Migraine

Migraine is a syndrome characterized by recurrent attacks of intense headache and nausea that occur at irregular intervals and last for several hours. In classical migraine, the attack is typically heralded by an “aura” accompanied by spreading homonymous visual field defects with colored sharp edges (“fortification” spectra). In addition, the patient cannot focus on certain objects, has a ravenous appetite for particular foods, and is hypersensitive to odors (hyperosmia) or light (photophobia). The exact cause of these complaints is unknown; conceivably, the underlying pathogenetic mechanisms involve local release of proinflammatory mediators from nociceptive primary afferents (neurogenic inflammation) or a disturbance in cranial blood flow. In addition to an often inherited predisposition, precipitating factors are required to provoke an attack, e. g., psychic stress, lack of sleep, certain foods. Pharmacotherapy of migraine has two aims: stopping the acute attack and preventing subsequent ones.

Treatment of the attack. For symptomatic relief, headaches are treated with analgesics (acetaminophen, acetylsalicylic acid), and nausea is treated with metoclopramide (pp.116, 342) or domperidone. Since there is delayed gastric emptying during the attack, drug absorption can be markedly retarded and hence effective plasma levels are not obtained. Because metoclopramide stimulates gastric emptying, it promotes absorption of ingested analgesic drugs and thus facilitates pain relief.

If acetylsalicylic acid is administered i.v. as the lysine salt, its bioavailability is complete. Therefore, i.v. injection may be advisable in acute attacks.

Should analgesics prove insuf ciently effective, sumatriptan (prototype of the triptans) or ergotamine may help prevent an imminent attack in many cases. Both substances are effective in migraine and cluster

headaches but not in other forms of headache. The probable common mechanism of action is a stimulation of serotonin receptors of the 5-HT1D subtype. Moreover, ergotamine has af nity for dopamine receptors (†nausea, emesis), as well as α-adrenocep- tors and 5-HT2 receptors (⁄ vascular tone, ⁄ platelet aggregation). With frequent use, the vascular side effects may give rise to severe peripheral ischemia (ergotism). Paradoxically, overuse of ergotamine (> once per week) may provoke “rebound” headaches, thought to result from persistent vasodilation. Though different in character (tensiontype headache), these prompt further consumption of ergotamine. Thus, a vicious circle develops with chronic abuse of ergotamine or other analgesics that may end with irreversible disturbances of peripheral blood flow and impairment of renal function.

Administered orally, ergotamine and sumatriptan have only limited bioavailability. Dihydroergotamine may be given by i.m. or slow i.v. injection, sumatriptan subcutaneously, by nasal spray, or as a suppository. When given orally, other triptans such as zolmitriptan, naratriptan, and rizatriptan have higher bioavailability than sumatriptan.

Prophylaxis. Taken regularly over a longer period, a heterogeneous group of drugs comprising propranolol, nadolol, atenolol, and metoprolol (β-blockers), flunarizine (H1-his- tamine, dopamine, and calcium antagonist), pizotifen (pizotyline, 5-HT antagonist with structural resemblance to tricyclic antidepressants), and methysergide (partial 5-HT antagonist) may decrease the frequency, intensity, and duration of migraine attacks. The drug of first choice is one of the β-block- ers mentioned.

Common Cold

The common cold—colloquially the flu, catarrh, or grippe (strictly speaking the rarer infection with influenza viruses)—is an acute infectious inflammation of the upper respiratory tract. Its symptoms—sneezing, running nose (due to rhinitis), hoarseness (laryngitis), dif culty in swallowing and sore throat (pharyngitis and tonsillitis), cough associated with first serous then mucous sputum (tracheitis, bronchitis), sore muscles, and general malaise—can be present individually or concurrently in varying combination or sequence. The term stems from an old popular belief that these complaints are caused by exposure to chilling or dampness. The causative pathogensare differentviruses (rhino-, adeno-, and parainfluenza viruses) that may be transmitted by aerosol droplets produced by coughing and sneezing.

Therapeutic measures. Causal treatment with a virustatic is not possible at present. Since cold symptoms abate spontaneously, there is no compelling need to use drugs. However, conventional remedies are intended for symptomatic relief.

Rhinitis. Nasal discharge could be prevented by parasympatholytics; however, other atropine-like effects (p.108) would have to be accepted. Parasympatholytics are threfore hardly ever used, although a corresponding action is probably exploited in the case of H1-antihistaminics, an ingredient of many cold remedies. Locally applied (nasal drops), vasoconstricting α-sympatho- mimetics decongest the nasal mucosa and dry up secretions, clearing the nasal passage. Long-term use may cause damage to nasal mucous membranes (p. 94).

Sore throat, swallowing problems. Demulcent lozenges containing surface anesthetics such as lidocaine (caveat: benzocaine and tetracaine contain an allergenic p-ami- nophenyl group; p. 207) may provide shortterm relief; however, the risk of allergic reactions should be kept in mind.

Cough. Since coughing serves to expel excess tracheobronchial secretions, suppression of this physiological reflex is justified only when coughing is dangerous (after surgery) or unproductive because of absent secretions. Codeine and noscapine (p. 210) suppress cough by a central action. A different, though incompletely understood, mechanism of action is evident in antitussives such as clobutinol, which do not derive from opium. The available clinical studies concerning the benefits of antitussives in common colds do not present a convincing picture.

Mucous airway obstruction. Expectorants are meant to promote clearing of bronchial mucus by a liquefying action that involves either cleavage of mucous substances (mucolytics) or stimulation of production of watery mucus (e.g., hot beverages). Whether mucolytics are indicated in the common cold and whether expectorants such as bromohexine or ambroxole effectively lower viscosity of bronchial secretions may be questioned. In clinical studies of chronic obstructive bronchitis (but not common cold infections), N-acetylcysteine was shown to have clinical effectiveness, as evidenced by a lowered incidence of exacerbations during chronic intake.

Fever. Antipyretic analgesics (acetylsalicylic acid, acetaminophen, p.198) are indicated only when there is high fever. Fever is a natural response and useful in monitoring the clinical course of an infection.

Muscle aches and pains, headache. Antipyretic analgesics are effective in relieving these symptoms.

Mucosal decongestion

Nose breathing facilitated

Caution: habituation

H1-Antihistamines

Caution: sedation

Viral infection

Causal therapy impossible

Surface anesthetics

Caution:

risk of sensitization

Bromhexine

Sniffles, runny nose

Common cold

Flu

Sore throat

Cough

Airway congestion

Accumulation in airways of mucus, inadequate expulsion by cough