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71 Cards in this Set

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Metronidazole kinetics
- good p.o. absorption
- metabolized by the liver and cleared by the kidneys
Is metronidazole safe for children? Pregnant women?
Yes; Pregnancy category B, but avoid use in first semester
Metronidazole MOA
- kills directly
- enzymes involved in E metabolism in susceptible protozoans and anaerobic bacteria are different that that found in mammals
- ETC contains ferredoxins which denate electrons to metronidazole to form highly reactive nitro radical
- nitro radical attacks the protozoal DNA and destroys its helical structure to cause cell death
- aerobic organisms do not produce toxic metabolite from prodrug metronidazole
Metronidazole drug interactions
- Increased bleeding with warfarin
- Increased EtOH ingestion can cause n/v, abdominal pain, flushing
Metronidazole adverse effects?
-- Common: n/v (12%), dizziness, headache, metallic taste, xerostomia (dry mouth), abdominal pain
-- Uncommon: leukopenia, urticaria, vaginal candidiasis, periph neuropathy, pancreatitis, ataxia, seizure
-- monitor CBC and LFT with prolonged treatment of chronic recurrent trhicomoniasis
-- Pregnancy Category B, but avoid in first trimester
Clinical presentation of trichomoniasis?
Trichomonas vaginalis = flagellated
1. vaginal discharge -- copious, greenish-yellow, frothy
2. irritation of the vulva, vagina, and perineum
3. pain during urination and intercourse
4. frequently co-exists w/ gonorrhea
5. males may have discharge but are frequently asymptomatic
-- Incubation period is 5-28 days
-- Symptoms may begin or become worse with menstruation
Trichomoniasis treatment?
DOC is metronidazole

Oral tx = 2g x 1 or 250mg tid or 500mg bid x 7 days

Topical tx = one application (37.5mg/5g vaginal cream) bid for 5d

treat both the female (oral and topical) and the male consort (p.o. only)

cure rate is 80-90%
What is Giardiasis?
Giardia lamblia = beaver fever, camper's fever

Most common enteric parasite in the U.S. and Canada
- causes waterborne outbreaks of acute/chronic diarrhea

Risk factors
-- untreated surface water or inadequately treated surface water
-- groups with poor oral-fecal hygiene = small children in daycare, sexually-active male homosexuals, institutionalized patients
-- travel to endemic areas
Clinical presentation of Giardiasis?
1. Acute onset diarrhea, abdominal cramping, bloating, flatulence, n/v, anorexia, weight loss, malaise, fever
2. Stools: initally profuse, water and explosive; later, greasy and foul-smelling
3. No blood, pus, or mucus in stool
Giardiasis treatment?
DOC is metronidazole for both children and adults
What is Amebiasis?
Entamoiba histolytica

Amebic dysentera

-- 4% incidence in USA (highest in southwest) but 50% incidence in underdeveloped countries
-- infection varies in severity from asymptomatic to fatal liver abscess
What are the risk factors for Amebiasis?
-- low socioeconomic status in endemic areas (crowding, no indoor plumbing)
-- exposure to immigrants from endemic areas
-- institutionalized patients
-- promiscuous male homosexuality
Amebiasis prevention
- eradication of fecal contaminaton in food and water

- avoid fresh or unprocessed food or water in endemic areas
Amebiasis clinical presentation
Non-invasive infection:
-- abdom pain, chronic or intermittent liquid diarrhea

Invasive (forms cysts)
-- diarrhea (100%), abdom pain (85%), blood in stool (100%), fever (40%), enlarged liver
Amebiasis treatment?
DOC is metronidazole b/c it is a mixed amebicide
-- kills both the luminal and systemic organisms

Treatment with metronidazole may be followed with treatment with a luminal amebicide such as paromomycin.
What does Cryptosporidiosis cause clinically? Spread?
1. Severe, watery diarrhea
2. Infectious oocysts spread via direct contact or contaminated water
3. Individuals at risk include children in day care, male homosexuals, veterinarians, health care workers, travelers, and especially immunocomp patients
How do you treat Cryptosporidiosis?
An effective drug does not exist.

Combined therapy with paromomycin and azithromycin may be of benefin to some AIDS patients

Usually self-limiting unless you are immunocompromised
What causes Chagas' disease?
Trypanosoma cruzi

- spread by bite of blood-sucking triomatid bugs, commonly called the "kissing bug" because it bites the lip of humans
- occurs in Central and South America, especially Brazil
Chagas' disase treatment?
Nifurtimox is available from the CDC.
Malarial overview
1. Transmitted by bite of infected Anopheles mosquito
2. 200-300 million cases/yr worldwide with 1-2 million deaths
3. P. falciparum is the organism in most fatal infections because the parasite occludes capullaries in the lungs, kidneys, and brain to cause hypoxemia
4. U.S. incidence increasing since 7-8 mill citizens visit endemic areas each year
5. "Airport malaria"
6. Most tourists exhibit poor compliance to their prophylactic drug regimen
Malaria clinical presentation?
-- Cyclic fever q48-72h involving RBC lysis
-- Fever cycle begins with 30-60 minutes of shivering followed by hours of sweating and possible CNS dysfunction (confusion, seizure, coma)
-- Acute renal failure - black urine from hemoglonin and malarial pigment
-- Pulmonary edema
P. falciparum and P. malariae life cycle?
- Only one cell cycle occurs in the liver, so the liver is free of infection after >4wks. This is why prophylactic therapy must be continued for several weeks after the patient has returned home.
- Treatment of RBC stage cures the infection
P. ovale and P. vivax life cycle?
- The hepatic infection is persistent, so the infection can appear in the RBCs after the RBC stage of the organisms has been killed with drugs = RELAPSE
- In order to kill the infection, you have to kill both the RBC stage and the hepatic stage
Name the antimalarial drugs.
chloroquine MOA?
After parasites within RBCs digest hemoglobin in their food vacuoles, the released heme is rendered nontoxic to the parasite by non-enzymatic polymerization into the malarial pigment hemozoin.

Chloroquine prevents this polymerization and the free heme kills the parasite by oxidative damage of the cell membranes.
chloroquine use?
kills the erythrocytic state of P.vivax, P.ovale, and P.malariae and sensitive strains of P.falciparum.

NO effect on the exoerythrocytic (hepatic) stage of the disease
What is the only drug which kills the hepatic form of P.vivax and P.ovale?
Primaquine!! It is a gametocide against all Plasmodium.

Often given after erythrocytic form killed by chloriquine.
Primaquine MOA
Primaquine S/Es?
Hemolytic anemia in patients with a genetic deficiency of G-6-P dehydrogenase
-- usually in patients of Mediterranean or Asian ancestry
-- prevents RBCs from synth reducing equivalents (NADPH) which prptect cell membrane from oxidative damage
-- patients should be tested for deficiency before taking
Primaquine and pregnant women
Avoid use b/c fetus does not have well-developed G-6-P dehydronase system
- a controversial drug - given p.o. once a week

-- one of the only drugs able to suppress and cure infections caused by MDR strains of P. falciparum
Mefloquine S/Es?
1. frequent = n/v, diarrhea, abdom pain, dixxiness, dysphoria, may be difficult to distinguish from early stage of Plasmodium infection

2. 50% of patients = headache, ataxia, visual/auditory hallucinations, dizziness; usually mild and self-limiting

3. rare = disorientation, seizures, neurotic/psychotic symptoms
Doxycycline, clindamycin, and malaria??
active against the erythrocytic forms of all 4 species of Plasmodium

Used to treat MDR malaria.
Radical cure for P.ovale and P.vivax?
Use chloroquine to kill RBC form.

Use primaquine to kill liver hypnozoites
Malarial prophylaxis?
Chloroquine-sensitive areas:
Use chloroquine - safe in kids

Chloroquine-resistant areas:
1. atavaquone + proguanil - best tolerated tx
2. mefloquine - safe in children
3. doxycycline
4. primaquine is an alternative

Begin treatment two weeks prior to travel and continue four weeks after leaving the endemic areas
Toxoplasma gondii treatment (toxoplasmosis)?
-- pyrimethamine-sulfiazidine is the DOC for immunocomp patients

--Trim-sulfa is used for prophylaxis in AIDS patients
What are the helminthic parasites?
Round worms (nematodes)

Tape worms (cestodes)

Fluke worms (trematodes)
Pneumocystis jiroveci overview
--categorized as a fungus, but killed by antiprotazoal drugs

-- causes pulmonary infections in AIDS patients
Pneumocystis jiroveci treatment?
DOC is trim-sulfa

Pentamidine is second choice for treatment b/c less efficacious and more toxic
What are the round worms?
**the most common helminthic infection
1. pinworm (Enterobios vermicularis)
2. roundworm (Ascaris lumbricoides)
3. hookworm (Necator americanus and Ancyclostoma duodenale)
4. threadworm (Strongyloides stercoralis)
5. whipworm (Trichuris trichuria)
What are the tape worms?
cow - Taenia saginata

pig - Ternia solium
cysts in larval stage = cyticercosis

fish - Diphyllobothrium latum
What are the fluke worms?
Causes schistosomiasis...

Schistosoma haematobium, S.japonicum, and S.mansoni
albendazole and mebendazole MOA?
-- inhibits synthesis of microtubules needed for glucose uptake
-- causes decreased glycogen and ATP concentration
-- parasite dies or is immobilized and cleared from the GI tract
**also larvicidal and ovicidal
pyrantel pamoate MOA?
ganglionic nicotinic cholinergic agonists = muscular tetany

Resulting neuromuscular paralysis allows peristaltic clearance from GI tract
piperazine MOA?
-- a GABA agonist at the neuromuscular jxn
-- increased Cl conductance hyperpolarizes muscles and prevents the excitation caused by ACh
-- flaccid muscle paralysis as result
ivermectin MOA?
-- releases GABA and increases GABA binding
-- facilitates opening of Cl channels in NMJ
-- result is flaccid muscle paralysis of helminths, insects, and ectoparasites
-- may also cause tonic paralysis of musculature of nematodes via glutamate-gated Cl- channels found only in invertebrates
praziquantal MOA?
opens Ca channels to cause muscular tetany
-- spastic paralysis
-- causes tegmental damage which activates host immune system
p.o. qd

ATOVAQUONE -- is a ubiquinone which blocks cytochrome-mediated electron transport which in turn destroys the mitoch mbrn difference potential

PROGUANIL -- enhances stability of atavaquone to destroy the mitoch mbrn potential and also prevents development of resistance

Used for prophylaxis and treatment of MDR P.falciparum
niclosamide MOA?
kills cestodes by inhibition of oxidative phosphorylation
Pinworm incidence, clinical presentation?
**most common helminthic infection in the USA
-- about 40 million cases/yr, primarily in children 4-14

- local itching, especially severe at night
- local irritation from scratching
- positive cellophane tape test for eggs
Pinworm treatment?
mebendazole -- kills round and tape worms

pyrantel pamoate -- kills round worms

albendazole -- kills all worms in mixed infections
Roundworm incidence, clinical presentation?
**most common helminthic infection in the world
--about 4 mil cases/yr in U.S., mostly in SE
--prevalent in very young children

- usually asymptomatic
- malnutrition
- bowel obstruction
Roundworm treatment?
albendazole, although piperazine is also effective

(piperazine is not used for other helminthic infections and has several contraindications)
Hookworm incidence, clinical presentation?
Low incidence in U.S.; found in SE
Risk factors: walking barefoot in endemic areas, poor sewage system

-- iron-deficiency anemia (worm ingests 0.02-0.02ml of blood/day)
Hookworm treatment?
albendazole,pyrantel pamoate, or mebendasole
Threadworm incidence, clinical presentation?
Uncommon, but potentially lethal, espec. in immunocomp patients
**0.4-4.0% incidence in U.S.

--n/v/d, abdom pain, weight loss, malnutrition, pulmonary drainage
Threadworm treatment?
DOC - ivermectin
Ivermectin uses?
1. Single dose giver twice yearly kills the filarial infection causing river blindness

2. single dose given to livestock kills all roundworms and arthropods (ticks, mites, other insects) for 30 days
Cestode incidence, clinical presentation?
**low incidence in U.S. - acquired via ingestion of infected raw meat

-- usually asymptomatic except for cysticercosis caused by the pork tapeworm
-- usually seen in children with focal neural findings, increased intracranial pressure and seizures
-- larval cysts can become calcified and seen with radiological imaging
-- milf abdom pain, eggs and proglottids in feces
Cestode treatment?
DOC is albendazole b/c it kills all worms including larval stage of pork tapeworm (cysticercosis)
-- follow treatment with laxative drug to expel remaining eggs in GI tract

Niclosamide listed as DOC in many textbooks, but not available in U.S.
Trematode incidence, clinical presentation?
**400,000 cases/yr in USA, mainly immigrants and travelers to endemic areas (Africa, S. America, Middle East, China, Japan, Phillipines, Puerto Rico)
-- infection cannot be transmitted in USA b/c intermediate snail host does not live in USA

-- dermatits from penetration, anemia, chills, abdom pain, fatigue, intermittent diarrhea, sweating, enlarged liver/spleen/lymph nodes, hepatitis
Trematode treatment?
DOC is praziquantal

("fluky" word b/c has q,z--treats flukes)
Albendazole...wide use?
Broad spectrum: kills pinworms, hookworms, roundworms, threadworms, tapeworms, and flukes.

DOC for mixed infections by roundworms and tapeworms

Low F - okay b/c worms live in GI

S/Es -- abdominal pain, reversible alopecia, increased LFT
What are ectoparasites?
Pediculosis (lice)
- Pediculus humanus capitus
- Pediculus humanus corporus
- Phthirus pubis (genital)

- Sarcoptes sabiei
What causes pediculosis?
Pediculus humanus capitus
Pediculus humanus corporus
Phthirus pubis (genital)

risk factors: poor hygiene, social or sexual contact with infected host

lice feed on blood and lay eggs in hair
Pediculosis clinical presentation?
--severe itching in infested areas
--dried blood
--secondary bacterial infections
--eggs may be seen attached to base of hairs
--chronic body infection can lead to hyperpigmentation and skin thickening
Pediculosis treatment?
DOC is permethrin cream
HEAD: saturate with solution after shampooing and drying; wrap head in towel and wait 10 minutes; rinse drug from hair
BODY - treat clothes
PUBUS - apply 1% permethrin cream for 10 minutes, rinse
EYELASHES - treat with 1% yellow mercury oxide ointment
Malathion avb for infestations caused by lice resistant to permethrin
-- A 1% lindane shampoo is available
What causes scabies?
Itch mite - Sarcoptes sabiei

Any part of skin may be infested, but prefers interdigital, popliteal, and axillary folds, umbilicus and scrotum

Mites feed on blood and lay eggs in epidermis

Risk factors:
- poor hygiene, overcrowding, social and sexual contact with infested hosts
Scabies clinical presentation?
-- classic burrows made by tunneling mites
-- intense itching which is more severe at night
-- scratching btwn fingers, buttocks, groin, and scalp lead to secondary bacterial infections
-- skin scrapings examined under microscope reveal mite presence
Scabies treatment?
DOC is 5% permethrin
1. Scrub skin with warm, soapy water using a soft brush to remove mites
2. Apply 5% permethrin to entire body avoiding face, mucous mbrn, and eyes
3. Wait 8-14h before bathing
4. Repeated treatment may be necessary
-- Ivermectin not FDA approved for scabies, but p.o. admin VERY effective
--espec useful in treatment of scabies in immunocomp, patients with severly encrusted scabies, and patients who have failed therapy with topical permethrin
Adjunctive treatments for lice and scabies?
Calamine lotion
Topical steroid
Improved personal hygiene