This document summarizes various antiparasitic agents used to treat protozoal infections. It discusses the classification, mechanisms of action, administration, pharmacokinetics, side effects, drug interactions, and uses of different classes of drugs including nitroimidazoles, artemisinins, quinine, mefloquine, and halofantrine for treating diseases caused by protozoa such as Entamoeba histolytica, Plasmodium spp., Giardia lamblia, and Trypanosoma spp. The agents described target various protozoa that infect the intestinal tract, blood, and tissues.

1. ANTIPROTOZOAL AGENTS

2. PROTOZOA
(single celled, eukaryotes)
INTESTINAL
♦ E. histolytica [Amebiasis, liver
abscess]
♦ G. lamblia [Giardiasis]
♦ Cryptosporidium sp [Crytosporidiosis]
♦ Balantidium coli [Dysentery]
♦ Isospora belli [Isosporosis]
Urogenital tract (men and women)
♦ T. vaginalis [Trichomoniasis]
BLOOD AND TISSUE
♦ Plasmodium sp [Malaria]
♦ Trypanosoma sp [Trypanosomiasis]
T. cruzi [Chagas’ disease]
T. gambiense [sleeping sickness]
T. rhodensiense [sleeping sickness]
♦ Leishmania sp [Leishmaniasis]
Visceral (Kala-azar)
Cutaneous (old world)
Cutaneous (new world)
Mucocutaneous
♦ Toxoplasma gondii [Toxoplamosis]
♦ Naegleria sp [Meningoencephalitis]
♦ Acanthamoeba [Meningoencephalitis]
♦ Babesia microti [Babesiosis]
NB. ♦ Pneumocystis jirovecii
Pneumonia
Not a protozoa but a fungi but some
behaviors like that of protozoa e.g.
response to treatment

3. AMOEBIASIS (E. HISTOLYTICA)
►Trophozoites and cysts
► Trophozoites can
(i) Live in lumen
(ii) Invade colon epithelium – ulceration
(iii) Spread to other organs/tissues e.g. liver
Trophozoites can simply live on gut bacteria – addition of a
broadspectrum antiobiotic, e.g. a Tetracycline can lead
to rapid improvement as the parasites major food
source is depleted
Range of illness/symptoms
(i) Asymptomatic carrier
(ii) Mild intestinal infection - diarrhea
(iii) Severe intestinal infection - dysentery
(iv) Amoebic liver hepatitis and abscess
(V) Amoeboma & extraintestinal infection

5. ANTI-AMOEBIC AGENTS
Classification – based on global site of action
Luminal
1. The amides - Diloxanide furoate, Etofamide, teclozan
2. Iodoquinol, clioquinol (Halogenated hydroxyquinolines)
3. Antibacterials- Tetracyclines, Paramomycin, Erythromycin
Extra luminal /Tissue
1. Chloroquine
2. Emetine, dehydroemetine (Alkaloids)- restricted use ‘coz of
toxicity on almost all tissues
(Both) Luminal and Tissue
Nitroimidazoles – Metronidazole, tinidazole, secnidazole

6. 1. The AMIDES - diloxanide furoate, etofamide, teclozan
Mxn: not clear, amebicidal
-Split in the GIT to diloxanide and furoic acid,
Adm; oral
Abs: most of diloxanide is absorbed (90%) what is left is still
effective
Elimination: metabolized then renal excretion
S/e
♦ Flatulence
♦ Dry mouth
♦ Nausea, abdominal cramps
♦ Pruritus, urticaria
♦ Avoid in pregnancy and young children (<2yrs)
Uses
Luminal amoebiasis (rx asymptomatic or along w. Tissue
amebicide to eradicate infection)

7. 2. PARAMOMYCIN Sulphate (an aminoglycoside)
Mxn: (i) directly amoebicidal: interferes w/ cell membrane to cause
leakage
(ii) antibacterial – reduces food source for trophozoites
Adm: oral
Abs; insignificant
S/E
♦ GIT irritation, diarrhea
Caution
♦ Persons with GIT ulcers
♦ Persons with renal dysfxn (the little abs can accumulate)
Uses
1. Mild to moderate intestinal (Luminal) amoebiasis
2. Giardiasis
3. Leishmaniasis
4. Tapeworm infestation (not DOC)

8. 3. Halogenated hydroxyquinolines - IODOQUINOL and clioquinol
Mxn: unclear, Directly amoebicidal (trophozoite, cyst) in lumen
Adm: oral Abs: poor (10%)
S/E
♦ GIT distress - (take w/ meals)
♦ Allergic rxn (skin)
♦ Goitre
♦ Neurotoxic e.g. optic atrophy (limits its use), peripheral neuropathy
D/I
♦ Increases protein binding of iodine, ↓ iodine uptake by thyroid
C/I
♦ In persons intolerant to iodine
♦ Caution in renal impairment, optic neuropathy or thyroid disease, or
hepatic disease (non amoebic)
Uses (2nd
line) :
1. Luminal amebicide (add metronidazole for systemic infection)
2. Superficial fungal infections e.g. Tinea pedis
3. Trichomonal vaginitis (as inserts)
4. Balantidium coli

9. 4. NITROIMIDAZOLES – Metronidazole, tinidazole,
secnidazole, Ornidazole, nimorazole, etc
Mxn: reduced by the parasite/bacteria to metabolites that are
toxic to DNA and proteins – cell death (trophozoites only)
Adm: oral, parenteral
Distributn: widely into all tissues (including CNS, saliva, breast
milk)
Elimination: Metabolized (NB.liver failure) then renal excretion
S/E
♦ Metallic (unpleasant) taste in the mouth
♦ Monoliasis (furry tongue), glossitis, stomatitis
♦ Sig. GIT irritation –take w/ food
♦ Disulfiram-like rxn w/ alcohol
♦ Neurotoxic - (esp w/ parenteral)
♦ Mutagenic (in bacteria) and tumorigenic in mice – best
avoided in pregnancy

10. 4. Nitroimidazoles – Metronidazole, tinidazole
D/I
♦ Potentiates - oral anticoagulants (warfarin)
♦ Enzyme inducers e.g. Phenytoin and phenobarb increase
metronidazole elimination
♦ Enzyme inhibitors e.g. Cimetidine decreases its elimination
Uses (Metronidazole and members)
1. DOC for all extra-intestinal amoebiasis e.g. liver abscess and
amoebic dysentery (w/ a luminal agent for eradication of infection)
2. DOC for giardiasis
3. DOC for trichomoniasis
4. Anaerobic bacteria (e.g. C. difficile, B. fragilis,
Peptostreptococcus)
5. Balantidium coli (alternative)
6. Drucunculiasis
5. CHLOROQUINE
Uses:
1. Extra-intestinal amebiasis (along w/ metronidazole and diloxanide)
2. Sensitive malarial parasites

11. 6. EMETINE (natural alkaloid) & DIHYDROEMETINE (synthetic analogue)
Mxn: Inhibits protein synthesis
Adm: under observation- parenteral (SC or IM NEVER IV)
(erratic GIT abs)
Serious S/E
●Cardiotoxic - arrhythmias, hypotension, CHF
C/I
● Heart disease ● Renal failure
●Children ● Pregnancy
Uses: where no better alternatives
1. Extra–intestinal amebiasis
2. Fasciola hepatica (alternative)
3. Paragonimus westermani

12. NITAZOXANIDE
Mxn: a prodrug converted to tizoxanide the active drug,
inhibits an oxidoreductase enzyme involved in anaerobic
metabolism
Spectrum; G. Lamblia, Cryptosporidium parvum, E.
Histolytica, H.pylori
P’kinetics: oral; rapidly hydrolyzed to tizoxanide
A/E: GIT abdominal pain, vomiting, headache, nausea and
diarrhea.
Uses: Cryptosporidiosis
Others:
Named antibacterials act only by decreasing lumen
bacterial population- food source for trophozoites

13. GIARDIASIS –
♦ Metronidazole / tinidazole
♦ Mepacrine/quinacrine
♦ Paramomycin (pregnancy)
TRICHOMONIASIS -
♦ Tinidazole (DOC)
♦ Metronidazole
Less common intestinal & tissue
protozoa
CRYPTOSPORIDIOSIS
(usually self limiting in the
immunocompetent)
♦ Spiramycin, Azithromycin
♦ Paramomycin ♦Nitazoxanide
BALANTIDIUM COLI
♦ Tetracycline
♦ Metronidazole
♦ Iodoquinol
ISOSPORA BELLI
♦ Co-trimoxazole
♦ Pyrimethamine (supplement folic
acid)
TOXOPLASMOSIS
♦ Cotrimoxazole
♦ Pyrimethamine+Sulphadiazine
♦ Pyrimethamine+clindamycin
♦ Pyrimethamine+azithromycin
♦ Pyrimethamine+atavaquone
BABESIOSIS
Quinine + clindamycin

15. Various ways of classifying
A) Based on chemical structure
i) Sesquiterpenes (endoperoxides) e.g. Artemisinin
ii) Quinoline methanols (Cinchona alkaloids) e.g. quinine
iii) Quinoline-methanols (synthetic) e.g. mefloquine
iv) Phenanthrene methanols e.g. halofantrine
v) 4-aminoquinolines e.g. amodiaquine, chloroquine (CQ)
vi) 8-aminoquinolinese.g. Primaquine
vii) Diaminopyrimidines e.g. pyrimethamine, trimethoprim
viii) Biguanides e.g. Proguanil
ix) Antibacterials e.g. Sulphonamides, tetracylines, lincomycins
x) Acridine dyes e.g. quinacrine

16. B) Based on stage of plasmodial parasite affected and
rapidity of effect – provide clinical cure by eradicating
erythrocytic stages
i) Rapid blood schizonticides e.g. Artemisinin, quinine,
chloroquine, amodiaquine, mefloquine, halofantrine
ii) Slow blood shizonticides e.g. Pyrimethamine, Proguanil, the
antibiotics
iii) Tissue schizonticides e.g. primaquine
iv) Gametocides e.g. Primaquine, artemisinin, chloroquine
C) Suppressive Prophylactic agents e.g. Mefloquine,
proguanil, doxycycline, Atavaquone-proguanil, primaquine
True Causal prophylaxis – preventing the ‘cause’ from infecting
any human cell – before 1° infection of the liver

17. Malaria
1. ARTEMISININ and its derivatives
♦ Artemisinin – water insoluble, ltd to oral use
♦ Artesunate – water soluble, oral, IV, IM, rectal
♦ Artemether – lipid soluble - oral, IM, rectal
♦ Arteether, Artelinic acid
Uses:
♦ Increasingly the DOC for P. falciparum
♦ Quinine resistant P. falciparum
Mxn: Fast acting blood schizonticide on all species
♦ The endoperoxide ring is cleaved w/in parasite to release
free radicals that damage the parasite

18. 1. ARTEMISININ and its derivatives
Abs; rapid
Elimination: metabolized to active drug - dihydroartemisinin
♦ Short t1/2 - (leads to high recrudescence rate, best co-
adm with other drugs)
i.e. Artemisinin-based combination Therapy - ACT)
e.g. lumefantrine, fansidar, doxycycline
amodiaquine
S/E (fairly well tolerated)
♦ GIT disturbance (nausea, vomiting, diarrhea)
♦ Teratogenic in high doses (so far only in animals)
♦ Cardiac conduction defects
P/C: ♦ 1st
trim Pregnancy,
♦ Lumefantrine: those on previous halofantrine
♦ Cardiac dse

19. 2. QUININE, QUINIDINE
Mxn: - Actual mxn not clear
- rapid blood schizonticide against all 4 sp
♦ NOT active against liver stages
♦ Other P’cological effects
i) curare-like effect (use on leg cramps)
ii) oxytoxic effect – esp with advanced pregnancy
iii) local irritant action – site of adm
iv) mild analgesic and antipyretic effect
Adm: oral, parenteral
Abs: rapid, impaired by Al3+
containing antacids
Distribution: wide, protein- bound, (give a loading dose to
achieve peak levels soonest)
Elimination: Quinidine shorter t1/2
Metabolized, renal excretion

20. S/E
1. Cinchonism –Tinnitus, impaired hearing, visual
disturbance, dizziness, headache, nausea, flushed skin
Serious S/E
2. Audio-visual disturbance
3. GIT irritation – abdominal pain, vomiting, diarrhea
4. Hypersensitivity rxns – e.g. urticaria, bronchocospasm,
angioedima, (some hematological, below)
5. Hematological abnormalities –
● Thrombophlebitis at site of infusion
6. Hypoglycemia (stimulates insulin release, most felt by
pregnant patients)
7. GIT irritation –pain, vomiting, diarrhea
8. Uterine contractions in pregnancy (esp 3rd trimester) –
still DOC for severe falciparum but observe patient
9. Hypotension – with rapid infusion
10. ECG changes

21. 2. Quinine:
Precautions/ avoid:
♦ If severe cinchonism occurs (discontinue therapy)
♦ Auditory or visual problems
♦ Cardiac abnormalities
♦ Patients who have recently received mefloquine
♦ Hypersensitivity rxns - hemolysis
D/I
♦ Mefloquine (increases its toxicity) – do not co-administer
♦ Warfarin and Digoxin – quinine raises their plasma conc.
Uses:
1. Severe falciparum malaria (DOC, parenteral)
often combined w/ another drug (fansidar, doxycycline) to
shorten duration of Rx and limit toxicity.
2. Babesiosis (Babesia microti) DOC in combination w/
clindamycin

22. 3. MEFLOQUINE
Mxn: unclear
Blood schizonticide (NOT gametocytes or liver stages)
Resistance: not common in E. Africa
●Associated w/ resistance to quinine and halofantrine but
not CQ
Adm: oral only (severe local irritation with parenteral use)
Abs: good, slow
Distribution: extensively in tissues
Elimination: t1/2- long
● Some metabolism, Biliary excretion mainly
S/E
● GIT irritation
● Sleep disorders
● Neuropsychiatric disturbance, discontinue if serious
● Hepatic damage (mild)
● Cardiac (conduction) defects – arrhythmias, bradycardia

23. 3. MEFLOQUINE
C/I – presence or Hx of
1. Cardiac conduction defects, use of cardiotoxic drugs
2. Epilepsy
3. Neuropsychiatric disorders
4. Hypersensitivity (to related drugs)
5. Quinine, quinidine or halofantrine (do not co-adm)
6. 1st
trimester of pregnancy
(NB can use in pregnancy 2nd
, 3rd
trimester – as last option)
Uses:
1.Chemoprophylaxis (all 4 sp) (CQ preferred in areas
where it is still sensitive)
2. Rx of falciparum malarial infection – not DOC, not
recommended

24. 4. HALOFANTRINE
Mxn: not clear
Rapid blood schizonticide against all 4 sp (NOT gametes or hepatic
stages)
Resistance: cross resistance w/ mefloquine
Oral Abs: variable, enhanced with meals (esp fatty foods)- but take on
empty stomach to avoid high plasma conc. ass. w/ toxicities
S/E
♦ GIT irritation ♦ Headache, cough
♦ Pruritus, rash ♦ Mild hepatic damage (elevated liver
enzymes)
♦ Cardiac conduction defects – arrhythmias, death
dose – related, worsened by prior mefloquine therapy
♦ Embryotoxic in animals
C/I
♦ Persons w/ cardiac conduction defects
♦ Persons recently on mefloquine
♦ Use of other drugs that prolong Q-T interval
♦ Pregnancy & lactation
Uses:

25. 5. CHLOROQUINE (CQ) Synthetic, 4-aminoquinoline
Mxn: prevents polymerization of heme to hemozoin, heme
accumulates and is toxic to parasite
♦ Rapid blood schizonticide (v. effective on sensitive strains)
♦ Moderately effective on gametes of all except P.
falciparum
♦ Not effective against hepatic forms
Other p’cological effects
i) anti-inflammatory,
ii)Anti-amoebic
iii)Quinidine –like effect
Adm: oral, parenteral
Abs: rapid, almost complete, Ca2+
, Mg2+
antacids and Kaolin
interfere w/ abs.
Distribution: wide, sequestration in tissues - loading dose,

26. 5. CHLOROQUINE
S/E: fairly well tolerated (in small malarial doses) reduced by
taking after food
♦ Pruritus (esp in Africans), urticaria
♦ GIT irritation, anorexia
♦ Malaise
♦ Blurred vision
♦ Large or rapid parenteral adm – hypotension (severe),
respiratory and cardiac arrest (always infuse slowly)
Rare S/E
♦ Hemolysis (w/ G6PDH deficiency), agranulocytosis
♦ CNS disturbance –
♦ Impaired hearing
♦ Allergic rxn –
♦ Cardiac conduction defects
S/E -Long –term and high doses
♦ Irreversible ototoxicity, rethinopathy, myopathy, peripheral
neuropathy, CNS disturbance

27. 5. CHLOROQUINE
C/I
• Psoriasis, porphyria – it precipitates these diseases
• Visual& muscle disorders
• Caution in persons w/ Liver, hematological or neurologic
disorders
Uses:
1. Hepatic amebiasis (where Metronidazole has failed or is C/I)
+ a lumicide
2. Anti-inflammatory – rheumatoid arthritis, SLE etc –
alternative
3. Infection w/ Clonorchis sinensis, Fasciola hepatica,
Paragonimus spp, giardia spp
4a. Rx of Acute P. vivax, ovale, malariae infection (+ primaquine
for radical cure)
4b. Rx of sensitive forms ONLY of acute falciparum malaria –
•Advantages: Rapid clearance of parasitemia, cheap,
convenient regimen, few S/E
5.Suppressive Chemophrophylaxis –ONLY in areas w/out
resistance, (+ primaquine for radical cure)

28. 6. AMODIAQUINE (Similar to CQ in many ways)
Adm: oral
S/E •Agranulocytosis, hepatotoxic
Uses:
•Sensitive strains of malaria
•(don’t use for prophylaxis due to S/E)
7. ATAVAQUONE + proguanil = malarone - Still under study
Atavaquone
Adm: oral
Abs: erratic – improved by fatty food
Distribution: sig. protein binding
S/E
• GIT effects- nausea, vomiting diarrhea
• Fever, Headache, insomnia
• Rash
Uses
• Uncomplicated malaria and prophylaxis – combined w/ proguanil
• Alternative in P. jirovecii infection (not as efficacious as Co-
trimox)
• Toxoplasmosis

29. 8. PRIMAQUINE
Mxn: Molecular mxn not clear
Active against all hepatic stages (the only drug against
hypnozoites) but too toxic for causal prophylaxis
♦ Gametocytocidal to all 4 sp (prevents transmission - to
mosquitoes)
♦(schizonticidal power is too weak to be significant)
Adm: oral (NEVER give parenteral – severe hypotension)
S/E
♦ GIT distress -improved if taken w/ food
♦ Hemolysis and methemoglobinemia esp in G6PDH
deficiency
Serious
♦ Hematological abnormalities – leucopenia,agranulocytosis
♦ Cardiac arrhythmias

30. 8. PRIMAQUINE
C/I
♦ Those at risk of granulocytopenia, methemoglobinemia,
mylosuppression
♦ In pregnancy (just in case fetus is G6PDH deficient)
Uses:
1. Radical cure of P. vivax & P. ovale infections (add a
schizonticide too)
2. Terminal prophylaxis (after end of travel) to eradicate any
liver forms
3. May be used for causal prophylaxis of malaria (any sp)-
given before travel to endemic area (then it need not be
continued for long after return from endemic area
4. Alternative for mild Pnuemocystis jirovecii infection (along
w/ clindamycin)

31. 9. Sulphonamide-pyrimethamine (SP)
Pyrimethamine
Mxn: plasmodial dihyrofolate reductase inhibitor
Acts slowly against erythrocytic stage of all 4 sp.
Resistance: altered enzyme, increased enzyme synthesis
Adm: oral
Elimination: Extensive metabolism, t1/2 allows once a week
dosing
S/E (few)
♦ GIT irritation
♦ Rashes, itching
♦ Teratogenic in animals (but fansidar still used in
pregnancy)
NB. Always supplement folic acid if antifolates are used in
pregnancy)

32. 9. Sulphonamide-pyrimethamine (SP)
Pyrimethamine
Uses:
1. Acute attacks and suppression of Malaria (in combination)
(sensitive strains)
2. Toxoplasmosis (1st line - combined w/ sulfadiazine or
clindamycin and folic acid tabs) congenital, acute infection,
immunocompromized
FANSIDAR = SULPHADOXINE (500 mg) +
PYRIMETHAMINE (25 mg)
METAKELFIN = SULFALENE (500 mg) + PYRIMETHAMINE
(25 mg)
MALOPRIM = DAPSONE (100mg) + PYRIMETHAMINE
(12.5mg)
NB. Sulfonamides and sulfones – weak blood schizonticide,
must not be used alone but combined

33. 10. PROGUANIL (a biguanide)
Mxn: A dihydrofolate reductase inhibitor
♦ A prodrug – must be metabolized to cycloguanil
♦ Its activity as a blood schizonticide is slow
♦ not gametocidal
Abs; oral, adequate
Elimination: t1/2 – once daily dosing
S/E
♦ GIT irritation
♦ Skin rash
♦ Mouth ulcers
♦ Alopecia
♦ Headache, vertigo
Uses:
1. Prophylaxis of malaria – (alternative to mefloquine) in combination
w/ choloroquine (sensitive strain areas), (not acute attack)
NB it is safe in pregnancy

34. 11. Antibacterial antimalarials – schizonticides
E.g.Tetracycline and Doxycycline
♦ Are SLOW – never use alone for Rx (e.g .
used w/ quinine – to shorten course)
Uses:
1. Rx of falciparum malaria in conjuction w/ other
drugs e.g. quinine
2. Chemoprophylaxis of malaria (Doxy)
♦ Clindamycin – along w/ quinine (e.g. where tet is
not indicated - children)

35. TRYPANOSOMIASIS
♦ Objective of Rx is to clear blood, tissue and CSF of
parasite
♦ Available drugs are not that efficient and have serious
S/E
1. SURAMIN
Mxn: not established – may inhibit critical enzymes and
energy metabolism
Adm: IV
Distribution – does NOT enter CNS
Elimination: t1/2 - 50 days, Slow renal excretion

36. 1. SURAMIN
S/E; common severe
Immediate
♦ Minor; urticaria, harmless albuminuria (cloudy urine)
♦ Fatigue, vomiting
♦ Seizures, hypotension, shock, death
Later rxns
♦ Neuropathy, paresthesias, photophobia
♦ Renal damage
♦ Hematologic effects – hemolysis, agranulocytosis
Adrenal cortical damage
Uses:
♦ Early (hemolymphatic) stages of East African
trypanosomiasis (eflornithine is preferred for West African)
♦ Onchocerciasis
♦ Has been tried in some cancers e.g. prostate

37. 2. PENTAMIDINE (others – stilbamidine, propamidine)
Mxn: not clear
Adm: parenteral
Distribution: sequestered and accumulates in tissues (high
affinity) but NOT CNS, slow release back into circulation
Elimination: t1/2 – long
S/E (highly toxic, and common- 50%)
♦ CVS - Due to rapid IV – hypotension, arrhythmias,
dizziness, dyspnea
- IM adm – local pain and abscess
♦ Pancreatic toxicity – hypoglycemia (inappropriate release of
insulin, later hyperglycemia)
♦ Renal damage
♦ Liver damage
♦ Hematological disorders
♦ Neurological disorders
♦ Metallic taste etc

38. 2. PENTAMIDINE
D/I with other nephrotoxic drugs
Uses
1. Alternative (to Suramin) in early (hemolymphatic stages) of T.
rhodesiense (not gambiense)
2. Visceral leishmaniasis – Alternative to sodium stibogluconate
3. P. carinii infection: Alternative to Co-trimox
4. Acanthamoeba
3. MELARSOPROL, Tryparsanide – (arsenicals)
Mxn: binds sulfhydryl gps of proteins, selective uptake by parasite
Adm: slow IV (water soluble melarsoprol by IM), under hospital
supervision
Distribution: slow accumulation in the CNS
Elimination: rapid, fecal (but accumulates to effective conc. over days)

39. 3. MELARSOPROL
S/E (v. toxic)
♦ Fever, arthalgia, vomiting
♦ Reactive encephalopathy (rxn to byproducts of trypanosome death) –
♦ Renal damage
♦ Myocarditis
♦ Hypersensitivity
♦ thrombophlebitis
Uses
1. Advanced trypanosomiasis (CNS disease) - 1st line drug
2. Early trypanosomiasis (as alternative for patients who can not stand
suramin or pentamidine, its toxicity precludes use as a 1st
line agent)
3. Tryparsanide (pentavalent arsenical)- alternative for Gambiense (+
suramin) for those intolerant to melarsoprol

40. 4. EFLORNITHINE
Mxn: inhibits ornithine decarboxylase and prevents nucleic acid
synthesis
Adm: oral, IV
Distribution: effective CNS penetration
Elimination: renal excretion
S/E (most reversible, less toxic than melarsoprol)
♦ GIT disturbance – nausea, vomiting diarrhea
♦ Hematologic abnormalities – anemia, leucopenia,
thrombocytopenia
♦ Hair loss ♦ Seizures
♦ Hearing loss (ototoxicity) ♦ Teratogenic risk
Uses:
1. Advanced (CNS) & early West African trypanosomiasis
(scarce, expensive)

41. 5. NIFURTIMOX
Mxn: formation of radicals by parasite enzymes
Adm: oral
Abs: good
Elimination: metabolized
S/E (often reversible but contribute to non-completion of dose)
♦ GIT irritation
♦ Fever, restlessness, insomnia
♦ hypersensitivity rxns
♦ Neuropathies including seizures
Uses:
1. Acute Chaga’s disease (American trypanosomiasis) –
early stages, decreases symptoms and but does not fully
eradicate parasite, and does not prevent progression to GIT
and heart disorders) (not effective in chronic disease)

42. 6. BENZNIDAZOLE (a nitroimidazole)
Use: Acute chaga’s disease
S/E GIT disturbance
♦ Peripheral neuropathy
♦ Mylesuppression
♦ Rash (dermatitis)

43. LEISHMANIASIS
1. SODIUM STIBOGLUCONATE and Meglumine
antimonate (Pentavalent antimonials)
Mxn: is a prodrug, converted to the active trivalent
antimonial
- Actual mxn not clear – may inhibit glucose metabolism
Adm: parenteral (not abs orally)
Distribution: some sequestration
Elimination: renal excretion
S/E (toxicity increases w/ time on therapy)
♦ Pain at injection site
♦ GIT disturbance
♦ Pancreatitis
♦ Fever, headache, myalgias, arthralgias, rash
♦ Cardiac conduction defects
♦ Hepatic and renal damage (monitor their fxn
periodically)
♦ Hemolytic anemia

44. 1. SODIUM STIBOGLUCONATE and Meglumine
antimonate (Pentavalent antimonials)
C/I pancreatitis, hepatitis, mycocarditis
Uses:
1. Cutaneous leishmaniasis (1st line in areas w/
minimal resistance)
2. Visceral leishmaniasis (1st line)
Other antileishmanial agents
2. Amphotericin B
3. Pentamidine
4. Miltefosine
5. Paramomycin
6. Ketoconazole (L. mexicana not L. braziliensis)
7. Imiquimod cream - immune response modulator

45. MILTEFOSINE
Mxn; not clear probably via effects on cell-
signaling pathways and membrane
synthesis
Uses
Visceral leishmaniasis
Cutaneous metastases of breast cancer
C/I; Pregnancy

46. Intestinal nematodes
• Roundworm
• Hookworm
• strongyloides
• Pinworm
• Whipworm
• T.spiralis
Tissue nematodes (filaria)
• O. volvulus
• W. bancrofti
• B. malayi
• Loa loa
• D. medinensis (guinea
worm)
• Toxocara larva
(Roundworm) (visceral
larva migrans)
• Dog & cat hookworm –
cutaneous larva migrans
• T. spiralis larva
Cestodes (tapeworms)
• T. solium
• T. saginata
• D. latum
• E. granulosus
• H. nana (dwarf)
Trematodes (flukes)
• S. mansoni
• S. japonicum
• S. hematobium
• Fasciola hepatica (liver fluke)
• Clonorchis sinensis (liver fluke)
• Paragonimus westermani (lung fluke)
• Fasciolopsis buski (intestinal fluke)
COMMOM HELMINTHS

47. ANTIHELMITICS
Most are parasite specific thus one has to be fairly definite
about the parasite
1. BENZIMIDAZOLES
Albendazole, mebendazole, thiabendazole, triclabendazole
Spectrum: broad
Mxn: inhibit microtubule assembly and microtubule-
dependent glucose uptake; - parasite immobilized
Adm: oral
Abs: minimal for Meb and Alb (empty stomach, Fatty meals
increase), rapid for Thia. Triclabendazole -taken with food
to enhance absorption
Distribution: plasma conc. of albendazole is x100 that of
mebendazole
Elimination: rapid conjugation; Biliary & renal excretion

48. ANTIHELMITICS
1. BENZIMIDAZOLES
S/E (Short & long term)
-GIT irritation
-Rash
-Teratogenic and embryotoxic in animals (best avoided
in pregnancy)
-More toxic effects w/ Thia (CNS disturbance,
hypotension, erythema multiforme, Steven Johnsons
syndrome, dizziness, GIT)
Long term Albendazole-alopecia, leucopenia, eosinophilia,
pruritus
Uses (nematodes, few cestodes)
- Mebendazole: Hook, round, pin, whipworms
- Thia – strongyloidiasis, cutaneous larva migrans
- Triclabendazole — DOC for Fasciola hepatica

49. Uses of albendazole
1. Intestinal Nematode infestation
-Hookworm
-Round worms
-Pin/Threadworm
-Whipworm
-Threadworm - moderately effective NB. objective to cure to prevent
autoinfection
2. Hydatid disease – DOC, Rx (long- 3 months) and pre & post surgery
Rx; (+ praziquantel)
3. Neurocysticercosis – co-adm w/ a steroid, (steroids also increase
abs of albendazole)
(albendazole is C/I in the acute phase of cysticercotic encephalitis –
where steroids should be used)
4. Cutaneous larva migrans
5. Others - Trichinosis
Toxocariasis
Loiasis

50. 2. LEVAMISOLE
Mxn: Nicotinic action - continuous stimulation of muscle leading to blockage
and paralysis and expulsion
Adm: oral
Abs: rapid
Distribution: wide including CSF
Elimination: metabolized (to inactive cpds) renal elimination
S/E (Few w/ single doses)
♦ GIT irritation
♦ High conc. – nicotinic effects on mammalian autonomic ganglia
Uses: Round worms
3. PYRANTEL PAMOATE
Mxn: Depolarizing NMJ blocker, immobilizes parasite
Adm: oral
Abs: poor (intestinally active)
S/E
♦ GIT irritation (nausea, vomiting, diarrhea)
♦ Mild CNS –headache, insomnia, drowsiness
Uses:
1. Hook, round, pin worms

51. 4. PIPERAZINE
Mxn: inhibitor of neuromuscular transmission – Blocks Acetylcholine at
NMJ in nematode muscle- paralyzes parasite
Adm: oral
Abs: moderate
Elimination: part metabolized, part renal excretion
S/E
-GIT disturbance
-Allergic rxns: Urticaria, fever, bronchospasm,
-Mild neurotoxicity – dizziness, somnolence, paresthesia, vertigo,
incoordination, visual disturbance
C/I
-Persons with Hx of neurological disease esp epileptic seizures
-Persons w/ impaired hepatic or renal fxn
-Do not co-adminster w/ phenothiazines
-Avoid in pregnancy
Uses:
1. Round (single dose) and pin worms (lower multiple doses)
2. Rx of filariasis –(last option) often elicits rxn (skin, eye, systemic)
to parasite particles, severity varying with drug & intensity of
infection.

52. 5. IVERMECTIN
Mxn: binds and opens glutamate-gated chloride channels in invertebrate
nerve and muscle cells, increasing chloride conductance- then
hyperpolarization of the nerve or muscle cell, paralysis & death ffed by
elimination by reticuloendothelial system
-Microfilaricidal, embryotoxic
Adm: oral (on empty stomach)
Abs: rapid
Distribution: wide, slowly into eyes (NOT meninges)
Elimination: metabolism, biliary excretion
USES:
1. Onchocerciasis - DOC (co-adm a steroid w/ 1st Rx for eye infestation)
2. Strongyloidiasis - (aim always to cure)
- Repeat Rx in immunonusuppressed
3. Elephantiasis (2nd line, or combined w/ diethlycarbazine)
4. Others – not DOC
-B. malayi
-Cutaneous larva migrans
-Scabies and head lice
NB: in loiasis it induces a severe rxn if there is heavy load of parasite
(>3000/ml)

53. 5. IVERMECTIN
S/E
-Rashes, fever, headache, dizziness
-GIT irritation – nausea, vomiting, abdominal pain
-Myalgia, arthralgia
-Mazotti rxn (dying parasites – peaks on 2nd day, correlates w/ skin microfilaria
load, more frequent in non-residents persons and children, lessen w/
antihistamines and anti-inflammatory (aspirin) or steroids, they lessen
w/ subsequent dosing)
Features of mazotti rxn –
○CVS/lymphatic – hypotension (advice lying down), tachycardia,
lymphadenopathy, limb edema,
○ GIT effects,
○ CNS - headache, dizziness, somnolence,
○ Miscellaneous - rash, pruritus, myalgia, arthralgia
○ Bronchospasm,
○ Eye effects – ocular inflammation
Caution & C/I
-Avoid simultaneous use w/ other GABA agonists e.g. barbiturates,
benzodiazepines, valproic acid
-Avoid in pregnancy, breastfeeding and children < 5 yrs
-Avoid in those with impaired BBB – meningitis, African trypanosomiasis

54. 6. DIETHYLCARBAMAZINE - micro and macrofilaricide
Mxn: interferes with parasite surface structures making them more susceptible to
host immune mxns, immobilizes microfilaria,
Adm: oral
Abs: rapid
Distribution: into all tissues except fat
Elimination: Mainly renal excretion, some metabolism, (increased in acidic urine),
adjust dose with renal impairment or alkaline urine
S/E
-GIT irritation – nausea, vomiting, anorexia
-Headache, dizziness, malaise, sleepiness
- some s/e due to symbiotic parasite on the filarial worms (Wolbachia)
Uses
1. DOC in Rx (may also be used for prophylaxis)-
-W. bancrofti (elephatiasis)
-B. malayi
-Loa loa (loiasis)
2. Onchocerciasis – (2nd
line, microfilaricide) – adm under observation (Mazzoti rxn)
3. Mass Rx for W. bancrofti to reduce transmission (once wkly or monthly for 1 yr)
Caution: persons w/
♦ Hypertension, Renal disease
NB. Rx any malaria first (may exacerbate it)

55. 7. NICLOSAMIDE
Mxn: Inhibits oxidative phosphorylation (ATP syn), leads to death of
scoleces and segments (but not eggs), digested or expelled;
purge in T. solium
Adm: oral (chew, on empty stomach - best 2hrs before breakfast)
Abs: minimal
S/E
- GIT effects
- Headache, vertigo
- Rash, urticaria, pruritus ani (allergy to parasite parts
Caution:
- Avoid alcohol (up to 1 day after Rx)
- Avoid in pregnancy and children below 2 yrs (no drug tests done on
these gps)
Uses:
1. DOC in beef, pork (w/ purge) and fish tapeworms
2. Dwarf tapeworm (alternative to praziquantel) (must be given for long
(7 days) and effective only on intestinal lumen parasite and not those
lodged in villi
3. Alternative in intestinal flukes (e.g. Fasciolopsis buski)

56. 8. PRAZIQUANTEL
Mxn: increases cell membrane permeability to calcium leads to – vacuolization,
contraction, paralysis and dislodgment from host, death, immune defense is
essential
Adm: Oral (don’t chew, vomiting – regurgitation of T. solium segment is
dangerous)
Abs: rapid, increased with carbohydrate meal & cimetidine
Bioavailability reduced with some drugs – antiepileptics & corticosteroids
Distribution: wide including CSF, breast milk, NB. Protein binding,
Elimination: first pass metabolism (NB. liver dysfxn), renal, biliary excretion
S/E (due to drug - increase w/ dosage)
- Fever, headache, dizziness, drowsiness, lassitude
- GIT effects
- Rash, pruritus, urticaria
- Mild liver damage
- Effects of dying parasites - eosinophilia
rxn to dying parasite (antiemetics, analgesics, diuretics and anticoncvulsants)
– e.g. hydatid Rx
- Meningismus, mental changes, seizures, increased CSF fluid, intracranial
HPTn, arachnoiditis, hyperthermia,
NB steroids reduce the plasma conc. of praziquantel (upto 50 %)

57. 8. PRAZIQUANTEL
C/I
- Ocular cysticercosis –parasite degeneration → irreparable damage
- Avoid in pregnancy
- stop breastfeeding for 3 days after Rx
Uses: trematodes, cestodes (not active against F. hepatica)
1.Schistosomiasis – DOC for all forms
Use in early infection may lead to severe hypersensitivity rxn and also
young schistosomes (2-5 wks old) are not very insensitive to
praziquantel
2. H. nana - DOC
3. Taeniasis (saginata and solium w/ purge) and D. latum infections
NB. In cysticercosis endemic areas – best use a lower dose to minimize
rxns from any existing/ unknown cysticercosis
4. Neurocysticercosis – alternative to albendazole, to be adm under
supervision
5. Hydatid disease – added to albendazole (pre and post surgery – it
increases albendazole sulfoxide conc. and kills protoscoleces)

58. 9. METRIFONATE – active only on S. hematobium
Mxn: an organophosphate, a prodrug – active metabolite - dichlorvos
-Inhibits cholinesterase – paralysis of the parasite, detach from the
bladder, transported to lungs where they are trapped and killed by the
immune system
-Active against both mature and immature stages but not eggs
Adm: oral
Abs: ready
Distribution: well, wide
Elimination: metabolized to dichlorvos (active drug, forms only 1%)
S/E
- cholinergic symptoms (inhibition of cholinesterase (plasma and
erythrocyte) – e.g. bronchospasm, diarrhea, abdominal spasms
- CNS- dizziness, vertigo
- Sweating
C/I
- Avoid use of muscle relaxants, or in persons recently exposed to
organophosphates
- Avoid in pregnancy

59. 10. OXAMNIQUINE –acts only on S.mansoni
Mxn: unclear – causes detachment of parasites from venules (in the
mesentery) and relocation to liver, an unsuitable environment where
they die.
Active against mature and immature stages, but not cercaricidal
Adm: oral, take w/ food
Abs: ready
Distribution:
Elimination: t1/2 – 2.5 hrs. metabolized, renal excretion
S/E -fairly safe
- CNS effects – fever, headache, dizziness, drowsiness
- GIT effects –
-Urticaria, pruritus
-Orange discoloration of urine
(Uncommon)
- CNS- seizures, insomnia, amnesia (avoid activities requiring
attention), behavioral change, hallucinations
- Microhematuria, proteinuria

60. 10. OXAMNIQUINE
Effects due to dying parasite
- Liver damage
- Pulmonary infiltrates (cough)
Caution
- In patients w/ epilepsy (should be hospitalized)
- C/I in pregnancy
Uses:
1. S. mansoni infection – all stages (acute – katayama syndrome or
late – hepatosplenomegaly)
Other drugs (Schistosomes)
Bithionol – DOC for liver fluke (Fasciola hepatica), paragonimiasis,
Emetine and dehydroemetine – alternative for fascioliasis