Antimalarials/Protozoals Flashcards
Most lethal and resistant protozoa
P. falciparum
Have dormant liver stages (hypnozoites) (2)
- P. vivax
- P. ovale
Rare protozoa
P. malariae
- Act on ERYTHROCYTIC forms of the parasite
- Do NOT affect secondary tissue forms of Ovale and Vivax
Blood schizonticides
- Eliminate proliferation
- Act on GAMETOCYTES
- Do NOT help individuals suffering from malaria, but may help SLOW SPREAD
Gametocidal agents
- Act on HEPATIC stages
- Do NOT suppress symptoms one erythrocytic stages have been established
- Kill secondary tissue forms of Ovale and Vivax
- Can prevent prophylaxis but are too toxic
Tissue schizonticides
Provide “RADICAL CURE”
Tissue schizonticides
Can be used to suppress symptoms –> “CLINICAL CURE”
Blood schizonticides
Most effective means of controlling malaria
- Avoid being bitten
- Eradicate mosquitoes and habitates
- Insect repellent
- Mosquito netting, tents with permethrin
Drug effective against gametocytic and exoerythrocytic (tissue) formation
Primaquine
Drugs effective against erythrocytic form, from illustration (5)
- Artemisinin
- Chloroquine
- Quinine
- Mefloquine
- Pyrimethamine
DOC for Malaria (2)
- Chloroquine
- Hydroxychloroquine
Blood schizonticides
- Chloroquine
- Hydroxychloroquine
- Mefloquine
- Quinine sulfate and quinidine gluconate
- Doxycycline or Clindamycin
- Atovaquone + Proquanil
DOC and prophylaxis for sensitive organisms
Chloroquine
- Prophylaxis due to long duration of action (take once weekly)
What form is resistant to Chloroquine and why?
- P. falciparum
- TRANSPORT PUMP removes drug from parasite
Chloroquine MOA (2)
- Actively concentrated within plasmodia that reside in RBC
- May interfere with lysosomal degradation of Hgb
Chloroquine Admin
- Oral
- Parenteral (slow)
Chloroquine accumulates where? (2)
- Skin
- Retina
Chloroquine SE (6)
- CNS (dizziness, HA, tinnitus)
- Retinal and corneal tox
- Ototoxicity
- Rash, pruritis
- HEMOLYSIS - G6PD (use caution, but not absolute CI)
- INCREASED RISK FOR QT prolongation (torsades)
Chloroquine CI (2)
- Psoriasis
- Porphyria
First line drug for tx and prophylaxis of chloroquine resistant strains?
Mefloquine
Mefloquine Admin
Oral as single mega dose
Mefloquine Features -
- Distributed to blood, urine, CSF, tissues and concentrated in RBC
- Metabolized by liver
- Eliminated very slowly
Mefloquine SE
- SEIZURES AND PSYCHOSIS aggravation
- Potential CARDIAC TOX (do NOT combine with quinine)
Mefloquine CI
- In pts with any neuropsych problems
Quinine Admin and t 1/2
Oral, 5 - 16 hrs
DOC for complicated, chloroquine resistant plasmodia
Quinine and Quinidine Glyconate
- Combined with Doxycycline or Clindamycin (if
Quinidine Glyconate Admin
IV
Other actions of Quinine and Quinidine Glyconate
- Analgesia
- Antipyretic
Which drug has a narrow margin between an effective dose and toxic dose?
Quinine
Quinine and Quinidine Glyconate SE
- CINCHONISM (tinnitus, HA, dizziness, flushing, visual disturbances)
- ANTIARRYTHMIC agent (Quinidine)
- QT ELONGATION (do not combine with mefloquine)
- HEMOLYSIS in G6PD
- Stimulates insulin (caution in hypoglycemia)
Antibiotic combined with Quinine or Quinidine Glyconate for tx of complicated chloroquine resistant malaria
Doxycycline
Used for prophylaxis against multidrug resistant malaria, taken daily
Doxycycline
Atovaquone MOA
Interferes with mitochondrial process such as
- electron transport
- ATP synthesis
- pyrimidine synthesis
Proguanil MOA
- Inhibits dihydrofolate deductase
- Blocks dihydrofolic acid to tetrahydrofolic acid
SYNERGISTIC combo effective in regions where chloroquine and mefloquine resistance is high
- Atovaquone + Proguanil
Atovaquone + Proguanil Tx (2)
- Uncomplicated, chloroquine resistant malaria
- Prophylaxis against chloroquine resistant Falciparum
Atovaquone + Proguanil absorption increased by _____
- Fatty foods
Atovaquone + Proguanil Admin
Oral
Atovaquone + Proguanil active against what form?
- Tissue
- Erythrocytic
- NOT for radical cure
Atovaquone + Proguanil SE
Require D/C
- Rash, fever, V/D
- Caution in preg: mutanogenesis in mice
Tissue Schizonticide, only active against TISSUE FORMS AND GAMETOCYTES
Primaquine
Drug that will NOT suppress disease once developed
Primaquine
Primaquine Admin
Oral
Used with chloroquine as alternative tx for chloroquine-resistant Falciparum
Primaquine
Primaquine CI
NEVER GIVE THIS DRUG TO
- G6PD (hemolytic anemia)
- SLE or RA (granulocytopenia)
- Pregnancy (fetal hemolytic anemia)
Most drugs can provide a clinical cure to which species?
All four
Most drugs can provide a radical cure to which species?
Falciparum and Malariae
Drug used for radical cure of Vivax and Ovale, when used with RBC Schizonticide
Primaquine
Amebiasis infective form? invading and replicating form?
Infective: Cyst
Invade/replicate: Trophozoite
Most common cause of non-bacterial diarrhea in N. America
Giardia
Trichomoniasis: who needs to be treated?
both partners
- Men often asymptomatic
- Women frothy, yellow, discharge
Toxoplasmosis during pregnancy (3)
- Heart problems
- Hydrocephalus
- Retinochorditis
P jirovecii: what is it?
Not a protozoa –> yeast-like fungus
Major cause of death in AIDs pt
P jirovecii
DOC for Amebiasis, Giardiasis, Trichomoniasis
Metronidazole
DOC for pneumocystosis
Bactrim (Trimethoprim plus sulfamethoxazole)
Drugs used for Amebiasis, Giardiasis, Trichomoniasis (5)
- Metronidazole (DOC)
- Tinidazole
- Iodoquinol
- Tetracycline & Erythromycin
- Paromomycin
Drug for Toxoplasmosis
Pyrimethamine + Sulfadiazine + Folinic acid (Leucovorin)
Alternate tx for Sulfa allergy, Pneumocystosis
Pentamidine
Tx Amebiasis
Metronidazole + Luminal amebicide
— Metronidazole is NOT AFFECTIVE AGAINST LUMINAL PARASITES
Tx for Giardiasis
Metronidazole
Tx for Trich
Metronidazole
Metronidazole MOA (2)
- Prodrug: non-enzymatically reduced by reacting with reduced ferredoxin (only found in anaerobes)
- Metronidazole metabolites are TAKEN UP INTO DNA, and form unstable molecules
Metronidazole Admin
- Oral
- IV
- Topical
Does metronidazole get into CSF?
Yes
Metronidazole SE (4)
- CNS toxicity: seizures and neuropathy
- Red urine
- Not to be taken with alcohol
- Metallic taste
Similar drug to Metronidazole, but better tolerated
Tinidazole
Luminal parasite drugs (3)
- Iodoquinol
- Paromomycin
- Tetracycline and Erythromycin
Drug that is useful for asymp amebiasis
- Iodoquinol
- Paromomycin (also for asymp giard, trich)
Iodoquinol SE (3)
- Skin rxn, NA, D
- High IODINE CONTENT –> thyroid enlargement
- Optic neuritis and optic atrophy –> blindness
Drug class Paromomycin
Aminoglycoside
Alternative drugs for tx of amebiasis and giardiasis
Tetracycline and Erythromycin
Bactrim MOA
Inhibits folate metabolism
Bactrim SE
- Rash, pruritis
- Cytopenias and transaminase elevation
Pentamidine MOA
Inhibit DNA replication
Pentamidine Admin and when to use
- IM (active infection)
- Neubulization (prophylaxis)
Pentamidine SE
- Hypotension, arrythmias, hypoglycemia
- Tachycardia, HA, V, bronchospasms
- RENAL DYSFUNCTION
- Hepatic failure
DOC P. jirovecii
Bactrim + Folinic acid
