Exam 3: Antimalarial Drugs

Question 1

What is the DOC for Malaria that does not have any drug resistance?

Answer 1

Chloroquine

Question 2

What genus does Protozoa belong to?

Answer 2

Plasmodia

Question 3

What are the 4 Protozoa species that cause malaria in humans?

Answer 3

• P. Falciparum
• P. Vivax
• P. Ovale
• P. Malariae

Question 4

What are the two types of malaria protozoa that are dormant and stay in the liver?

Answer 4

P. Vivax and P. Ovale

Question 5

What is the most lethal form of malaria?

Answer 5

P. Falciparum

Question 6

What symptoms does P. Falciparum malaria cause?

Answer 6

• Fever every 3rd day
• Severe blood loss anemia
• Cerebral malaria (clogs vessels in the brain)

Question 7

What is the most common form of malaria?

Answer 7

P. Vivax

Question 8

What are the malaria species called when they are dormant in the liver?

Answer 8

Hyponozoites

Question 9

What symptoms does malaria caused by P. Vivax cause?

Answer 9

• Chills and fever every 3rd day

- Relapses months to years after mosquito bite due to dormant forms

Question 10

What is the most rare form of malaria?

Answer 10

P. Ovale

Question 11

What are the two types of malaria that cause relapses and why?

Answer 11

P. Ovale and P. Vivax because they have dormant stages in the liver and can be reactivated at any time

Question 12

What symptoms does malaria caused by P. Malaria have?

Answer 12

• Fever every 4th day

- Chronic infection that can last a lifetime

Question 13

What is a clinical cure for malaria?

Answer 13

Erythrocytes forms of the parasite have been eradicated and the patient is symptom free (Dormant Protozoa in the liver do no get eradicated)

Question 14

What is a radical cure for malaria?

Answer 14

All forms of the parasite, including any secondary tissue forms have been eradicated.
-Infections by P. Vivax and P. Ovale need radical cures

Question 15

What do blood schizonticides do?

Answer 15

They act on erythrocytes forms of the malaria parasite and can be used to suppress symptoms and provide a so-called “clinical cure”
-Does NOT affect secondary tissue forms of P. Vivax or P. Ovale

Question 16

What do tissue schizonticides do?

Answer 16

Eliminate the Protozoa from the tissue (acts on the dormant hepatic stages)

• Does not suppress symptoms once erythrocytes stages have been established
• Prevents relapse

Question 17

If you have a patient with a dormant form of malaria, how should you treat them?

Answer 17

A blood and a tissue schizonticide

Question 18

What are the recommended treatments for uncomplicated malaria with a chloroquine resistance?

Answer 18

Artesunate + Atovoquone/proguanil

OR

Artemether-lumefantrine

“ACT” drugs

Question 19

How does malaria form resistance against Chloroquine?

Answer 19

Transport pumps

Question 20

What is the MOA of Chloroquine?

Answer 20

Interferes with lysosomal degradation of hemoglobin

Question 21

How is chloroquine absorbed and what inhibits its absorption?

Answer 21

Taken orally, absorbed in the GI tract.

-Mg+ and Ca+ antacids inhibit absorption

Question 22

Where does chloroquine accumulate once absorbed? What can this cause?

Answer 22

Melanin-rich tissues, like the skin and retina.

This can cause retinal and cornea toxicity and is contraindicated in patients with ocular disease

Question 23

How is chloroquine metabolized?

Answer 23

In the liver by a substrate of CYP34A

Question 24

What are the toxicities associated with chloroquine?

Answer 24

Retinal and corneal toxicity, hemolysis (G6PD patients), and QT prolongation

Question 25

What are the contraindications of Chloroquine?

Answer 25

Patients with ocular disease, psoriasis, and porphyria

Question 26

What drugs have the fastest action against P. Falciparum?

Answer 26

The artemisinin - artesunate and artemether **They do have a short half life and are always combined with other antimalarial drugs

Question 27

What type of drugs are Proguanil and pyrimethamine + sulfadoxine? What type of malaria do they attack?

Answer 27

Folate metabolism inhibitors Main effect on erythrocytic forms

Question 28

How does resistance develop against the folate metabolism inhibitors?

Answer 28

Mutations in Dihydrofolate reductase

Question 29

What is the MOA of the folate metabolism inhibitors?

Answer 29

Suldadoxine inhibits the incorporation of PABA into the folic acid. Pyrimethamine and proguanil inhibit dihydrofolate reductase, blocking conversion of dihydrofolate reductase into tetrahydrofolic acid

Question 30

What antimalarials are often used in conjunction with artemisinins?

Answer 30

Atovoquone, lumefantrine, mefloquine, and sulfadoxine-pyrimethamine

Question 31

What is the MOA of Atovoquone + Proguanil?

Answer 31

- Atovoquone interferes with mitochondrial electron transport, ATP, and pyrimidine biosynthesis - Proguanil- Prodrug that is converted to cycloguanil, inhibits dihydrofolate reductase Together, they are synergistic

Question 32

What is Atovoquone + Proguanil often combined with and why?

Answer 32

Artesunate for rapid clearance and decrease in resistance

Question 33

What are the side effects of Atovoquone + Proguanil that require discontinuation of the drug?

Answer 33

Rash, fever, vomiting, diarrhea *caution with pregnancy, caused mutations in mouse tests

Question 34

What is lumefantrine used in combination with?

Answer 34

Artemether

Question 35

What are the toxicities associated with lumefantrine?

Answer 35

Headache (56%) and QT prolongation

Question 36

What kind of malaria does Quinine and Quinidine gluconate treat?

Answer 36

Complicated, chloroquine resistance plasmodia

Question 37

What is Quinine and Quinidine Gluconate often combined with and why?

Answer 37

Doxycycline, tetracycline, or Clindamycin because it reduces the length of the treatment and therefore the adverse side effects are reduced

Question 38

What is important to remember about the dosing for Quinine?

Answer 38

It have a very narrow margin between effective dose and toxic dose

Question 39

What are the toxicities associated with quinine and quinidine Gluconate?

Answer 39

- Cinchonism: Tinnitus, headache, dizziness, flushing, visual disturbance - Anti-arrhythmic agent - Hemolysis in G6PD deficient patients - QT prolongation - Diarrhea

Question 40

What form of malaria do antibiotics help treat?

Answer 40

Complicated, chloroquine-resistance malaria (quinine and Clindamycin in children/pregnant women)

Question 41

What form of malaria does Mefloquine act on?

Answer 41

Erythrocytic forms, however resistance and toxicity limits use (drug of last resort)

Question 42

How is Mefloquine metabolized?

Answer 42

Absorbed in the GI tract with a bioavailability greater than 85%, metabolized in the liver, and eliminated very slowly via bile in the feces (permits single dose regimen)

Question 43

What are the toxicities associated with Mefloquine?

Answer 43

Depression of the myocardium (do NOT combine with quinine!) Seizures Latent psychosis Vivid dreams

Question 44

When is mefloquine not recommended?

Answer 44

Should not be used in patients with mental illness or epilepsy Not recommended in pregnancy due to teratogenicity

Question 45

When is pyrimethamine + sulfadoxine used for malaria tx?

Answer 45

Empirical treatment and preventative intermittent therapy in pregnant women

Question 46

What type of drug is Primaquine?

Answer 46

Tissue schizonticide- only active against tissue forms.

Question 47

What are the contraindications of Primaquine?

Answer 47

SLE or RA (granulocytopenia) *not recommended in pregnancy, infancy, breastfeeding due to fatal hemolytic anemia (G6PD status of baby is unknown)

Question 48

What is the major toxicity associated with Primaquine?

Answer 48

Hemolytic anemia in G6PD patients

Question 49

What type of drug is Tafenoquine?

Answer 49

Tissue schizonticide against against ALL stages of disease

Question 50

What are the contraindications of Tafenoquine?

Answer 50

G6PD deficiency or G6PD status is unknown

Question 51

What are the uses of Tafenoquine in malaria tx?

Answer 51

Used as a radical cure and terminal prophylaxis

Question 52

What is Cinchonism and what drug is it associated with?

Answer 52

Tinnitus, headache, dizziness, flushing, visual disturbance -Quinine/Quinidine