ANTIPARASITICS Flashcards
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
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
MIXED ANTIAMEBICS
METRONIDAZOLE
TINIDAZOLE
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
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*****_
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
LUMINAL ANTIAMEBICS
- 1) Diloxanide furoate
- 2) Iodoquinol
- 3) Paromomycin
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
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)***
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
SYSTEMIC ANTIAMEBICS
1) CHLOROQUINE
2) EMETINE
3) DEHYDROEMETINE
- useful for treating liver abscesses or intestinal wall infections
CHLOROQUINE
SYSTEMIC ANTIAMEBIC
• Used in combination with
- metronidazole & (“mixed” luminal and systemic agent)
- diloxanide furoate (luminal agent)
MOA
• Eliminates trophozoites in liver abscesses
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
EMETINE +
DIHDYROEMETINE
AE:
_• Pain at site of injection****** on exam!!!_
• Transient nausea
• Cardiotoxicity
• Neuromuscular weakness
- Dizziness
- Rash
TREATMENT OF AMEBIASIS
ASYMPTOMATIC, INTESTINAL INFECTION
DOC:
1) DILOXANIDE FUROATE
ALTERNATIVE DRUG(S):
1) IODOQUINOL
2) PAROMOMYCIN
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
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
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
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
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)
BENZIMIDAZOLES
ANTIHELMINTHICS
1) ALBENDAZOLE
2) MEBENDAZOLE
3) THIABENDAZOLE
NOTE: ALL are CATEGORY C and CONTRINDICATED IN PREGNANCY!!!!
ALBENDAZOLE
BENZIMIDAZOLE - an ANTIHELMINTHIC DRUG
• Used in the treatment of CESTODE infestations, such as
- cysticercosis (Taenia solium larvae) and
- 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
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)
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)
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
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
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
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
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)
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)
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
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)
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)
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
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)
PRAZIQUANTEL
- Drug of choice for all forms of schistosomiasis & most trematode & cestode infections
- Cysticercosis – albendazole is drug of choice (praziquantel has similar efficacy)
MOA
• I_ncreases 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
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)*****
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)
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
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
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
TRICHURIASIS
Trichuris trichiuria (whipworm)
DOC:
1) MEBENDAZOLE OR
2) ALBENDAZOLE
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
ONCHOCERCIASIS (RIVER BLINDNESS)
ONCHOCERCA VOLVULUS
B) ONCHOCERCA VOLVULUS (bug man) FOUND NEAR RIVERS (sign at the back of the room)
DOC:
1) IVERMECTIN!!!
CUTANEOUS LARVA MIGRANS (Creeping eruption, dog + cat hookworm)
-ANCYCLOSTOMA SP.
DOC:
1) ALBENDAZOLE
2) IVERMECTIN
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
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
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
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
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
FASCIOLA HEPATICA (LIVER FLUKE)
- no sketchy for it
1) BITHIONOL
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
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
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
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
TAENIASIS (Taenia solium, pork tapeworm)
OR
saginata (beef tapeworm)
DOC:
1) PRAZIQUANTEL
2) NICLOSAMIDE
CYSTERCERCOSIS
Taenia solium LARVAE
1) ALBENDAZOLE OR
2) PRAZIQUANTEL
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
GIARDIA LAMBLIA
TRICHONOMAS VAGINALIS
METRONIDAZOLE
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)
1) HEMOLYMPHATIC STAGE of TRYPANOSOMIASIS
2) PNEUMOCYSTIC JIROVECI INFECTIONS
DOC:
1) PENTAMIDINE
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
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)
PNEUMOCYSTIC JIROVECI INFECTIONS
DOC:
1) TRIMETHOPRIM-SULFAMETHOXAZOLE = COTRIMOXAZOLE
ping pong match;
