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Pharmacology - Midterm 2 > Antimalarials > Flashcards

Antimalarials Flashcards

1
Q

Life Cycle of P. falciparum and P. malariae

A

1 cycle of liver invasion; only erythrocytic parasites have to be eliminated

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2
Q

Life Cycle of P. vivax and P. ovale

A

dormant (hypnozoite) hepatic stage; erythrocytic and hepatic parasites have to be eliminated

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3
Q

What is malarial paroxysm?

A

Fever, anemia, hepatosplenomegaly, jaundice; occurs every 2-3 days in established infections

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4
Q

Which plasmodium species is cerebral malaria associated with?

A

P. falciparum; includes irritability, seizures, and coma

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5
Q

Most severe malaria due to microvascular effects

A

P. falciparum

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6
Q

How should uncomplicated malaria be treated?

A

Oral antimalarials

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7
Q

How should complicated malaria be treated?

A

Aggressively with parenteral antimalarials

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8
Q

MOA of Chloroquine

A

Concentrates in parasite food vacuoles and prevents biocrystallization of heme to non-toxic hemozoin ==> lysis of RBC and parasite

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9
Q

Antimalarial Action of Chloroquine

A

Only effective against blood parasites; NO ACTIVITY AGAINST LIVER PARASITES

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10
Q

Resistance to Chloroquine

A

P. falciparum has mutations in putative transporter (PfCRT)

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11
Q

PK of Chloroquine

A

Oral; take once a week due to long half-life

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12
Q

AE of Chloroquine

A

Well tolerated; pruritus in Africans, Hemolysis in G6PD deficiency, GI effects, headache, blurred vision, ECG changes

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13
Q

Contraindications of Chloroquine

A

Patients with Psoriasis, Porphyria, retinal or visual field abnormalities

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14
Q

True or False: Chloroquine is safe in pregnancy and young children

A

True

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15
Q

First line therapies derived from Cinchona tree and used for severe falciparum disease

A

Quinine and Quinidine

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16
Q

Oral treatment of falciparum malaria that is alternative to in Chloroquine-resistant areas

A

Quinine

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17
Q

Parenteral treatment of severe falciparum malaria

A

Quinidine

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18
Q

Antimalarial action of Quinine and Quinidine

A

Active against blood parasites but NO ACTIVITY AGAINST LIVER STAGE PARASITES

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19
Q

MOA of Quinine and Quinidine

A

Decreases oxygen uptake and carbohydrate metabolism; intercalates into parasite’s DNA, disrupting replication and transcription

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20
Q

PK of Quinine

A

Oral treatment for uncomplicated malaria

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21
Q

PK of Quinidine

A

IV treatment of severe malaria

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22
Q

Resistance to Quinine and Quinidine

A

Increasing; common in Southeast Asia

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23
Q

AE of Quinine and Quinidine

A

Cinchonism (tinnitus, flushing, headache, visual disturbance), Black water fever, QT prolongation, hypoglycemia (stimulates insulin release), uterine contractions (still used in severe falciparum treatment), hemolysis in G6PD deficiency

ALSO:
hypersensitivity (angioedema, urticaria, bronchospasm), other hematologic abnormalities

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24
Q

Contraindications of Quinine and Quinidine

A

Concurrent use with Mefloquine, Warfarin, and Digoxin; pregnancy (Cat. C), patients with auditory or visual problems, underlying cardiac problems, G6PD deficiency

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25
Q

PK of Quinine and Quinidine

A

Reduce dose in renal insufficiency

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26
Q

MOA of Mefloquine

A

Chemically related to Quinine; destroys asexual blood forms of malarial pathogens

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27
Q

Activity of Mefloquine

A

Effective against many Chloroquine-resistant strains

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28
Q

Only medication recommended for chemoprophylaxis in pregnant women in Chloroquine-resistant areas

A

Mefloquine

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29
Q

Treatment for uncomplicated malaria in Southeast Asia

A

Mefloquine + Artesunate

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30
Q

Chemoprophylactic effective against most strains of P. falciparum and P. vivax

A

Mefloquine

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31
Q

Can be used to treat mild moderate acute malaria caused by P. falciparum and P. vivax

A

Mefloquine

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32
Q

Resistance is uncommon but associated with resistance to Quinine but not Chloroquine

A

Mefloquine

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33
Q

PK of Mefloquine

A

Oral; weekly prophylactic dosing

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34
Q

Contraindications of Mefloquine

A

Coadministration with Quinine, Quinidine, or Halofantrine; patients with history of epilepsy, psychiatric disorders, arrythmias, drug sensitivities

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35
Q

True or False: Mefloquine is considered safe in young children and pregnancy.

A

True

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36
Q

AE of Mefloquine

A

Neuropsychiatric toxicities (hallucinations, tinnitus, loss of balance, etc.); weekly dosing causes N/V, dizziness, sleep and behavioral disturbances; high doses cause hematologic disorders, arrhythmias, bradycardia, elevations in aminotransferases

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37
Q

DOC for eradication of hypnozoites in P. vivax and P. ovale

A

Primaquine

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38
Q

Clinical applications of Primaquine

A

Therapy and terminal prophylaxis against P. vivax and P. ovale

39
Q

MOA of Primaquine

A

Metabolites may act as oxidants that disrupt mitochondria and binding to DNA

40
Q

PK of Primaquine

A

Oral; metabolites are less active but have more potential to induce hemolysis

41
Q

What should be done when treating resistant strains with Primaquine?

A

Give repeated therapy with higher doses

42
Q

AE of Primaquine

A

Well tolerated; Hemolysis or methemoglobinemia, especially in G6PD deficiency

43
Q

Contraindications of Primaquine

A

Pregnancy and G6PD deficiency

44
Q

Which antimalarial requires testing for G6PD deficiency before being prescribed?

A

Primaquine

45
Q

Which 2 drugs make up Malarone?

A

Atovaquone + Proguanil

46
Q

Clinical applications of Malarone

A

Treatment and prophylaxis of uncomplicated P. falciparum

47
Q

Antimalarial action of Malarone

A

Active against tissue and erythrocytic schizonts

48
Q

MOA of Malarone

A

Disrupts mitochondrial ETC

49
Q

Contraindications of Malarone

50
Q

AE of Malarone

A

Well tolerated; N/V/D, etc.

51
Q

Antimalarial Inhibitors of Folate Synthesis

A

Pyrimethamine, Proguanil, and Sulfadoxine

52
Q

Clinical applications of Antimalarial Inhibitors of Folate Synthesis

A

Chemoprophylaxis, Intermittent preventive therapy in high risk patients, and treatment of Chloroquine-resistant falciparum malaria (give Pyrimethamine + Sulfadoxine)

53
Q

Contraindications of Antimalarial Inhibitors of Folate Synthesis

A

Severe malaria

54
Q

Antimalarial Action of Antimalarial Inhibitors of Folate Synthesis

A

Pyrimethamine + Proguanil: slow action against erythrocytic forms of all malaria species

Proguanil: some activity against hepatic forms

Sulfonamides: weak activity against erythrocytic schizonts

55
Q

MOA of Antimalarial Inhibitors of Folate Synthesis

A

Proguanil + Pyrimethamine inhibit plasmodial dihydrofolate reductase

Sulfonamides inhibit dihydropteroate synthase

56
Q

AE of Antimalarial Inhibitors of Folate Synthesis

A

Proguanil: oral ulcers, alopecia

Pyrimethamine + Sulfadoxine: Erythema multiforme, Stevens-Johnson syndrome

Sulfadoxine: hematologic, renal, etc.

57
Q

True or False: Proguanil and Pyrimethamine + Sulfadoxine are safe in pregnancy.

58
Q

Tetracycline that is active against erythrocytic schizonts of all malaria species

A

Doxycycline

59
Q

Clinical Applications of Doxycycline in malaria

A

Doxycycline + Quinine for severe falciparum after initial treatment with Quinine, Quinidine, or Artesunate;

Chemoprophylaxis against most forms; taken daily.

60
Q

AE of Doxycycline

A

Photosensitivity, Hypoplasia and discoloration of teeth, stunting of growth

61
Q

Contraindications of Doxycycline

A

Pregnancy (fatal hepatotoxicity); children < 8 yoa

62
Q

Antimalarial agent derived from Qinghaosu plant

A

Artemisinin

63
Q

Artemisinins

A

Artesunate, Arthemether, Dihydroartemesinin, Coartem

64
Q

Which 2 drugs make up Coartem?

A

Artemether + Lumefantrine

65
Q

PK of Artemisinins

A

Artesunate: oral, IV, IM, rectal
Artemether: oral, IM, rectal
Dihydroartemisinin: oral only

66
Q

Antimalarial activity of Artemisinins

A

No effect on hepatic stages

67
Q

Clinical applications of Artemisinins

A

Severe falciparum malaria; given IV

68
Q

How do you protect against resistance to Artemesinins?

A

Do not use as a single agent

69
Q

MOA of Artemisinins

A

Binds iron –> breaks down peroxide bridges, leading to generation of ROS that damage parasite proteins

70
Q

PK of Artemisinins

A

Very short half-life

71
Q

AE of Artemisinins

A

Neurotoxicity and QT prolongation at high doses

72
Q

Use of Artemisinins in Pregnancy

A

Can be used throughout pregnancy; 1st Trimester: used for severe malaria

73
Q

Can be used as antimalarial alternative to Doxycycline

A

Clindamycin

74
Q

Which stages of malarial parasites is Halofantrine useful for?

A

Erythrocytic stages of all malarial parasites

75
Q

Contraindications of Halofantrine

A

Pregnancy (teratogenic)

76
Q

What limits the use of Halofantrine?

A

Irregular absorption and cardiac toxicity

77
Q

Which stages of malarial parasites is Lumefantrine useful for?

A

Erythrocytic stages of all malarial parasites

78
Q

Which drug is only available as a fixed-dose combination with Artemether?

A

Lumefantrine

79
Q

AE of Lumefantrine

A

Clinically insignificant QT prolongation; well tolerated

80
Q

Malarial chemoprophylaxis in general or in pregnant women: Chloroquine-sensitive

A

Chloroquine

81
Q

Malarial chemoprophylaxis in pregnant women: Chloroquine-resistant

A

Mefloquine

82
Q

Malarial chemoprophylaxis in general: Chloroquine-resistant

A

Mefloquine, Doxycycline, and Primaquine

83
Q

Treatment for severe malaria (all species) with no known resistance: 1st trimester

A

Quinidine or Artesunate

84
Q

Treatment for severe malaria (all species) with no known resistance: 2nd and 3rd trimesters

A

First option: Artesunate

Second option: Artemether

85
Q

Treatment for severe malaria (all species) with no known resistance

A

IV Quinidine + Doxycycline or Clindamycin (can progress to oral Quinine + Doxycycline) OR

IV Artesunate followed by Atovaquone-Proguanil, Clindamycin, or Mefloquine

86
Q

For uncomplicated malaria in pregnancy and all species: Chloroquine-sensitive

A

Chloroquine/Hydrochloroquine

87
Q

For uncomplicated malaria in pregnancy and all species:

Chloroquine-resistant P. falciparum

A
  1. Mefloquine

2. Quinine + Clindamycin

88
Q

For uncomplicated malaria in pregnancy and all species: Chloroquine-resistant P.vivax

A

Mefloquine

89
Q

Fo pregnant patients with P.vivax or P.ovale infections

A

Chloroquine prophylaxis for duration of pregnancy

90
Q

Uncomplicated malaria with P.vivax or P.ovale and little resistance

A
  1. Chloroquine + Primaquine

2. Hydroxychloroquine + Primaquine

91
Q

Uncomplicated malaria with P.vivax and Chloroquine-resistant

A
  1. Quinine + Doxycycline + Primaquine
  2. Atovaquone + Proguanil + Primaquine
  3. Mefloquine + Primaquine
92
Q

Uncomplicated malaria with P.falciparum and no known resistance

A

Chloroquine or Hydroxychloroquine

93
Q

Uncomplicated malaria with P.falciparum and Chloroquine resistant or unknown

A
  1. Atovaquone + Proguanil
  2. Artemether-Lumefantrine (Coartem)
  3. Quinine + Doxycycline
  4. Mefloquine
94
Q

Uncomplicated malaria with P.malariae and no known resistance

A

Chloroquine/Hydroxychloroquine

Pharmacology - Midterm 2 (16 decks)

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