Antiprotozoal And Anti-Helminthic Pharmacology

Front 1

Metronidazole (Flagyl)

Back 1

Indications/Spectrum
o Invasive Entamoeba histolytica
o Giardia lamblia
o Trichomonas vaginalis
MOA: Free radical damage to DNA causes cell death via parasite-specific
pyruvate:ferrodoxin oxidoreductase
Pharmaokinetics
o PO, IV
o Hepatic
o 3A4 interactions
ADEs
o Anorexia
o Nausea/vomiting/diarrhea
o Abdominal cramping
o Metallic taste
o Dizziness, vertigo
o Headache, paresthesia
o Disulfiram-like reaction

Front 2

Tinidazole (Tindamax)

Back 2

Indications/Spectrum
o Invasive E. histolytica
o G. lamblia
o T. vaginalis (Metronidazole-resistant)
MOA – same as metronidazole
Pharmacokinetics
o PO
o Renal
o Long t1/2 - Shorter regimen
o 3A4 interactions
ADEs
o Anorexia
o Nausea/vomiting

Front 3

Paromomycin (Humatin)

Back 3

Indications/Spectrum
o Intestinal E. histolytica
o Dientamoeba fragilis
o Crytosporidium parvum
MOA: interrupting protein synthesis through irreversible binding to 30S
ribosomal subunits
Pharmacokinetics
o PO with food
o Poorly absorbed
3
Major ADEs
o More common when high dose and/or long duration
o Cramping/abdominal pain
o Epigastric pain
o Nausea/Vomiting
o Steatorrhea
o Diarrhea

Front 4

Iodoquinol (Yodoxin)

Back 4

Indications/Spectrum
o Intestinal E. histolytica
o Use after systemic agent
MOA: Kills trophozoite and cystic forms of E. histolytica in the gut
Pharmacokinetics
o PO - poorly absorbed
o Avoid long-term use
Major ADEs
o Rash
o Diarrhea
o Dose-related peripheral neuropathy
o Discolored sweat, hair, and nails (iodine content)
o Pruritis
o Rarely: optic neuritis, blindness (dose-related)

Front 5

Dihydroemetine (Dametine) – CDC

Back 5

Indications/Spectrum
o Acute intestinal invasive E. histolytica
o Extra-intestinal amebiasis (i.e. liver abscess)
MOA
o Tissue-active amoebicide prepared from ipecac
o Inhibits protozoal protein synthesis through chain elongation
blockage
Pharmacokinetics
o IV
o Hepatic
o 5-day t 1/2
ADEs
o May precipitate heart failure
o Prolong ECG segments
o Hypotension in 25% of patients
o Diarrhea
o Nausea
o Injection site reactions
o Rarely: Transient paralysis and polyneuritis may last up to 2
months.

Front 6

Nitazoxanide (Alinia)

Back 6

Indications/Spectrum
o C. parvum
o G. lamblia
MOA: Interferance with parasitic pyruvate:ferrodoxin oxidoreductase
(PFOR)
Pharmacokinetics
o PO and suspension
o Hepatic
ADEs
o Mild and transient
o Abdominal pain
o Diarrhea
o Nausea/vomiting
o Headache
o Dizziness

Front 7

Sodium Stibogluconate (Pentostam – CDC)

Back 7

Indications/Spectrum
o Leismania brasiliensis (Mucocutanous leishmaniasis)
o L. donovani (kala-azar)
o L. tropica (Cutaneous)
MOA
o Pentavalent antimony prodrug
o M-chlorocresol, a preservative, interferes with glycolysis and fatty
acid oxidation in protozoal glycosomes
Pharmacokinetics
o IM or IV
o Hepatic
Major ADEs
o Myalgias/arthralgias
o Nausea/vomiting
o Abdominal pain
o HA
o ECG changes
o Hepatotoxicity

Front 8

Pentamidine (Pentam)

Back 8

Indications/Spectrum
o Leishmania spp.
o Trypanosoma spp.
o Pneumocystis jiroveci prophylaxis / treatment
MOA: Interferes with nucleic acid synthesis, uptake and function of
polyamines, phospholipids and proteins
Pharmacokinetics
o IM, IV, aerosolized
5
o Hepatic
o Poor CNS penetration
Major ADEs
o Reversible nephrotoxicity
o Hypotension (IV)
o Tachycardia (IV)
o Hypoglycemia
o Electrolyte imbalances
o Rash
o Dizziness

Front 9

Miltefosine (Impavido) – CDC

Back 9

Indications: Visceral cutaneous forms of Leishmania spp.
Pharmacokinetics: PO
Major ADEs
o Nausea
o Vomiting

Front 10

Eflornithine (Ornidyl)

Back 10

Indications: Neurologic stage of T. bruzei gambiense
MOA: Irreversible suicide inhibition of ornithine decarboxylase enzyme
Pharmacokinetics
o IV
o Topical (US) – upper lip hair bleacher
o Renally cleared
Major ADE
o Anemia, leukopenia, thrombocytopenia (dose-related)
o Eosinophilia
o Seizures (CNS penetration)
o Nausea/Vomiting/Diarrhea
o Hearing loss (cumulative dose - also reversible)

Front 11

Melarsoprol (Mel B) – CDC

Back 11

Indications: Neurological T. bruzei rhodesiense, T. bruzei gambiense
MOA
o Derived from trivalent arsenical agent
o Inactivates sulfhydryl groups to become trypanasomicide
Pharmacokinetics
o Slow IV injection
o Short t 1/2
o CNS penetration
ADEs
o Encephalopathy (often subsides) - 25% of patients
o Hypersensitivity reactions
o Nausea, vomiting
o Abdominal pain
o Contraindicated in influenza infection
o G6PD deficiency caution

Front 12

Suramin – CDC

Back 12

Indications: T. bruzei rhodesiense, (African Trypanosomiasis)
MOA: Inhibits sn-glycerol phosphate oxidase and glycerol 3-phosphate
dehydrogenase, leading to decreased ATP synthesis
Pharmacokinetics
o IV
o Hepatic (caution)
o Lacks CNS penetration
ADEs
o Fatal hypersensitivity rxns
o Fever, rash
o nausea, vomiting
o Loss of consciousness
o Bone marrow suppression
o Dose-related peripheral neuropathies
o Nephrotoxicity
o Adrenal insufficiency

Front 13

Nifurtimox (Lampit) – CDC

Back 13

Indications: Trypanosoma cruzi (American Trypanosomiasis, Chagas’
disease)
MOA
o Suppressive, not curative treatment
o Directly inhibits DNA biosynthesis though reduction to intracellular
oxygen radicals
Pharmacokinetics: PO
Major ADEs
o Dizziness
o Nausea, vomiting
o Rash

Front 14

Pyrimethamine (Daraprim)

Back 14

Indications/Spectrum
o Toxoplasma gondii - ONLY combined with sulfadiazine
o Chloroquine-resistant Plasmodia spp. – ONLY combined with
sulfadoxine (Fansidar)
MOA
o Inhibits parasitic dihydrofolate reductase
o Ten-fold greater potency than trimethoprim
Pharmacokinetics
o PO
o Long t 1/2
Major ADEs
7
o Bone marrow suppression (pancytopenia)
o Folinic acid given to prevent or reduce extent of suppression
o Caution G6PD deficiency

Front 15

Sulfadiazine or Sulfadoxine

Back 15

Indications/Spectrum
o Toxoplasma gondii combination treatment
o Chloroquine-resistant Plasmodia spp. Combination treatment /
prophylaxis
MOA
o Competitive inhibition of para-aminobenzoic acid (PABA)
o Interferes with folic acid synthesis
Pharmacokinetics
o PO
o Renal – caution in impairment
Major ADEs
o Hypersensitivity
o Hepatitis
o Blood dyscrasias
o Methemoglobinemia
o N/V/D
o Drug fever

Front 16

Atovaquone/proguanil (Malarone)

Back 16

Indications: Prophylaxis and treatment of malaria species
MOA: Atovaquone
o Selectively interferes with parasite mitochondrial electron transport
o Impairs fertilized gametes development in mosquito
MOA: Proguanil
o Inhibits DNA synthesis and depletes folate cofactors in blood
schizont forms
o No effect on extra-erythrocytic malarial forms
Pharmacokinetics
o PO
o Absorption increased with food or milky drink
Major ADEs
o Abdominal pain
o N/V/D
o HA
o Anorexia
o Dizziness

Front 17

Artesunate/lumefantrine

Back 17

Indication: Treatment of Plasmodia spp.
MOA
o Artesunate: Interact with heme metabolism, causing free radical
damage to parasite membranes
o Derived from qinghaosu plant, used to treat „fever‟ for millennia in
China
o Lumafantrine: Interferes with heme metabolism and parasitic
nucleic acid and protein synthesis
Pharmacokinetics
o IV, rectal, PO
o Rapidly acting
o Short t 1/2
Major ADEs
o Remarkably safe
o Nausea
o Vomiting
o Diarrhea
o LFT increases

Front 18

Quinine / Quinidine (Qualaquin)

Back 18

Indications: Chloroquine-resistant malaria treatment combined with
doxycycline or clindamycin
MOA
o Interferes with heme polymerization
o Kills intra-erythrocytic form of the parasite
Pharmacokinetics
o PO (quinine)
o IV (quinidine)
ADEs
o hemolytic anemia (G6PD)
o Arrhythmias, ECG changes, tachycardia syncope, TdP
o “Cinchonism” – nausea, vomiting, tinnitus, vertigo, deafness, shock
(rare)
o Rashes, lupus-like syndrome (both rare)
o OD: Dizziness, hypotension, respiratory arrest

Front 19

Chloroquine (Aralen)

Back 19

Indications
o Susceptible Plasmodia spp treatment
o Used in pregnancy
MOA
o Concentrates only in plasmodia found in erythrocytes
o Interferes with hemoglobin degradation by raising intravesicular pH
o Prevents parasitic polymerization of toxic heme compounds
9
Pharmacokinetics
o PO
Major ADEs
o ECG changes
o HA
o N/V
o Dose-related blurring of vision
o Rash
o Pigmentation changes
o Photosensitivity
o Bone marrow depression
o Reversible hearing loss

Front 20

Primaquine

Back 20

Indications/Spectrum
o Pre-erythrocytic and exoerythrocytic forms of Plasmodia spp.
o Tissue schizonticide, Gametocide
o ONLY combined with blood-active drug
MOA: Interferes with plasmodial DNA and mitochondrial function
Pharmacokinetics
o PO
o Take with meals for adequate absorption
ADEs
o Hemolytic anemia (G6PD - check before giving)
o Methemoglobinemia (rare)
o N/V/D
o Adbominal cramping

Front 21

Mefloquine (Lariam)

Back 21

Indications: Chloroquine resistant Malaria prophylaxis/treatment
Note: Mefloquine resistance – SE Asia
MOA
o Inhibits replication of asexual erythocytic parasites
o NO effect on gametocytes, OR on tissue stages of P. vivax and P.
ovale
Pharmacokinetics: PO
Major ADEs
o Suicidal ideation
o Forgetfulness
o High doses
o Nausea
o Vomiting
o Dizziness
o Hallucinations
o Depression
o ECG changes

Front 22

Nematodicides(roundworms)

Back 22

o Albendazole
o Mebendazole
o Pyrantel pamoate
o Piperazine
o Diethylcarbazine
o Ivermectin

Front 23

Trematodicides (flukes)

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o Praziquantel
o Triclabendazole
o Albendazole

Front 24

Cestodicides (tapeworms)

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o Albendazole
o Praziquantel
o Niclosamide

Front 25

Amebicides

Back 25

 Mixed
Metronidazole
Tinidazole
 Luminal
Paromomycin
Iodoquinol
 Other
Dihydroemetine (CDC)
Nitazoxanide

Front 26

Anti-leishmanials

Back 26

 Sodium stibogluconate (CDC)
 Pentamidine
 Miltefosine

Front 27

Anti-trypanosomals

Back 27

 Pentamidine
 Eflornithine
 Melarsoprol (CDC)
 Suramin (CDC)
 Nifurtimox (CDC)

Front 28

Anti-toxoplasmodials

Back 28

Pyrimethamine + Sulfadiazine

Front 29

Anti-malarials

Back 29

Combinations
 Pyrimethamine + sulfadoxine
 Artesunate/lumefantrine
 Atovaquone/proguanil
Anti-malarials
 Quinine (po)
 Quinidine (iv)
 Chloroquine
 Primaquine
 Artesunate (CDC)
 Mefloquine

Front 30

Albendazole ( Albenza)

What are its indications?

Back 30

Indications
o Ascaris lumbricoides (roundworm)
o Enterobius vermicularis (pinworm)
o Ancyclostoma duodenale (Old World hookworm)
o Necator americanus (New World hookworm)
o Cutaneous larva migrans (creeping eruption)
o Toxocara spp. (visceral larva migrans)
Alternative therapy
o Strongyloides stercoralis (threadworm)
o Trichinella spiralis (trichinosis)
o Trematodes
o Taenium solium (pork tapeworm)
o Taenium saginata (beef tapeworm)
o Echinococcus granulosus (cystic hydatid disease, s, dog tapeworm)
o Echinococcus multilocularis (alveolar hydatid disease)
Second-Line Indications
o Taenium saginata (beef tapeworm)
o Taenium solium (pork tapeworm)
 Eggs can hatch in, migrate to and create cysts in muscles,
eyes, and CNS (neurocysticercosis).
 Neurologic sequelae result – and this is only indication
for drug therapy with albendazole (+ dexamethasone)

Front 31

Albendazole (Albenza)

Back 31

MOA: Cytoplasmic microtubule degeneration
Inhibits parasitic fumarate reductase  ↓ ATP
PO, Fatty meals increase bioavailability 5X
Side effects
o Elevated serum concentrations with corticosteroids
o Drowsiness
o Dizziness
o Headache

Front 32

Mebendazole (Vermox)

Back 32

MOA: Inhibits protein function through selective beta-tubulin binding,
inhibiting polymerization; Inhibits glucose metabolism and depletes ATP
Broad-spectrum anti-helminthic (not for hydatid disease)
PO - Poorly absorbed
Side effects (Related to worm load)
o Diarrhea
o Abdominal discomfort
Indications
o A. lumbricoides
o T. Trichuria (primary – Whipworm)
o E. vermicularis
o N. americanus
o A. duodenale
o Cutaneous larva migrans (alternate)
o T. spiralis (primary)

Front 33

Pyrantel Pamoate (Pin-X)

Back 33

Indications
o Enterobius vermicularis (pinworm) (Drug of Choice)
o Alternative: A. lumbricoides, A. duodenale, N. americanus
MOA: Depolarizes parasite-specific nicotinic acetylcholine receptors

spastic paralysis
Administration: PO - Poorly absorbed
Side effects
o Headache
o Dizziness
o Drowsiness

Front 34

Diethylcarbazine citrate

Back 34

Indications
o Wuchereria bancrofti
o Brugia malayi
o Onchocerca volvulus (Onchocerciasis, River blindness)
MOA
o Enhances microfilaria killings through reticuloendothelial system
trapping and phagocytosis
o Interferes with arachadonic acid metabolism  capillary
vasoconstriction impairing microfilariae passage
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Specific treatment for filariasis
ADE from Rapid killing of organisms
o Fever
o Swelling
o Leukocytosis
o Edema
o Rashes
o Eosinophilia
o Headache
o Tachycardia

Front 35

Ivermectin (Stromectol)

Back 35

Indications
o Filarial river blindness Ochocerca volvulus
o Stronglyoidiasis
o MORE effective than DEC for W. bancrofti
o Cures river blindness with annual treatment
o Scabies (non-FDA)
MOA
o Paralyzes helminth muscle by blocking transmission of nerve
signals through interactions with parasite-specific glutamate-gated
chloride channels
o Hyperpolarizes parasite cell membranes
Side effects (from adult filaria disintegration): Fever, Lymphadenopathy,
Pruritis

Front 36

Praziquantel (Biltricide)

Back 36

Indications
o S. haematobium (Old World Schistosomiasis)
o S. mansoni, S. japonicum (New World Schistosomiasis)
o Clonorchis sinensis (Chinese liver fluke)
o Paragonimus westermani (Lung fluke)
o Fasciolopsis buski, Heterophyes heterophyes, Metagonium
yokogawai (Intestinal flukes)
o Taenia saginata (Beef tapeworm)
o Taenia solium (Pork tapeworm)
o Diphyllobothrium latum (Fish tapeworm)
o Hymenolepis nata (Dwarf tapeworm)
MOA: Paralyzes helminth muscle by increasing parasite-specific ion
membrane calcium permeability
 Worm detachment
 Calcium accumulates, surface proteins are unmasked to
immune defenses such as host antibodies and complement
Administration: PO
Adjust for renal impairment, watch for P450 interactions
Side effects (from dead worms): Nausea, vomiting, abdominal discomfort
13
Disappear 48 hours into treatment

Front 37

Triclabendazole

Back 37

Indication: Liver fluke – Fasciola hepatica – Drug of Choice
MOA: Inhibits protein function through selective beta-tubulin binding and
polymerization inhibition
PO

Front 38

Niclosamide

Back 38

Second line cestodicide: T. saginata, T. solium, D. latum, H. nana
MOA: Uncouples anaerobic phosphorylation of adenosine diphosphate
(ADP) in parasitic mitochondria
Kills cestode segments and scolex
Administration: Purge gut with 15-30 grams of magnesium sulfate prior to
and after administration of niclosamide – NOT for T. saginata
PO – not absorbed