23 - Antiprotozoals & Malaria Flashcards
Distributional selectivity
A drug equally toxic to host and parasite is useful if parasiting cell is exposed to a higher concentration than the host cell
Distributional selectivity can be achieved by…
- Selective distribution
- Selective accumulation by the parasite
- Selective administration
4 types of protozoal infections
Sporozoa, flagellates, ciliates and amoeba
The most common protozoal infections are _______, such as ________.
The most common protozoal infections are sporozoa, such as malaria.
Leishmania is caused by which class of protozoa?
Flagellates
Malaria is a sporozoa parasite of which genus?
Plasmodium
Symptoms of malaria include…
Fever, pain, convulsions (which can lead to coma and death)
Name the 4 types of malaria and state their severity…
- P. falciparum - severe
- P. vivax - mild to severe
- P. ovale - mild
- P. malarie - mild
Which types of malaria can lie dormant?
a) falciparum
b) vivax and falciparum
c) ovale and vivax
d) malarie
e) all four types
Which types of malaria can lie dormant?
a) falciparum
b) vivax and falciparum
c) ovale and vivax
d) malarie
e) all four types
P. vivax and P. ovale malaria can lie dormant with possibility of relapse. This dormant state is also known as…
hypnozoite
The lifecycle of the malaria parasite corresponds to the cycle of…
Symptoms
Outline the lifecycle of the malarial parasite (Plasmodium) (8)…
- Sporozoites enter capillary via female mosquito
- Liver cell entry
- Liver cell rupture, release of merozoites
- RBC penetration
- Asexual reproduction
- Rupture of RBCs
- Development into gametocytes
- Uptake by mosquito during blood meal
Malarial parasites require treatment with a drug with very high activity because of their…
High replication rate
A drug with 94% activity against plasmodium results in:
a) slight decrease in numbers
b) significant decrease in numbers
c) stasis in numbers
d) slower increase in numbers
A drug with 94% activity against plasmodium results in:
a) slight decrease in numbers
b) significant decrease in numbers
c) stasis in numbers
d) slower increase in numbers
So to eliminate plasmodium, drug activity >>94% required
Treatment for malaria can be divided into prevention and drug therapies. Describe 3 methods of prevention…
- Insect repellent
- Mosquito nets
- Covering skin
Drug cures for malaria can be divided into 3 categories…
- Clinical cures (no significant symptoms)
- Radical cures (complete)
- Prophylaxis (preventative)
Name the 5 classes of antimalarial drugs…
- 4-Aminoquinolones
- Quinoline-methanols
- 8-Aminoquinolones
- Antifolates
- Hydroxynaphthonquinone
An example of a 4-aminoquinolone is chloroquine…
- Accumulates in parasite lysosomes
- Inhibits digestion of Hb/ free haem conversion
- Oral administration
- Well absorbed with few side effects
- BUT resistance issues (must be combined w/ other drugs)
Examples of quinoline-methanosl are quinine and mefloquine…
- may intercalate with malarial DNA
- works against erythrocytic forms
- Oral administration w/ rapid metabolism
- 30 day t1/2
- Quinine has higher side effects
An example of an 8-aminoquinoline is primaquine…
- Radical cure for exoerythrocytic forms
- Kills gametocytes
- Metabolised by liver to quinoline (quinine derivative cytoxic to host and parasite)
- Used after curing clinical symptoms
- Causes haemolytic anaemia in patients with G6PDH deficiency :-(
An example of an antifolate is proguanil…
- Dihydrofolate reductase inhibitor
- Inhibits DNA synthesis
- Resistance issues
- Co-administered with atovaquone
An example of a hydroxynaphthoquinone is atovaquone…
- Inhibits mitochondrial electron transport chain in parasites
- Co-administered with proguanil (antifolate)
- Used for prophylaxis in areas with resistant strains
A new treatment for malaria is ACT, which stands for…
Artemisinin-based Combination Therapy
Malarial resistance is the result of…
Monotherapy drug use
Key targets of malarial resistance…
-
Plasmodial (Pf) transporter gene
- Chloroquine resistance (CR)
- Multidrug resistance (mdr1)
- P. falciparium Na+/H+ exchanger
- Folate biosythesis
- Cytochrome bc1 complex
Mutation in which malarial gene is responsible for chloroquine resistance?
Plasmodial (Pf) transporter gene
Name 3 antigens present on the malarial parasite (there are many more)…
- Histidine-rich protein 2 (HRP-2)
- Plasmodium lactate dehydrogenase (pLDH)
- Aldolase
Antibodies to these proteins key to aquired immunity, corresponding to high serum prevalence of IgG
Which method of early detection is more cost and time effective than microscopy lateral flow ‘immuno-chromatographic’ antigen-detection tests…
Rapid diagnostic tests (RDTs)
