It would hardly be possible within one chapter to discuss the innumerable drugs and toxins that affect the nervous system. The interested reader is referred to a number of comprehensive monographs and references such as Casarett and Doull’s Toxicology, edited by Klaassen and Occupational Neurology edited by Lotti and Bleecker. In addition, a current handbook of pharmacology and toxicology is a useful part of the library of every physician. The scope of this chapter is also limited because the therapeutic and adverse effects of many drugs are considered elsewhere in this volume in relation to particular symptoms and diseases. Thus, the adverse effects of antibiotics on cochlear and vestibular function and on neuromuscular transmission are discussed in Chaps. 14 and 46, respectively. Many of the undesirable side effects of the common drugs used in the treatment of extrapyramidal motor symptoms, pain, headache, seizure, sleep disorders, psychiatric illnesses, and so forth are also considered in the chapters dealing with each of these disorders and in the chapters that cover psychiatric diseases. Cyanide and carbon monoxide poisoning are discussed in relation to anoxic encephalopathy (see Chap. 39). A number of therapeutic agents that predictably damage the peripheral nerves (e.g., cisplatin, disulfiram, vincristine) are mentioned in this chapter but are discussed further in Chap. 43, and those that affect muscle are included in Chap. 45.
The presentation of this subject is introduced by some general remarks on the action of drugs on the nervous system and is followed by discussion of the main classes of agents that affect nervous function: 1. Alcohol and alcoholism 2. Opiates and synthetic analgesic drugs 3. Sedative-hypnotic drugs 4. Antipsychosis drugs 5. Antidepressant drugs 6. Stimulants 7. Psychoactive drugs and hallucinogens 8. Bacterial toxins 9. Plant poisons venoms, bites, and stings 10. Heavy metals and industrial toxins 11. Antineoplastic and immunosuppressive agents 12. Antibiotics
The rational use of any drug requires knowledge of the best route of administration, the drug’s absorption characteristics, its distribution in the nervous system and other organs, and its biotransformations and excretion (pharmacokinetics). Because every drug, if given in excess, has some adverse effects, therapeutics and toxicology are inseparable.
All systems of neurons are not identical; each has its own vulnerabilities to particular drugs and toxic agents. This principle, originally enunciated by Oskar and Cecile Vogt in their theory termed pathoclisis is now embodied as “selective vulnerability.” For example, selective vulnerability explains the production of parkinsonism by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), in which a synthetic toxin affects a progressive loss of melanin- bearing dopaminergic nigral neurons (see Chap. 38). Another example is the preferential effects of anesthetics on the neurons of the upper brainstem reticular formation. Not only may certain groups of nerve cells be selectively destroyed by a particular agent, but particular parts of their structure may be altered as well. Drugs may be targeted even to the terminal axons, dendrites, neurofilaments, or receptors on preand postsynaptic surfaces of neurons or to certain of their metabolic activities, whereby they synthesize and release neurotransmitters or maintain their cellular integrity by the synthesis of RNA, DNA, and other proteins. An intriguing extension of this theme relates to the manner in which certain drugs or toxins affect individuals differently with a genetic disposition by way of single nucleotide polymorphisms; this is the field of pharmacogenetics.