Exam 9: Antimalarial Drugs Flashcards
What is the most effective way to combat malaria?
Prevention
Killing the mosquitos
What is the difference between a clinical cure and a radical cure?
Clinical cure- erythrocytic forms of the parasite are eradicated and the patient has no symptoms.
Radical Cure- All forms of the parasite have been eradicated
What is the difference between Causal Prophylaxis and Suppressive Agents?
Causal prophylaxis targets the primary (hepatic) form of the parasite (less practical)
Suppressive Agents- Target erythrocytic forms and suppress symptoms
What forms do Chloroquine and Hydroxychloroquine act on?
Erythrocytic forms
Chloroquine and Hydroxychloroquine mechanism
Affect the pH of the parasite’s food vacuoles, interfering with their feeding
For what species are Chloroquine and Hydroxychloroquine clinical cures? Radical cures?
Clinical cures for all
Radical cures for P. falciparum and P. malariae (not vivax and ovale)
What is a problem with the use of Chloroquine and Hydroxychloroquine?
Resistance, especially with P. falciparum
What causes resistance to Chloroquine and Hydroxychloroquine?
A transport pump that removes the drug from the parasite
How are Chloroquine and Hydroxychloroquine metabolized?
Liver
What are adverse effects of Chloroquine and Hydroxychloroquine?
CNS- dizziness, headache, tinnitus
GI Upset
Retina and corneal toxicity
Immunological problems
In whom are Chloroquine and Hydroxychloroquine contraindicated?
Patients with psoriasis or porphyria
Due to immune effects
What is a special use of Hydroxychloroquine?
Rheumatoid Arthritis and SLE due to its anti-inflammatory actions at high doses
(potential for serious toxicity at these doses though…)
What is the mechanism of Quinine and Quinidine?
Interference with digestion of hemoglobin
What is a time when you’d use Quinine or Quinidine?
Chloroquine-resistant P. falciparum
How are Quinine and Quinidine taken?
Orally.
Also an IV preparation of Quinidine in the US
What are adverse effects of Quinine and Quinidine?
GI irritation Visual and auditory disturbances Bradycardia Teratogenic/abortion Skeletal muscle relaxation Cinchonism (headache, nausea, vomiting, dizziness, tinnitus, blurred vision)
When might you use Mefloquine?
Chloroquine-resistant P. falciparum
When shouldn’t you use Mefloquine?
Serious, life threatening infections.
It can only be taken orally.
Adverse effects of Mefloquine?
Seizures
Activates latent psychosis
GI and cardiac problems
When is Mefloquine contraindicated?
Patients with epilepsy, mental illness, or cardiovascular problems
What are two inhibitors of folic acid synthesis that are used to treat Malaria?
Pyrimethamine and Proguanil
What is the mechanism of Pyrimethamine and Proguanil?
Inhibition of DHFR
When are Pyrimethamine and Proguanil mostly used?
Prophylaxis, especially against Chloroquine-resistant P. falciparum
When might you use pyrimethamine plus sulfadoxine combination?
Presumptive treatment (person shows symptoms, but you haven’t diagnosed them for sure yet)
What is the mechanism of Atovaquone?
Depolarizes the parasite’s mitochondria and inhibiting electron transport
What is often used in combo with Atovaquone?
Proguanil (DHFR inhibitor)
When might you use Atovaquine + Proguanil?
Prophylaxis against Chloroquine-resistant P. falciparum
What are two downsides to Atovaquine + Proguanil?
- Expensive
2. Must be taken daily
What is artemisinin?
An isolate of an herbal preparation that is part of Coartem.
What is Coartem?
A product that contains an artemisinin derivative and is quickly becoming the primary drug used to treat most forms of malaria including Chloroquine-resistant P. falciparum
What are a couple of regular antibiotics that have activity against plasmodium species?
Tetracycline//doxycycline
What is Primaquine used for?
Follow up treatment when you think a person may have been infected with P. vivax or ovale
What is the advantage of Primaquine? Disadvantage?
Can kill the plasmodium parasites in the liver (eradicate latent phase)
Disadvantage is that it has toxicities (CNS, GI, and can cause hemolytic anemia in patients with G6PD deficiency)
Primaquine toxicity
Hemolytic anemia in patients with G6PD deficiency
GI upset
Headaches/dizziness
What would you use for an acute, uncomplicated attack of malaria?
Chloroquine Quinine/Quinidine Coartem (artemether/lumefantrine) Mefloquine Atovaquine + Proguanil Doxycycline
What is used for a radical cure of P. vivax/ovale?
Primaquine
What are 5 drugs used for malaria prophylaxis?
Chloroquine (mostly)
Mefloquine (Chloroquine-resistant P. falciparum)
Doxycycline
Atovaquine + Proguanil
Primaquine (follow up therapy to eradicate P. vivix/ovale
