He-Bridges Pharm Antimalarial Drugs

Front 1

Recall the stage of malaria infection that most drugs target

Back 1

blood schizonts (asexual blood stage of the parasite)

Front 2

Name the only agent that prevents relapses by eliminating hypnozoites and name the affected Plasmodium species

Back 2

primaquine against p. vivax & ovale

Front 3

Explain a likely basis for the highly selective toxicity of chloroquine for the malaria parasite

Back 3

interferes with metabolism and hemoglobin utilization by parasites & concentrates within parasite acid vesicles and raises internal pH resulting in inhibition of parasite growth

Front 4

Identify which antimalarial agents may produce cinchonism and be able to recognize the symptoms of cinchonism

Back 4

quinine, symptoms include tinnitus, nausea, headaches, dizziness & disturbed vision

Front 5

Name the agents that are used for chemoprophylaxis (prevention) of malaria

Back 5

atovaquone/proguanil
primaquine
chloroquine
mefloquine
doxycycline
atovaquone/proguanil
primaquine
(NOT sylfadoxine/pyrimethamine, artemether/lumefantrine or quinine)

Front 6

Name the antimalarial agent that is a broad spectrum antibiotic and explain why it is contraindicated during pregnancy and childhood

Back 6

doxycycline b/c it can cause permanent teeth discoloration in children & inhibited bone growth & teeth discoloration in fetus

Front 7

Explain the pathophysiology of glucose-6-phosphate dehydrogenase deficiency in hemolytic anemia triggered by antimalarial drugs. Recall which drug requires G6PD screening before use

Back 7

Sulfadoxine & pyrimethamine, this is b/c these drugs are oxidants and in this deficiency exposure to them will cause intravascular hemolysis. this is b/c G6PD is required to supply NADPH to reduce glutathione which is used to reduce ROS's

Front 8

Describe the following for mefloquine:
1. adverse effects
2. disease-related concerns
3. mechanism of action

Back 8

1. CNS, rash, GI upset, myalgia, tinnitus, aplastic anemia
2. use with caution for pts w/CVD, hepatic impairment, seizure disorder
3. destroys asexual blood forms of malarial pathogens (p. falciparum, vivax)

Front 9

Describe the following for primaquine:
1. adverse effects
2. disease-related concerns
3. mechanism of action

Back 9

1. arrhythmia, headahce, pruritis, GI upset, anemias, visual accomodation disturbance
2. Don't use in pt's with G6PD deficiency
use w/caution in pt's w/methemoglobin reductase def.
3. eliminates primary tissue exoerythrocytic forms of P. ovale, vivax; disrupts mitochondria & binds to DNA

Front 10

Describe the following for chloroquine:
1. adverse effects
2. mechanism of action

Back 10

1. CV, CNS, dermatologic, GI, hematologic, neuromuscular/MSK, Ocular, Otic issues & anaphylaxis/angioedema
2. Binds to and inhibits DNA and RNA polymerase; interferes with metabolism and hemoglobin utilization by parasites; inhibits prostaglandin effects; concentrates within parasite acid vesicles and raises internal pH resulting in inhibition of parasite growth; may involve aggregates of ferriprotoporphyrin IX acting as receptors causing membrane damage; may also interfere with nucleoprotein synthesis

Front 11

Describe the following for Doxycycline:
1. adverse effects
2. disease-related concerns
3. mechanism of action
4. special populations

Back 11

1. CV, derm, endocrine/metabolic, GI, & hematologic issues, hepatotoxicity, & increased BUN
2. may cause autoimmune syndrome, hepatotoxicity, increased BUN, photosensitivity, pseudotumor cerebri, superinfection, tissue hyperpigmentation
3. inhibits protein synthesis by binding with the 30S and possibly the 50S ribosomal subunit(s) of susceptible bacteria; may also cause alterations in the cytoplasmic membrane
4. pediatrics: may cause tissue hyperpigmentation, permanent tooth discoloration, don't use in children < 8 y/o
pregnancy: DO NOT USE, associated w/reduced bone growth

Front 12

Describe the following for Atovaquone & proguanil:
1. adverse effects
2. disease-related concerns
3. mechanism of action
a. atovaquone
b. proguanil

Back 12

1. GI upset, transminase increase, headache/dizziness, pruritis, diarrhea, weakness
2. may cause diarrhea, use with caution for pt w/renal disease
not indicated for severe/complicated malaria
3.
a. Selectively inhibits parasite mitochondrial electron transport.

b. The metabolite cycloguanil inhibits dihydrofolate reductase, disrupting deoxythymidylate synthesis. Together, atovaquone/cycloguanil affect the erythrocytic and exoerythrocytic stages of development.

Front 13

Describe the following for Sulfadoxine & pyrimethamine:
1. adverse effects
2. disease-related concerns
3. mechanism of action
a. sulfadoxine
b. pyrimethamine

Back 13

1. CV, CNS, Derm, thyroid, GI, GU, hemeatologic, hepatic, neuromuscular, renal & respiratory issues. also hypersensitivity
2. use with caution for pt's with folate & G6PD deficiency
3.
a. interferes with bacterial folic acid synthesis and growth via competitive inhibition of para-aminiobenzoic acid

b. inhibits microbial dihydrofolate reductase, resulting in inhibition of tetrahydrofolic acid synthesis

Front 14

Describe the following for artemether & lumefantrine:
1. adverse effects
2. mechanism of action

Back 14

1. palpitation, CNS, GI, neuromuscular, & respiratory issues
2. rapid schizontocides with activity attributed to the endoperoxide moiety common to each substance. inhibits an essential calcium adenosine triphosphatas

Front 15

Describe the following for quinine:
1. adverse effects
2. disease-related concerns
3. mechanism of action

Back 15

1. CV, CNS, derm, GI, hypoglycemia, hematologic, hepatic, MSK, ocular, otic, renal, respiratory issues
2. use caution in pt's w/conditions that involve QT interval prolongation, heart disease.
3. Depresses oxygen uptake and carbohydrate metabolism; intercalates into DNA, disrupting the parasite's replication and transcription