Lecture 8 Antiprotozoals

Question 1

What are the symptoms of malaria? What causes it?

Answer 1

Periodic attacks of chills and fever, anaemia, splenomegaly and often fatal complications. Caused by 5 species of protozoa, that have part of their life cycle in the female Anopheles mosquito.

Question 2

What are the 5 species of protozoa that cause malaria?

Answer 2

Plasmodium falciparum (most deadly and mostly resistant to chloroquine). Resistance forced the use of combination therapy.
P vivax: most common worldwide. Tissue schizonts may be dormant for years.
P Ovale: Tissue schizonts may be dormant for years.
P knowlesi: Common in SE Asia
P malariae: Rare

Question 3

Describe the lifecycle of Plasmodium falciparum.

Answer 3

1. Infected mosquito injects sporozoites.
2. Sporozites migrate to the liver, where they form merozoites.
3. Merozoites are released and invade RBCs.
4. In the RBC, the merozoite becomes a trophozoite.
5. In the RBC, the trophozoite multiples to produce more merozoites. The RBC ruptures, releasing merozoites which infect other RBCs.
6. Some merozoites become gametocytes.
7. the female mosquito picks up gametocytes from in infected human. the sexual cycle occurs in the mosquito where sporozoites are formed.

Question 4

List drugs effective against the erythrocytic form of plasmodium.

Answer 4

Artemisinin, chloroquinine, quinine, mefloquine and pyrimethamine.

Question 5

Which drug is effective against the exoerythrocytic and the gametocytic form of plasmodium?

Answer 5

Primaquine.

Question 6

Which antimalarial drugs are rapid acting and used to treat clinical attacks of malaria?

Answer 6

Chloroquine, quinine, mefloquine, atorvaquone with proguanil and atemether with lumefantrine.

Question 7

What use does proguanil have?

Answer 7

Slow acting and so used for prophylaxis of malaria.

Question 8

What uses do Mefloquine, atorvaquone with proguanil, and quinine have?

Answer 8

Used for both prophylaxis and treatment of malaria.

Question 9

Which drug are most Plasmodium falciparum now resistant to?

Answer 9

Chloroquine.

Question 10

Why can’t quinine be used for prophylaxis?

Answer 10

It is too toxic.

Question 11

What are tissue schizonticides used for? Give and example and their MOA.

Answer 11

Proguanil is used for prophylaxis and acts on primary tissue forms in the liver that will develop into erythrocytic stage within a month (causal prophylaxis).
Primaquine is used to prevent relapse and acts on latent tissue forms of P vivax and P oval remaining in the liver, which can cause relapse months or years after initial infection.

Question 12

Give examples of the 2 types of blood schizonticides for prophylaxis or treatment.

Answer 12

Rapid acting agents: atovaquone, chloroquine, quinine and mefloquine.
Slower acting agents: eg antifolates and antibacterials, which are usually used with a rapid acting antimalarial. This type of prophylaxis is known as suppressive.

Question 13

Describe suppressive prophylaxis of malaria.

Answer 13

Prophylactic agents such as chloroquine, proguanil, mefloquine and doxycycline are only effective at killing the malaria parasite once it has entered the erythrocytic stage, and thus have no effect until the liver stage is complete. This is why they must be taken for 4 weeks after leaving the area of risk.

Question 14

What is a gametocytocide, and give an example.

Answer 14

Gametocytocides interrupt the transmission of the infection from the human host to the mosquito vector, e.g. primaquine.

Question 15

Which is the only antimalarial that will kill the chizonts of P vivax and P ovale lying dormant in the liver?

Answer 15

Primaquine (it acts as a tissue schozonticide).

Question 16

In patients with a glucose-6-phosphate dehydrogenase deficiency, primaquine can cause_____________?

Answer 16

Haemolytic anaemia, which occurs as a result of the abnormal breakdown of RBCs.

Question 17

What is the mode of action of chloroquine?

Answer 17

Rapidly acting blood schizonticide with some gametocytocidal activity. Concentrates in erythrocytes and prevents the erythrocytic stage of malarial parasite reproduction.

Question 18

What is a counselling point of Chloroquine?

Answer 18

Tell your doctor if you notice any difficulty with your eyesight or any weakness in your legs.

Question 19

What type of antimalarial is mefloquine? Describe the practice points and adverse reactions.

Answer 19

Rapid acting blood schizonticide. Used prophylactically only in areas of chloroquine resistance and when doxycycline is not appropriate.
It may cause neuropsychiatric reactions.

Question 20

Describe the use of quinine, and its major adverse effects.

Answer 20

Quinine is reserved for severe infestations, and to treat resistant strains. A major adverse effect is cinchonism, which is a syndrome characterised by nausea, vomiting, tinnitus and vertigo. Quinine is also fetotoxic.

Question 21

Discuss the prevention of malaria.

Answer 21

Preventing bites is important as drug prophylaxis is only 75-95% effective.
Start prophylaxis 1 week before entering endemic area and continue for 4 weeks after leaving the area.
Pregnant women should not travel to areas where malaria is endemic.

Question 22

Describe the use of doxycycline for malaria.

Answer 22

Used prophylactically where there is chloroquine or mefloquine resistance.
Start 2 days before entering and continue for 4 weeks after leaving endemic area. If febrile illness develops within 12 months of possible exposure, see doctor.
Can be used with quinine to treat uncomplicated P. falciparum.

Question 23

What are the 2 general practice points for antimalarials?

Answer 23

Give an additional dose if an oral dose is vomited within 1 hour of admin (switch to parenteral route if necessary).
Advise travellers to take antimalarials with them rather than buying them overseas.

Question 24

What type of antimalarial is atovaquone? What is its MOA, and describe its use?

Answer 24

Rapidly acting blood schizonticide. It is a ubiquinone analogue, thought to selectively inhibit protozoal mitochondrial electron transport and reduce pyramiding synthesis, preventing protozoal replication.
Used in combination with proguanil in chloroquine or mefloquine-resistant malaria.

Question 25

What are the indications for use of atovaquone, other than malaria?

Answer 25

Treatment of mild to moderate PCP in HIV patients when other treatment is contraindicated.
Prevention of PCP in patients unable to take other agents.
Treatment of cerebral toxoplasmosis in people unable to tolerate pyrimethamine with either sulfadiazine or clindamycin.

Question 26

What are the indications for use of atovaquone with proguanil?

Answer 26

Prophylaxis of chloroquine or mefloquine-resistant malaria, or treatment of uncomplicated P falciparum malaria.

Question 27

What is the mechanism of action of proguanil?

Answer 27

Slow acting blood schizonticide. Proguanil is converted to cycloguanil which is a plasmodial dihydrofolate reductase inhibitor. It inhibits folate production by the malarial parasite.

Question 28

What type of antimalarial is pyrimethamine, and what is its MOA?

Answer 28

Slow acting blood schizonticide and is a folic acid antagonist.

Question 29

What is the MOA of nitroimidazoles. Give examples of the drugs and the protozoal infections they can be used to treat.

Answer 29

Metronidazole and tinidazole are metabolised to active metabolites that are thought to interfere with DNA synthesis. They are used to treat Giardiasis, Trichomoniasis, Amoebiasis (intestinal and extra-intestinal).

Question 30

What sort of drug is paromomycin? What are its indications for use?

Answer 30

It is an oral amino glycoside, indicated for use in Amoebiasis due to E hystolytica. It eradicates cysts in the GIT in both asymptomatic infection, or after treatment of invasive or symptomatic intestinal disease with metronidazole or tinidazole.

Question 31

How is Amoebiasis caused? Describe its treatment.

Answer 31

Caused by ingestion of cysts of E histolytica which develop into motile trophozoites in the GIT. Cause dysentery in GIT and amoebic abscess in the liver. Treated with metronidazole. Diloxanide furoate or paramomycin eliminates the cyst stage.

Question 32

Describe the lifecycle of Entamoeba.

Answer 32

1. ingestion of cysts.
2. Formation of trophozoites.
3. Penetration of intestinal wall.
4. Multiplication of trophozoites within the colon wall.
5. Systemic invasion (eg liver)
6. Cysts discarded with faeces.

Question 33

Describe the occurrence of Giardiasis.

Answer 33

Infection is common worldwide, and occurs where poor sanitation allows contamination of food and water with Giardia lamblia cysts from human or possibly animal faeces.

Question 34

What are the symptoms of Giardiasis?

Answer 34

Anorexia, crampy abdo pain, borborygmi and flatus with offensive, fatty stools.

Question 35

Describe the treatment of Giardiasis.

Answer 35

Do not treat asymptomatic carriers unless they handle food.
Give tinidazole as a single dose, or metronidazole for 3-7 days.
Use metronidazole in kids (oral liquid available).

Question 36

Describe the cause, symptoms and treatment of Trichomoniasis infections.

Answer 36

Caused by a pear shaped protozoa with 4 flagella. Common in women: frothy, offensive greenish-yellow discharge. Bladder may become involved causing dysuria and frequency. Males are usually symptomless.
Treat with metronidazole 2g single dose (or 400mg bd for 5 days for preg or breastfeeding. Treat sexual partners.

Question 37

Describe the transmission, cause and treatment of Toxoplasmosis.

Answer 37

Caused by Toxoplasma gondii. Oocysts from cat poo, or eating raw or poorly cooked infected meat are methods of infection. Treatment of choice is pyrimethamine-sulfadiazine.

Question 38

What is the MOA, and indications for use of pyrimethamine?

Answer 38

Folic acid antagonist. Used for the treatment of congenital or acquired toxoplasmosis with sulfadiazine (or clindamycin of sulfadiazine is not tolerated).
Accepted for use as a primary preventative for todo with dapsone, and maintenance of suppressive therapy for toxic with sulfadiazine.