Anti-viral and anti-parasitic drugs Flashcards
(39 cards)
What are viruses?
Replicate by inserting their genetic code inside host cells.
Use the host machinery to generate new viral particles. This makes it difficult to target as it is not selective.
They often get to an advanced stage before detection.
What are DNA viruses?
Herpesviruses - chickenpox, cold sores, glandular fever and multiple sclerosis.
Adenoviruses - sore throat, conjuctivtis.
Papillomaviruses - warts.
What are RNA viruses?
Orthomyxoviruses - influenza.
Paramyxoviruses - measles, mumps, rubella.
Retroviruses - AIDS - HIV.
Coronaviruses - SARS, MERS, COVID 19.
What are drug strategies?
Target virus outside host cell - vaccines.
Target viral nucleic acid replication.
Target viral nucleic acid integration.
Target viral protein manufacture.
What is targeting outside the host cell important for?
For viruses - HIV.
This is a viral infection of CD4 T cells, a major immune cell, and then causes other infections like TB which cause death.
Anti-viral therapies prevent the depletion of CD4 T cells to maintain an effective immune system.
How is the virus targeted outside the host cell?
Vaccines - induces an immune response.
e.g. MMR, Covid 19.
What is inhibition of viral nucleic acid replication?
Reverse transcriptase inhibitors prevent RNA forming DNA copies.
Reverse transcriptase is a virally encoded enzyme, so can selectively target to stop viral replication.
Other targets are viral integrase, which integrates the genetic material into the human genetic code.
What are reverse transcriptase inhibitors?
Nucleoside Reverse Transcriptase Inhibitors (NRTIs) e.g. zidovudine.
It is a thymidine analogue, activated by phosphorylation.
It is incorporated into the elongating DNA chain, and prevents further elongation, and therefore viral replicaiton.
How is AIDs targeted?
CCR5 antagonists block the virus attaching to the cell, which prevents intergration into the human genome.
Protease inhibitors to prevent the virus escaping the cell and releasing viral particles.
2 reverse transcriptase inhibitros can be used to maximise prevention of elongation.
This increases life expectancy to normal.
What is Schistosomiasis?
A parasitic disease where male and femal parasites wrap around and produce eggs.
The eggs should be defecated, but some escape from the intestines into the hepatic portal vein and into the liver which causes liver failure and death.
Can be treated by a single dose of Praziquantel.
What is ancylostomiasis?
Larvae from worm eggs enter the skin, enter the blood stream and travel to the lungs, then go into the throat and is swallowed into the oesophagus then goes into the oesophagus and into the stomach, the small intestine then grows into an adult.
As the liver fails, there is fluid accumulation in the peritoneal cavity.
What is Leishmaniasis?
Parasite is transmitted by the sandfly, and then lives in a macrophage, the principal cells of the innate immune system, which makes it difficult to clear.
Cutaneous, mucocutaneous or visceral disease.
Treated by Amphotericin B.
What is Visceral Leishmaniasis?
Can cause post Kala-azar dermal Leishmaniasis.
This lives in the liver macrophages and is fatal.
What is Malaria?
Caused bu the Plasmodium parasite.
Variations are P. falciparum which kills, P. Vivax, P. Ovale, P.malariae.
Transmitted by the female anopheles mosquito which uses blood to produce eggs to reproduce.
What is the Malarial lifecycle?
Hepatic
Erythrocytic
Mosquito cycle
What is the hepatic cycle of Malaria?
Mosquito injects sporozoites into the body, which invades liver cells and produce Schizonts.
Schizonts rupture and release merozoites.
In vivax and ovale malaria, hypnozoites lie dormant in the liver.
What is the erythrocytic cycle of malaria?
Merozoites infect erythrocytes, form schizonts, which rupture and release more merozoites which invade more erythrocytes.
Some merozoites form ring stage trophozoites that invade other trophozoites that feed on haemoglobin and mature into schizonts and rupture and release merozoites.
This kills the RBCs and makes you anaemic.
Some trophozoites differentiate into sexual stages.
How can trophozoites be targeted?
Haem is iron, which is toxic to them, so they polymerise and detoxify it.
The enzyme to polymerise it can be targeted by drugs to stop them feeding and becomes toxic and they die.
What is the mosquito cycle of malaria?
Gametocyte sexual reproduction in female anopheles.
Gametocytes differentiate into gametes which fuse in the gut forming an ookinete, which penetrates the gut wall and forms an oocyst.
What is the life cycle in vivax and ovale malaria?
Have an extra cycle - hypnozoites.
The parasite sleeps in a hepatocyte, then can wake up after any period of time and cause malaria.
What are the Malarial symptoms?
Paroxysms - short attacks.
Cold, then hot then sweating.
There are only symptoms when the parasite is outside the cells, and can be attacked by white blood cells.
Anaemia increases with each cycle.
Cerebral malaria - the parasite RBCs blocks the blood vessels in the brain and causes stroke symptoms.
What is primaquine?
The drug is activated in the liver by CYP450s.
This then kills the hypnoizite which lives in the liver, by producing reactive oxygen species like H2O2.
What is chemoprophylaxis for malaria?
Drugs given before travelling to an area with malaria.
Eradicate parasites when they emerge from the liver.
What drugs are given for chemoprophylaxis?
Atrovaquone is a competitive inhibitor of ubiquinol. It targets mitochondrial generation of orotate, so decreases pyrimidine synthesis.
Proquanil inhibits dihydrofolate reductase. This causes a decrease in folate production, so decreases purine synthesis.
These collectivitly block cell synthesis.
