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- 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

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 drugsSide effects of drugsin oral cavityin oral cavity

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

lichenoid reactions lupus lichenoid reactions lupus erythematosuserythematosus

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 ),

pemhigus erythema pemhigus erythema multiformemultiforme

PemfigusPemfigus

After glucocorticoids

NifedipinNifedipin

Phenytoin