PED1003/L24 Antiprotozoals Flashcards
What organism is malaria caused by?
Plasmodium
When can a drug equally toxic to both parasite and host be useful?
When parasitising cell is exposed to a higher concentration than the host
How can distributional selectivity be achieved? (3)
Selective accumulation by parasite
Selective distribution into limited compartment colonized by parasite
Selective administration into limited compartment colonized by parasite
What are the clinical symptoms of malaria? (3)
Fever
Pain
Convulsions
Coma
Death
Which is the most severe Plasmodium species?
P. falciparum
How is malaria spread?
Female Anopheles mosquito
Needs blood to make eggs
Describe the life cycle of Plasmodium. (8)
Mosquito bites human
Sporozites enter blood and lymph
Liver cell entry & rupture
Merozyte release
RBC penetration
Asexual reproduction
Development into gametocytes
Uptake during blood meal
How can malaria be prevented? (3)
Insect repellents
Nets
Covering skin
Insecticides (DDT)
Give 3 pharmacological interventions to combat malaria.
Symptomatic relief
Radical cure
Prophylaxis
Give 3 kinds of antimalarial drug.
4-aminoquinolones
Quinoline-methanols
8-aminoquinolines
Antifolates
Hydroxynaphthoquinone
How do 4-aminoquinolones work?
Accumulate in lysosomes of parasite and may inhibit digestion of host haemoglobin
Describe the distribution of 4-aminoquinolones. (2)
Given orally
Well-absorbed and distributed
Give one problem with 4-aminoquinolones.
Resistance due to efflux from cells
How do quinine-methanols work?
May bind to malarial pigment haemozoin and intercalate into DNA
Which forms are quinine-methanols effective against?
Erythrocytic & chloroquine-resistant forms
NOT gametocytes or exo-erythrocytic forms
Describe the metabolism of quinine. (2)
Given orally with loading dose
Metabolised rapidly
What is the half-life of mefloquine?
30 days
Which forms are 8-aminoquinolines effective against? (2)
Exoerythrocytic forms
Gametocytes
What is the prodrug 8-aminoquinoline metabolised to in the liver?
Quinoline-quinone derivatives
Cytotoxic to host and parasite
Which genetic deficiency is associated with serious haemolytic anaemia when given 8-aminoquinolines?
Glucose-6-phosphate dehydrogenase defiiciency (G6PDH)
What is the prodrug anti-folate proguanil activated by?
CYP2C19 to cycloguanil
What kind of drug is proguanil (anti-folate)?
Dihydrofolate reductase inhibitor
Inhibits DNA synthesis
Which form are anti-folates effective against?
Plasmodial form
By which mechanism does atoaquone (hydroxynaphthoquinone) work?
Inhibits mitochondrial electron transport in parasite
Which drug is usually co-administered with atovaquone?
Proguanil (malarone)
What is the purpose of in vitro studies of malaria? (2)
Measure intrinsic sensitivity of parasite to antimalarial drugs
Identify genetic mutations related to antimalarial drug resistance in parasite genome
Characterise antimalarial drug pharmacokinetics
What may give rise to drug resistance?
Monotherapy
Give 2 malarial parasite antigens.
Histidine-rich protein 2 (HRP2)
Plasmodium lactate dehydrogenase (pLDH)
Aldolase
Why is rapid diagnostic testing useful? (2)
Early detection
Most cost and time effective than microscopy
Give 2 alternatives to rapid diagnostic testing.
Microscopy
PCR
Immunoassays
