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The document discusses antimalarial drugs, including their mechanisms of action and structure-activity relationships. It describes how drugs like quinine and chloroquine work by intercalating DNA or accumulating in the parasite's food vacuole to inhibit enzymes. Other drugs like pyrimethamine prevent polymerization of the heme-digestion byproduct to form a toxic complex that destroys the parasite cell. The document examines the structures and SAR of various antimalarial drugs, including quinacrine, pyrimethamine, and halofantrine.
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Natural compounds from the bark of the cinchona tree, most notably quinine was observed to exhibit antimalarial activity.
Until the development of synthetic derivatives (ie. 4-aminoquinoline antimalarials), quinine continued to be the first choice to treat malaria.
Quinine is associated with side effects such as diarrhœa.
4-aminoquinoline antimalarials such as amodiaquine and chloroquine largely replaced quinine because of reduced unpleasant side effects.
The life cycle of the parasite and the immunological defence mechanisms against the parasite are complex.
Part of the parasite’s life cycle involves invasion of red blood cells (erythrocytes).
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The 4-aminoquinolines act at the erythrocytic stage of the parasite.
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2. Factors like age, diet, diseases, genetic factors and simultaneous administration of other drugs can influence drug metabolism by inducing or inhibiting drug-metabolizing enzymes. Metabolism can convert drugs to active, inactive or less active forms.
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Quinine is associated with side effects such as diarrhœa.
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Part of the parasite’s life cycle involves invasion of red blood cells (erythrocytes).
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14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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- 1. Antimalerial Drugs BY Umesh D. Joshi
- 2. Continued..
- 3. Life Cycle of Malerial parasite
- 15. MOA • Intercalation of DNA : Quinine, chloroquine intercalate the DNA but concenration of drug needed high. • Weak base hypothesis : these drugs accumulate in food vacuole of parasite which inhibits parasitic digestive enzymes involved in hemoglobin degradation.conc. Needed high of drug for activity. • Interaction between drug and FPIX complex:parasite obtaining amino acids from hemoglobin for growth. If this complex is unbound form is toxic to parasite since it generate active oxygen which destroys cell of parasite.parasite having defence mechanism to convert FPIX complex by enzyme hempolymerase to hematin which is non toxic to parasite which forms hemozoin pigment these drugs bind to the complex and prevent polymerization. This results in destruction of parasite.
- 28. MOA
- 31. SAR
- 34. SAR Continued..
- 39. SAR
- 43. Halofantriene • MOA is similar to chloroquine, Amodiaquine form toxic complexes with ferritoporphyrin IX that damage cell membrane of parasite.