Parasitic Infections Flashcards
Major targets for chemotherapy for parasitic infections:
- Unique essential molecule found only in the parasite
- Similar molecules found in both the host and parasite but indispensable for the parasite only
- Common biochemical functions found in both parasite and host but with different pharmacological properties
Categories of parasites found in humans:
- Macroscopic (ringworm, tapeworm, head louse)
- Microscopic (trichomonas, malaria, beaver fever)
Two examples of taenia species which can affect humans:
- Taenia saginata (beef tapeworm) and taenia solium (pork tapeworm)
How do pigs and cows get infected with tapeworm?
- Parasite eggs get released into environment
- Get infected when ingesting vegetation that has been contaminated
- Oncospheres hatch and penetrate the intestinal wall of the intermediate host
Where does the parasite attach within the host/intermediate host?
- Scolex (worm’s head) attaches to the intestine, matures, produces more eggs
What does praziquantel treat?
Targets and treats parasitic worms
What is praziquantel?
A synthetic isoquinoline derivative
Praziquantel bioavailability after oral dosing?
80%
MOA of praziquantel:
Exact unknown, but it binds to the integument of the parasite and produces focal vacuolization
Drug of choice against cestode infections:
- Praziquantel
Pros of praziquantel:
- Safe and effective
- Single oral dose
- Impairs the function of hooks and suckers at the anterior end of the worm
When is the bioavailability of praziquantel diminished?
When taken concurrently with corticosteroids
Adverse reactions of praziquantel:
Nausea, headaches, abdominal discomfort
What is niclosamide?
Salicylanilide derivative used to treat parasitic worms
MOA of niclosamide:
Rapidly killing scolex and producing segments of adult tapeworms
- Inhibition of mitochondrial anaerobic phosphorylation of ADP results in a decrease in ATP production
What is the second line choice of treatment for parasitic worms?
Niclosamide
Administration of niclosamide:
Single oral dose tablet, chewed thoroughly and swallowed with water
Adverse effects of niclosamide:
GI complaints
- Avoid alcohol for 24 hours
Common name of enterobius vermicularis:
Pinworm
Life cycle of pinworms:
- Eggs on perinanal folds that contain larvae which mature in 4-6 hours
How does a human get infected with pinworms?
- Ingesting embryonated eggs which hatch in the small intestine, adults form in the lumen of the cecum
- Eggs can also contaminate nightclothes and bedding
Drugs of choice for pinworm:
Mebendazole and pyrantel
What is mebendazole?
Broad spectrum drugs effective against parasites
How do you administer mebendazole?
Administered orally
- Less than 10% absorbed
- Absorption can be increased if ingested with a fatty meal
- Twice over a two week interval
MOA of mebendazole:
- Binds to B-tubulin and inhibits polymerisation to microtubules
- This inhibits parasite motility, glucose uptake and cell division
- Once parasite is killed, it is expelled in feces
Do not administer mebendazole if…
Pregnant
Pyrantel class:
Tetrahydropyrimidines
MOA of pyrantel:
- Poorly absorbed within the gut
- Acts selectively at neuromuscular junctions of parasites on nicotinic acetylcholine receptors
- This causes the release of ACh and inhibition of acetylcholinesterase
- Results in paralysis of worms
Differences between pyrantel and mebendazole
Pyrantel has a narrower spectrum of activity than mebendazole
Adverse effects of pyrantel:
Mild, nausea, vomiting, diarrhea
Common name of pediculus capitis:
Head lice
How do head lice grow and mature?
Feeding on human blood
Treatment for head lice:
Permethrin, Malathion
Class of permethrin:
Phyrethroids
MOA of permethrin:
Causes voltage-gated sodium channels to remain open which causes membrane depolarization and rapid paralysis in the parasite
- Absorbed through the skin
Class of malathion
organophosphate
When is malathion used?
In cases where permethrin fails due to resistance
MOA of malathion:
- Irreversible inhibition of acetylcholinesterase, causes accumulation of ACh and rapid paralysis
Adverse effects of head lice drugs (malathion and permethrin):
Itching, mild burning of the scalp, inflammation of the skin
Definition of protozoa:
- Eukaryotes
Common name of entamoeba histolytica:
Ameobiasis
Symptoms of ameobiasis:
Can range of mild diarrhea to blood and mucus in the stool
- Asymptomatic intestinal infection
- Mild to moderate colitis
- Dysentery
- Amoeboma
- Liver abscess
Entamoeba histolytica exists in two forms:
Cysts and trophozoites
Entamoeba histolytica cysts:
Can transform into trophozoites
Entamoeba histolytica trophozoites:
Invasive, can reproduce and invade the wall of the large intestine. Can transform to cysts when excreted
Infection of entamoeba histolytica occurs when _____ invades the ____ ____.
Trophozoites, intestinal epithelium
Spread of entamoeba histolytica via the portal vein can result in ____
Liver abscesses
Types of amoebicidal drugs:
- Luminal amoebicides
- Systemic amoebicides
- Mixed amoebicides
Luminal amoebicides treat:
Parasites in bowel lumen
Systemic amoebicides treat:
Parasites in intestinal wall and liver
What does metronidazole treat?
Trophozoites but not cysts
What class of amoebicide is metronidazole?
Mixed
What class of amoebicide is iodoquinol?
Luminal
Side effects of iodoquinol:
Rash, diarrhea, dose-related peripheral neuropathy
Metronidazole eliminates trophozoites in which areas of the body?
- Liver abscess
- Intestinal wall
- NOT gut lumen
Metronidazole is a derivative of:
Nitroimidazole
Metronidazole can be administered:
Orally and is readily absorbed
How is metronidazole distributed:
Tissue distribution via simple diffusion
Metabolism of metronidazole:
Hepatic oxidation by mixed-function oxidase, followed by glucuronylation
How is metronidazole excreted:
Urine
Side effects of metronidazole:
Nausea, vomiting, headache, abdominal cramps, metallic taste in mouth
What is giardia lamblia?
Beaver fever
Two life-cycle stages of beaver fever:
Trophozoites and cysts
Infection of beaver fever occurs following:
Ingestion of contaminated water
Two types of beaver fever:
People-specific and zoonotic
Prescription for beaver fever:
Metronidazole
Is trichomonas trophozoites or cysts?
Trophozoites, does not have a cyst form
Common symptoms of trichomonas:
Women: Vaginal discharge, vulvar itching, discomfort in urination
Men: No signs or symptoms, occasional urethral discharge and burning post urination
Treatment plans for trichomonas:
Metronidazole, single or multiple dose regimens
What treatment plan can be done for trichomonas resistant to metronidazole?
Repeat treatment at higher doses
Systemic treatment or topical treatment for trichomonas?
Systemic due to multifocal nature of the infection
Human malaria is caused by:
P. falciparum, P. vivax, P. malariae, P. knowlesi
Most serious strain of malaria resulting in most deaths:
P. falciparum
Treatment for malaria is dependent on:
Liver stage- tissue schizonticides
Erythrocytic stage- blood schizonticides
Sexual stages- Gametocides
In humans, sporozoites leave the blood and multiply in the ____ forming _____
Liver, tissue schizonts
Treatment of malaria is dependent on ____
Species that caused the infection
P. falciparum and P. malariae treatment:
- One cycle of multiplication in liver
- Liver infection ceases in less than 4 weeks
- Elimination of erythrocytic parasites cures infection
P. vivax and P. ovale:
- Dormant hepatic stage (hypnozoite) not killed by most drugs
- Must eliminate both erythrocytic and hepatic parasites
According to the CDC, most malaria drugs are:
Chemoprophylaxis recommendations (chloroquine, mefloquine, doxycycline)
Chloroquine is the drug of choice for ___
Chemoprophylasis, drug sensitive P. falciparum
How is chloroquine administered:
Orally, rapidly absorbed and distributed to tissues where it has blood schizonticide activity
Adverse effects of chloroquine:
Nausea, vomiting, blurred vision ( at high doses )
How to reduce adverse effects of chloroquine:
Dosing after meals
What is mefloquine used to treat:
Drug resistant P. falciparum
How is mefloquine distributed:
Orally, well absorbed, extensive distribution
Method of action of mefloquine:
- Has blood schizonticide activity against P. falciparum but not against hepatic stages of gametocytes
- Concentration in the parasite
Adverse effects of mefloquine:
Neuropsychiatric toxicities, nausea, vomiting, dizzyness, sleep and behaviour disturbances
Do not use mefloquine if:
History of epilepsy and other psychiatric disorders
When is doxycycline used:
areas with a multidrug resistance to parasites
MOA of doxycycline:
Inhibits protein synthesis, blood schizonticide activity, not active against liver stages of malaria
