Antiparasitic drugs Flashcards
(104 cards)
1
Q
Antiparasitic drugs
Groups of drugs that treat malaria
A
- Heme polymerization drugs (quinolones)
- Tissue schizonticide drugs
- Artemisin derivatives
2
Q
Antiparasitic drugs
Chloroquine and Quinidine/quinine are _________ drugs
A
Quinolones (Heme polymerization)
3
Q
Antiparasitic drugs
Chloroquine admin. and absorption
A
- Well absorbed from the gastrointestinal (GI) tract.
- Rapidly absorbed from intramuscular (IM) and subcutaneous (SC) sites.
4
Q
Antiparasitic drugs
How does cloroquine work against plasmodium?
A
- Inhibits heme polymerization, preventing detoxification of toxic heme, leading to parasite death.
- Accumulates in the parasite’s digestive vacuole.
5
Q
Antiparasitic drugs
What is chloroquine used for?
A
- Malaria treatment & prophylaxis (P. vivax, P. ovale, P. malariae, P. knowlesi).
- Autoimmune diseases (RA, lupus – hydroxychloroquine preferred).
- Hepatic amebiasis
6
Q
Antiparasitic drugs
First line agent for P. ovale and P. malariae
A
Chloroquine
7
Q
Antiparasitic drugs
Since it has no activity on liver-stage parasites, Chloroquine requires _____ to prevent relapses in P. vivax and P. ovale stages
A
Primaquine
8
Q
Antiparasitic drugs
Chloroquine is ineffective against…
A
Chloroquine-resistant P. falciparum
9
Q
Antiparasitic drugs
If there is no response to chloroquine, the alternative treatment of choice would be
A
Quinine + tetracycline/doxycycline
10
Q
Chloroquine
Cardiovascular toxicity
A
- Hypotension
- Vasodilation
- Suppressed myocardial function
- Cardiac arrhytmias
- Cardiac arrest!!
11
Q
Chloroquine
Neurological toxicity
A
Confusion, convulsions, coma
12
Q
Chloroquine
Cardiac adverse effects
A
- Widening of QRS
- T wave abnormalities
- Cardiomyopathy
13
Q
Antiparasitic drugs
T/F: Retinopathy and ototoxicity may occur under chloroquine use
A
True
14
Q
Chloroquine
Hematological and skin/mucosa adverse effects
A
- Hemolysis in G6PD-deficient patients
- Lichenoid skin eruptions
- Bleaching of hair and nail/mucous membranes discoloration
15
Q
Chloroquine
Absolute contraindications
A
- Epilepsy
- Myasthenia gravis
- Psoriasis
- GI, neurological, liver or hematological disorders
16
Q
Chloroquine
Safe in pregnancy?
A
Safe in pregnancy
Caution is advised
17
Q
Chloroquine
How do plasmodium species develop resistance to chloroquine?
A
- Mutations in pfcrt (chloroquine resistance transporter) reduce drug accumulation.
- P. vivax resistance linked to pvcrt overexpression.
18
Q
Antiparasitic drugs
Quinidine/quinine are drugs used for ________ tx. and they target ___________
A
- Malaria treatment
- Heme polymerization
19
Q
Antiparasitic drugs
Quinine/quinidine
A
- Readily absorbed when given orally or intramuscularly (IM).
- Oral absorption >80%, even in patients with diarrhea.
20
Q
Antiparasitic drugs
Standard of care for severe malaria
A
IV quinine ONLY until artemisin therapy can begin
21
Q
Antiparasitic drugs
Slower acting blood schintozides such as (–) and (–) are given with quinines to enhance their efficacy
Especially for multi-drug resistant P. falciparum
A
Tetracyclins or clindamycin
22
Q
Quinine/quinidine
MOA against plasmodium
A
- Blood schizonticide, disrupts parasite metabolism.
- Used in combination therapy to prevent resistance.
23
Q
Quinine/quinidine
Major side effects
A
- Cinchonism (tinnitus, headache, visual disturbances, nausea).
- Hypoglycemia, hypotension, cardiac arrhythmias.
- Severe hemolysis (Blackwater fever in G6PD deficiency).
24
Q
Antiparasitic drugs
In malaria tx. quinines should be avoided in
A
- Patients with tinnitus or optic neuritis.
- Patients with cardiac dysrhythmias (requires same precautions as quinidine).
- Pregnancy (risk of hypoglycemia)
25
# Drug interactions
Quinine + antacids (aluminum containing)
Delayed absorption
26
# Drug interactions
Warfarin, anticoagulants, glycosides, neuromuscular blockers + quinine/quinidine
Quinine/quinidine increases plasma levels of those drugs
27
# Antimalaria drugs
Urine acidification/rifampin + quinine/quinidine
Faster elimination of quinine
28
# Resistance
Quinine/quinidine vs. chloroquine
There are more chloroquine-resistant strains
29
# Antimalarial drugs
Primaquine is a
Tissue schizonticide
30
# Antimalarial drugs
Primaquine's absorption
Nearly 100% from GI tract
31
# Antimalarial drugs
Acts against primary and latent hepatic stages of Plasmodium spp.
| Tissue schizonticide
Primaquine
32
# Antimalarial drugs
Primaquine prevents relapses in
P. vivax and P. ovale
33
# Antimalarial drugs
Why is primaquine unsuitable in acute episodes of malaria?
Inactive against asexual blood-stage parasites
34
# Antimalarial drugs
Primaquine therapeutic uses
* Prevents malaria relapses (terminal prophylaxis).
* Destroys gametocytes, blocking transmission
35
# Antimalarial drugs
Primaquine should be administered with a blood schizonticide like (--) or (--) to...
1. Quinine
2. Chloroquine
* Erradicate erythrocitic stages of the parasite
* Reduce drug resistance risk
36
# Antimalarial drugs
Primaquine's major toxicities
Mild anemia, metahemoglobinemia (cyanosis), leukocytosis, **hemolysis and hemolytic anemia in G6PD-deficient individuals**
| Other: hypertension, arrhytmias, CNS symptoms
37
# Antimalarial drugs
When using primaquine, chloroquine and dapsone may enhance _______ risk
Metahemoglobinemia
38
# Antimalarial drugs
Primaquine contraindications
* G6PD deficiency
* Pregnancy
* Acutely ill patients with systemic diseases (active RA, lupus) causing granulocytopenia
## Footnote
Patients should watch out for dark/blood urine - hemolysis
39
# Antimalarial drugs
Primaquine MOA
* Acts on liver hypnozoites (P. vivax, P. ovale).
* Gametocytocidal against P. falciparum.
* Disrupts mitochondrial electron transport, leading to oxidative stress and parasite death.
40
# Antimalarial drugs
Primaquine resistance
* Alterations in mitochondrial electron transport proteins = < drug effectiveness
* Increased antioxidant defenses that counteract oxidative stress
41
# Antimalarial drugs
Food + primaquine
Best taken with food to reduce GI irritation
42
# Primaquine
CYP3A4 inhibitors (ketoconazole, erythromycin)
Increase drug levels
43
# Antimalarial drugs
Rifampin + primaquine
Reduced efficacy
44
# Antimalarial drugs
QT-prolonging drugs
| Chloroquine, Moxifloxacin
Enhanced cardiotoxic effects
45
# Antimalarial drugs
Artemisin derivatives
Artemisin
46
# Artemisin
Derivatives and administration
* dihydroartemisinin (PO)
* artemether (PO, IM, IV)
* artesunate (IV, IM, Rectal)
47
# Antimalarials
Optimized tx. for P. falciparum malaria and P. vivax
Artemisins (specifically parenteral artesunate)
48
# Antimalarials
Unless it is parenteral artesunate, the rule of artemisins is
THEY ARE NOT USED AS MONOTHERAPY
| Combine with slower-eliminated partner drugs with different MOA = 1st LT
49
# Antimalarial drugs
Artemisin MOA
* Activated by heme in parasite food vacuole, producing free radicals and protein alkylation
Disrupts parasite proteins & membranes (by alkylation and oxidation), leading to rapid parasite death.
50
# Antimalarials
Highly potent against asexual blood-stage parasites.
Artemisin
51
# Antimalarial drugs
Artemisin common side effects
* Reticulocyte and neutrophil count decrease
* Increased transaminase levels = mild liver stress
* Allergic reactions
52
# Artemisin
Plasmodium resistance mechanisms
Mutations in K13-propeller protein (kelch13 gene) linked to delayed clearance.
Altered parasite stress response reduces drug susceptibility.
Combination therapy (ACTs) is used to prevent resistance.
53
# Antimalarials
Food/drugs + artemisin
* Food = improved torelability
* rifampin, phenytoin, carbamazepine = reduce efficacy
* Ketoconazole, clarithromycin = increase toxicity risk
54
# Artemisin
QT prolonging drugs like quinolones and antipsychotics should be
Avoided
55
# Antiparasitic drugs
Drug groups that treat amebiasis
*DNA synthesis inhibitor
56
# Antiparasitic drugs
Metronidazole is a
DNA synthesis inhibitor
| Used to treat amebiasis
57
# Metronidazole
Admin. form
Oral
IV
Intravaginal
Topical
58
# Metronidazole
Has activity against
Anaerobic microorganisms (protozoas and bacteria (+/-/spore/microaerophillic)
59
# Antioarasitic drugs
Metronidazole therapeutic uses
* Trichomoniasis (T. vaginalis)
* Amebiasis (Entamoeba histilytica)
* Giardiasis
* Prophylaxis in C. difficile infections before colorrectal surgery
60
# Antiparasitics
First line of treatment for giardiasis and agent of choice ot symptomatic amebiasis
Metronidazole
61
# Metronidazole
MOA
* Prodrug gets reductive activation of the nitro group
* Electro-transfer to drugs forms free radicals
* Interaction of free radicals w/DNA leads to strand breaks and lethal damage
* Cycle of regeneration leads to continous activation of the drug
| Amebiasis
62
# Metronidazole
Common side effects
* Headache, nause
* Dry mouth
* Metallic taste
* GI distress
* NEUROTOXICITY
* Steven-Johnson
63
# Antiparasitics
Neurotoxicity by metronidazole use can be seen as
Encephalopathy and convulsions
64
# Antiparasitic drugs
Metronidazole is refused by ____ and should be withdrawn if ____, paretesthesias or urticaria/sensitivity are present
* Pediatric patients
* Numbness
65
Patients that shouldn't take metronidazole
* 1st trimester of pregnancy
* Severe hepatic disease
* CNS disease
66
# Antiparasitic drugs
T/F: metronidazole and disulfiramic-like drugs or warfarins can be taken together
NO
| False
67
# Antiparasitic drugs
Aerobic microorganisms are resistant to metronidazole because...
* Reduced activation of the prodrug by decreased ferredoxin levels.
* Upregulation of antioxidant defenses neutralizing toxic free radicals.
* Efflux pumps reducing intracellular drug concentration.
68
# Antiparasitic drugs
Disulfiram-like reaction with alcohol happens with
Metronidazole
69
# Antiparasitics
Quinfamide is an:
Amebicide
70
# Antiparasitic drugs
Drug used to treat ONLY the luminal form of amebiasis (asymptomatic carriers of Entamoeba histolytica)
| Non effective for extraintestinal amebiasis
Quinfamide
71
# Antiparasitic drugs
Quinfamide's action
* Acts locally in the intestinal lumen
* Disrupts the membrane integrity of Entamoeba histolytica and leads to parasite death
| Exact molecular mechanism is not known
72
# Amebicides
Quinfamide's adverse effects
* Mild GI symptoms
* Headache, dizziness, skin and rash
73
# Amebicides
Quinfamide should not be used in cases of:
* Severe liver disease
* Pregnancy
* Systemic amebiasis
74
# Antiparasitics
Broad spectrum activity against protozoa drug
Pentamidine
75
# Amebiasis
Pentamidine ADME
IV
Aerosol
Doesn't cross BBB
76
# Amebiasis
Pentamidine has activity against ______ and _______ some fungi, and it is the tx. early stage T. brucei gambiense
Protozoa and fungi
77
# Antiparasitics
First line of treatment for children under 6 years or 20 kg in cases of amebiasis
Quinfamide
78
# Antiparasitics
Alternative treatment of cutaneous leishmainiasis and prophylaxis of P. jirovecii pneumonia
Quinfamide
79
# Antiparasitic drugs
Pentamidine's MOA
Unknown mechanism
80
# Antiparasitic
Hypotension + tachychardia
Pancreatitis and hyperglucemia (insulin-dependent diabetes)
Renal toxicity
Side effects of...
Pentamidine
| Amebiasis
81
# Antiparasitics
Pentamidine MOA
* Uptake by high affinity transportet TbAQP2
* Affection of mitochondrial function and DNA integrity
| Molecular mechanism not fully understood
82
# Antiparasitics
Pentamidine contraindications
* Hypersensitivity
* Renal failure or disfunction
* Cardiovascular conditions (arrhytmia or heart disease)
* TERATOGENIC EFFECTS
| Contraindicated in pregnancy during the firs trimester
83
# Antiparasitic drugs
Pentamidine
* Decreased drug uptake due to mutations in transport proteins.
* Efflux pump activation, reducing intracellular drug concentration.
* Altered mitochondrial metabolism, decreasing drug-induced toxicity.
* Overexpression of detoxification enzymes, neutralizing pentamidine's effects.
84
# Helmintic infections
Microtubule inhibitors include
* Albendazole
* Mebendazole
85
# Microtubule inhibitors
Albendazole ADME
* Oral
* Absorption enhanced by the presence of fatty food
* Given to children over 2 years of age
86
# Antiparasitics
What GI nematodes does albendazole treat?
* Ascaris lumbricoides (roundworm)
* Trichuris trichiura (whipworm)
* Enterobius vermicularis (pinworm)
87
# Antiparasitics
How does albendazole help in hydatid cyst infections?
Preoperative use reduces the risk of cyst rupture
88
What parasites does albendazole prevent from producing eggs?
Echinococcus
Taenia solium
89
# Antiparasitics
Preferred treatment for T. solium larval infection in the brain
| Neurocysticercosis
Albendazole
90
# Antiparasitics
Because of its broad-spectrum, safety, and efficacy this is a key drug in parasitic disease control programs
Albendazole
91
# Albendazole
MOA
## Footnote
Antiparasitics
* Binds to B-tubulin preventing microtubule polymerization
* This leads to glucose uptake which then starves the parasite
* Causes the disruption of cell division and motility
* Worm death
92
# Antiparasitics
In echinococcus and T. solium, albendazole disrupts ________ and prevents ________
| Albendazole sulfoxide inhibits fumarate reductase
* Reproductive structures
* Egg reproduction
93
# Antiparasitics
Albendazole crosses the intestinal wall, this makes it effective for:
Helmintic infections
94
# Antiparasitics
Albendazole adverse effects
* Hepatotoxicity
* Long term = bone marrow toxicity
95
# Antiparasitics
This microtubule inhibitor has poor absorption and rapid first-pass metabolism at intestinal wall and liver
## Footnote
Anti-helmintic
Mebendazole
96
# Antiparasitics
Mebendazole is a first line treatment for common GI nematode infections incluiding:
* Pinworm
* Round
* Whipworm
* Hookworm
97
# Antiparasitics
T/F: mebendazole is easier to use in pediatric populations
True
98
# Antiparasitics
Mebendazole MOA
* Selective binding to β-tubulin.
* Inhibits microtubule polymerization, reducing glucose uptake and disrupting cell division.
* Inhibits mitotic spindle formulation and affects secretory granule transport --> toxic metabolites
99
Mebendazole adverse effects
- Gastrointestinal issues (abdominal pain, diarrhea).
- Rare: Bone marrow suppression.
100
# Antiparasitics
Why is mebendazole avoided in <1 year olds?
Risk of convulsion
101
Mebendazole contraindications
* Grapefruit juice
* AVOID IN PREGNANCY (CAT. C)
* Anaphylaxis to other benzimidazoles
* Not recommended in liver disease patients
102
# Anti-helmintics
Resistance to microtubule inhibitors is given by
* Due to genetic mutations in the B-tubulin gene that reduce drug binding and decreased efficacy
* Drug efflux mechanisms because of P-glycoprotein overexpression
103
# Anti helmintics
What is the most common mutation associated with resistance to mebendazole?
F200Y
104
# Anti helmintics
Cimitidine + Mebendazole
Mebendazole increases plasma levels and time of action
