prevents polymerization of the hemoglobin breakdown product heme into hemozoin blood schizonticide - Intracellular accumulation of heme is toxic to the parasite

- form complexes with double-stranded DNA to prevent strand separation --\> block of DNA replication and transcription to RNA - it is blood schizonticide

- 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

- GI upset - skin rash, headache, and dizziness - At high doses: cardiac conduction abnormality, psychiatric disorders, and seizures

- unknown mech - it is a tissue schizonticide - limits malaria transmission by acting as a gametocide

C3 Flashcards by M AAB

Antiprotozoal and antihelminthic drugs

Antiprotozoal agents:
- Antimalarials
  - chloroquine
  - mefloquine
  - primaquine
  - quinine
  - artemether
  - atovaquone
  - proguanil
- Anti-amebic:
  - metronidazole, tinidazole
  - paromomycin
Anti-helminthic agents:
- mebendazole
- ivermectin
- niclosamide

How well did you know this?

Not at all

Perfectly

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.

How well did you know this?

Not at all

Perfectly

Chloroquine MOA?

prevents polymerization of the hemoglobin breakdown product heme into hemozoin

blood schizonticide

Intracellular accumulation
of heme is toxic to the parasite

How well did you know this?

Not at all

Perfectly

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.

How well did you know this?

Not at all

Perfectly

Chloroquine Clinical use?

Blood schizonticide

ALL non-resistant malarias

autoimmune disorders (rheumatoid arthritis)

How well did you know this?

Not at all

Perfectly

Chloroquine Toxicity?

GI irritation
skin rash
headaches

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Quinine MOA?

form complexes with double-stranded DNA to prevent strand separation –> block of DNA replication and transcription to RNA
it is blood schizonticide

How well did you know this?

Not at all

Perfectly

Quinine PharmacoKinetix?

orally
- metabolized before renal excretion

I.V. administration is possible in severe infections

How well did you know this?

Not at all

Perfectly

Quinine Clinical use?

in P.falciparum infections resistant to chloroquine (for those who tolerate oral treatment)
should not be used routinely for prophylaxis

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

Mefloquine, primaquin MOA?

unknown :)

How well did you know this?

Not at all

Perfectly

Mefloquine PharmacoKinetix?

orally because of local irritation

How well did you know this?

Not at all

Perfectly

Mefloquine clinical use?

first-line drug (taken weekly) for prophylaxis
daily for infection

How well did you know this?

Not at all

Perfectly

Mefloquine Toxicity?

GI upset
skin rash, headache, and dizziness
At high doses:
cardiac conduction abnormality, psychiatric disorders, and seizures

How well did you know this?

Not at all

Perfectly

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