BIIC Pharmacology Lecture 5_Pharmacology of Anti Malarial & Parasitics Flashcards
What are the two groups of anti malarial drugs that inhibit heme metabolisium?
Quinolines and Artemisinin Derivatives
What are the 4 Quinolines type drugs?
- Chloroquine
- Quinine
- Quinidine
- Mefloquine
What are the 4 Artemisinin Derivatives
- Artemisinin
- Artesunate
- Artemether
- Dihydroartemisinin
What are the two anti-malarial drugs that inhibit the electron transport chain?
- Primaquine
* Atovaquone
What are the three anti-malarial drugs that inhibit translation?
- Doxycycline
- Tetracycline
- Clindamycin
What are the two anti malarial drugs that inhibit folate metabolisium?
- Sulfadoxine-pyrimethamine
* Proguanil
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.
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
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.
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
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
What are the 12 Antiprotozoal Agents?
- Metronidazole
- Tinidazole
- Nitazoxanide
- Pentamidine
- Suramin
- Melsarsoprol
- Eflornithine
- Nifurtimox
- Sodium stibogluconate
- Meglumine antimonate
- Amphotericin
- Miltefosine
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
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.
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