Haematotoxicity & Local Toxicity.pptx

1. Haematotoxicity & Local
Toxicity
Dr. Sarita Sharma
Assistant Professor
Department Of Pharmacology

2. Haematotoxicity
 Hematotoxicity essentially affects two basic homeostatic
functions:
(1)RBC-mediated
oxygen transport
(2)
the production of red and
white blood cells
and platelets.

3. Basic Hematopoiesis: The Formation Of Blood Cells &
Their Differentiation

5. MOA of Haematotoxicity
RBC-mediated
oxygen transport fails
the production of red and
white blood cells & platelets.
HYPOXIA Bone marrow suppression
Tissue respiration impaired
Anaerobic Respiration
1) RBC: Oxygen transport fails
2) WBC: Impaired defence and
Immune system
3) Platelets: Impaired coagulation
mechanism
Acidosis & Cells damage

6.  blood toxicities that were commonly encountered in
occupational settings such as
1. benzene-induced bone marrow suppression, Acute
Leukemia
2. aniline and nitrobenzene induced methemoglobinemia,
3. hydrogen sulfide–induced effects.
4. carbon monoxide (impairment of oxygen transport)

7.  Exposure to hydrogen sulfide can be a significant industrial
concern in the refining of petroleum products and the
biological degradation of Grain, corn etc.
 As for the number of workers affected, benzene and
hydrogen sulfide probably constitute the most significant
risk factors for toxicity

8.  dapsone (used to treat leprosy) and primaquine (used to
treat malaria) can produce a fatal hemolytic anemia in
certain genetically predisposed individuals (those with a
deficiency in glucose-6-phosphate dehydrogenase).

12. Local Toxicity

13. Introduction:
 The skin is the largest organ in the body and is continually
exposed to external stimuli, such as chemical and
environmental substances.
 Cutaneous toxicity can be broadly classified according to
the mechanism of onset, namely:

14. 1)Contact dermatitis:
damage resulting from
contact with a substance
(irritant dermatitis,
allergic contact
dermatitis, chemical
burns)
2)Photosensitivity:
caused by combined
effects of a substance &
ultraviolet light
(phototoxic dermatitis,
photoallergy contact
dermatitis);
3) Contact urticaria:
chemical-induced acne;
pigmentary disturbance;
drug rash;
hair disturbance;
nail disturbance; or
tumor-induced.

18. Skin carcinogenesis
 Some photoirritants, such as 8-methoxypsoralen, have
been associated with UV-induced skin carcinogenesis.
 p53 is a protein that causes cell cycle arrest, apoptosis, or
 senescence that is crucial in the process of tumor
suppression in several cell types

19. DMBA/TPA two-stage skin carcinogenesis model, the absence of p53 in
stratified epithelia leads to the appearance of a higher number of tumors that
grow faster and become malignant more frequently than tumors arising in
mice with the wild type p53 genotype