ADRs Affecting the Peripheral and Central Nervous Systems

Headaches (ADR #3) may be primary or secondary.⁴⁹ 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.⁴⁹

Fatigue (ADR #8) or weakness is a subjective feeling of tiredness and may have physical or mental causes.⁵⁰ 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.⁵⁰ Fatigue is common with medications such as antihistamines and β1-adrenergic receptor antagonists.

Tremor (ADR #23) is unintentional, rhythmic muscle activity involving to-and-fro movements (oscillations) affecting most commonly the hands, arms, head, face, and legs.⁵¹ 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.⁵¹

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.⁵² Symptoms include oral dyskinesia characterized by involuntary lip-smacking, tongue protrusion, perioral movements, chewing movements, or a puffing of cheeks. Involvement of the neck and facial muscles, truncal musculature, and limbs may also occur.⁵²

Paresthesia (ADR #20) is a form of neuropathy and refers to an unpleasant, abnormal sensation of tingling, numbness, or burning sensation.⁵³ Causes include diabetes mellitus, chronic alcoholism, nutritional deficiencies (e.g., B1, B6, B12, and vitamin E), hypothyroidism, autoimmune disease (e.g., Sjogren syndrome, lupus, rheumatoid arthritis), infections (e.g., Lyme disease, Epstein-Barr virus, hepatitis C, shingles, leprosy, HIV), toxins (heavy metals, chemicals), chemotherapy agents, medications (antibiotics, cardiovascular agents), and trauma/injury.⁵³

Fever is elevated body temperature, i.e., > 37.8° C orally.⁵⁴ 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. Drugs that can increase heat production include amphetamines, cocaine, general anesthetics, and methylenedioxymethamphetamine (MDMA, or Ecstasy), antipsychotic agents, thyroxine, and interferons. Fever due to a hypersensitivity may occur with beta-lactam antibiotics, sulfa drugs, phenytoin, carbamazepine, procainamide, quinidine, and amphotericin B.⁵⁴