C3 Flashcards
Antiprotozoal and antihelminthic drugs
- Antiprotozoal agents:
- Antimalarials
- chloroquine
- mefloquine
- primaquine
- quinine
- artemether
- atovaquone
- proguanil
- Anti-amebic:
- metronidazole, tinidazole
- paromomycin
- Antimalarials
- Anti-helminthic agents:
- mebendazole
- ivermectin
- niclosamide
DRUGS FOR MALARIA?
Chloroquine
Artemether
Quinine
Mefloquine
Primaquine
atovaquone
proguanil
lumefantrine , minimal cardiotoxicity, is now used in fixed combination with artemether
(Coartem) for uncomplicated falciparum malaria.
Chloroquine MOA?
prevents polymerization of the hemoglobin breakdown product heme into hemozoin
blood schizonticide
- Intracellular accumulation
of heme is toxic to the parasite
Chloroquine PharmacoKinetix?
orally
large volume of distribution ( needs a loading dose in lifethreatening infection)
- Antacids may decrease oral absorption
of the drug - Elimination: unchanged in the urine.
Chloroquine Clinical use?
Blood schizonticide
ALL non-resistant malarias
- autoimmune disorders (rheumatoid arthritis)
Chloroquine Toxicity?
- GI irritation
- skin rash
- headaches
what about Artemether?
- metabolized in the food vacuole of the parasite –> toxic free radicals
- blood schizonticides active against P.falciparum (also MDRs)
- Adverse effects are mild : GI upset
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?
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)
- 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, primaquin MOA?
unknown :)
Mefloquine PharmacoKinetix?
orally because of local irritation
Mefloquine clinical use?
- first-line drug (taken weekly) for prophylaxis
- daily for infection
Mefloquine Toxicity?
- GI upset
- skin rash, headache, and dizziness
- At high doses:
cardiac conduction abnormality, psychiatric disorders, and seizures
Primaquine MOA?
- unknown mech
- it is a tissue schizonticide
- limits malaria transmission by acting as a gametocide
Primaquine PharmacoKinetix?
Absorption is complete after oral administration
Primaquine Clinical use?
- against liver stages of P.Vivax and P.Ovale
- PCP ( P.jiroveci pneumonia)
- should be used in conjunction with a blood schizonticide
Primaquine Toxicity?
- well tolerated but may cause:
1. GI distress
2. headaches
3. . Blood cytopenias - More serious toxicity:
hemolysis (G6PD-deficients)
*contraindicated in pregnancy*
what about Atovaquone ?
- disrupt mitochondrial metabolism ( electron transport in protozoa)
Malarone (Atova + Proguanil) for both chemoprophylaxis (taken daily) and treatment of falciparum malaria
- rash , fever, GI effects occur at the higher doses
DRUGS FOR AMEBIASIS?
Metronidazole, tinidazole
Paromomycin
Antihelminthic drugs
- Round worms (Nematodes):
- Mebendazole
- Ivermectin
- Albendazole
- Diethylcarbamazine
- FLUKES (Trematodes)
- Praziquantel
- Tape worm (Cestodes)
- Albendazole
- Mebendazole
- Niclosamide
- Praziquantel
Proguanil MOA, administration
Antifolate
-inhibits folate synthesis
oral
Proguanil effects
Mostly blood schizonticide
Proguanil toxicity
GI upset
rash (sometimes severe)
cytopenia
metronidazole MOA
reactive metabolic products
Anti-amebic agents
metronidazole clinical uses
- Luminal amebiasis
- Extra-intestinal amebiasis
- giardiasis
- trichomoniasis
metronidazole pharmacokinetic
- oral
- rapid diffusion into all tissues
metronidazole toxicity
- Nausea
- headache
- paresthesia
- disulfiram effect
Mebendazole MOA
Selective inhibiton of microtubule synthesis and glucose uptake in round worms
Mebendazole clinical uses
- Ascariasis
- pinworm
- whipworm infections
mebendazole pharmacokinetics
- less than 10% is absorbed systematically after oral use
- metabolised by hepatic enzymes
plasma levels can be increased by cimetidine
decreased by carbamazepine or phenytoin
mebendazole toxicity
- GI irritation
- granulocytopenia (high dose)
- alopecia (high dose)
- teratogenic ; CI in pregnancy
Ivermectin MOA
- intensifies GABA-mediated neurotranmission in round worms
- causes immobilization of parasite; facilitate their removal by reticuloendothelial system.
- DOESNT cross BBB
Ivermectin clinical use
- Onchocerciasis
- cutaneous larva migrans
- stronglodiasis
against round worms
Ivermectin SE
- reactions due to dying worms :
- fever
- headache, dizziness
- rash
- pruritis
- tachycardia
- hypotension
- joint pain
- muscle pain
- lymph gland pain
- controlled with NSAID, Antihistamines
- CI in pregnancy
Niclosamide MOA
- Uncoupling oxidative phosphorylations
- OR by activating ATPases.
Niclosamide Clinical uses
- Beef, pork, fish tapeworm
- small, large intestinal flukes
Niclosamide toxicity
- GI distress
- headache
- rash
- fever
Avoid ethanol consumption 24-48 hres
