Antiprotozoa + Helminthic

Question 1

Antimalarial drug list

Answer 1

Quinine,

Quinidine

Chloroquine (*hydroxychloroquine)

Mefloquine

Primaquine

Atovaquone + praguanil

Artemether + lumefantrin

*+Doxycylclin / Clindamycin

Question 2

Mechanism of action of the quinolones

Answer 2

( Blood Schozonticides )
They enter the plasmodium in the erythrocyte stage and bind to heme, inhibiting its conversion to Hemezoin.

Since heme is toxic to the plasmodium, it causes death.

Primaquine - kills hypnozoites in the Liver
(Tissue Schizonticide)
- by oxidative damage to the cell

Quinidine - is a class Ia Antiarrhythmic drug 
(Along with ; Disopyramide, Procainamide)

classIb - lidocaine, Mexiletine
classIc - Flecainide, Propafenone

Question 3

Side effects, resistance and specificity of the quinolones

Answer 3

Quinine and Quinidine used in drug resistant

• Cinchonism (flushing, blurry vision, headache, tinnitus)
• Arrhythmia, prolonged QT
• teratogenic

Chloroquine

• resistance by P.falciparum (efflux pump)
• Itching, Retinopathy, prolonged QT

Mefloquine
- CNS - Depression, Psychosis, Anxiety, Seizures

Primaquine used for hypnozoites

• teratogenic
• Hemolytic anemia in G6PD

Question 4

Mechanism of action of Artemether + Lumefantrin

And Atovaquone + Praguanil

Answer 4

Atovaquone - inhibits electron transport chain and disrupts the mitochondrial membrane potential
*also treats pneumocystis jirovecii, Toxoplasmosis & Babesia

Praguanil - antimetabolite - inhibits folate synthesis

Artemether - binds iron in heme and produces free radicals within the plasmodium.

Lumefantrin - unknown mechanism

Question 5

Side effects of Atovaquone + Praguanil and Artemether + Lumefantrin

Answer 5

Atovaquone - GI distress, fever, rash
+ praguanil

Artemether - GI distress

Lumefantrin - QT prolongation

Question 6

Malaria treatment regimen/prophylaxis

Answer 6

1st-line - Chloroquine *except for P. Falciparum

2nd -line - Quinine/Quinidine
( for Chloroquine resistant )

Multidrug resistant
= Quinine + Quinidine + Doxycyclin
/Atovaquone + Proguanil

Primaquine + Chloroquine = for liver stages

Prophylaxis
= Doxycyclin/ Pyrimethamine-Sulfadoxine

Complicated Malaria (*cerebral, acidosis, anemia..)
= Artemether + Lumefantrin

Question 7

Anthelmintic drug list

Answer 7

Praziquantel - Tapeworms and Flukes

Albendazole - Nematodes (Ascariasis), pinworms, Hookworm, whipworm
Mebendazole

Pyrantel Pamoate- Nematodes,

Ivermectin - Threadworms, Ascaris, Hookworm

Diethylcarbamazine - Wuchereria Bancrofti, Loa loa

Niclosamide - Tapeworms

Question 8

Anthelmintic mechanism of action

Answer 8

Praziquantel

• increase permeability of ca2+ in parasites = paralysis and death
• *metabolised by CYP450
• *no effect in neurocysticercosis
• **contraindicated in ocular cysticercosis

Albendazole & Mebendazole

• inhibits formation of microtubules
• *effective in Neurocysticercosis

Pyrantel Pamoate
- stimulates muscle’s nicotinic receptors = uncontrollable contractions = paralysis & expulsion in stool

Ivermectin
- binds glutamate gated Cl- channels = open permanently = Hyperpolarization = paralysis

Diethylcarbamazine - unknown mechanism

Niclosamide - inhibits glucose uptake by parasite

Question 9

Anthelmintic side effects

Answer 9

Praziquantel - Headache, Fatigue

Albendazole & Mebendazole
- Teratogenic, Bone marrow suppression, Hepatotoxic

Pyrantel Pamoate - Headache, GI distress

Ivermectin - Headache, Dizziness, Muscle pain, GI

Diethylcarbamazine
- Itching, Face swelling, Headache, Vision loss

Niclosamide - Itching, GI distress

Question 10

Types of helminthic diseases and treatment

Answer 10

Taeniasis = Praziquantel
Cysticercosis - neuro = Albendazole/Mebendazole

Schistosomiasis, Liver flukes = Praziquantel

Ascariasis = Albendazole/Mebendazole
= Pyrantel Pamoate
= Ivermectin

Tapeworms = Niclosamide

Threadworms, Ascaris & Hookworms
= Ivermectin
= Albendazole

Wuchureria Bancrofti & Loa Loa
= Diethylcarbamazine

Question 11

Special Antibiotic against Protozoa?

Answer 11

Metronidazole (bactericidal)

MOA;

• prodrug reduced by Ferredoxin (not in humans)
• only in Anaerobic bacteria & Protozoa
• creates free radicals that damage, fragment DNA

Spectrum;
Bacteroides Fragilis, Prevotella, Fusobacterium
C. Difficile 
Lactobacillus spp - Bacterial Vaginosis
Helicobacter pylori 

Entamoeba Histolytica
Giardia Lambia
Trichomonas Vaginalis
Gardnerella Vaginalis

Side effects;
Disulfiram reaction = inhibit aldehyde dehydrogenase (Nausea, vomiting, headache)

Inhibitor of CYP450

• *Seizures
• *Confusion
• *Peripheral neuropathy
• Headache
• decreased appetite, Metallic taste, Nausea,

Question 12

Describe Fidaxomycin and Rifaximin

Answer 12

Fidaxomycin

MOA;

• inhibits bacterial RNA polymerase (bactericidal)
• against Gram- Positive anaerobes = C. Difficile
• poor systemic absorption
• negligible side effects

Rifaximin

MOA;
- inhibits DNA-dependent RNA polymerase
- against gram positive and negative aerobes and anaerobes
- management of IBS, Traveler’s diarrhea, Diverticula disease.
- management of Hepatic Encephalopathy
(kills deaminating enteric bacteria - decrease production of nitrogenous compounds)
- poor systemic absorption
- negligible side effects