PED1003/L24 Antiprotozoals

Question 1

What organism is malaria caused by?

Answer 1

Plasmodium

Question 2

When can a drug equally toxic to both parasite and host be useful?

Answer 2

When parasitising cell is exposed to a higher concentration than the host

Question 3

How can distributional selectivity be achieved? (3)

Answer 3

Selective accumulation by parasite
Selective distribution into limited compartment colonized by parasite
Selective administration into limited compartment colonized by parasite

Question 4

What are the clinical symptoms of malaria? (3)

Answer 4

Fever
Pain
Convulsions
Coma
Death

Question 5

Which is the most severe Plasmodium species?

Answer 5

P. falciparum

Question 6

How is malaria spread?

Answer 6

Female Anopheles mosquito
Needs blood to make eggs

Question 7

Describe the life cycle of Plasmodium. (8)

Answer 7

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

Question 8

How can malaria be prevented? (3)

Answer 8

Insect repellents
Nets
Covering skin
Insecticides (DDT)

Question 9

Give 3 pharmacological interventions to combat malaria.

Answer 9

Symptomatic relief
Radical cure
Prophylaxis

Question 10

Give 3 kinds of antimalarial drug.

Answer 10

4-aminoquinolones
Quinoline-methanols
8-aminoquinolines
Antifolates
Hydroxynaphthoquinone

Question 11

How do 4-aminoquinolones work?

Answer 11

Accumulate in lysosomes of parasite and may inhibit digestion of host haemoglobin

Question 12

Describe the distribution of 4-aminoquinolones. (2)

Answer 12

Given orally
Well-absorbed and distributed

Question 13

Give one problem with 4-aminoquinolones.

Answer 13

Resistance due to efflux from cells

Question 14

How do quinine-methanols work?

Answer 14

May bind to malarial pigment haemozoin and intercalate into DNA

Question 15

Which forms are quinine-methanols effective against?

Answer 15

Erythrocytic & chloroquine-resistant forms
NOT gametocytes or exo-erythrocytic forms

Question 16

Describe the metabolism of quinine. (2)

Answer 16

Given orally with loading dose
Metabolised rapidly

Question 17

What is the half-life of mefloquine?

Answer 17

30 days

Question 18

Which forms are 8-aminoquinolines effective against? (2)

Answer 18

Exoerythrocytic forms
Gametocytes

Question 19

What is the prodrug 8-aminoquinoline metabolised to in the liver?

Answer 19

Quinoline-quinone derivatives
Cytotoxic to host and parasite

Question 20

Which genetic deficiency is associated with serious haemolytic anaemia when given 8-aminoquinolines?

Answer 20

Glucose-6-phosphate dehydrogenase defiiciency (G6PDH)

Question 21

What is the prodrug anti-folate proguanil activated by?

Answer 21

CYP2C19 to cycloguanil

Question 22

What kind of drug is proguanil (anti-folate)?

Answer 22

Dihydrofolate reductase inhibitor
Inhibits DNA synthesis

Question 23

Which form are anti-folates effective against?

Answer 23

Plasmodial form

Question 24

By which mechanism does atoaquone (hydroxynaphthoquinone) work?

Answer 24

Inhibits mitochondrial electron transport in parasite

Question 25

Which drug is usually co-administered with atovaquone?

Answer 25

Proguanil (malarone)

Question 26

What is the purpose of in vitro studies of malaria? (2)

Answer 26

Measure intrinsic sensitivity of parasite to antimalarial drugs
Identify genetic mutations related to antimalarial drug resistance in parasite genome
Characterise antimalarial drug pharmacokinetics

Question 27

What may give rise to drug resistance?

Answer 27

Monotherapy

Question 28

Give 2 malarial parasite antigens.

Answer 28

Histidine-rich protein 2 (HRP2)
Plasmodium lactate dehydrogenase (pLDH)
Aldolase

Question 29

Why is rapid diagnostic testing useful? (2)

Answer 29

Early detection
Most cost and time effective than microscopy

Question 30

Give 2 alternatives to rapid diagnostic testing.

Answer 30

Microscopy
PCR
Immunoassays