C.3 Flashcards
Antiprotozoal and antihelminthic
Chloroquine,
Mefloquine,
Quinine,
Lumefantrine,
Artemether,
Primaquine,
Metronidazole,
Atovaquone,
Proguanil,
Mebendazole,
Ivermectin,
Niclosamide
Chloroquine
MOA: inhibits heme-polymerase →no heme breakdown→ IC accumulation of heme is toxic;
IND: Acutely and as prophylaxis - treatment of P. falciparum malaria (quickly terminated fever and clears parasitaemia), blood schizontocide;
Extra: resistance is more common;
SEs: GI symptoms, visual disturbances (cornea &retina deposits), dizziness, headache, pruritus, rarely hemolysis (G6PDH deficiency)
Mefloquine
MOA: Similar to chloroquine, slower acting;
ROA: p.o;
IND: mostly prophylaxis (1 tablet/week), effective in chloroquine resistance cases;
SEs: nausea, vomiting, sleep disturbances, depression and other psychoses, hallucinations, bradycardia, GI symptoms
Quinine
MOA: Similar to chloroquine;
IND: only for acute P. falciparum infections;
SEs: headache, visual disturbances, tinnitus, restlessness, QT↑, TdP, intravasal hemolysis, thrombocytopenia, leukopenia, respiratory depression, hypoglycemia, hepatotoxicity, severe hypotension, uterine contractions, Blackwater fever →severe hemolysis and hemoglobinuria
Atovaqoune +proguanil
IND: prophylactic in chloroquin resistant P. falciparum endemic areas, can be used in children, alternative treatment of Pneumocystis Jirovecii;
Contra-IND: not recommended in pregnancy;
SEs: GI symptoms, liver enzyme elevation
Atovaquone
MOA: Inhibits mitochondrial electron transport;
Extra: has both tissue and blood schizontocidal effects →requires shorter prophylactic and post exposure therapy
Proguanil
MOA: folate synthesis inhibitor
Primaquine
MOA: unknown, acts against hypnozoites in case of P. vivax/ovale;
IND: recurrent malaria (vivax/ovale malaria→ combined with chloroquine), prophylaxis, gametocidal action in P. falciparum malaria, Pneumocystis Jirovecii; SEs: well tolerated, mild GI symptoms, rarely (→leukopenia, agranulocytosis, arrhythmias), hemolysis in case of G6PDH deficiency (→patients should be tested for G6PDH)
Artemether with Lumefantrine
MOA: involves interaction with ferrous ions which results in formation of toxic free radials;
IND: fast acting schizontocide against all Plasmodia strains, artemisinins -based combination therapy is 1st line for uncomplicated P. falciparum;
SEs: safe, well-tolerated, rarely anemia, hemolysis
Metronidazole
MOA: the exact mechanism is not fully understood;
Spectrum: anaerobe bacteria (C.difficile), E. hystolytica, Trichomonas vaginalis, Giardia lamblia;
SEs: nausea, headache, metallic taste, insomnia, weakness, dizziness, rash, dark urine, vertigo, disulfiram-like effect (alcohol intolerance);
Drug-interacitions: potentiates coumarine anticoagulants, increases the risk of lithium toxicity;
Contra-IND: pregnancy (not safe!!!)
side-note: TINIDAZOLE: similar activity but better toxicity profile
Mebendazole
MOA: inhibits polymerization of the β-tubulin of the microtubules →inhibition of fumarate-reductase and the oxidative phosphorylation →paralysis;
IND: roundworms, pinworms, tapeworms (→Ascaris, Trichiura, Tenia, Trichostrongylus);
ROA: p.o;
SEs: nausea, vomiting, dizziness, headache, paresthesia, hypotention, bradycardia, visual disturbamces, elevation of liver enzymes, TERATOGENIC;
Contra-IND: pregnancy!!!
Ivermectin
MOA: enhance GABA effects in the worm→ paralysis;
IND: certain roundworms→ Wuchereria bancrofti (filaria), Loa loa, + veterinary use;
Kinetics: no CNS penetration;
SEs: mild, due to the disintegration of the worms (fever, headache, dizziness, sleepiness, itching, muscle and joint pain, lymphadenitis, edema, tachycardia, hypotension)
Niclosamide
MOA: inhibits oxidative phosphorylation;
IND: tapeworm infections (T.Saginata, T. solium, D. latum);
Kinetics: administered p.o, very bad absorption;
SEs: nausea, vomiting, diarrhea, abdominal discomfort;
Extra: alcohol consumption is forbidden for 1 day
Blackwater fever
a clinical entity characterized by acute intravascular hemolysis classically occuring after the re-introduction of quinine in long-term residents in Plasmodium falciparum endemic areas and repeatedly using the product.
