Antiprotozoal and antihelminthic drugs
chloroquine mefloquine quinine lumefantrine artemether primaquine metronidazole atovaquone proguanil mebendazole ivermectin niclosamide
DRUGS FOR MALARIA?
Chloroquine Artemether Quinine Mefloquine Primaquine
Chloroquine MOA?
- accumulates in the food
vacuole of plasmodia and prevents polymerization of the hemoglobin
breakdown product heme into hemozoin - Intracellular accumulation
of heme is toxic to the parasite - Resistance in P.falciparum: decreased
intravacuolar accumulation of chloroquine via a transporter
Chloroquine PharmacoKinetix?
- rapidly absorbed when
given orally - is widely distributed to tissues and have
large volume of distribution - Antacids may decrease oral absorption
of the drug - Elimination: unchanged in the urine.
Chloroquine Clinical use?
- acute attacks of non-falciparum and sensitive falciparum malaria
- chemoprophylaxis
- autoimmune disorders (rheumatoid arthritis)
Chloroquine Toxicity?
- Low doses:
1. GI irritation
2. skin rash
3. headaches - High doses:
1. severe skin lesions
2. peripheral neuropathies
3. myocardial depression
4. retinal damage
5. auditory impairment
6. toxic psychosis.
what about Artemether?
- metabolized in the food vacuole of the parasite –> toxic free radicals
- blood schizonticides active against P.falciparum (also MDRs)
- best used in combination with other agents
- the only drugs reliably effective against quinine-resistant strains
- Adverse effects are mild
Quinine MOA?
- form complexes with double-stranded DNA to prevent strand separation –> block of DNA replication and transcription to RNA
- it is blood schizonticide
Quinine PharmacoKinetix?
- bioavailability: rapidly absorbed orally
- metabolized before renal excretion
- I.V. administration is possible in severe infections
Quinine Clinical use?
- in P.falciparum infections resistant to chloroquine (for those who tolerate oral treatment)
- commonly used with doxycycline or clindamycin to shorten the duration of therapy and limit toxicity
- should not be used routinely for prophylaxis
Quinine Toxicity?
- cinchonism (GI distress, headache, vertigo, blurred vision, and tinnitus)
- Severe overdose: disturbances in cardiac conduction
- Hematotoxic effects: G6PD-deficient
- Blackwater fever (intravascular hemolysis) is a rare and sometimes fatal complication in quinine-sensitized persons
- it is contraindicated in pregnancy
Mefloquine MOA?
unknown :)
Mefloquine PharmacoKinetix?
can only be given orally because of local irritation
Mefloquine clinical use?
- first-line drug (taken weekly) for prophylaxis
- an alternative drug to quinine in acute attacks and uncomplicated infections resulting from P falciparum.
Mefloquine Toxicity?
- GI distress
- skin rash, headache, and dizziness
- At high doses:
cardiac conduction defects, psychiatric disorders, and neurologic effects
Primaquine MOA?
- forms quinoline-quinone metabolites –> electron-transferring redox compounds –> cellular oxidants
- it is a tissue schizonticide
- limits malaria transmission by acting as a gametocide
Primaquine PharmacoKinetix?
Absorption is complete after oral administration
Primaquine Clinical use?
- eradicates liver stages of P.Vivax and P.Ovale
- should be used in conjunction with a blood schizonticide
- 14-d course of primaquine is standard after treatment with chloroquinein –> acute attacks of vivax and ovale malaria
- alternative (daily) for primary prevention
Primaquine Toxicity?
- well tolerated but may cause:
1. GI distress
2. pruritus
3. headaches
4. ethemoglobinemia - More serious toxicity:
hemolysis (G6PD-deficients)
contraindicated in pregnancy
what about Atovaquone ?
- quinine derivative,
- disrupt mitochondrial electron transport in protozoa
Malarone (Atova + Proguanil) for both chemoprophylaxis (taken daily) and treatment of falciparum malaria
- Abdominal pain and GI effects occur at the higher doses
- an alternative treatment for P.jirovecii
DRUGS FOR AMEBIASIS?
chloroquine
metronidazole
