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Pharmacology - Midterm 2 > Antimalarials > Flashcards

Antimalarials Flashcards

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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
PK of Quinine and Quinidine
Reduce dose in renal insufficiency
26
MOA of Mefloquine
Chemically related to Quinine; destroys asexual blood forms of malarial pathogens
27
Activity of Mefloquine
Effective against many Chloroquine-resistant strains
28
Only medication recommended for chemoprophylaxis in pregnant women in Chloroquine-resistant areas
Mefloquine
29
Treatment for uncomplicated malaria in Southeast Asia
Mefloquine + Artesunate
30
Chemoprophylactic effective against most strains of P. falciparum and P. vivax
Mefloquine
31
Can be used to treat mild moderate acute malaria caused by P. falciparum and P. vivax
Mefloquine
32
Resistance is uncommon but associated with resistance to Quinine but not Chloroquine
Mefloquine
33
PK of Mefloquine
Oral; weekly prophylactic dosing
34
Contraindications of Mefloquine
Coadministration with Quinine, Quinidine, or Halofantrine; patients with history of epilepsy, psychiatric disorders, arrythmias, drug sensitivities
35
True or False: Mefloquine is considered safe in young children and pregnancy.
True
36
AE of Mefloquine
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
37
DOC for eradication of hypnozoites in P. vivax and P. ovale
Primaquine
38
Clinical applications of Primaquine
Therapy and terminal prophylaxis against P. vivax and P. ovale
39
MOA of Primaquine
Metabolites may act as oxidants that disrupt mitochondria and binding to DNA
40
PK of Primaquine
Oral; metabolites are less active but have more potential to induce hemolysis
41
What should be done when treating resistant strains with Primaquine?
Give repeated therapy with higher doses
42
AE of Primaquine
Well tolerated; Hemolysis or methemoglobinemia, especially in G6PD deficiency
43
Contraindications of Primaquine
Pregnancy and G6PD deficiency
44
Which antimalarial requires testing for G6PD deficiency before being prescribed?
Primaquine
45
Which 2 drugs make up Malarone?
Atovaquone + Proguanil
46
Clinical applications of Malarone
Treatment and prophylaxis of uncomplicated P. falciparum
47
Antimalarial action of Malarone
Active against tissue and erythrocytic schizonts
48
MOA of Malarone
Disrupts mitochondrial ETC
49
Contraindications of Malarone
Pregnancy
50
AE of Malarone
Well tolerated; N/V/D, etc.
51
Antimalarial Inhibitors of Folate Synthesis
Pyrimethamine, Proguanil, and Sulfadoxine
52
Clinical applications of Antimalarial Inhibitors of Folate Synthesis
Chemoprophylaxis, Intermittent preventive therapy in high risk patients, and treatment of Chloroquine-resistant falciparum malaria (give Pyrimethamine + Sulfadoxine)
53
Contraindications of Antimalarial Inhibitors of Folate Synthesis
Severe malaria
54
Antimalarial Action of Antimalarial Inhibitors of Folate Synthesis
Pyrimethamine + Proguanil: slow action against erythrocytic forms of all malaria species Proguanil: some activity against hepatic forms Sulfonamides: weak activity against erythrocytic schizonts
55
MOA of Antimalarial Inhibitors of Folate Synthesis
Proguanil + Pyrimethamine inhibit plasmodial dihydrofolate reductase Sulfonamides inhibit dihydropteroate synthase
56
AE of Antimalarial Inhibitors of Folate Synthesis
Proguanil: oral ulcers, alopecia Pyrimethamine + Sulfadoxine: Erythema multiforme, Stevens-Johnson syndrome Sulfadoxine: hematologic, renal, etc.
57
True or False: Proguanil and Pyrimethamine + Sulfadoxine are safe in pregnancy.
True
58
Tetracycline that is active against erythrocytic schizonts of all malaria species
Doxycycline
59
Clinical Applications of Doxycycline in malaria
Doxycycline + Quinine for severe falciparum after initial treatment with Quinine, Quinidine, or Artesunate; Chemoprophylaxis against most forms; taken daily.
60
AE of Doxycycline
Photosensitivity, Hypoplasia and discoloration of teeth, stunting of growth
61
Contraindications of Doxycycline
Pregnancy (fatal hepatotoxicity); children < 8 yoa
62
Antimalarial agent derived from Qinghaosu plant
Artemisinin
63
Artemisinins
Artesunate, Arthemether, Dihydroartemesinin, Coartem
64
Which 2 drugs make up Coartem?
Artemether + Lumefantrine
65
PK of Artemisinins
Artesunate: oral, IV, IM, rectal Artemether: oral, IM, rectal Dihydroartemisinin: oral only
66
Antimalarial activity of Artemisinins
No effect on hepatic stages
67
Clinical applications of Artemisinins
Severe falciparum malaria; given IV
68
How do you protect against resistance to Artemesinins?
Do not use as a single agent
69
MOA of Artemisinins
Binds iron --> breaks down peroxide bridges, leading to generation of ROS that damage parasite proteins
70
PK of Artemisinins
Very short half-life
71
AE of Artemisinins
Neurotoxicity and QT prolongation at high doses
72
Use of Artemisinins in Pregnancy
Can be used throughout pregnancy; 1st Trimester: used for severe malaria
73
Can be used as antimalarial alternative to Doxycycline
Clindamycin
74
Which stages of malarial parasites is Halofantrine useful for?
Erythrocytic stages of all malarial parasites
75
Contraindications of Halofantrine
Pregnancy (teratogenic)
76
What limits the use of Halofantrine?
Irregular absorption and cardiac toxicity
77
Which stages of malarial parasites is Lumefantrine useful for?
Erythrocytic stages of all malarial parasites
78
Which drug is only available as a fixed-dose combination with Artemether?
Lumefantrine
79
AE of Lumefantrine
Clinically insignificant QT prolongation; well tolerated
80
Malarial chemoprophylaxis in general or in pregnant women: Chloroquine-sensitive
Chloroquine
81
Malarial chemoprophylaxis in pregnant women: Chloroquine-resistant
Mefloquine
82
Malarial chemoprophylaxis in general: Chloroquine-resistant
Mefloquine, Doxycycline, and Primaquine
83
Treatment for severe malaria (all species) with no known resistance: 1st trimester
Quinidine or Artesunate
84
Treatment for severe malaria (all species) with no known resistance: 2nd and 3rd trimesters
First option: Artesunate | Second option: Artemether
85
Treatment for severe malaria (all species) with no known resistance
IV Quinidine + Doxycycline or Clindamycin (can progress to oral Quinine + Doxycycline) OR IV Artesunate followed by Atovaquone-Proguanil, Clindamycin, or Mefloquine
86
For uncomplicated malaria in pregnancy and all species: Chloroquine-sensitive
Chloroquine/Hydrochloroquine
87
For uncomplicated malaria in pregnancy and all species: | Chloroquine-resistant P. falciparum
1. Mefloquine | 2. Quinine + Clindamycin
88
For uncomplicated malaria in pregnancy and all species: Chloroquine-resistant P.vivax
Mefloquine
89
Fo pregnant patients with P.vivax or P.ovale infections
Chloroquine prophylaxis for duration of pregnancy
90
Uncomplicated malaria with P.vivax or P.ovale and little resistance
1. Chloroquine + Primaquine | 2. Hydroxychloroquine + Primaquine
91
Uncomplicated malaria with P.vivax and Chloroquine-resistant
1. Quinine + Doxycycline + Primaquine 2. Atovaquone + Proguanil + Primaquine 3. Mefloquine + Primaquine
92
Uncomplicated malaria with P.falciparum and no known resistance
Chloroquine or Hydroxychloroquine
93
Uncomplicated malaria with P.falciparum and Chloroquine resistant or unknown
1. Atovaquone + Proguanil 2. Artemether-Lumefantrine (Coartem) 3. Quinine + Doxycycline 4. Mefloquine
94
Uncomplicated malaria with P.malariae and no known resistance
Chloroquine/Hydroxychloroquine

Pharmacology - Midterm 2 (16 decks)

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