s Histopathology of the majority are benign, a malignant variant has been observed Skin. Sweat gland tumour of the eyelid with conjunc- Eccrine acrospiroma of the eyelid can assume any of a variety tival involvement. It is generally a rather rapidly growing oncocytic, apocrine and sebaceous differentiation.

Consequently order malegra fxt plus 160 mg otc erectile dysfunction is often associated with, patients may themselves adjust W Bisphosphonates the dose of Sativex until pain relief is achieved with toler- able side-effects generic malegra fxt plus 160mg with visa impotence diabetes. Bisphosphonates (previously known as diphosphonates) are analogues of inorganic pyrophosphate that inhibit os- Ziconotide teoclast activity and order generic malegra fxt plus online erectile dysfunction 23 years old, consequently, reduce bone resorp- tion in a variety of illnesses. Currently the evidence for analgesic found in the venom of the Pacific fish-hunting snail, Conus effects is best for pamidronate. Notably, ziconotide is the only truly novel analgesic analgesia produced by the various drugs in this class that has emerged from decades of pharmaceutical research require additional study, and neither dose-dependent and development. The use of any bisphosphonate requires voltage-sensitive calcium channels (N-type channels) monitoring of serum calcium, phosphate, magnesium which are found in the dorsal horn of the spinal cord and potassium. The binding of ziconotide inhibits these channels, which reduces nociceptive transmission at the spinal level. More severe, but rare Migraine is characterised by episodic attacks of moderate- side-effects are hallucinations, thoughts of suicide, new severe throbbing headache with a number of associated or worsening depression. Consequently, the drug is contra- symptoms that include nausea, vomiting, photophobia indicated in patients with a history of psychosis, schizo- and phonophobia. In around one third of patients with mi- phrenia, clinical depression or bipolar disorder. The optimal dose is achieved by slow 18% of women and 6% of men suffered at least one mi- titration over weeks as an infusion via an intrathecal pump. Its Consequently, ziconotide is only approved for the manage- socioeconomic impact is substantial, with an estimated ment of severe chronic pain in patients for whom intrathe- annual cost of $17 billion for treatment costs alone. Drug tolerance does not occur and there are geal blood vessels, causing dilatation of the arteries in minimal withdrawal effects after prolonged infusion. Controlled studies show good analgesic efficacy of autonomic symptoms such as nausea and vomiting. Recent com- possesses features of inflammatory and functional pain, parative randomised trials of triptans show efficacy rates as well as objective neurologic dysfunction. In pa- is based on the headache’s characteristics and associated tients without cardiovascular contraindications, triptans symptoms. Triptan therapy is Migraine is best thought of, and managed as, a chronic pain most effective when used early when the headache is mild, syndrome. Non-pharmacological management of migraine but it is uncertain if they are best used after the resolution involves helping patients to identify and avoid triggering of the aura and the optimal timing is probably patient- factors such as stress, foods containing vasoactive amines dependent. Other behavioural ence, as well as the character, duration and severity of the and psychological interventions used for prevention in- headache, convenience and cost. Non-oral administration clude relaxation training, thermal biofeedback combined may be beneficial in cases when the headache intensifies with relaxation training, electromyography biofeedback rapidly, or severe nausea and emesis are early features of and cognitive behavioural therapy. Only sumatriptan is available for parenteral Pharmacotherapy of migraine is either abortive or administration. If the appropriate dose of triptan is ineffective Abortive treatment of migraine or has unacceptable side-effects, consider a switch to an al- ternative triptan formulation. There is a risk of developing serotonin syndrome Simple analgesics such as acetylsalicylic acid (900 mg) or (see p. The addition of domperidone (10 mg by mouth) or low,triptansshould not beused routinely duringpregnancy. In most cases, this is not caused rectally, with an antiemetic), ibuprofen (400–800 mg by by coronary vasoconstriction. There are reported cases of mouth), or tolfenamic acid (200 mg by mouth) can also serious cardiovascular events and triptans should be be very useful, when tolerated. All tend to be most effective avoided in patients who have, or are at high risk of devel- when given early during the headache. Patients who require regular analgesics may be more easily treated with standard Sumatriptan preventatives. When simple measures fail, or more aggressive treatment Sumatriptan (Imigran) is rapidly absorbed after oral ad- is required, more specific drugs are required. As well as the Headache Classification Subcommittee of the International Headache Society 2004 International classification of headache disorders. All have started at a low dose and increased slowly until therapeutic similar safety profiles, but varying duration of action. A full ther- therapeutic response and adverse effects of different trip- apeutic trial may take 2–6 months. Patients should try to tans are often idiosyncratic, and several drugs may have avoid overusing drugs for acute attacks during the trial to be tried before one is found that offers relief with min- period. Ergotamine Although ergotamine is a useful antimigraine compound, it is no longer considered a first-line drug for migraine be- Pizotifen cause of its adverse effects. It is structurally related to the tricyclic dopaminergic receptors compared to triptans. Peripheral antidepressant drugs and shares their potential for antimus- vasoconstriction that results from ergotamine administra- carinic adverse effects such as dry mouth, urinary retention tion can persist for as long as 24 h, and repeated doses lead and constipation. Its antihistamine action produces drows- to cumulative effects long outlasting the migraine attack. Treatmentisusu- may precipitate angina pectoris, probably by increasing car- ally started at 500 micrograms at night and titrated upwards diac pre- and afterload. It is rare to exceed a dose of 1 mg three times daily for prophylaxis of migraine. Preventive treatment for migraine Topiramate For patients who are unable to achieve adequate pain relief with the use of the standard analgesic medications and The introduction of topiramate is arguably the most impor- triptans, the use of medications to reduce the frequency tant recent advance in migraine prophylaxis. The net result is a reduction in excitatory transmis- Medications used for prophylaxis include b-adrenergic sion and an increase in inhibitory neurotransmission. The optimal effect occurs at 100 mg daily, with little with the best documented effectiveness are b-adrenergic effecThat 50 mg, and an increased incidence of unwanted ef- blockers, pizotifen, and the anticonvulsant drugs, sodium fects at higher doses. Unlike many of the antineuropathic medications, educated about the risk of drugs in pregnancy and topiramate is not associated with weight gain. Nociceptors – noxious practice and future directions in the cerebral signature for pain perception stimulus detectors. The problem of inducing The administration of general anaesthetics and neuromus- quick, safe and easily reversible unconsciousness for any cular blocking drugs is generally confined to trained desired length of time in humans began to be solved only specialists. Nevertheless, non-specialists are involved in in the 1840s when the long-known substances nitrous perioperative care and will benefit from an understanding oxide, ether and chloroform were introduced in rapid of how these drugs act. Connecticut, introduced nitrous oxide to produce • Obstetric analgesia and anaesthesia. Surgeons did their best for terrified patients by using alcohol, opium, cannabis, hemlock or hyoscine. After removing the leg in 28 s, 1A Japanese pioneer in about 1800 wished to test the anaesthetic efficacy a skill necessary to compensate for the previous lack of anaesthetics, of a herbal mixture including solanaceous plants (hyoscine-type alkaloids). Robert Liston turned to the watching students, and said, ‘This Hiselderlymothervolunteeredassubjectasshewasanywayexpectedtodie Yankee dodge, gentlemen, beats mesmerism hollow’. But the pioneer administered it to his wife for, ‘as all three agreed, anaesthetised his house surgeon in the presence of two women he could find another wife, but could never get another mother’ (Journal (Merrington W R 1976 University College Hospital and its Medical of the American Medical Association 1966; 197:10).