Clinically relevant drug intoxications and their therapy Anton Kohút

Toxic effects of drugs Antidotes

Harmful effects of drugs Toxic effects -effects unrelated to the principal pharmacological action of the drug Overdosis – intoxication - these effects are closely associated with the pharmacodynamic action for which the drug is being used.

GENERAL MECHANISMS OF CELL DAMAGE AND CELL DEATH In most cases it is caused by interaction between reactive compounds formed during metabolism and cell constituents (lipids, proteins, DNA) 1. non-covalent bound 2. covalent bound

GENERAL MECHANISMS 1. non-covalent bound  lipid peroxidation generation of toxic oxygen species alteration (depletion) of GSH concentration  modification of SH- groups 2. covalent bound Targets are:  DNA, proteins/peptides, lipids, carbohydrates  binding to protein can produce an immunogen  binding to DNA can cause carcinogenesis, mutagenesis or teratogenesis

Toxic effects Hepatotoxicity Paracetamol, isoniazid (INH), iproniazid, halothane, methotrexate, chlorpromazine Nephrotoxicity NSAIDs, ACEI, Phenacetin, paracetamol, cyclosporin

Toxic and allergic reactions

HOW TO MINIMIZE THE SEVERITY OF TOXIC REACTIONS  Individualize drug therapy  Refer to the literature for information on drug interactions  Anticipate that after prolonged therapy patients are most likely to react adversely when new therapy is initiated or terminated  Teach patients to identify early signs of adverse reactions  Optimize the therapy

DRUG POISONING-TREATMENT General management 1. Observe vital function 2. Obtain history 3. Perform a toxicologicaly oriented physical examination Symptoms Extensions of pharmacological properties of drugs. Common causes of death include: CNS deppression, respiratory arrest, cellular hypoxia, hypothermia, hypotension and arrhytmias.

DRUG POISONING-TREATMENT - cont. a. Vital funcion support (ventilation, blood pressure, electrolyte balance) b. Prevention of drug absorbtion: -emetics (apomorphine), gastric lavage - chemical absorbtion with activated charcoal c. Promotion of elimination: - chemically enhancing urinary excretion, sodium bicarbonate-raises pH, ammonium chloride- decreases urinary pH) d. Hemodialysis Antidotes

Antidotes

Antidotes (contin.)