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Flashcards in ANTIPARASITICS Deck (64):
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)

31

PIPERAZINE

antihelminthic drug

Alternative drug for treatment of pinworm & roundworm infections

MOA

• GABA agonist
• Expulsion of worm occurs by peristalsis

Contraindications

Patients with seizure disorders

32

PYRANTEL PAMOATE

 

ANTIHELMINTHIC DRUG

Effective in treatment of infections by roundworms, pinworms and hookworms

MOA

• Acts as a depolarizing, neuromuscular-blocker (causes persistent activation of parasite’s nicotinic receptors by release of acetylcholine & inhibition of cholinesterase)

Pharmacokinetics

• Poorly absorbed orally (exerts effects in intestinal tract)

AE: 

• Mild (nausea, vomiting, diarrhea)

33

DIETHYLCARBAMAZINE

Drug of choice for treatment of

1) lymphatic filariasis, (WUCHERERIA BANCROFTI = “witch” --> elephantiasis)  

2) loiasis (loa loa = creepy blue worm guy, cause callabar swellings)

3) tropical eosinophilia. = WUCHERERIA BANCROFTI

MOA

Immobilizes microfilariae & renders them susceptible to host defense mechanisms

Pharmacokinetics

• Oral (rapidly absorbed with meals)

34

DIETHYLCARBAMAZINE

AE

• Most AE thought to be due to host responses following damage/death of parasite*****

• Fever, malaise, rash, myalgias, arthralgias, headache

 

• Leukocytosis (common)


• Antihistamines or steroids can be coadministered

35

DOXYCYCLINE

• Tetracycline antibiotic.
• Macrofilaricidal activity against Wuchereria bancrofti. (witch wearing the elephant pants) 

• Also active against onchocerciasis (bug man) FOUND NEAR RIVERS at the back with no dumping sign) 

MOA

Acts indirectly by killing Wolbachia (intracellular bacterial symbiont of filarial parasites)

36

PRAZIQUANTEL

•Drug of choice for all forms of schistosomiasis & most trematode & cestode infections

Cysticercosis – albendazole is drug of choice (praziquantel has similar efficacy)

MOA

• Increases permeability of cell membrane to calcium, causing contracture & paralysis of worm musculature, resulting in detachment of suckers from blood vessel walls.

PK: 

• Oral
• Extensive first-pass metabolism (CYPs)
• Inactive metabolites excreted via urine & bile

 

37

PRAZIQUANTEL

AE

• Drowsiness, dizziness, malaise, anorexia & GI upsets

• Drug interactions (CYP P450)

Contraindicated in pregnancy & nursing mothers (FDA Category B)

• Contraindicated for treatment of ocular cysticercosis *******(destruction of organism may damage eye)*****

38

BITHIONOL

ANTIHELMINTHIC DRUG

• Drug of choice for fasciolosis (sheep liver fluke)

• Alternative drug for pulmonary paragonimiasis

MOA

• Inhibition of helminth’s electron transport chain (probably)

39

NICLOSAMIDE

• 2nd line drug for treatment of most cestode infections

Use is uncommon due to excellent efficacy of praziquantel

• No longer available in US

MOA

Inhibition of the parasite’s mitochondrial phosphorylation of ADP. Anaerobic metabolism may also be inhibited

• Drug is lethal for cestode’s scolex & segments of cestodes but not for the ova

PK: 

• ****Laxative is admin. prior to niclosamide (oral) to purge bowel of all dead segments in order to preclude digestions & liberation of ova (may lead to cysticercosis)****

• ***Alcohol should be avoided within 1 day of dose***

• Safety has not been established in pregnancy or children <2

40

ASCARIASIS

caused by Ascaris lumbricoides (roundworm)

ASCARIS LUMRICOIDES = ROUNDWORM -->  huge lumbering tree man in back of tunnel

DOC

1) ALBENDAZOLE, 

2) PYRANTEL PAMOATE

OR

2) MEBENDAZOLE

41

ENTEROBIASIS

Enterobius Vermicularis (pinworm) 

A) ENTEROBIUS VERMICULARIS = “vermin lady” = PINWORM

--> coming out of a round hole that represents an ANUS -->  at night time the females migrate down to the anus and lay their eggs, so there are round eggs

DOC: 

1) MEBENDAZOLE 

OR

2) PYRANTEL PAMOATE 

42

TRICHURIASIS

Trichuris trichiuria (whipworm) 

 

DOC:

1) MEBENDAZOLE OR 

2) ALBENDAZOLE 

43

HOOKWORM DISEASE

-Ancyclostoma duodenale

-Necator Americanus (hookworm) 

B) ANCYLOSTOMA DUODENALE + NECATOR AMERICANUS = AMERICA DUDE à both found in the rural southern USA

à rings around ankle = ancylostoma, rings around neck = necator americanus

DOC:

1) PYRANTEL PAMOATE

OR

2) MEBENDAZOLE

OR

3) ALBENDAZOLE

44

ONCHOCERCIASIS (RIVER BLINDNESS)

ONCHOCERCA VOLVULUS

B) ONCHOCERCA VOLVULUS (bug man) FOUND NEAR RIVERS (sign at the back of the room) 

DOC:

1) IVERMECTIN!!!

45

CUTANEOUS LARVA MIGRANS (Creeping eruption, dog + cat hookworm)

-ANCYCLOSTOMA SP.

 

DOC:

1) ALBENDAZOLE

2) IVERMECTIN 

46

VISCERAL LARVA MIGRANS

(TOXOCARIASIS)

TOXOCARA CANIS, TOXOCARA CATI

D) TOXOCARA CANIS: = “wolfman”

à from contamination of food with dog or cat feces (or even wolf feces?) à can remember via the stinky poop bag that is hanging off wolf’s chair

DOC: 

1) ALBENDAZOLE

47

TRICHINOSIS

Trichinella Spiralis 

E) TRICHINELLA SPIRALIS (pig with spirals on his suit in tunnel)

à intestinal nematode found in undercooked meat like pork or bear

1) FEVER, VOMITING, PERIORBITAL EDEMA (large red glasses he’s wearing) and can see other symptoms on him as well

DOC:

1) ALBENDAZOLE 

or

2) MEBENDAZOLE

3) add CORTICOSTEROIDS for severe infeciton 

48

LYMPHATIC FILARIASIS

1) WUCHERERIA BANCROFTI

2) BRUGIA MALAYI

 

C) WUCHERERIA BANCROFTI = “witch” à kinda sounds like witchcraft (what’s more of witchcraft than turning someone into an elephant?)

1) ELEPHANTIASIS à longstanding lymphedema

 

DOC: 

1) DIETHYLCARBAMAZINE

 

49

LOIASIS

LOA LOA (african eye worm) 

E) LOA LOA: creepy blue worm guy

à transmitted by DEER FLIES (why flies are around him)

à migrates through the subcutaneous tissue of its host, and causes transient angioedema called CALLABAR SWELLINGS (shown by the swellings on blue guy)

à ADULT WORMS can MIGRATE ACROSS CONJUNCTIVA

DOC:

1) DIETHYLCARBAMAZINE

50

STRONGYLOIDIASIS

Strongyloides stercoralis (threadworm)

 

D) STRONGYLOIDES STERCORALIS = STRONG GUY

1) LARVAE PENETRATE SKIN OF SOLES OF FEET (red boots KICKING INTO WALL) 

DOC: 

1) IVERMECTIN 

51

FASCIOLA HEPATICA (LIVER FLUKE) 

-no sketchy for it 

1) BITHIONOL

 

52

SCHISTOSOMIASIS

Shistosoma mansomi, Shistosoma japonicum, Schistosoma hematobium 

TREMATODES (whale park scene) 

1) SHISTOSOMA  à SWIMMERS AT RISK OF INFECTION (why man is swimming)

                  à mature’s in the LIVER, and then is excreted in in feces

2) SNAILS = INTERMEDIATE HOST (why snails stuck to glass)

 

 

DOC: PRAZIQUANTEL

53

CLONORCHIS SINENSIS

(oriental liver fluke) 

CLONORCHIS SINENSIS = chinese liver fluke = “orcha whale… ClonORCHis”

1) SNAILS = INTERMEDIATE HOST

Clonorchis sometimes transmitted from the snails à fish, and we sometimes eat the fish uncooked à SUSHI!!!

à cysta larva will then go inside us and reside in the BILLIARY SYSTEM, eventually causing biliary tract fibrosis, pigmented gallstones and even cholangio carcinoma

DOC: 

1) PRAZIQUANTEL

54

PARAGONIMUS WESTERMANI (LUNG FLUKE)

 

PARAGONIMUS WESTERMANI à sounds kind of like penguins

à penguins mostly black, but have 2 large white lung spots on chest with bl. on them

à b/c has potential to cause CHRONIC COUGH with BLOOD SPUTUM

INTERMEDIATE HOST = SNAIL

TRANSMISSION à via raw/undercooked crab meat that carry the encysted larvae

DOC: 

1) PRAZIQUNATEL

55

ECHINOCOCCOSIS

ECHINOCOCUS GRANULOSUS (dog tapeworm) 

3) ECHINOCOCCUS GRANULOSUS (cockerspaniel dog…. Echinococcus)

-dogs are definitive host (why cockerspaniel is #1)

-sheep are intermediate host (why sheep dog is #2)

TRANSMISSION à via dog feces (why dog feces behind the winner)

1) HYDATID LIVER CYSTS à look like “EGG SHELL CALCIFICATIONS on CT)

à why there’s a trophy for the winning dog with a giant egg in it

à also why there’s a ribbon on the “liver spot” on the cockerspaniel

-LIVER CYSTS CAN RUPTURE --> cause anaphylactic reaction

 

DOC: ALBENDAZOLE

56

TAENIASIS (Taenia solium, pork tapeworm)

OR

saginata (beef tapeworm)

DOC:

1) PRAZIQUANTEL

2) NICLOSAMIDE 

57

CYSTERCERCOSIS

Taenia solium LARVAE

1) ALBENDAZOLE OR

2) PRAZIQUANTEL

 

58

DIPHYLLOBOTHRIASIS

(Diphyllobothrium latum) fish tapeworm

 

 

DOC: 

1) PRAZIQUANTEL

2) NICLOSAMIDE

 

DIPHYLLOBOTHRIUM LATUM = FISH TAPEWORM (guy running toward bathroom)

à bathroom sounds like bothrium, and who gets fish at a carnival…. Wtf?

à bathroom is beside a stand that says “MUST B12 to buy FIREWORKS (b/c fishworm stays in SI and inhibits absorption of VitB12 = COBALAMIN (cobalt blue firework)

à fireworks are bursting up in the sky and look like bursting RBCs à can remind us that it causes MEGALOBLASTIC ANEMIA

59

GIARDIA LAMBLIA

TRICHONOMAS VAGINALIS

METRONIDAZOLE

60

TRYPANOSOMIASIS

(AFRICAN SLEEPING SICKNESS)

 

1) MELARSOPROL

2) SURAMIN

 

prince charming etc

1) MELARSOPROL TREATMENT à used if it is a CNS INFECTION (can remember via the bar of soap prince bruce has)

2) SURAMIN TREATMENT à for a PERIPHERAL BLOOD INFECTION (life saving “SERUM” bottle for suramin)

61

1) HEMOLYMPHATIC STAGE of TRYPANOSOMIASIS 

2) PNEUMOCYSTIC JIROVECI INFECTIONS

 

 

DOC: 

1) PENTAMIDINE

62

TREATMENT OF TOXOPLASMOSIS (toxoplasmic encephalitis)

 

1) PYRIMETHAMINE AND

2) CLINDAMYCIN

or

2) SULFADIAZINE

or

2) FOLONIC ACID 

BACKYARD OF CRAZY CAT LADY

1) PREGNANT WOMEN AT RISK OF TRANSPLACENTAL TRANSFER (pregnant lady bending down taking a picture)

2) TRANSMISSION à VIA 3 WAYS

1) OOCYTES CAT FECES à why she’s near the litter box picking up poop, and why there’s a bird egg in the litter box to remind us it’s OOCYTES

2) via RAW/POORLY COOKED MEAT that contains toxic tissue CYSTS (the meat bowl that immunocompromised cat is kicking over… since ghandi doesn’t like to eat)

3) VEGETABLES CONTAMINED BY OOCYTES FROM FECES

3) VERTICAL TRANSMISSION à ToRCHeS INFECTION à Toxoplasma part = this!!! (why there’s a statue of liberty cat holding a torch)

TREATMENT:

1) SULFADIAZINE à shown the the “dyed” sulphur eggs

2) PYRIMETHAMINE à shown by the pyramids on the eggs, and they are “smoking” to remind us of the meth

63

TREATMENT OF LEISHMANIASIS (all stages)

 

DOC:

1) SODIUM STIBOGLUCONATE OR

2) AMPHOTERACIN B 

 

LEISHMANIASIS à “DESERT MANIA” à featuring L. donovani, and L. baziliensis

 

HUMANS = HOST

FLY’S = VECTOR = SANDFLY VECTOR = PHEBLOTOMINE SAND FLY (why the brazil guy has sand flies all around him) à is a WHITE SOCKED SANDLFY

TREATMENT:

1) STIBOGLUCONATE à used for CUTANEOUS LEISHMANIASIS (can remember stivo as t-bo à t bone steak on the ground)

2) AMPHOTERACIN B à used for VISCERAL LEISHMANIASIS (can remember via the frogs)

64

PNEUMOCYSTIC JIROVECI INFECTIONS

 

DOC:

1) TRIMETHOPRIM-SULFAMETHOXAZOLE = COTRIMOXAZOLE 

ping pong match;