Antiparasitic Drugs Flashcards
1
Q
3 targets for antiparasitic therapy?
A
- enzymes or processes only found in the parasite (PFOR, folate synth)
- Enzyme or proceses found both in the host and parasite but REQUIRED for parasite (purine salvage)
- Common biochemical functions found in both parasite and host, but with different pharmacological properties (DHFR, microtubule disrupt)
2
Q
Entamoeba histolytica
- causes what disease?
- important life-cycle stuff?
A
- amebiasis
- cyst form in poop that infects (FECAL ORAL) and trophozoites that are in intestines and almost anywhere else (disseminated = absceses)
- -> INTESTINES AND EVERYWHERE ELSE
3
Q
Giardia lamblia
- causes what disease?
- important life-cycle stuff?
A
- Giardiasis
- cyst from (dormant) and trophozoite form (growing & moving) in intestines
- ->STAYS IN INTESTINES
- FECAL ORAL
4
Q
Trichomonas vaginalis
- causes what disease?
- important life-cycle stuff?
A
- trichomoniasis
- SEXUALLY TRANSMITTED
- ONLY trophozoite form
- ALWAYS ONLY IN UROGENITAL TRACT
5
Q
*Tx for Trichomoniasis, giardiasis, and amebiasis?
MOA?
A
-Metronidazole (good for anaerobes aka parasites)
-targets pyruvate ferredoxin oxidoreducatase (PFOR) - converts pyruvate to acetyl CoA
==>HUMANS DO NOT HAVE PFOR
6
Q
Metronidazole
- tx for what?
- MOA?
- inactive/active
- reactive intermediates
A
- trichomoniasis, amebiasis, giardiasis
- electron sink –> takes electrons away from ETC chain (takes away energy source)
- reactive intermediates bind protein and DNA==> disruption
- ACTIVATED by PFOR enzyme in anaerobic conditions
7
Q
Metronidazole
- tx for what?
- side effects?
A
- trichomoniasis, amebiasis, giardiasis
- *disulfiram effect = avoid ETOH
- vomit, diarrhea, abdominal issues
- headache, dry mouth metalic taste
8
Q
Is metronidazole safe for pregnancy?
A
Yes ok but discouraged during 1st trimester
9
Q
- How long is treatment for trichomoniasis?
- Special thing about tx?
- method for administration?
A
- 7 day tx ORALLY
- must also tx sexual partners
- oral but topical gel or vaginal suppository if woman doesnt respond well to oral
10
Q
Giardiasis - tx duration and dosing?
A
1) metronidazole
- TID for 5 days
- 90% success rate
2) nitazoxanide
11
Q
Amebiasis
- tx dosing and duration?
- problem with tx amebiasis?
A
- tid for 7-10 days
- metronidazole treats the SYMPTOMATIC disease - so it helps with the bloody diarrhea due to trophozoite form – BUT WHAT ABOUT CYST FORM? – NEED TO FOLLOW UP WITH IODOQUINOL OR PAROMOMYCIN
12
Q
What drug is vital for extra-intestinal amebiasis?
A
Metronidazole! - helps with liver and brain abscesses or elsewhere - metro penetrates tissues very well
13
Q
- metronidazole resistance?
- mechanism for resistance?
A
- RARE but some showing up
- dec PFOR activity and inc other oxidoreducatase activity
14
Q
What drugs to give/add to kill cyst form of amebiasis & giardiasis?
A
iodoquinol or paromomycin
15
Q
Iodoquinol
- MOA?
- where is this drug good at killing parasite bastards?
A
-UNK MOA
-not absorbed well into system
-effective killing of E. histolytica cysts (and trophozoites) in LUMEN but it can disseminate so not complete fix
-good for giardia which has cysts only in lumen
ALSO kills the trophs
16
Q
Problems with Iodoquinol tx?
A
1) adverse effects are infrequent - maybe GI BUT must take with meal to avoid GI tox
2) in children high dose for long term=optic atrophy and perm vision loss
3) 20 day long tx!
17
Q
Paromomycin
- MOA?
- where is this drug good at killing parasite bastards?
A
- UNK MOA
- kills cyst for E histolytica in the LUMEN of intestine
- NO killing of trophozoite forms in EXTRA-INTESTINAL AREAS
18
Q
- Paramomycin dosing and frequency?
- why better than iodoquinol?
A
- tid for 7 days
- iodoquinol is for 20 days so to have a patient take metronidazole for a week and then iodoquinol for 20 days = poor patient compliance
19
Q
Cryptosporidium parvum
- transmission?
- symtpoms?
- healthy vs immunosuppressed?
A
- water-borne
- watery diarrhea
- healthy = self limited –> just rehydrate
- immunocomp = diarrhea - chronic and fatal
20
Q
Cryptosporidium parvum
- Tx?
- MOA?
A
-nitazoxanide
-INTERFERES with PFOR = disruption of anaerobic metabolism
(metronidazole is ACTIVATED by PFOR)
21
Q
nitazoxanide
- MOA?
- Tx for?
A
- Cryptosporidium parvum AND GIARDIASIS
- INTERFERES with PFOR = disruption of anaerobic metabolism
22
Q
Pneumocystis jirovecii
- tx?
- MOA?
- Why does this work?
A
-Trimethoprim-sulfamethoxazole = folate synth inh
- parasitic protozoa must synthesize their folic acid while humans can get from diet
- Low concentration wont INH OUR DHFR ENZYME
- combining drugs has additive effect bc it hits two enzymes in folate synth path
23
Q
Toxoplasma gondii
- tx?
- MOA?
- Why does this work?
A
-Pyrimethamine-sulfadiazine = folate synth inh
- parasitic protozoa must synthesize their folic acid while humans can get from diet
- Low concentration wont INH OUR DHFR ENZYME
- combining drugs has additive effect bc it hits two enzymes in folate synth path
24
Q
Pharmacodynamics for Pyrimethamine-sulfadiazine and TMP-SMX?
A
-oral and good absorption and distribution
25
Sulfonamide side effects?
* *RASH - Crystalluria - hemolysis - GI intolerance
| - Folate deficiency
26
- Toxoplasmosis
- Tx of choice?
- dosing-active disease and maintenance?
- pyrimethamine-sulfadiazine
- higher doses for active treatment
- lower doses for long term maintenance
- does not help with dormant tissue cyst
27
- Resistance to TMP-SMX and pyrimethamine-sulfadiazine?
| - Mechanism for resistance?
- widely reported
| - amino acid mutations in target enzymes
28
Pyrimethamine-sulfadiazine tx of choice for?
toxoplasmosis
29
Pneumocystis jirovecii
- Tx of choice
- dosing-active disease and maintenance?
- Trimethoprim-sulfamethoxazole (TMP-SMX)
- high dose for active disease
- low dose for long term maintenance
30
Malaria
| -life cycle?
-begins in mosquito and bites human --> hepatic stage (replication) --> blood stream cycle (playing with RBCs)
31
Hepatic stage Malaria - DRUG?
-primaquine
32
Blood stream stage Malaria -DRUG?
-cloroquine
-quinine
-mefloquine
...
33
Chloroquine
- MOA?
- Dosing?
- Side effects
- messes with ability of parasite to detoxify compounds generated during Hb degredation
- once weekly for prophylaxis
- higher doses 4x onver 48 hrs
- headache, nausea, vomit, blurred vision, dizzy, fatigue, confusion
34
Chloroquine is effective against which stage and which species of malaria?
- kills asexual erythrocytic stages
| - ALL SPECIES of plasmodium
35
Chloroquine
- Resistance?
- Mechanism of resistance?
- HUGE - limited use
- esp P Falciparum & Vivax
-rapid export pump
36
Quinine
| -MOA?
- hits the digestive vacuoles - interferes with Hb metabolism/detox
- complex with parasite DNA = issue with replication and transcription
37
Quinine
| -Side effects?
- Poorest therapuetic ratio of all antimalarials
- CINCHONISM - tinnitis, temp hearing loss, headache, nausea, vomit, visual disturbances
- HYPOGLYCEMIA - quinine induced release of insulin.
38
- Is quinine used for prophylaxis?
| - What are the prophylaxis drugs?
- NOT QUININE
- chloroquine
- mefloquine
- primaquine
- malarone (used with chloroquine)
- doxycyclne
39
Quinine is effective against which stage and which species of malaria?
- kills asexual erythrocytic stage
| - kills ALL SPECIES of plasmodium
40
Resistance to quinine?
-yes esp in asia
41
Mefloquine
| -MOA?
- like quinine (hits the digestive vacuoles - interferes with Hb metabolism/detox
- complex with parasite DNA = issue with replication and transcription)
42
Mefloquine
- Toxicity?
- Dosing?
- SOME neuropsychiatric reactions in small number patients
| - long half life = easy weekly dosing
43
Mefloquine is effective against which stage and which species of malaria?
- kills asexual erythrocytic stage
| - kills ALL SPECIES of plasmodium
44
Primaquine
| -MOA?
- needs to be activated by host metabolism
- interferes with mitochon ETC
- interferes with pyrimidine synthesis
45
ONLY drug for liver stage of malaria?
| -good for which species and which cycle form??
- primaquine
- vivax and ovale
- these two are only ones with hypnozoite form
46
Primaquine
| -toxicity?
-must check for G6PD deficiency
==> RBC lysis - hemolysis
SCREEN FOR THE G6PD STATUS
47
What drug must you give for vivax and ovale species of malaria?
-Primaquine to kill the hypnozoites in the liver
48
Malarone
- combo of what drugs?
- MOA?
- Effective against which species?
- atovaquone and proguanil
- atova = MOA UNK - ALL SPECIES - lipophilic so take with fatty meal
- prog = MOA= DHFR (dihydrofolate reductase) inhibitor
- p falcip
49
Malarone
| -good for treating which species?
P falciparum
50
Doxycycline
- MOA?
- tx how?
- side effects?
- inh growth by messing with protein synthesis
- use in combo with other drugs
- photosensitivity & staining teeth in children
- -DO NOT give to children and pregnant women
51
What are the chinese wormwood extract drug derivatives?
arteminisin derivs
52
Arteminisin Derivatives
- MOA?
- good for which species of malaria?
- interacts with iron = radical damage of membrane
| - ALL species of plasmodium
53
Enterobius vermicularis
| -disease name?
pinworm
54
Ascaris lumbricoides
| -disease name?
ascariasis
55
Necator americanus
| -disease name?
-hookworm
56
Trichuris trichiura
| -disease name?
whipworm
57
Strongyloides stercoralis
| -disease name?
strongyloidiasis
58
Tapeworms are?
cestodes
59
Fluke worms are?
trematodes
60
Antihelminthic MOA?
1) inhibit mitosis in parasite (benzimidazole compounds)
| 2) cause muscle paralysis of parasite (ivermectin, pyrantel pamoate and praziquantel)
61
- What are the benzimidazole compounds?
| - Which is most absorbed?
- albendazole
- mebendazole
- thiabendazole
-ALL have poor absorption (GOOD BC WORM IS IN GI LUMEN) but thiabendazole is most absorbed = most toxicity
62
WHich is the most toxic benzimidazole compound?
- Side effects?
- MOA?
- thiabendazole - most absorption
- GI -anorexia, nausea, vomit
- CNS - delirium, hallucinations
ALL inhibit mitosis in parasite
63
How to administer benzimidazoles?
- On an empty stomach
- With fatty meal to kill worms more in tissue
inhibit mitosis in parasite
64
resistance to benzimidazoles?
not a problem in human medicine
65
Contraindication for benzimidazoles?
-Prego and if under 2 yo
66
Albendazole and mebendazole good for killing? Dosing?
- ascariasis
- pinworm
- hookworm
- whipworm
Single high dose but meben can be given 3x lower dose
inhibit mitosis in parasite
67
Thiabendazole good for killing what bugs?
| -MOA?
-second line for strongyloidiasis (intestinal and tissue infection) -- IVERMECTIN IS #1
inhibit mitosis in parasite
68
- What drug is given to treat cutaneous larval migrans?
| - Transmission/How do you get cutaneous larval migrans?
- thaibendazole topical prep
| - from dog or cat hookworms - dont play with poop
69
Ivermectin
- MOA?
- tx for what kinds of infections?
- cause muscle paralysis of parasite = hyperpolarization
| - for intestinal and extra intestinal infections
70
Drug of choice for strongyloides?
ivermectin - no resistance
71
Obscure/rare tropical infection - probs which drug?
ivermectin
72
Pyrantel pamoate
- MOA?
- good for which infections?
- cause muscle paralysis of parasite - nicotinic agonist in somatic muscles = depolarizing blockade
- most good toxicity for intestinal nematodes
73
Pyrantel pamoate - drug of choice for what condition?
-pinworm!!
| -Tx the WHOLE FAMILY
Single dose and 2nd dose in 2 weeks
74
Only drug used to treat tapeworms (Cestodes) and fluke (trematodes)?
-Praziquantel
75
praziquantel
| MOA?
-cause muscle paralysis of parasite = increase Ca permeability of tegument covering of worm
== depolarizing block
== more detecable by immune system
76
Fluke drug and dosinng?
-praziquantel - 3 doses in 1 day
77
Tapeworm drug and dosing?
-praziquantel - single dose
78
Cysticercosis drug and dosing?
-praziquantel- 2 week tx
79
no resistance or rare with which drugs?
- bendazoles for helminthic inf
- ivermectin for strongyloides
- metronidazole - for amebiasis, thrichomoniasis, giardiasis
