Zi

Infection trauma

Synovitis

JvAvW Pain

Synovitis

Skin Reaction From Methotrexate

Non-steroidal anti-inflammatory drugs (NSAIDs)

Glucocorticoids

Methotrexate, p.o. /s.c. weekly dosing

Pneumonitis, nausea, vomiting, myelosuppression

Sulfasalazine p.o.

allergic reaction, nephrotoxicity, gastrointestinal disturbances

Gold parenteral

Lesions of mucous membranes, kidney, skin, blood dyscrasias

Relief of symptoms

Relief of symptoms

Discontinuation because of: side effects or insufficient efficacy Years

Months

Months

Discontinuation because of: side effects or insufficient efficacy Years

A. Rheumatoid arthritis and its treatment

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 classic 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 (hyperos-mia) or light (photophobia). The exact cause of these complaints is unknown; however, a disturbance in cranial blood flow is the likely underlying pathoge-netic mechanism. 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 (p. 330) or domperidone. Since there is delayed gastric emptying during the attack, drug absorption can be markedly retarded, 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 bioavail-ability is complete. Therefore, i.v. injection may be advisable in acute attacks.

Should analgesics prove insufficiently effective, ergotamine or one of the 5-HTi, agonists may help control the acute attack in most cases or prevent an imminent attack. The probable common mechanism of action is a stimulation of serotonin receptors of the 5-HT1D (or perhaps also the iB and iF) subtype. Moreover, ergotamine has affinity for dopamine receptors (^ nausea, eme-

sis), as well as a-adrenoceptors and 5-HT2 receptors ( f vascular tone, f platelet aggregation). With frequent use, the vascular side effects may give rise to severe peripheral ischemia (ergotism). Overuse (>once per week) of ergotamine may provoke "rebound" headaches, thought to result from persistent vasodilation. Though different in character (tension-type 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, eletriptan, naratrip-tan, rizatriptan, and zolmitriptan have only limited bioavailability. Dihydroer-gotamine may be given by i.m. or slow i.v. injection, sumatriptan subcutane-ously or by nasal spray.

Prophylaxis. Taken regularly over a longer period, a heterogeneous group of drugs comprising propranolol, nadolol, atenolol, and metoprolol (ß-blockers), flunarizine (Hi-histamine, dopamine, and calcium antagonist), pizotifen (pi-zotyline, 5-HT-antagonist), methyser-gide (partial 5-HTiD-agonist and nonselective 5-HT-antagonist, p. 126), NSAlDs (p. 200), and calcitonin (p. 264) may decrease the frequency, intensity, and duration of migraine attacks. Among the ß-blockers (p. 90), only those lacking intrinsic sympathomimetic activity are effective.

Acetylsalicylic acid 1000 mg or acetaminophen 1000 mg

When therapeutic effect inadequate

Sumatriptan or

Migraine attack:

Headache

Hypersensitivity of olfaction, gustation audition, vision Nausea, vomiting

When therapeutic effect inadequate

Sumatriptan or

Effects Cold Exposure
A. Migraine and its treatment

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), difficulty 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 pathogens are different viruses (rhino-, adeno-, parainfluenza v.) that may be transmitted by aerosol droplets produced by coughing and sneezing.

Therapeutic measures. First attempts of a causal treatment consist of zanamavir, an inhibitor of viral neura-minidase, an enzyme necessary for virus adsorption and infection of cells. However, since symptoms of common cold abate spontaneously, there is no compelling need to use drugs. Conventional remedies are intended for symptomatic relief.

Rhinitis. Nasal discharge could be prevented by parasympatholytics; however, other atropine-like effects (pp. 104ff) would have to be accepted. Therefore, parasympatholytics are hardly ever used, although a corresponding action is probably exploited in the case of Hi antihistamines, an ingredient of many cold remedies. Locally applied (nasal drops) vasoconstricting a-sympathomimetics (p. 90) decongest the nasal mucosa and dry up secretions, clearing the nasal passage. Long-term use may cause damage to nasal mucous membranes (p. 90).

Sore throat, swallowing problems. Demulcent lozenges containing surface anesthetics such as ethylamino-benzoate (benzocaine) or tetracaine (p. 208) may provide relief; however, the risk of allergic reactions should be borne 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. 212) suppress cough by a central action.

Mucous airway obstruction. Mu-colytics, such as acetylcysteine, split di-sulfide bonds in mucus, hence reduce its viscosity and promote clearing of bronchial mucus. Other expectorants (e.g., hot beverages, potassium iodide, and ipecac) stimulate production of watery mucus. Acetylcysteine is indicated in cystic fibrosis patients and inhaled as an aerosol. Whether mucolytics are indicated in the common cold and whether expectorants like bromohexine or am-broxole effectively lower viscosity of bronchial secretions may be questioned.

Fever. Antipyretic analgesics (ace-tylsalicylic 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.

Local use of a-sympathomimetics

(nasal drops or spray)

Acetylsalicylic acid

Acetaminophen

* Soreness Headache Fever

Sniffles, runny nose

Surface anesthetics

Caution:

risk of sensitization

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