Antiparasitic Drugs Flashcards
What is a parasite?
Something that is totally dependent on another organism for its survival. Some of the bacteria in our gut or skin are parasites. Their dependence on us hasnt reached a point where they are exerting significant harm on us though. The parasites we are focusing on do in fact create harm on their hosts because of their need to take nutrients from us to an excess.
Protozoal Diseases
- Malaria
- Pneumocystis pneumonia: opportunistic infection commonly seen in AIDS patients.- Amoebic dysentery
- Sleeping sickness
- Giardiasis
- Vaginitis
- Toxoplasmosis
- Parasitic worm infections
What’s A definitive host?
Definitive host: where reproduction of the parasite occurs. Because of this, a number of strategies to prevent the transmission of parasitic organisms is to eliminate the definitive host. In the case of malaria that is the mosquito.
Malaria
Malaria
- Transmitted by bite of an Anopheles mosquito: 4 species associated with human malaria.
- Species: Plasmodium falciparum (fever is most severe with falciparum) , p. malariae (erythrocytic only); P. vivax, P. ovale (erythrocytic and exoerythrocytic)
- Symptoms include fever, joint pain, convulsions, coma, and death
- Prevention: ITNs: insecticide treated nets = biggest help.
- Goals of drug treatment: (1) acute attack, (2) radical cure, (3) prophylaxis, (4) block transmission
What’s a benefit of sickle cell anemia?
People with sickle cell anemia (or even carriers) are less susceptible to
infections of malaria.
What are the different malaria species?
Its important to know which species of malaria you are dealing with. The first two listed (Plasmodium falciparum and Plasmodium malariae) have only
an erythrocytic stage (red blood cells invaded by organism). Vivax and ovale
have both erythrocytic and exoerythrocytic stage (cells of the liver). If you’re dealing with these latter two, you have to use a treatment that also hits the liver cell stage, not just the blood cell stage.
Malaria life cycle
Sporozite is injected into blood and goes to the liver. Transient liver infection stage with vivax and ovale
species. Sporozite becomes schizont in the liver and then subsequently leaves the liver in the form of a
merozoite (free swimming stage that lives outside of cells until it finds an erythrocyte.). Once its in a cell
it develops into a gametocyte. You can only spread malaria by getting bit by a mosquito and then the
mosquito biting someone else. This is because the organism needs both humans and the mosquito
to complete its life cycle and survive.
Important Characteristics of Parasitic Diseases
- Most human parasites are eukaryotes; many are animals!
- Animals are typically definitive hosts. The closer and closer you get to using meds against organisms that are similar to humans, the bigger possibility of side effects occurring.
- Protozoal parasites avoid the host immune system by hiding out in host cells
- Some parasites produce cytokines that turn down the host immune response
- Protozoal diseases are largely restricted to the tropics but travelers can acquire them. Travelers are often at higher risk because they dont have developed immunity that some of the locals have through exposure.
What’s the cause of symptoms of malaria?
cause of symptoms is hemolysis of red blood cells. In order for the malaria to reproduce, they end up destroying the red blood cells which releases heme.
What’s the primary mode of treatment for acute attack?
Artemseinins are the primary mode of attack but are often given in combo with others to try and help prevent resistance. Any time you give drugs
in combo you reduce the chance of resistance occurring. This is because it is unlikely that the organism will develop resistance to both drugs simultaneously and survive.
Historically how has the world been doing with malaria?
Malaria used to be REALLY bad, but by eliminating the definitive host species we were able to bring it
down to a very low level. Recently, however, it has been making a comeback. This is because of resistance
developing. One of the main insecticides used to try to eradicate mosquitos was DDT. The mosquitos
gradually became resistant, and other insecticides were used as well but the mosquitos were able to
reproduce very rapidly and develop progeny that were even resistant to these drugs.
What’s acute attack good for?
Acute Attack
Targets blood schizonts. Only curative for species with no exoerythrocytic stage. falciparum and malariae
Artemesinin MOA
Artemesinin derivatives
Inhibit calcium dependent ATPase that’s important for membrane function
in cells of the malaria organism. So part of its energy metabolism is being
inhibited.
Chloroquine, quinine MOA
Block plasmodial enzyme called heme polymerase. This carries out a
detox reaction where the heme is converted to a polymer called hemozoin,
which is a less toxic form of heme. This allows the malaria organism to survive
in the presence of a high level of heme. Because the enzyme is not secreted, the host doesnt benefit.
By blocking this enzyme, the organism is now susceptible to the damaging effects of destroying the red blood
cells that it puts the host through.
Pyrimethamine+dapsone
Folate synthesis inhibitors. The organisms lacks a salvaging pathway for bases, so blocking the
synthesis pathway is effective in blocking th ability of parasites to undergo DNA syntehsis
