1. Clinically relevant drug intoxications and their therapy
Anton Kohút

2. Toxic effects of drugs Antidotes

3. 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.

4. 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

5. 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

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

7. Toxic and allergic reactions

8. 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

9. 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.

10. 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

11. Antidotes

12. Antidotes (contin.)