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Pharmacology > Anti Protozoal /malaria > Flashcards

Anti Protozoal /malaria Flashcards

1
Q

What does distributional selectivity mean

A

Where the drug is directed/administered to into a limited compartment concentrated with parasite

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2
Q

Why are protozoan plasmodium hard to target

A

Eukaryotic

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3
Q

What causes malarial symptoms like fever pain

A

Rbc lysis

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4
Q

What are the 4 types of plasmodium

A

Falciparum

Virax

Ovale

Malarie

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5
Q

Which plasmodium takes shortest time (6 days) to infect

A

Falciparum

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6
Q

Which 2 plasmodium exist as hypnozoites in liver

A

Virax and ovale

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7
Q

Who is the definitive host for plasmodium (sexual reproduction)

A

Female mosquito

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8
Q

What are injected into our blood from mosquito saliva and where do they go

A

Sporozoites

Enter blood to the liver

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9
Q

After replication in liver what is released to go to the rbc

A

Merozoites

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10
Q

What is the stage in the liver called

A

Exo erythrocytic cycle

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11
Q

Once merozoites penetrate rbc, what are they called

A

TrophoZoites

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12
Q

What are trophozoites whixh then lay dormant in liver called

A

Hypnozoites (ovale and virax)

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13
Q

Name some things which trophozoites do in asexual reproduction in the rbc

A

Digest AA, Hb for energy

Convert heme to hemeozoin (less toxic for them)

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14
Q

Trophozoites which are released from burst rbc are called merozoites again. What do they develop into

A

Gametocytes

Which then infect next mosquito in blood

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15
Q

What are the 4 targets in life cycle

A

Exo erythrocytic cycle

Erythrocytic cycle

Link between liver and rbc

Gametocytes infecting a new mosquito

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16
Q

What are drugs called which act on exo erythrocytic cycle and which parasites do they work best on

A

radical cure

Work best on hypnozoites eg virax or ovale

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17
Q

What is a clinical cure

A

Works on erythrocytic cycle for ones which don’t reproduce in the liver

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18
Q

What do prophylaxis treatment do

A

Stop the transfer between liver and rbc

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19
Q

What are 4 amino quinolones and give example

A

Drugs which target clinical and prophylaxis (erythrocytic forms)

Chloroquine example

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20
Q

What 2 effects do 4 amino quinolones have eg chloroquine

A

Stop Hb digestion in RBCs to stop energy transfer

Stop production of hemeozoin from toxic heme

21
Q

Which enzyme does chloroquine (4amino quinolones) inhibit to stop production of hemeozoin

A

Heme polymerase

22
Q

What are the good things about chloroquine (4 amino quinolone)

A

Well absorbed

Long t1/2

23
Q

How do chloroquines stay in the parasite to block heme polymerase and digestion of Hb

A

Get ionised by acid in the parasitic lysosomes

24
Q

What is an issue with chloroquine 4 amino quinolone for clinical cure

A

Parasites become resistant due to efflux of drug

25
Q

Which types of drugs are quinine methanols

A

Also clinical / prophylaxis

26
Q

Give 2 examples of quinine methanols which target erythrocytic forms (clinical)

A

Quinine

Mefloquine

27
Q

Which 2 effects does quinine methanols like quinine have on erythrocytic forms

A

Bind to their dna to prevent rep

Block heme polymerase forming hemeozoin

28
Q

What is a disadvantage to quinine compared to chloroquine

A

Quinine has shorter half life

29
Q

Which Quinine methanol has longest half life

A

Mefloquine

30
Q

What are the side effects of Quinine methanols eg quinine

A

Cns effects like delerious or headache

31
Q

What do 8 amino quinolones target

A

Exo erythrocytic stages / radical cure/ hypnozoites eg ovale or virax

32
Q

Which 2 types of cells do 8 amino quinolone skill

A

Hypnozoites and gametocytes

33
Q

What is produced by pro drugs 8 amino quinolones when metabolised in liver which is cytotoxic to host

A

Quinolone

34
Q

What does metabolism of 8 amino quinolones cause in people with a G6PDH deficiency

A

Haemolysis of rbc

35
Q

Which ADME negative do 8 amino quinolone have

A

Short t1/2

36
Q

How do 8 amino quinolone a work for radical / exo erythrocytic cure

A

Produce ROS which stops dna synthesis and also mt disruption of energy

37
Q

What type of drugs are anti folates and give example

A

Prophylaxis

Proguanil

38
Q

Which metabolic enzyme activated proguanil prodrug

A

Cyp 2c19

39
Q

Which enzyme does anti folate proguanil inhibit (type II anti folate)

A

Dihydrofolate reductase

40
Q

How have parasites become resistant to anti folates like proguanil

A

Mutation to their dihydrofolate reductase enzyme

41
Q

What can anti folates type II like proguanil be given with to stop full dna synthesis

A

Type I eg sulphonamides

42
Q

What is the other prophylaxis drug apart from anti folates

A

Hydroxynapthoquinone

43
Q

How does hydroxynapthoquinone work

A

Disrupts ETC to stop getting mt energy

Looks like ubiquinol

44
Q

What is hydroxynapthoquinone given with for synergistic reasons and to stop resistance

A

Proguanil anti folate

45
Q

Which mutation acquired by parasites causes its resistance to hydroxynapthoquinone

A

Cyt BC1 complex in mitochondria

46
Q

What are given with anti malarial drugs to stop resistance and enhance their ADME

A

Artemisin (ACTs)

47
Q

Which 4 mutations have given malarial parasites resistance

A

Falciparum transporter gene

Falciparum Na/H exchanger gene

Dihydrofolate reductase (stop anti folates)

Cyt BC1 complex (stops hydroxynapthoquinone)

48
Q

Which antigen on falciparum is used to detect type

A

HRP 2

49
Q

Which other 2 other than falciparum HRP2 antigen is used for diagnostic

A

Aldolase

Lactate dehydrogenase

Pharmacology (24 decks)

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