Drugs for Parasitic Infections

What are the two broad groups of endoparasites?

protozoa or helminths

Malaria

Amebiasis

Giardiasis

Trichomoniasis

Toxoplasmosis

Protozoa or helminths?

Protozoa

Nematodes (roundworms), Trematodes (flukes), Cestodes (tapeworms)

Protozoa or helminths?

Helminths

Ectoparasites live on

skin or hair shafts (lice, scabies)

What is the worlds most important parasitic disease

malaria

Most malaria cases are caused by

P. falciparum and P. vivax (Other species: P. ovale and P. malariae)

In malaria, there is periodic rupture of _____ from erythrocytes into the bloodstream along with other _____ which lead to symptoms

merozoites

pyrogens

What is the life cycle of malaria

1. mosquito infects human

2.injected sporozoites migrate to liver; sporozoites enter liver cells, multiply, and emerge as merozoites

3. merozoites enter red blood cells and destroy them

4. mosquito ingests gametocytes with blood meal

____ from mosquitos are not affected by drugs

sporozoites

What is the term for asexual multiplication that malaria undergoes in the liver

Exoerythrocytic schizogeny

Schizonts mature and release _____ into the blood

merozoites

Dormant schizonts must be treated with

primaquine

What is the term for the multiplication that malaria undergoes in the RBCs

erythrocytic schizogeny

Most antimalarial drugs prevent replication during what stage?

Erythrocytic schizogeny

What are the three forms of malaria therapy?

Suppressive (prophylactic), treatment of acute attack, prevention of relapse

What must be confirmed before drug treatment of malaria?

diagnosis

Which malaria infections are most severe?

P. falciparum

___ and ___ are species of malaria that can persist in the liver and cause relapses

P. vivax and P. ovale

What is the prophylactic rx given pre-travel for malaria

Chloroquine 500 mg once per week started 1-2 weeks before travel

What is the adult dose of chloroquine given for active erythrocytic stage malaria

Treatment: 1 g once, then 500 mg at 6 h, 24 h and 48 h

What are the adverse effects of chloroquine

Nausea, abdominal pain, headache, visual disturbances

Quinine sulfate is derived from the bark of the

cinchona tree in south america

What is the 1st line agent used for malaria in chloroquine resistant straints

quinine sulfate

Does quinine sulfate have a short or long half life

short

What is the dose given for quinine sulfate

Quinine sulfate 650 mg TID x 3-7 days

Quinine sulfate can be used in combination with what abx depending on the region

Doxycycline, tetracycline, or clindamycin for 3 to 7 days

What are the adverse effects of quinine sulfate

•GI symptoms: nausea, vomiting, diarrhea

•Cinchonism: tinnitus, vertigo, deafness, headache, and dysphoria

•Hypoglycemia

What is blackwater fever

QUININE SULFATE causes possible hypersensitivity reaction causing massive hemolysis, hemoglobinemia, and hemoglobinuria

What cocktail was originally developed in British colonial india to hide the bitter taste of quinine

Gin and tonic

Are quinine products still on the market?

Taken off market in 2007 and only used for malaria now

Quinidine gluconate is a _____ of quinine

stereoisomer

What drug is used for severe, life threatening malaria

quinidine gluconate

What form is quinidine gluconate administered in?

parenteral

What is quinidine gluconate given with (same as quinine sulfate)?

doxycycline, tetracycline, clindamycin

What is the risk of quinidine gluconate from a cardiac perspective

Class 1a antiarrhythmic agent: need cardiac monitoring because of proarrhythmias

Quinidine gluconate is a potent inhibitor of ____ enzyme

CYP 2D6 (many drug interactions)

What is the drug of choice for patients with malaria requiring parenteral therapy?

artesunate IV

Artesunate IV is a derivative of the herbal artemisinin which is extracted from the ____ plant

wormwood plant

Artesunate IV is more effective than ____ and safer than _____

>effective than quinine

>safer than quinidine

what is the adverse effect of artesunate IV

hemolytic anemia

Artesunate IV is followed by the oral combination drug

Coartem

What are the drugs used for the erythrocytic stage of malaria

Cloroquine

Quinine sulfate

Quinidine gluconate

Artesunate IV

Malarone

Coartem

Mefloquine

Malarone is a combination of

atovaquone and proguanil

What is the 1st line agent for both prophylaxis and tx against chloroquine resistant plasmodia

Malarone

What is the dosage for Malarone

single dose w/ meals x3 days

What are the adverse effects of malarone

nausea, vomiting, rash, and headache

Coartem is a combination of

artemether and lumenfantrine

What is the first line treatment of chloroquine resistant plasmodia

Coartem

What is the dosage info for Coartem

twice daily w/ meals for 3 days

What are the adverse SE's for Coartem

n/v, headache, dizziness, weakness

Coartem can cause what cardiac related SE

prolonged QT interval

What should you AVOID when taking Coartem

CYP 3A4 inhibitor drugs

What antibiotic can be an alternative for prophylactic treatment against chloroquine resistant plasmodia

Doxycycline (100 mg daily 1-2 days before travel)

Mefloquine can be used for

prophylaxis and treatment of chloroquine-resistant Plasmodia

What is the half life of mefloquine

20 days

What are the adverse SE's of mefloquine

neuropsychiatric syndrome (depression, psychosis, and seizures) makes this a 2nd line agent for treatment

What 2 drugs does mefloquine interact with

quinine and beta blockers (lead to cardiac arrest)

Which antimalarial drug is used very frequently in the military

Mefloquine

Primaquine is a drug that works during the ____ stage

extra-erythrocytic

What is the only drug that prevents relapse from P. vivax and P. ovale

Primaquine

What is the dose given for primaquine

15 mg/day x14 days

You should use primaquine with either ____ or ____

chloroquine or quinine

What are the adverse effects of primaquine

abdominal cramps, nausea, hemolytic anemia 2nd to G6PD deficiency

Before using primaquine you must screen for

G6PD deficiency

G6PD deficiency

X-linked recessive trait resulting in hemolytic anemia

Entamoeba histolytica is caused by

Ingestion of cysts in contaminated food and water

What systemic symptoms can amebiasis cause

•Ulceration of the bowel and amebic dysentery

•Liver abscesses from entry through the portal vein

What are the two broad categories of amebicides used

luminal and tissue

Luminal amebicides are

poorly absorbed drugs used to treat asymptomatic disease

What are the 2 luminal amebicides we should know

•Iodoquinol - take with meals to limit GI toxicity

•Paromomycin - an aminoglycoside

Tissue amebicides are drugs of choice for _____ disease

invasive

What are the 2 tissue amebicides we should know

•Metronidazole (Flagyl) 750mg po tid x 10 days

•Tinidazole (Tindamax) 2 gm po qd x 3 days

Metronidazole is well absorbed from the ____ and widely distributed to most tissues including the brain

GI tract

What is the half life of metronidazole

8 hours (excreted in urine)

Metronidazole undergoes an intracellular conversion to toxic _____ by process unique to _____ bacteria and protozoans. This results in cell death by destruction of _____.

nitro radical

anaerobic bacteria

DNA

Metronidazole is active against protozoa causing what 3 diseases we've learned about?

amebiasis, giardiasis, trichimoniasis

Metronidazole is also active against most anaerobic bacteria including:

Bacteroides fragilis, Clostridia difficile, and Peptostreptococcus

Metronidazole is contraindicated in what portion of pregnancy

during 1st trimester

Considered a category B drug in 2-3rd trimesters

What are the adverse effects of metronidazole

Nausea, headache, dry mouth, metallic taste

Metronidazole should be taken with

food to minimize GI effects

Name two drugs that metronidazole interacts with

Warfarin and ethanol

When warfarin is taken with metronidazole, what can occur?

increase in INR (bleeding risk)

When ethanol is taken with metronidazole, what can occur?

acetaldehyde poisoning resulting in flushing, nausea, vomiting, and throbbing headache (metronidazole inactivates aldehyde dehydrogenase enzyme necessary for metab of acetaldehyde)

Tinidazole is a ____ generation nitroimidazole

2nd gen

What are 3 advantages of Tinidazole over metronidazole (hint: what is it active against, half-life, Giardia use)

•Active against some metronidazole-resistant strains of Trichomonas

•Longer half-life allows single daily dosing

•Can use single dose against Giardia

Tinidazole has the same adverse effect profile as

metronidazole

Tinidazole is a category ____ drug in pregnancy

C

What are the two treatments used for Giardiasis

•Metronidazole 250mg tid x 7days

•Tinidazole - single dose of 2 gm

What is the treatment used for Trichomoniasis

Metronidazole or tinidazole 2 gm x 1 dose

What is the treatment for Toxoplasmosis

pyrimethamine + sulfadiazine

Pyrimethamine and sulfadiazine are potent inhibitors of _____ reductase and can induce ____ deficiency

dihydrofolate, folate

Nematodes are also called

round worms

Ascariasis

giant round worm

Trematodes are

flukes

what is the 2nd leading cause of morbidity from parasitic diseases

Schistosomiasis (snail vector)

Cestodes are

tapeworms

How does one acquire tapeworms

pork, beef, fish tapeworms

What is the drug of choice for nematode infections

albendazole

Albendazole inhibits _____ function and depletes ____ stores leading to worm death

microtubules, glycogen

albendazole should be avoided during the ___ trimester

1st