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Classification of harmful effects
1. Pharmacodynamic effects - related to the principal pharmacological action of the drug
They are:- predictable,
- dose-dependent
-bleeding after anticoagulants treatment
-bronchoconstriction with -adrenoreceptor-blocking drugs
-AV block after digitalis administration
2. Toxic effects - unrelated to the principal pharmacological action
Are usually due to reactive metabolites of the drug and are often
more serious.
cell damage and cell death (a liver or kidney damage, bone marrow supression)
mutagenesis and carcinogenesis
teratogenesis drug allergy
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.
Toxic effects- mechanismsIn most cases it is caused by interaction between reactive
compounds formed during metabolism and cell constituents (lipids, proteins, DNA)
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 - organotoxicity
• Hepatotoxicity• Paracetamol, isoniazid
(INH), iproniazid, halothane, methotrexate, chlorpromazine
• Nephrotoxicity
NSAIDs, ACEI,
Phenacetin, paracetamol, cyclosporin
Teratogenic effects (gross structural malformations during foetal)
development
it has been known since 1920 (X-irradiation) since 1940 - Rubella infection only 35 years ago were drugs recognised as teratogenic agents (thalidomide) 1-5% congenital defects is caused by drugs
• Heavy metals - mercury, lead, cadmium• Antiepileptic drugs - 2-3 more malformations in
babies born to epileptic mothers (fenythoin) • Antiemetics - have been widely used in treatment of
morning sickness in early pregnancy it is prudent to avoid the use of these drugs in pregnant
• patients if possible
Drug alergy
it is delayed in onset, occuring a few days after administration of the drug or occurs only with repeated exposure to the drug
may occur with very small doses of the drug, too small to elicit its pharmacodynamic effects
- incidence of allergic drug reactions is between 2-25% - great
majority are relatively harmless skin eruptions- serious reactions (e.g. anaphylaxis, hemolysis, bone marrow
depression) which may be life-threatening are rare- the incidence of death from allergic reactions is estimated at
1:10 000
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
1. LICHENOID DRUG 1. LICHENOID DRUG REACTIONSREACTIONS
2. LUPUS ERYTHEMATOSUS -2. LUPUS ERYTHEMATOSUS -LIKE ERUPTIONSLIKE ERUPTIONS
3. PEMPHIGUS-LIKE DRUG 3. PEMPHIGUS-LIKE DRUG ERUPTIONSERUPTIONS
4. ERYTHEMA MULTIFORME4. ERYTHEMA MULTIFORME
5. GINGIVAL HYPERPLASIA5. GINGIVAL HYPERPLASIA
1. LICHENOID DRUG REACTIONS1. LICHENOID DRUG REACTIONS DRUGS : Allopurinol, furosemide, DRUGS : Allopurinol, furosemide,
chloroquine, gold salts, chloroquine, gold salts, methyldopa, lithium salts, methyldopa, lithium salts, penicillamine, phenothiazines, penicillamine, phenothiazines, propranolol, quinidine, propranolol, quinidine, spironolactone, thiazides, spironolactone, thiazides, tetracyclines, tolbutamidetetracyclines, tolbutamide
2. LUPUS ERYTHEMATOSUS -LIKE 2. LUPUS ERYTHEMATOSUS -LIKE ERUPTIONSERUPTIONS
DRUGS : Gold salts, phenytoin, DRUGS : Gold salts, phenytoin, griseofulvin, isoniazid, griseofulvin, isoniazid, procainamide, thiouracil, procainamide, thiouracil, hydralazine, streptomycin, hydralazine, streptomycin, methyldopamethyldopa
3. PEMPHIGUS-LIKE DRUG ERUPTIONS3. PEMPHIGUS-LIKE DRUG ERUPTIONSDRUGS : Penicillamin, phenobarbital, DRUGS : Penicillamin, phenobarbital,
rifampin, captopril, corticoidsrifampin, captopril, corticoids4. ERYTHEMA MULTIFORME4. ERYTHEMA MULTIFORMEDRUGS : Antimalarials, barbiturates, DRUGS : Antimalarials, barbiturates,
carbamazepine, salicylates, carbamazepine, salicylates, sulphonamides, clindamycin, sulphonamides, clindamycin, tetracyclinestetracyclines
5. GINGIVAL HYPERPLASIA5. GINGIVAL HYPERPLASIA DRUGS : Phenytoin, cyclosporin, DRUGS : Phenytoin, cyclosporin,
nifedipine ( and other Ca nifedipine ( and other Ca antagonists ),antagonists ),