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Pharmacology and Toxicology
PHAR 100
Bill Racz

Lesson A. 4 - Drug Toxicity & Routes of Drug Administration Drug Accidents • Widespread distribution of drugs: hazard of accidental poisoning and suicide • Largest case of accidental poisoning occurs in children under five o Top 10 common things include:  aspirin, acetaminophen, bleach, diaper-pail deodorizer, chocolate flavoured laxatives, children’s fever drops, cough syrups, tranquillizers, birth control pills, and cigarette butts Types of Adverse Effects to Drugs and Why They Occur: • extension of therapeutic effect o When a benzdiazepine is taken for its sedative effects, an overdose will produce over-sedation. Similarly, when an anticoagulant is used for its anticoagulant effect, an overdose will cause bleeding • Unrelated to main drug action o The digitalis group of drugs is used to strengthen heart muscle in patients with congestive heart failure. However, in many cases, these drugs will produce nausea, vomiting, and abnormal colour vision, which is totally unrelated to their main action. • Idiosyncrasy o The drug succinylcholine is used to produce muscle relaxation. It is normally inactivated by an enzyme present in the blood. Approximately one in 3,000 patients lack the enzyme normally present in blood and are unable to inactivate the drug • Drug allergy o The basis of the allergic reaction to drugs in some patients is the following. The first time the drug is administered, it combines with a protein to form a complex known as an antigen. The antigen provokes the body to make a substance named an antibody. The next time the drug is administered it will combine with the protein to produce an antigen and the antigen will combine with the antibodies which were produced when the drug was first administered. The antigen-antibody combination provokes an adverse reaction in the patient. The reaction may be very mild; for example, a skin rash. On the other hand, the reaction can be very severe. Lesson A. 4 - Drug Toxicity & Routes of Drug Administration Why is Toxicity Hard to Predict - introduction of most new drugs proceeds through three stages: • Panacea - When the drug is first marketed with considerable advertising, it is thought that the drug is a major new advance. • Poison - After the drug has been used for a few months, additional adverse effects usually become apparent and sales of the drug drop precipitously. The drug is then thought to be a poison. • Pedestrian - With the further passage of time, the benefit/risk ratio of the drug is easier to assess and it is realized that the drug is neither a panacea nor a poison, but rather an average (or pedestrian) drug A drug said to have little or no toxicity when first introduced later turns out to be significantly toxic. Let us consider the reasons for this: • Toxic reaction may be a rare event o The antibiotic, chloramphenicol, was used for several years before it was realized that in one in 50,000 patients, it could cause death of the cells in the bone marrow leading to death of the patient. • Toxic reaction may only appear after drug has been in prolonged use o When streptomycin was first introduced for the treatment of tuberculosis, it was not realized that it could cause deafness if used for an extensive period • Toxic effects no detectable in animals o headache, insomnia, nausea and mental disturbances will not be readily picked up in animal testing • toxic effect may be unique to a particular period o Thalidomide produced adverse effects on the fetus. However, its adverse effects are confined to the pregnant patient. Until it was demonstrated that thalidomide produced abnormal limb growth (phocomelia) in the fetus
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