ANTIPROTOZOAL AGENTS

Question 1

This disease are highly prevalent in tropical third world countries

Answer 1

Antiprotozoal Agents

Question 2

The common protozoal diseases:

Answer 2

-malaria
-amebiasis
-giardiasis
-trichomoniasis, toxoplasmosis & as a direct consequence of the AIDS
epidemic, pneumocystis carinii pneumonia

Question 3

Entamoeba
histolytica

Answer 3

Amebiasis

Question 4

Balantidium coli

Answer 4

Balantidiasis

Question 5

Giardia lamblia

Answer 5

Giardiasis

Question 6

Cryptosporidium
spp

Answer 6

Cryptosporidiosis

Question 7

Trichomonas vaginalis

Answer 7

Trichomoniasis

Question 8

Genital infection

Answer 8

Trichomoniasis

Question 9

Pneumocystis carinii
(opportunistic pathogen)

Answer 9

Pneumocystis carinii
pneumonia

Question 10

Best known for causing blindness in neonates

Answer 10

Toxoplasmosis

Question 11

Leishmania donovani

Answer 11

Lieshmaniasis

Question 12

2-methyl-5-nitroimidazole-1-ethanol

Answer 12

Metronidazole (Flagyl)

Question 13

-Most useful of a group of antiprotozoal nitroimidazole derivatives

-First marketed for topical tx Trichomonas vaginalis vaginitis; effective
orally against both acute & carrier states of disease

-Possess amebicidal activity; effective against both intestinal & hepatic
amebiasis

-Also use in the tx for giardiasis & balantidiasi

Answer 13

Metronidazole (Flagyl)

Question 14

Because of its bactericidal action, it has become an important agent
for treatment of serious infections (septicemia, pneumonia,
peritonitis, pelvic infections, abscesses, meningitis) caused by anaerobic bacteria

Answer 14

Metronidazole

Question 15

Effective against obligate anaerobic bacteria but ineffective against
facultative anaerobes or obligate aerobes

Answer 15

Metronidazole

Question 16

Despite its low water solubility, it is well absorbed following oral administration

Answer 16

Metronidazole

Question 17

Is administeres parenterally only via slow infusion

Answer 17

Metronidazole

Question 18

are unsuitable for IV administration
because of their extreme acidity

Answer 18

Metronidazole

Question 19

-Possessed amebicidal activity in vitro
-Treatment of asymptomatic carriers of E. Histolytica
-Administered orally only as 500 mg tablets

Answer 19

Diloxanide Furoate

Question 20

For acute & chronic intestinal amebiasis but not effective in extraintestinal
disease

Answer 20

Lodoquinol

Question 21

Relatively high incidence of neuropathy occurs, so it should not be used
routinely for traveler’s diarrhea

Answer 21

Lodoquinol

Question 22

-Obtained by separation from extracts of ipecac
 Exert direct amebicidal action on various forms of E. Histolytica

-Protoplasmic poisons that inhibit protein synthesis in protozoal &
mammalian cells by preventing protein elongation

-Used only in combination w/ other agents because their effect in intestinal
amebiasis is solely symptomatic & cure rate only 10%-15%

-Toxic effect limit its usefulness

Answer 22

Emetine & Dehydroemetine

Question 23

Causes high frequency of GI distress (nausea & diarrhea), cardiovascular
effects (hypotension & arrhythmia) & neuromuscular effects (pain &
weakness)

Answer 23

Emetine & Dehydroemetine

Question 24

Lower incidence of cardiotoxicity w/ dehydroemetine

Answer 24

Emetine & Dehydroemetine

Question 25

-Treatment of pneumonia caused by opportunistic pathogenic protozoan P. Carinii, a frequent secondary invader associated w/ AIDS -Administered by slow IV infusion or by deep IM injection for PCP -Aerosol form – used by inhalation for prevention of PCP in high-risk patients infected w/ HIV -Both inhalant & parenteral dosage forms are sterile lyophilized powders that must be made up as sterile aqueous solutions prior to use. -Sterile water for injection must be used to reconstitute the aerosol, to avoid precipitation of pentamidine salt

Answer 25

Pentamidine Isethionate

Question 26

Cough & bronchospasm

Answer 26

Inhalation

Question 27

Hypertension & hypoglycemia

Answer 27

Injection

Question 28

-Prophylaxis and treatment of African trypanosomiasis -Also for treating visceral leishmaniasis -Prophylactic agent – rapidly disappears from plasma after IV injection and is distributed to tissues, where it is stored for a long period.

Answer 28

Pentamidine Isethionate (NebuPent®)

Question 29

-Highly lipophilic, water-insoluble analog of ubiquinone 6, an essential component of mitochondrial electron transport chain in microorganisms -Act as an antimetabolite for ubiquinone, thus interfere w/ function of electron transport enzymes -Originally developed as antimalarial drug but Plasmodium falciparum developed rapid tolerance to its action

Answer 29

Atovaquone (Mepron)

Question 30

-Recommended alternative to TMP-SMX for tx & prophylaxis of PCP in patients intolerant to this combination -Effective in eradicating T. Gondii in preclinical animal studies -Slow & incomplete oral absorption because of low water solubility of drug -Aqueous suspensions have better absorption than tablets -Food (esp. high fat content) increases absorption

Answer 30

Atovaquone

Question 31

Half life of Atovaquone is

Answer 31

62 to 80 hours

Question 32

Side effects of Atovaquone

Answer 32

GI intolerance

Question 33

-Treatment of West African sleeping sickness (Trypanosoma brucei / gambiense) -Indicated for meningoencephalitic stage of disease -Myelosuppressive drug that causes high incidences of anemia, leukopenia, thrombocytopenia -Monitor CBC during course of therapy -Irreversible inactivation of ornithine decarboxylase by eflornithine is accompanied by decarboxylation & release of fluoride ion from inhibitor, suggesting enzymecatalyzed activation of inhibitor -Administered either IV or orally -Penetration into CSF is facilitated by inflammation of meninges

Answer 33

Elfornithine

Question 34

-In addition to their antibacterial & antifungal properties, also have antiprotozoal activity w/c led to discovery of particular nitrofurans w/ antitrypanosomal activity -Effective against T. cruzi (South American) -Only clinically proven treatment for both acute and chronic forms of disease -Administered orally -Oral bioavailability is high but first-pass metabolism occurs - Half-life: 2-4 hrs -High incidence of n&v, abdominal pain & anorexia

Answer 34

Nifurtimox

Question 35

-Nitroimidazole derivative -Treament of Chagas disease -Effectiveness similar to that of nifurtimox -Therapy w/ oral benznidazole requires several weeks -A/E: peripheral neuropathy, bone marrow depression, allergic-type reactions

Answer 35

Benznidazole (Radanil®, Rochagan®

Question 36

-Prepared by reduction of corresponding pentavalent arsanilate to the trivalent arsenoxide followed by reaction of latter w/ BAL -DOC for treatment of later stages of both forms of African trypanosomiasis -Advantage: excellent penetration into CNS, thus effective against meningoencephalitic forms of T. gambiense & T. Rhodesiense -Trivalent arsenicals tend to be more toxic to host than corresponding pentavalent compounds -Shares toxic properties of other arsenicals, so its use must be monitored for signs of arsenic toxicity

Answer 36

Melarsopol

Question 37

-Pentavalent antimonial compound - Treatment of various forms of leishmaniasis -10% aqueous solution used for either IM or IV injection has pH of approximately 5.5 -Low therapeutic index, thus monitor carefully for signs of heavy metal poisoning - Antileishmanial action requires its reduction to trivalent form, w/c is believed to inhibit phosphofructokinase in parasite

Answer 37

Sodium Stibogluconate

Question 38

-2,3-Dimercapto-1-propanol, BAL, dithioglycerol - Developed by British during WWII as antidote for “Lewisite”, hence the name British anti-Lewisite - Effective topically & systematically as antidote for poisoning caused by arsenic, antimony, mercury, gold & lead -Antidotal properties are associated w/ property of heavy metals to react w/ sulfhydryl groups in proteins & interfere w/ their normal function - Topically as ointment or IM as 5% or 10% sol’n in peanut oil

Answer 38

Dimercaprol

Question 39

-High-molecular-weight bisurea derivative containing 6 sulfonic acid groups as their sodium salts - Developed in Germany after WWI as byproduct of research efforts directed toward development of potential antiparasitic agents from dyestuffs -Treatment of early cases of trypanosomiasis - Long-term prophylactic agent (effectiveness after single IV injection maintained up to 3 months) - Tissue penetration of drug does not occur bec. of its high molecular weight & highly ionic character. - Thus, injected dose remains in plasma for very long period -Prophylaxis of onchocerciasis

Answer 39

Suramin Sodium