1.Unwanted drug effects, allergy. 2. Effects of age and disease on drug disposition, Anton Kohút

1.Unwanted (side) drug effects

ALL DRUGS ARE CAPABLE OF PRODUCING BENEFICIAL AS WELL AS HARMFUL EFFECTS, DRUGS CAN DAMAGE HEALTH

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- mechanisms In 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 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 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

Born to thalidomide mothers

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

Types of allergic response to drugs

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

Side effects of drugs in oral cavity

1. LICHENOID DRUG REACTIONS 1. LICHENOID DRUG REACTIONS 2. LUPUS ERYTHEMATOSUS -LIKE ERUPTIONS 2. LUPUS ERYTHEMATOSUS -LIKE ERUPTIONS 3. PEMPHIGUS-LIKE DRUG ERUPTIONS 3. PEMPHIGUS-LIKE DRUG ERUPTIONS 4. ERYTHEMA MULTIFORME 5. GINGIVAL HYPERPLASIA

1. LICHENOID DRUG REACTIONS DRUGS : Allopurinol, furosemide, chloroquine, gold salts, methyldopa, lithium salts, penicillamine, phenothiazines, propranolol, quinidine, spironolactone, thiazides, tetracyclines, tolbutamide DRUGS : Allopurinol, furosemide, chloroquine, gold salts, methyldopa, lithium salts, penicillamine, phenothiazines, propranolol, quinidine, spironolactone, thiazides, tetracyclines, tolbutamide 2. LUPUS ERYTHEMATOSUS -LIKE ERUPTIONS DRUGS : Gold salts, phenytoin, griseofulvin, isoniazid, procainamide, thiouracil, hydralazine, streptomycin, methyldopa DRUGS : Gold salts, phenytoin, griseofulvin, isoniazid, procainamide, thiouracil, hydralazine, streptomycin, methyldopa

lichenoid reactions lupus erythematosus lichenoid reactions lupus erythematosus

3. PEMPHIGUS-LIKE DRUG ERUPTIONS DRUGS : Penicillamin, phenobarbital, rifampin, captopril, corticoids 4. ERYTHEMA MULTIFORME DRUGS : Antimalarials, barbiturates, carbamazepine, salicylates, sulphonamides, clindamycin, tetracyclines 5. GINGIVAL HYPERPLASIA DRUGS : Phenytoin, cyclosporin, nifedipine ( and other Ca antagonists ), DRUGS : Phenytoin, cyclosporin, nifedipine ( and other Ca antagonists ),

pemhigus erythema multiforme pemhigus erythema multiforme

Pemfigus After glucocorticoids

Nifedipin Phenytoin