Transcript 1.Unwanted drug effects, allergy. 2. Effects of age and disease on

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 SHgroups
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 drugs
in oral cavity
1. LICHENOID DRUG REACTIONS
 2. LUPUS ERYTHEMATOSUS -LIKE
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
2. LUPUS ERYTHEMATOSUS -LIKE
ERUPTIONS
DRUGS : Gold salts, phenytoin,
griseofulvin, isoniazid, procainamide,
thiouracil, hydralazine, streptomycin,
methyldopa

lichenoid reactions
erythematosus
lupus
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 ),

pemhigus
multiforme
erythema
Pemfigus
After glucocorticoids
Nifedipin
Phenytoin