K15-Mekanisme Kerja Zat Toksik (Dr.nendyah)
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Transcript of K15-Mekanisme Kerja Zat Toksik (Dr.nendyah)
Mekanisme Kerja Zat ToksikNendyah Roestijawati
31 Mei 2013
General Classification
Chemical allergiesIdiosyncratic reactionsImmediate vs delayed effectsReversible vs irreversibleLocal vs sistemic
Chemical Interactions
PotentiationAdditiveSynergisticAntagonistic
Chemical allergies
Type I antibody-mediated reactionsType II antibody-mediated cytotoxic
reactionsType III immune complex reactionsType IV delayed-type hypersensitivity,
cell-mediated immunity
Type ISensitization phase : triggered by contact
with unrecognized antigen binding of the antigen to immunoglobulin E present on the surface of mast cells and basophiles
Activation phase : follows after an additional dermal or mucosal challenge with the same antigen degranulation of mast cell and basophils with subsequent release of histamine and other soluble mediators
Type I
Effector phase : accumulation of preformed and newly synthesized chemical mediators that precipitate local and systemic effects
Degranulation of neutrophils and eosinophils completes the late-phase cellular response
Mediators Primary mediators Histamine Vascular permeability, sm
contractionSerotonin vascular permeability, sm
contractionECF-A eosinophil chaemotaxisNCF-A neutrophil chaemotaxis,
proteases mucus secretion, connective tissue degradation
Mediators
Secondary mediatorsLeukotrienes vascular permeability, sm
contractionProstaglandins vasodilation, sm contraction,
platelet activationBradykinin vascular permeability, sm
contractionCytokines numerous effects inc. activation of
vascular endothelium, eosinophil recruitment and activation
Type II
Differ from type I in the nature of antigen, the cytotoxic character of the antigen-antibody reaction, and the type of antibody form (IgM or IgG)
Antibodies are formed against target antigens that are altered cell membrane determinants
Complement-mediated reactions (CM), antibody-dependent cell mediated cytotoxicity (ADCC), antibody mediated cellular dysfunction (AMCD), transfusions reactions, Rh incompatibility reactions, autoimmune reactions, and drug induced reactions
Type III
Localized response mediated by antigen-antibody immune complexes
Stimulated by microorganism and involve activation of complement trigger release of cytokines and recruitment of granulocytes increased vascular permeability and tissue necrosis
Post-infection complications such as arthritis and glomerulonephritis.
Arthus reaction
Local type III hypersensivitySlow, max 4-8hrsPigeon fanciers lung
Type IV
Intradermal or mucosal challenge CD4+ T-cells recognize MHC II (major histocompatibility class-II) antigens on antigen-presenting cells (Langerhans cell) differentiate to Th1 cells
Sensitization phase requires prolonged local contact at least two weeks
Repeat challenge induced Th1 cells release cytokines stimulating attraction phagocytic monocytes and granulocytes release lysosomal enzymes local tissue necrosis
Plant resins, jewelry
TYPE DESCRIPTIVE INITIATION MECHANISM EXAMPLES
NAME TIME
I IgE-mediated hypersensitivity 2-30 minsAg induces cross-linking of IgE bound to mast cells with release of vasoactive mediators
Systemic anaphylaxis, Local anaphylaxis, Hay fever, Asthma, Eczema
II Antibody-mediated cytotoxic hypersensitivity 5-8hrsAb directed against cell-surface antigens mediates cell destruction via ADCC or complement
Blood transfusion reactions, Haemolytic disease of the newborn, Autoimmune Haemolytic anaemia
III Immune-complex mediated hypersensitivity 2-8hrs
Ag-Ab complexes deposited at various sites induces mast cell degranulation via FcgammaRIII, PMN degranulation damages tissue
Arthus reaction (Localised); Systemic reactions disseminated rash, arthritis, glomerulonephritis
IV cell-mediated hypersensitivity 24-72hrsMemory TH1 cells release cytokines that recruit and activate macrophages
Contact dermatitis, Tubercular lesions
Idiosyncratic Reactions
Abnormal responses to drugs or chemicals resulting from uncommon genetic predisposition
Succinylcholine deficiency in plasma cholinesterase reduction in the rate of SC deactivation respiration fail to return to normal during postoperative period
Immediate vs Delayed Effects
Depending on the mechanism of toxicitySedatives-hypnotics immediateCarcinogens delayed
Reversible vs Irreversible The effects of most drugs or chemicals are
reversible until a critical point is reachedReversibility of chemicals effect may be enacted
through 1. Administration of antagonist2. Enhancement of metabolism or elimination3. Delaying absorption4. Intervening with another toxicological procedure that decrease toxic blood concentration 5. Terminating of the exposure
Local vs systemic
Depend on site of exposureSkin or lungs are frequent targets of
chemical exposureOral exposure systemic effectHypersensivity types I and IV precipitated
by local activation of immune response following a sensitization phase
Drug-induced type II elicited through oral or parenteral administration
Potentiation
The toxic effect of one chemical is enhanced in the presence of toxicologically unrelated agent
A relatively nontoxic chemical alone has little or no effect (0), may enhance the toxicity of another co administered chemical (2) 0 + 2 > 2
Hepatotoxicity of carbon tetrachloride is greatly increased in the presence of isopropanol
Additive
Two or more chemicals whose combined effects are equal to the sum of the individual effects
2 + 2 = 4Combination of sedative-hypnotics and
ethanol (drowsiness, respiratory depression)
Synergistic
By definition, synergistic effect is indistinguishable from potentiation, except in some references, both chemicals must have cytotoxic activity
1 + 2 > 3Combinations of ethanol and
antihistamine
Antagonistic
The opposing actions of two or more chemical agents, not necessarily administered simultaneously
Type :
1. Functional antagonism
2. Chemical antagonism
3. Dispositional antagonism
4. Receptor antagonism
Functional antagonism
The opposing physiological effects of chemical
CNS stimulants vs depressants
Chemical antagonism
Drugs or chemicals that bind to, inactivate, or neutralize target compounds
Chelators in metal poisoning
Dispositional antagonism
Interference of one agent with the ADME of another
Activated charcoal, Phenobarbital, diuretics
Receptor antagonism
The occupation of pharmalogical receptors by competitive or noncompetitive agents
Tamoxifen in the prevention of estrogen-induced breast cancer