PHAR1101 Lecture Notes - Lecture 17: Hemolytic Anemia, Primaquine, Heinz Body
Why do some drugs work so poorly in some patients?
Malaria:
Infectious disease caused by several strains of plasmodium (protozoa – single celled parasites)
- Anopheles mosquitos are vectors
- Disease can devastate troops in jungle war zones (fever, chills, lethargy, death)
China – 1967
- Search for antimalarial drugs
- Identified artemisinin – new class of drugs.
Quinine only ueful for acute malaria (not prophylaxis)
At start of pacific war, 95% of quinine from JAVA
- Plantations capture by japanese
- US army desperate for alternatives.
8 year program led to 8-aminoquinolines:
Primaquine (1944) – cures relapsing malaria in returned troops.
- Korean war – administered to US troops on return voyage (2 wks, every 6 hours).
Problem with primaquine: unexpected patient variability.
- army doctors needed to use high PQ doses to cure all plasmodium strains
- higher doses carried risk of haemolytic anaemia (loss of red blood cells)
- African americans very vulnerable (10%) – sometimes fatal but not normally.
- due to inherited glucose-6-phosphate dehydrogenase deficiency
- toxic PQ metabolites cause Heinz bodies in red blood cells from G6PDH-def. patients.
Key terms:
Beneficial or therapeutic response
Partial response
Non responsive
Full adverse response
Pharmacogenetics – studies how variation in a single
gene can influence the response of a drug
Pharmacogenomics – studies how all the genes in the human genome can influence responses to drugs.
find more resources at oneclass.com
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Document Summary
Infectious disease caused by several strains of plasmodium (protozoa single celled parasites) Disease can devastate troops in jungle war zones (fever, chills, lethargy, death) Quinine only ueful for acute malaria (not prophylaxis) At start of pacific war, 95% of quinine from java. Primaquine (1944) cures relapsing malaria in returned troops. Korean war administered to us troops on return voyage (2 wks, every 6 hours). Problem with primaquine: unexpected patient variability. army doctors needed to use high pq doses to cure all plasmodium strains. Higher doses carried risk of haemolytic anaemia (loss of red blood cells) African americans very vulnerable (10%) sometimes fatal but not normally. Due to inherited glucose-6-phosphate dehydrogenase deficiency toxic pq metabolites cause heinz bodies in red blood cells from g6pdh-def. patients. Pharmacogenetics studies how variation in a single gene can influence the response of a drug. Pharmacogenomics studies how all the genes in the human genome can influence responses to drugs.
