ADRs Affecting the Peripheral and Central Nervous Systems

Headaches may be primary or secondary.34 Primary headaches include migraine, cluster, and tension headaches. Secondary headaches may be related to extracranial causes (e.g., dental problems, sinusitis, and carotid artery disorders), intracranial causes (e.g., brain tumors and vascular disorders), and exposure to toxins and drugs. Secondary headache may be a symptom of exposure to monosodium glutamate (MSG); analgesic overdose; caffeine withdrawal; and treatment with estrogen and nitrates.34

Fatigue or weakness is a subjective feeling of tiredness and may have physical or mental causes.35 Mental fatigue is due to prolonged periods of cognitive activity. Physical fatigue may be due to normal muscle exertion; or it may be caused by endocrine/metabolic problems, cardiopulmonary abnormalities, psychiatric disorders, vitamin deficiencies, or drug withdrawal.35 Fatigue is common with medications such as antihistamines and β1-adrenergic receptor antagonists.

Tremor is unintentional, rhythmic muscle activity involving to-and-fro movements (oscillations) affecting most commonly the hands, arms, head, face, and legs.36 Tremor may be a symptom of a neurological disorder; it is most often associated with Parkinson’s disease. It is also a well-recognized adverse reaction to such drugs as amphetamines, cocaine, thyroid hormones, mercury poisoning, corticosteroids, SSRIs, and alcohol abuse; and alcohol and benzodiazepines withdrawal.36

Tardive dyskinesia (TD) is an ADR related to long-term dopamine2-receptor blockade by antipsychotic drugs such as haloperidol, chlorpromazine, thioridazine, trifluoperazine, fluphenazine, and perphenazine.36 Symptoms include oral dyskinesia, i.e., involuntary muscle movements characterized by continual chewing, intermittent darting of the tongue (fly fishing) and lip-smacking, pursing, or puckering.8 TD is sometimes associated with abnormal, uncontrollable, writhing movements of the arms and/or legs.

Paresthesia is an unpleasant, abnormal sensation of tingling, numbness, or burning usually felt in the hands, feet, arms, or legs, but can also manifest in other part of the body.37 Chronic paresthesia is many times a symptom of an underlying neurological disease or traumatic nerve damage. Drugs associated with paresthesia include LAs, long-term exposure to nitrous oxide, mercury poisoning, heavy metal poisoning, led poisoning, anticonvulsant drugs; and withdrawal of benzodiazepines and SSRIs.37

Fever is elevated body temperature, i.e., > 37.8° C orally.38 It is regulated by the hypothalamic thermoregulatory center that maintains the internal temperature within a maximum fluctuation of 0.6° C. Fever results when something raises the hypothalamic set point and triggers peripheral vasoconstriction to preserve heat and shivering, which increases heat production.38 Drugs that can increase heat production include amphetamines, cocaine, general anesthetics, and antipsychotic agents.38