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Flashcards in Antiprotozoal Drugs Deck (87):
0

Mention 5 antimalarial agents.

1. Chloroquine
2. Mefloquine
3. Primaquine
4. Quinine
5. Antifolates

1

Mention 4 drugs used for amebiasis.

1. Metronidazole
2. Diloxanide
3. Emetine
4. Iodoquinol

2

What is the action of primary tissue schizonticides (primaquine)?

Kill schizonts in the liver.

3

What is the action of blood schizonticides (chloroquine, quinine)?

Kills the parasitic forms only in the erythrocyte.

4

What is the action of sporonticides (proguanil, pyrimethamine)?

Prevent sporogony and multiplication in the mosquito.

5

How is chloroquine administered?

Orally - extremely large Vd (widely distributed).

6

What may decrease the oral absorption of chloroquine?

Antacids.

7

Where is chloroquine secreted?

Largely unchanged in the urine.

8

What is the mechanism of action of chloroquine?

1. Accumulates in the food vacuole of plasmodia.
2. Prevents polymerization of the heme into hemozoin - heme is toxic to the parasites.

9

What is the primary mechanism of resistance to chloroquine and other antimalarial drugs?

Decreased heme accumulation via increased activity of membrane "pumps".

10

Besides the primary mechanism, what other mechanism can result to resistance in P. falciparum?

Decreased intravacuolar accumulation of chloroquine via a transporter encoded by the pfcrt (P. falciparum chloroquine resistance transporter).

11

What is the clinical use of chloroquine?

1. Drug of choice for acute attacks of nonfalciparum and sensitive falciparum malaria.
2. For chemoprophylaxis, except regions where P. falciparum is resistant.

12

Where else are chloroquine and hydroxychloroquine used?

Autoimmunes, including RA.

13

What are the side effects at low doses of chloroquine?

1. GI irritation
2. Skin rash
3. Headaches

14

What are the side affects at high doses of chloroquine?

1. Severe skin lesions
2. Peripheral neuropathies
3. Myocardial depression
4. Retinal damage
5. Auditory impairment
6. Toxic psychosis
7. Also porphyria attacks

15

What are the pharmacokinetics of quinine?

1. Oral administration
2. Renal elimination
3. Can be given IV in severe infections

16

What is the mechanism of action of quinine?

Complexes with dsDNA to prevent strand seperation, resulting in block of DNA replication and transcription to RNA.
Solely a BLOOD schizonticide.

17

What is the main use of quinine?

P. falciparum infections resistant to chloroquine in patients who can tolerate oral treatment.

18

With what other drugs is quinine commonly used?

With doxycycline and clindamycin to shorten the duration of therapy and limit toxicity.

19

Where is quinidine (a stereoisomer of quinine) used?

IV in the treatment of severe or complicated malaria.

20

What are the side effects of quinine?

1. Cinchonism
2. Quinidine-like cardiac toxicity
3. Hematologic effects (hemolysis in G6PD)

21

What are the symptoms of cinchonism?

1. GI distress
2. Headache
3. Vertigo
4. Blurred vision
5. Tinnitus

22

Mention a rare toxicity of quinine.

Blackwater fever:
1. Intravascular hemolysis
2. Sometimes fatal

23

Is quinine contraindicated in pregnancy?

Yes.

24

How is mefloquine administered?

Orally - variable absorption.

25

What is the clinical use of mefloquine?

1. First-line drug for prophylaxis in chloroquine-resistant regions.
2. Alternative drug to quinine in acute attacks and uncomplicated infections resulting from P.falciparum.

26

What are the common side effects of mefloquine?

1. GI distress
2. Skin rash
3. Headache
4. Dizziness

27

What are the side effects at high doses of mefloquine?

1. Cardiac conduction defects
2. Psychiatric disorders
3. Neurologic symptoms
4. Seizures

28

What are the pharmacokinetics of primaquine?

Complete absorption after oral administration, followed by extensive metabolism.

29

What is the mechanism of action of primaquine?

1. Forms quinoline-quinone metabolites - cellular oxidants.
2. Tissue schizonticide
3. Also gametocide --> limits malaria transmission.

30

What is the clinical use of primaquine?

1. Eradicates liver stages of P.vivax and P.ovale.
2. Used in conjuction with a BLOOD schizonticide.
3. 14d treatment after chloroquine in vivax and ovale malaria.

31

What are the side effects of primaquine?

1. GI distress
2. Pruritus
3. Headaches
4. Methemoglobinemia
5. Hemolysis in G6PD-deficient patients.

32

Can primaquine be used in pregnancy?

No.

33

What antimalarial drugs does the antifolate group include?

1. Pyrimethamine
2. Proguanil
3. Sulfadoxine
4. Dapsone

34

What are the pharmacokinetics of antifolate drugs?

1. Oral administration
2. Largely unchanged excretion in urine

35

From the antifolate drugs, what has the shortest half-life?

Proguanil (12-16h).
The others >100h.

36

What is the mechanism of action of proguanil?

Bioactivated to cycloguanil. Together with pyrimethamine --> selective inhibitors of protozoan dihydrofolate reductases.

37

What is the main clinical use of antifolates?

BLOOD schizonticides that act mainly against P.falciparum.

38

For what is proguanil with atovaquone used?

Daily for chemoprophylaxis of chloroquine-resistant malaria - also fro mefloquine-resistant falciparum strains.

39

What can pyrimethamine cause when used in high doses?

Folic acid deficiency.

40

What is the use of doxycycline?

Chemoprophylaxis daily - for travelers to regions with multidrug-resistant P.falciparum.

41

What is the use of the antimalarial amodiaquine?

1. Wide use due to low cost.
2. In some areas effective against the chloroquine-resistant P.falciparum.
3. Also used with artesunate.

42

What are the hematologic side effects of amodiaquine?

1. Agranulocytosis
2. Aplastic anemia

43

What is the mechanism of action of atovaquone?

Appears to disrupt mitochondrial electron transport chain. Used together with proguanil (Malarone).

44

What is the use of malarone?

For BOTH chemoprophylaxis (daily) and treatment of falciparum malaria.

45

What are the main side effects of atovaquone?

Abdominal pain and GI effects occur at the higher doses needed for treatment.

46

For what other infection is atovaquone used as an alternative?

P.jiroveci

47

What is the mechanism of action of halofantrine?

Not known - active against erythrocytic stages of ALL 4 human malaria species, including chloroquine-resistant falciparum.

48

What is the clinical use of halofantrine?

Not used for chemoprophylaxis because of its potential for quinidine-like cardiotoxicity and embryotoxicity.

49

Mention a drug similar to halofantrine, but with minimal cardiotoxicity.

Lumefantrine.

50

Mention the 3 artemisinin derivatives used in malaria.

1. Artesunate
2. Artemether
3. Dihydroartemisinin

51

What is the mechanism of action of artemisinin derivatives?

Metabolized in the food vacuole forming toxic free radicals.

52

Against what are artemisinin derivatives active?

BLOOD schizonticides against P.falciparum, including drug-resistant strains.

53

What is the half-life of artemisinin derivatives?

Short half-life 1-3h.

54

What is important to remember about artemisinins?

The ONLY drugs reliably effective against quinine-resistant strains.

55

What drugs do we use for the prevention of malaria in travelers?

1. Chloroquine (weekly) for non resistant strains.
2. Mefloquine (weekly) for chloroquine-resistant regions.
3. In areas with multidrug resistant --> Doxycycline or malarone daily (atavaquone + proguanil).
4. Primaquine daily for 14d --> for ovale and vivax terminal prophylaxis.

56

Mention 4 tissue amebicides.

1. Chloroquine
2. Emetines
3. Metronidazole
4. Tindidazole

57

Mention 3 luminal amebicides.

1. Diloxanide furoate
2. Iodoquinol
3. Paromomycin

58

What do we give in asymptomatic form of amebiasis?

Diloxanide furoate is the first choice.

59

What do we give for mild to severe amebiasis?

Metronidazole or tinidazole is used with a luminal agent. Also recommended for hepatic abscess and other extraintestinal disease.

60

What are the alternative drugs for asymptomatic amebiasis?

1. Iodoquinol
2. Paramomycin

61

What are the alternative drugs for mild to moderate amebiasis?

1. Tinidazole
2. Tetracycline
3. Erythromycin plus a luminal agent

62

What are the alternative drugs for severe amebiasis?

1. Tetracycline
2. Emetine
3. Dihydroemetine plus a luminal agent

63

What are the alternative drugs for hepatic abscess and other extraintestinal disease?

1. Emetine
2. Dihydroemetine + chloroquine (for liver abscess) + luminal agent

64

What is the mechanism of action of emetines?

Inhibit protein synthesis.

65

How are emetines administered?

Parenterally (SC or IM).

66

What are the side effects of emetines?

Severe toxicity:
1. GI distress
2. Muscle weakness
3. Cardiovascular dysfunction

67

Systemic absorption after high doses of iodoquinol may lead to what?

1. Thyroid enlargement
2. Skin reactions
3. Possibly neurotoxic effects
4. Peripheral neuropathy
5. Visual dysfunction

68

What is the half-life of metronidazole?

6-8h

69

What is the half-life of tinidazole?

12-14h.

70

What is the mechanism of action of metronidazole?

Undergoes a reductive bioactivation of its nitro group by ferredoxin (present in anaerobic parasites) to form reactive cytotoxic products.
Tinidazole is assumed to have similar mechanism.

71

What is the clinical use of metronidazole?

1. Drug of choice in severe intestinal wall disease + hepatic abscess + extraintestinal amebic disease.
2. Drug of choice for trichomoniasis.
3. Giardiasis
4. Gardnerella vaginalis
5. Anaerobic bacteria (B.fragilis, Clostridium).
6. In regimens for H.pylori

72

What are the side effects of metronidazole?

1. GI distress (best taken with meals).
2. Headache
3. Paresthesias
4. Dark coloration of urine

73

Mention some more serious effects of metronidazole?

1. Neutropenia
2. Dizziness
3. Ataxia
4. Disulfiram-like reaction with ethanol
5. Potentiation of coumarin anticoagulant effects

74

Where is paromomycin used?

Aminoglycoside antibiotic:
1. As a luminal amebicide - may be superior to diloxanide in asymptomatic infection.
2. Also some efficacy against cryptosporidiosis in AIDS.

75

What are the problems with paromomycin in renal insufficiency?

1. Headaches
2. Dizziness
3. Arthalgias
4. Rashes

76

What is the clinical use of pentamidine?

1. Aerosol pentamidine (monthly) can be used in primary/secondary prophylaxis for pneumocystosis.
2. Daily IV or IM for 21d is needed in the Tx of active pneumocystosis in HIV-infected patient.
3. Also in trypanosomiasis.

77

What are the side effects of pentamidine?

Severe side effects follow parenteral use.
1. Respiratory stimulation
2. Depression
3. Hypotension
4. Hypoglycemia
5. Anemia/Neutropenia
6. Hepatitis
7. Pancreatitis

78

When the side effects of pentamidine are minimal?

When pentamidine is inhaled.

79

What is the clinical use of TMP-SMZ?

1. First choice in prophylaxis and Tx of pneumocystis pneumonia.
2. Prophylaxis against toxoplasmosis
3. Infections by Isospora belli
4. Tx of active pneumocystis pneumonia.

80

What are the side effects of TMP-SMZ?

1. 50% of AIDS patients have problems.
2. GI distress
3. Rash
4. Fever
5. Neutropenia/thrombocytopenia

81

What is the clinical use of atovaquone?

1. Mild/moderate pneucystis pneumonia.
2. For chemoprophylaxis/Tx of chloroquine-resistant malaria.

82

What are the common side effects of atovaquone?

1. Rash
2. Cough
3. Nausea
4. Vomiting
5. Diarrhea
6. Abnormal liver function tests

83

Atovaquone should be avoided in what patients?

Patients with:
1. Cardiac conduction defects
2. Psychiatric disorders
3. Seizures

84

What drugs do we use in trypanosomiasis?

1. Pentamidine
2. Melarsoprol
3. Nifurtimox
4. Suramin
5. Eflornithine

85

What do we give in leishmaniasis?

Sodium stibogluconate.

86

Mention some alternative agents for leishmaniasis.

1. Pentamidine or miltefosine --> visceral leishmaniasis.
2. Fluconazole or metronidazole --> cutaneous lesions.
3. Amphotericin B --> mucocutaneous lesions.

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