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Flashcards in ANTIPARASITICS Deck (64)
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1

AMEBIASIS

•Amebiasis (amebic dysentery) is an intestinal tract

infection caused by Entamoeba histolytica

• GI disease can be acute or chronic
• Infection can be symptomatic or latent

•Symptoms can range from mild diarrhea to fulminating dysentery

• E.Histolytica exists in two forms
(1) cysts (can survive outside body)
(2) trophozoites (do not survive outside body)

• Trophozoites are liberated from ingested cysts within the intestinal lumen

• Liberated trophozoites migrate to the large intestine where they multiply and invade the intestinal mucosa.

•Trophozoites can enter bloodstream to result in a systemic invasion

• Life cycle completes by trophozoites returning to the cyst

form in the rectum and being expelled in the feces

2

ANTIAMEBICS: GAOLS OF THERAPY

 

1) Eliminate invading trophozoites

&
2) Eradicate intestinal carriage of the organism

 

ANTIAMEBICS: 

• Luminal
Act on parasite in bowel lumen

• Systemic
Active both in intestinal wall and liver

• Mixed
Active against both luminal & systemic disease

3

MIXED ANTIAMEBICS

METRONIDAZOLE

TINIDAZOLE

4

METRONIDAZOLE

MOA:

• Once absorbed, metronidazole is non-enzymatically

reduced by reacting with reduced FERREDOXIN

• This reduction causes the production of cytotoxic compounds

• The cytotoxic compounds bind to proteins & DNA, resulting in unstable molecules and cell death

5

METRONIDAZOLE 

PK

AE

MIXED LUMINAL + SYSTEMIC AGENT

PK: 

• Oral

• Well distributed (inc. vaginal & seminal fluids, saliva, breast milk & CSF)

• Undergoes hepatic oxidation & glucuronidation (CYP P450’s)

AE: 

• GI distress
• ***Disulfiram-like reaction*** (avoid alcohol intake)

Unpleasant metallic taste
• Oral moniliasis
Dark coloration of urine
• Leukopenia, dizziness, ataxia.
Safety in pregnancy NOT established*****

6

TINIDAZOLE

MIXED LUMINAL + SYSTEMIC AGENT

• 2nd generation nitroimidazole

• Similar to metronidazole but better tolerated and has shorter treatment course

Clinical Applications

• Amebiasis
• Amebic liver abscess

• Giardiasis
• Trichomoniasis

AE:

• Same as metronidazole but reports indicate shorter duration of effects with tinidazole

 

7

LUMINAL ANTIAMEBICS

 

• 1) Diloxanide furoate

 

• 2) Iodoquinol


• 3) Paromomycin

8

DILOXANIDE FUROATE

• Used as sole agent for treatment of ASYMPTOMATIC AMEBIASIS 

Converted in gut to active form

Adverse Effects

• Mild (GI distress)

Not currently available in US – however remains

luminal amebicide of choice

9

IODOQUINOL

LUMINAL AGENT (ANTIAMEBIC)

• Orally active against luminal trophozoite and cyst forms of E.histolytica

• Used as an alternative to diloxanide furoate for mild- severe infections

Adverse Effects

• Rash, diarrhea, dose-related ***peripheral neuropathy**** (exam Q) 

Long term use should be avoided (due to risk of optic neuritis)***

10

PAROMOMYCIN

 

LUMINAL ANTIAMEBIC

Aminoglycoside antibiotic
• Effective only against luminal forms of E.histolytica and tapeworm
•Sometimes used with tetracyclines for mild intestinal

disease
Alternative agent for cryptosporidiosis in AIDS patient

MOE/AE: 

AmebiCIDAL (causes cell membranes to leak)

Interferes with bacterial protein synthesis (binds to 30S ribosomal subunits)

Reduces intestinal flora population

Adverse Effects

• GI distress & diarrhea

• Systemic absorption may lead to headaches, dizziness, rashes and arthralgia

11

SYSTEMIC ANTIAMEBICS

 

1) CHLOROQUINE

2) EMETINE

3) DEHYDROEMETINE

-useful for treating liver abscesses or intestinal wall infections 

12

CHLOROQUINE

SYSTEMIC ANTIAMEBIC

• Used in combination with

  1. metronidazole & ("mixed" luminal and systemic agent)
  2. diloxanide furoate (luminal agent) 

MOA

Eliminates trophozoites in liver abscesses

13

EMETINE +

DIHDROEMETINE

SYSTEMIC ANTIAMEBIC

BACKUP DRUGS for treatment of SEVERE intestinal or hepatic amebiasis

• Used in combination with a luminal agent

MOA

• Inhibit protein synthesis by blocking ribosomal movement along messenger RNA

PK: 

• IM or SC
Concentrate in liver (persists for 1 month)

Slowly metabolized & eliminated

 

14

EMETINE +

DIHDYROEMETINE

AE:

• Pain at site of injection****** on exam!!! 
• Transient nausea
• Cardiotoxicity
• Neuromuscular weakness

• Dizziness

• Rash

15

TREATMENT OF AMEBIASIS

ASYMPTOMATIC, INTESTINAL INFECTION

DOC: 

1) DILOXANIDE FUROATE

 

ALTERNATIVE DRUG(S):

1) IODOQUINOL

2) PAROMOMYCIN

16

TREATMENT OF AMEBIASIS

MILD-MODERATE INTESTINAL INFECTION 

DOC: 

1) METRONIDAZOLE AND

2) DILOXANIDE FUROATE

 

ALTERNATIVE DRUGS:

1) Tinidazole OR

2) Tetracycline OR

3) Erythromycin + diloxanide furoate

17

TREATMENT OF AMEBIASIS

SEVERE INTESTINAL INFECTION

 

DOC: 

1) METRONIDAZOLE OR TINIDAZOLE 

AND

2) DILOXANIDE FUROATE

ALTERNATIVE DRUGS: 

1) Tetracycline OR Emetine OR Dihydroemetine 

AND

2) DILOXANIDE FUROATE

18

TREATMENT OF AMEBIASIS

HEPATIC ABSCESS + OTHER EXTRAINTESTINAL DISEASE

 

 

DOC:

1) METRONIDAZOLE OR TINIDAZOLE

AND

2) DILOXANIDE FUROATE

Alterative drugs: 

1) Emetine OR Dihydroemetine 

AND

2) Chloroquine

AND

3) Diloxanide Furoate

19

HELMINTHS

 

Nematodes

• Elongated roundworms that possess a complete digestive system.

• Cause infections of intestine as well as blood & tissue.

Trematodes

• Leaf-shaped flatworms generally characterized by tissues they infect: liver, intestinal, blood flukes

Cestodes

Flat, segmented body which attach to host’s intestine

Lack mouth & digestive system throughout life cycle

20

ANTIHELMINTHIC DRUGS

 

• In most cases broad spectrum agents cure or control most human worm infections

• Some systemic infections only respond partially to

antihelminthic drugs (cysticercosis, echinococcosis,

filariasis, trichinosis)

Antihelminthic drugs can act either:

locally (to expel worms from GI tract) or,

systemically (to eradicate adult helminths or developmental forms)

21

BENZIMIDAZOLES

ANTIHELMINTHICS

1) ALBENDAZOLE

2) MEBENDAZOLE

3) THIABENDAZOLE 

NOTE: ALL are CATEGORY C and CONTRINDICATED IN PREGNANCY!!!! 

22

ALBENDAZOLE 

BENZIMIDAZOLE - an ANTIHELMINTHIC DRUG

• Used in the treatment of CESTODE infestations, such as

  1. cysticercosis (Taenia solium larvae) and
  2. hydatid disease (Echinococcus granulosis)

MOA

• Inhibits microtubule synthesis & glucose uptake

• ATP production is decreased resulting in worm immobilization and death

PK: 

• Oral (erratically absorbed, enhanced by high-fat meal)

• Extensive first-pass metabolism, including rapid sulfoxidation to active metabolite

 

 

23

ALBENDAZOLE 

AE

Short course therapy (1-3 days) = mild & transient (headache, nausea)

• ****HYDATID treatment (3 months) = risk of hepatotoxicity, agranulocytosis or pancytopenia**************

• Treatment is associated with inflammatory responses to dying parasites in CNS******* (headache, vomiting, hyperthermia, convulsions, mental changes)

• Contraindicated in pregnancy & children < 2y (FDA Category C)

24

MEBENDAZOLE

DOC FOR? 

BENZIMIDAZOLE - ANTIHELMINTHIC DRUG

Drug of choice in the treatment of infections by:

• 1) Whipworm (Trichuris trichiura) (in tunnel) pig with spirals on his suit

• 2) Pin worm (Enterobius vermicularis) (in tunnel, "vermin lady" who's first character introduced, going into the hole)

• 3) Hookworms (Necator americanus & Ancylostoma duodenale) (in tunnel, is american dude swinging) 

• 4) Roundworm (Ascariasis lumbricoides) (in tunnel, huge lumbering tree man in back) 

25

MEBENDAZOLE

BENZIMIDAZOLE (Antihelminthic drug)

Inhibits formation of helminth microtubules

Irreversibly blocks glucose uptake
• Affected parasites are expelled with feces

Pharmacokinetics

• Oral (chewable) – nearly insoluble in aqueous solution, take with high-fat meal

• Undergoes first-pass metabolism to inactive compounds

26

MEBENDAZOLE

AE

• Abdominal pain, diarrhea, headache, dizziness

• Contraindicated in pregnancy (FDA Category C)

• Use with caution in children < 2

• Use with caution in patients with cirrhosis

27

THIABENDAZOLE

Effective in treatment of

1) strongyloidiasis caused by Strongyloides stercoralis (threadworm), (strong guy in tunnel kicking wall in on right side) 

2) CUTANEOUS LARVA MIGRANS, and

3) early stages of TRICHINOSIS 

MOA

• Affects microtubular aggregation

Pharmacokinetics

• Oral
• Nearly insoluble in H20

28

THIABENDAZOLE

AE

MOST TOXIC of all the benzimidazoles

• Dizziness, anorexia, nausea, vomiting

CNS disturbances (dizziness --> seizures)

• Cases of erythema multiforme & Stevens-Johnson reported

• Contraindicated in pregnancy (FDA Category C)
• Should not be used in presence of liver or kidney disease

29

IVERMECTIN

Drug of choice for the treatment of

1) onchocerciasis (Onchocerca volvulus), (movie scene, back of the room guy covering one eye near the no dumping in river sign) 

2) cutaneous larva migrans &

3) strongyloides (in tunnel, guy on right kicking in wall) 

MOA

GABA agonist*******
• Cl- influx increases leading to hyperpolarization of nerve /

muscle cell. Death occurs due to paralysis of parasite*****

Pharmacokinetics

• Oral (does not cross BBB)

30

IVERMECTIN 

AE

• ***Mazotti-like reactions with onchoceriasis (fever, dizziness, somnolence, hypotension)**** --> IS D/T DEATH OF THE PARASITE

Contraindicated in pregnancy (FDA Category C)

Contraindicated in meningitis (may cross BBB)******

Best to avoid concomitant use of ivermectin & other drugs that enhance GABAergic activity (eg, barbiturates, benzodiazepines)