BIIC Pharmacology Lecture 5_Pharmacology of Anti Malarial & Parasitics Flashcards by Stephen Hutchins

What are the two groups of anti malarial drugs that inhibit heme metabolisium?

Quinolines and Artemisinin Derivatives

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What are the 4 Quinolines type drugs?

Chloroquine
Quinine
Quinidine
Mefloquine

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What are the 4 Artemisinin Derivatives

Artemisinin
Artesunate
Artemether
Dihydroartemisinin

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What are the two anti-malarial drugs that inhibit the electron transport chain?

Primaquine

* Atovaquone

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What are the three anti-malarial drugs that inhibit translation?

Doxycycline
Tetracycline
Clindamycin

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What are the two anti malarial drugs that inhibit folate metabolisium?

Sulfadoxine-pyrimethamine

* Proguanil

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What are the

MOA:
Pharmaco:
Indications:
Common ASEs:
Serious ASEs:
Considerations:

For Quinolines (Chloroquine, Quinine, Quinidine, Mefloquine)

MOA: Drug binds to free heme in the parasites food vacuole. This prevents the parasite from polymerizing the heme. Unpolymerized heme leads to oxidative membrane damage of the parasite.
Pharmaco: Chloroquine and Mefloquine are dosed once weekly. Quinine and Quinidine are dosed every 8 hours.
Indications:Prophylactical and therapeutic treatment of malaria infection
Common ASEs: tinnitus,headaches, nausea
Serious ASEs: Prolonged QT interval, Chloroquine is toxic at high doses. Mefloquine has Neuropsychiatric effects
Considerations: Chloroquine is the first line choice for prophylactic treatment but is ineffective against resistant strains of P. falciparum.

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What are the

MOA:
Pharmaco:
Indications:
Common ASEs:
Serious ASEs:
Considerations:

For Artemisinins (Artemisinin, artesunate, artemether, dihydroartemisinin)

MOA: Is activated by Iron to form free radical that then alkylates heme or proteins to form adducts that are toxic to the parasite.
Pharmaco: metabolised by CYP3A4. Dosed once daily
Indications: therapeutic treatment of malaria
infections
Common ASEs: Nausea, vomiting, dizziness, tinnitus
Serious ASEs: type 1 hypersensitivity
Considerations: First-line treatment for P. falciparum, WHO recommends against using artemisinins as monotherapy

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What are the

MOA:
Pharmaco:
Indications:
Common ASEs:
Serious ASEs:
Considerations:

For Primaquine & Atovaquone (Inhibitors of electron transport)

MOA: Interupts parasitic electron transport chain. This leads to oxidative damage.
Pharmaco: Dosed daily
Indications: Prophylactical and therapeutic treatment of malaria infections
Common ASEs: Abdominal pain, nausea (Atovquone is better tolerated than)
Serious ASEs: Hemolytic anemia (in patients with G6PD deficiency)
Considerations: Primaquine inhibits hepatic stage caused by P. vivax and P. ovale. Co-administer atovaquone with doxycycline as polytherapy to avoid resistance.

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What are the

MOA:
Pharmaco:
Indications:
Common ASEs:
Serious ASEs:
Considerations:

Inhibitors of Translation (Doxycycline, Tetracycline, Clindamycin)

MOA: doxycycline and tetracycline, bind to 30S ribosomal subunit and blocks binding of tRNA to the A site. Clindamycin binds to 50S ribosomal subunit and prevents the transfer of amino acids
Pharmaco: Doxycycline daily dosing, Tetracycline dosed every 6 hours, Clindamycin ?
Indications: prophylactic and therapeutic treatment of
malaria infections
Common ASEs: Tetracyclines - photosensitivity, tooth discoloration and disruption bone development in children (not used until 8+ years)
Serious ASEs: Clostridium difficile diarrhea
Considerations:Used in combination with artesunate
or quinine

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What are the

MOA:
Pharmaco:
Indications:
Common ASEs:
Serious ASEs:
Considerations:

Inhibitors of Folate Metabolism (Sulfadoxine-pyrimethamine, Proguanil)

MOA: Disrupte folate metabolic pathway by inhibiting dihydrofolate reductase and dihydropteroate synthase. This prevents the formation of purines and inhibits DNA synthesis in the parasite
Pharmaco: Sulfadoxine-pyrimethamine single dose as treatment and once weekly as prophylaxis. Proguanil
Indications: Prophylachcal and therapeuhc treatment of malaria infechons, sulfadoxine-pyrimethamine can be used in pahents 2 months and older
Common ASEs: diarrhea, nausea, vomiting, headache
Serious ASEs: Stevens Johnson Syndrome
Considerations: highly effective against blood schizont stages of Plasmodiu falciparum

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What are the 12 Antiprotozoal Agents?

Metronidazole
Tinidazole
Nitazoxanide
Pentamidine
Suramin
Melsarsoprol
Eflornithine
Nifurtimox
Sodium stibogluconate
Meglumine antimonate
Amphotericin
Miltefosine

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What is the target of Antiprotozoal Agents?

pyruvate-ferredoxin oxidoreductase (PFOR) which metabolizes pyruvate to acetyl CoA. This enzyme is not found in most eukaryotes

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What are the

MOA:
Pharmaco:
Indications:
Common ASEs:
Serious ASEs:
Considerations:

Metronidazole, Tinidazole

MOA: Anaerobic and microaerophilic pathogens contain electron transport components that have a sufficiently negative redox potential to donate electrons to metronidazole and tinidazole. The single-electron transfer forms a highly reactive nitro radical anion that kills susceptible organisms by radical-mediated mechanisms that target DNA
Pharmaco: Metronidazole - dosed every 8 hours. Tinidazole - dosed daily
Indications: against a wide variety of anaerobic protozoal parasites and anaerobic
bacteria such as amitochondriate protozoa T. vaginalis, E. histolytica, and G. lamblia
Common ASEs: nausea, headaches, Candida vaginitis
Serious ASEs: hypersensitivity reaction
Considerations: trichomoniasis and giardia. Metronidazole is used to treat ameba but Tinidazol is not. Helicobactor Pylori is resistant to metronidazole. Tinidazole has shorter treatment course.

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What are the

MOA:
Pharmaco:
Indications:
Common ASEs:
Serious ASEs:
Considerations:

Nitazoxanide (an Antiprotozoal)

MOA: It inhibits the achvity of pyruvate:ferredoxin oxidoreductase (PFOR)
Pharmaco: dosed every 12 hours
Indications: Effechve against protozoa, anaerobic bacteria and helminths
Common ASEs: Abdominal pain, nausea, headache
Serious ASEs: NA
Considerations:Active against Giardia lamblia and
Cryptosporidium parvum

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What is the MOA, ASE and use of Pentamidine?

MOA: Inhibition of DNA, RNA and protein synthesis and inhibition of dihydrofolate reductase
ASE:fatigue, dizziness, hypotension, pancreatitis, and kidney damage
Use: African Sleeping Sickness (African trypanosomiasis) in the early stage pre CNS envolvment.

What is the MOA, ASE and use of Suramin?

MOA: Interacts with macromolecules to inhibit energy metabolism and inhibits RNA polymeras
ASE: pruritus, paresthesia, vomiting and nausea
Use: African Sleeping Sickness (African trypanosomiasis) in the early stage pre CNS envolvment.

What is the

MOA:
ASE:
Use:

Melarsoprol

MOA:Inhibits trypanosomal pyruvate kinase, thereby inhibiting glycolysis and decreasing ATP production
ASE: Toxic to humans (4 – 6 % death rate)
Use: Late stage Tyypanosomiasis (african sleeping sickness) with CNS involvement

What is the

MOA:
ASE:
Use:

Eflornithine

MOA: inhibits polyamine synthesis which inhibits nucleic acid synthesis and protein synthesis
ASE: Less toxic than melarsoprol, acne
Use:Effective against early- and late-stage West African Sleeping Sickness but not East African Sleeping Sickness

What is the

MOA:
ASE:
Use:

Nifurtimox

MOA:generation of toxic oxygen free radicals inside parasite (note the parasite does not have catalase and therefore cannot protect itself from the free radicals)
ASE:anorexia, vomiting, memory loss, sleep disorders,
seizures
Use: treat Chaga’s Disease caused by Trypanosoma cruzi

What is the

MOA:
ASE:
Use:

Sodium stibogluconate and meglumine antimonate

MOA: inhibition of glycolytic pathway and fatty acid oxidation
ASE :prolonged QT interval, pancreatitis, and rash
Use: Treatment of Leishmaniasis

What are Amphotericin and miltefosine used to treat?

approved to treat resistant Leishmania

What are the 6 Anhhelminthic Agents

Ivermectin
Albendazole
Mebendazole
Triclabendazole
Diethylcarbamazine
Praziquantel

What are the

MOA:
Pharmaco:
Indications:
Common ASEs:
Serious ASEs:
Considerations:

Ivermectin (an Anthelmintic)

MOA: achvahon of glutamate-gated chloride channels which causes blockade of neuromuscular transmission and paralysis of the worm
Pharmaco: Given as a single dose then retreat either weeks or months later
Indications:the agent of choice for treahng individuals with onchocerciasis, is effechve only against microfilariae; the drug does not kill adult filarial worms
Common ASEs: inflammatory or allergic response to dying microfilariae
Serious ASEs: seizures
Considerations: Used to treat animals with nematode infections

What are the ``` MOA: Pharmaco: Indications: Common ASEs: Serious ASEs: Considerations: ``` Albendazole, mebendazole, Triclabendazole (Anthelmintics)

MOA:Inhibits tubulin polymerization by binding to nematodal isoform of b-tubulin disrupts nematodal motility and DNA replication Pharmaco: Albendazole dosed daily, mebendazole, Triclabendazole dosed every 12 hours Indications: tapeworms, hookworms, liver fluke Common ASEs: vomiting, nausea, diarrhea Serious ASEs: Stevens-Johnson syndrome Considerations: use effechve contracephon during treatment and for 3 days after the final dose

What are the ``` MOA: Pharmaco: Indications: Common ASEs: Serious ASEs: Considerations: ``` Diethylcarbamazine (Antifilarial agent)

MOA: Unknown Pharmaco: Dosed daily Indications:Drug of choice for treahng adult filariasis worms Common ASEs: anorexia, headache and nausea Serious ASEs: pregnancy X Considerations:

What are the ``` MOA: Pharmaco: Indications: Common ASEs: Serious ASEs: Considerations: ``` Praziquantel (Anthelmintic agent)

MOA:increase parasite membrane permeability to calcium, resulting in contraction and paralysis of the worms Pharmaco: Dosed every 8 hours, 80% renally excreted Indications: Drug of choice for treating adult cestode (tapeworm) and trematode (fluke) infections Common ASEs: nausea, headache, and abdominal discomfort Serious ASEs: Considerations: