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Infectious Disease Unit 3 > Anti-parasitics > Flashcards

Anti-parasitics Flashcards

1
Q

What are the major, potentially fatal parasitic infections?

A

Malaria
Schistosomiasis
Trypanosomiasis (Sleeping sickness)
Dengue Fever

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2
Q

What are the major protozoa infections?

A

Amebiasis
Giardiasis
Trichomoniasis

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3
Q

What are the major helminth infections?

A

Ascariasis
Pinworm
Hookworm

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4
Q

What are the major opportunistic parasitic infections?

A

Toxoplasmosis
Cryptosporidiosis
Pneumocystis carinii pneumonia

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5
Q

What are the four categories of anti-parasitic drug MOAs?

A
  1. Target enzyme or protein unique to parasite
  2. Enzyme or protein indispensable to parasite
    May share with host
    host has alternative metabolic pathway
  3. Different Pharmacology
    homologous proteins bind with different affinity
  4. Selectively concentrated in parasite
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6
Q

MOA, selectivity, resistance and elimination of Nitroimidazoles (Metronidazole)

A

Pro-drug targets enzyme (Pyruvate:ferrodoxin oxidoreductase) unique to the parasite
Target anaerobic organisms
Aerobic respiration in host regenerates parent drug
Resistance through down regulation of enzyme
Rapidly absorbed and distributed into tissues and body fluids
Metabolites: increased half life – retain activity (50% of parent drug)
Eliminated predominantly in urine

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7
Q

Which infections or conditions are treated with metronidazole?

A

Giardiasis
Severe amebiasis (systemic forms of E. histolytic)
Trichomoniasis (treat all partners)
Pseudomembranous colitis (replaces vancomycin)
Other anaerobic bacteria (peptic ulcers Helicobacter pylori)

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8
Q

What are the adverse reactions and contraindications of metronidazole?

A 
Alcohol (Disulfram-like reaction)
Headache and nausea				   
Peripheral neuropathy (long term)	  	
First trimester of pregnancy			   
Inducers of hepatic enzymes
Hepatic disease				
Renal dysfunction
Existing or development of CNS abnormalities increase levels in CSF
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9
Q

Drug class, uses, administration, and MOA of Paromomycin

A

Aminoglycoside antibiotic

Therapeutic Use:
Asymptomatic luminal amebiasis
Cryptosporidiosis (AIDS patients)
Visceral and cutaneous Leishmanias

Mechanism:
Oral administration - little systemic absorption
Concentrated in parasite in gut
Inhibits protein synthesis - binds to A-site of ribosome

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10
Q

Treatment of toxoplasmosis

A

Anti folate combinations that selectively targets parasite enzymes
(50% of all patients show limiting sensitivity to sulfonamides
Significantly higher in AIDS patients)

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11
Q

What are the effects of SMX-TMP and why are they considered synergistic?

A

Sulfonamides inhibit Dihydropteroic Acid Synthase
Trimethoprim inhibits Dihydrofolate Reductase
Both ultimately inhibit nucleic acid and protein synthesis

They are synergistic because dihydropteroic acid is a precursor of dihydrofolate. Inhibiting its formation makes the later inhibition of dihydrofolate reductase more effective.

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12
Q

What is the mechanism and uses of pentamidine?

A

Mechanisms (differ by species):
Concentrated in sensitive strains
Pyrimidine salvage pathway

Inhibits SAM-decarboxylase
inhibits polyamine biosynthesis
disrupts DNA structure and function

Binds to minor groove of DNA
inhibits protein synthesis

Inhibits type II topoisomerase
inhibits DNA replication

Interferes with glucose metabolism

Uses:
P. carinii pneumonia (Alternative to TMP-SMX)

West African Trypanosomiasis T. bruce gambiense
(Not effective in T.brucei rhodesiense (EAST) - very early infection of CNS)

Visceral Leishmanias
kala-azar - L. donovani

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13
Q

Benzimadazoles MOA

A

Inhibit microtubule formation by binding to beta-tubulin and prevent formation of alpha/beta dimers
Selectively binds to parasite tubulin 100x better than to human tubulin

Widespread resistance due to single point mutation Phe200 -> Tyr

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14
Q

Therapeutic uses of benzimadazoles

A 
Mebendazole:
Mixed Nematode infections
	Enterobiasis (pinworm)
	Ascariasis (common roundworm)
	Trichuriasis (whipworm)
	Hookworm (Necator americanus and Ancylostoma duodenale) 
	
Albendazole:
	Nematode infections
		Ascariasis, Enterobiasis, Hookworm
	     Prophylaxis of Filariasis with Ivermectin or Diethylcarbamazine
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15
Q

MOA and therapeutic use of pyrantel pamoate

A 
Mechanism:
Only given orally - very poor absorption
Concentrates in parasite 
Acetylcholine receptor agonist 
Complete spastic paralysis of worm (and host if given IV)

Therapeutic Use:
Ascariasis (roundworm)
Enterobiasis (pinworm) DOC
Hookworm infections

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16
Q

MOA and therapeutic use of praziquantel

A

Mechanism
Ca2+ ionophore - induces paralysis, detachment, excretion
Induces tegmental damage - activates immune system

Therapeutic Use
Cestode (tapeworm)
Trematode (flukes)

17
Q

MOA and therapeutic use of chloroquine

A 
Mechanism:
Concentrates in food vacuoles
Inhibits Heme polymerization
Inhibits peroxidase and catalase activity
Generates oxidative stress
Therapeutic Use:
Erythrocytic stages of 
P. vivax
P. ovale
P. malariae
CQ sensitive P. falciparum
18
Q

MOA and therapeutic use of quinine

A

Mechanism:
Inhibits parasite feeding mechanism
Generates oxidative stress

Therapeutic Use:
Treatment and cure of erythrocytic stages of
chloroquine resistant and MDR P. falciparum malaria

19
Q

MOA and therapeutic use of mefloquine

A

Mechanism:
Generates oxidative stress in same way as chloroquine

Therapeutic Use:
Alternative for treatment of erythrocytic
stages of chloroquine resistant and
MDR P. falciparum
CDC recommends against use US Army replaced use of Mefloquine with Doxycycline In Sept 2013 – considered a court martial offence to prescribe

20
Q

MOA and therapeutic use of Malarone - Proguanil with Atovaquone

A

Mechanism:
DHFR Inhibitor
Increases efficacy of Atovaquone to collapse proton gradient

Therapeutic use:
Malaria caused by P. falciparum (as Malarone)
P. carinii pneumonia (in patients who cannot tolerate TMP-SMX or pentamidine IV)
Toxoplasma gondii

21
Q

MOA and therapeutic uses of Primaquine

A

Mechanism of Action:
Uncertain
Inhibit electron transport chains

Therapeutic Use
Latent forms of P. vivax and P. ovale.
Only drug active against latent hepatic forms

22
Q

MOA and therapeutic uses of Artemisinin

A

Mechanism:
Interacts with heme to generate reactive oxygen species

Therapeutic use:
Arthemeter Combination Therapy (ACT) now recommended as primary treatment for multi-drug resistant P. falciparum in endemic areas

Used in conjunction with lumefantrine (chloroquine analogue), sulfadoxine-pryimethamine
Clinical cure rates of ~ 90% in P. falciparum

23
Q

Prophylaxis of chloroquine sensitive malaria

A

Chloroquine Phosphate(oral)

24
Q

Primary and alternative treatment of chloroquine sensitive malaria

A

Primary:
Chloroquine Phosphate

Alternative:
Chloroquine hydrochloride(IV)
25
Q

Primary and alternative prophylaxis of MDR malaria

A

Primary:
Atovaquone/proguanil or Doxycycline

Alternative:
Mefloquine

26
Q

Primary and alternative treatment of MDR malaria

A 
Primary:
Quinine sulfate (ORAL) 		
Quinidine gluconate (IV)		 
	plus
	Tetracycline		
	or plus 	
	pyrimethamine-sulfadoxine	
	or plus 	
	clindamycin	
plus Primaquine Phosphate for P. vivax

Alternative:
Atovaquone/proguanil (Malarone)
or
Mefloquine

Infectious Disease Unit 3 (15 decks)

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