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GI Year II repeat > GI infections SHEEHY > Flashcards

GI infections SHEEHY Flashcards

1
Q

agents associated with inducing C Diff

A
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2
Q

Agents AGAINST C dff

A
  • Vancomycin
  • Metronidazole
  • Fidaxomicin
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3
Q

CDI treatment: vancomycin and metronidazole

A
  • • Preferred treatment for severe CDI is vancomycin, equivalent to metronidazole for mild CDI
    • Mechanism of action
    • A glycopeptide
    • Cell wall synthesis inhibitor (D‐Ala‐D‐Ala)
  • • Pharmacokinetics
    • Oral vancomycin is not absorbed systemically and
    • achieves predictably high levels in the colon
    • IV vancomycin has no effect
  • • Adverse effects
    • Red man syndrome
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4
Q

CDI treatment: metronidazole

A
  • • Mostly used for mild CDI, sometimes used in severe cases if oral administration won’t work
    • • Mechanism of action
      • • A nitroimidazole with selective action against anaerobes
      • • Reduced toxic intermediates are incorporated into bacterial DNA
  • • Mechanism of drug activation
    • • Non‐enzymatically reduced by reacting with reduced ferredoxi
  • Pharmacokinetics
    • • Oral and IV administration has wide distribution including crossing the blood‐brain‐barrier
  • • Adverse effects and contraindications
    • • Disulfiram‐like effect (avoid alcohol)
      • • Metallic taste
      • • Nausea
  • • Peripheral neuropathy (dose limiting)
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5
Q

Metronidazole

A

Metronidazole

  • Trade name is Flagyl®
  • Kills flagellated pathogens

• Antiprotozoal drug with potent activity against anaerobes

  • Adverse effects
  • Disulfiram‐like effect (avoid alcohol) • Metallic taste
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6
Q

CDI treatment: fidaxomicin

A
  • CDI treatment: fidaxomicin
    • • Shown to be superior to vancomycin in treating recurrences of CDI
    • • Spares many anaerobic colonic flora
  • • Mechanism of action
    • • Bacterial protein synthesis inhibitor, binds sigma subunit of RNA polymerase
  • • Pharmacokinetics
    • • Given orally, limited distribution outside GI tract
  • • Adverse effects and contraindications •
    • Well tolerated, limited GI side effects
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7
Q

Helicobacter pylori

A

Helicobacter pylori

  • Most common cause of duodenal ulcers and chronic gastritis
  • Bismuth subsalicylate • Pepto‐Bismol®

Metronidazole

Tetracycline

• Protein synthesis inhibitor

  • Omeprazole
  • Proton pump inhibitor
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8
Q

Trophozoite ‐> binucleated

precyst ‐> tetranucleated cyst

A

Entamoeba histolytica

Trophozoite ‐> binucleated

precyst ‐> tetranucleated cyst

  • Trophozoites invade intestinal mucosa (10%)
  • Portal blood circulation
  • Liver abscesses
  • Pulmonary abscesses and often death
  • Pathogenic if red blood cells in cytoplasm (stool sample)
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9
Q

EA Tx

A

Therapeutic goals:

• Eliminate the invading trophozoites

  • • Metronidazole
  • • Tinidazole

• Eradicate intestinal carriage of the organism (luminal amebicide)

  • • Paromomycin
  • • Iodoquinol

• Asymptomatic carriage

  • • Cysts or trophozoites without internalized red blood cells
  • • Treated with luminal amebicide agents
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10
Q

Entamoeba histolytica treatment: Metronidazole and tinidazole

A

Metronidazole is the drug of choice in the treatment of extraluminal amebiasis

  • • Kills trophozoites but not the cysts of E. histolytica
  • • Eradicates intestinal and extraintestinal tissue infections

• Tinidazole

  • • Similar activity and similar adverse effects
  • • Somewhat better tolerated than metronidazole

• Both metronidazole and tinidazole must be given with a luminal amebicide to ensure eradication of the E. histolytica infection!

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11
Q

Entamoeba histolytica treatment: Paromomycin

A
  • Used as a luminal amebicide, no effect against extraintestinal organisms
  • The antiamebic luminal agent of choice in the USA
  • Mechanism of action
  • • An aminoglycoside antibiotic
  • • Irreversible protein synthesis inhibitor

• Pharmacokinetics

  • • No significant absorption outside of GI tract

• Adverse effects and contraindications

  • • Occasional abdominal distress and diarrhea
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12
Q

Entamoeba histolytica treatment: Iodoquinol

A

Entamoeba histolytica treatment: Iodoquinol

  • Used as a luminal amebicide, no effect against extraintestinal organisms
  • Mechanism of action
  • • A halogenated hydroxyquinoline
  • • Unknown mechanism in E. histolytica

• Pharmacokinetics

  • • 90% retained in the intestine and excreted in the feces

• Adverse effects and contraindications

  • • Diarrhea, anorexia, nausea, vomiting, abdominal pain,
  • headache, rash, pruritus
  • Severe neurotoxicity with high dose or prolonged use
  • Contraindicated in patients with intolerance to iodine
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13
Q

Giardia lamblia

A
  • Giardia lamblia
    • Trophozoite ‐> cyst
    • 5% of US adults infected
    • • Most asymptomatic
  • • Coating of small intestine interferes with fat absorption
  • • Stools packed with fat (smelly)
  • • Greasy, frothy diarrhea
  • • Abdominal gassy distension
  • • Cramps
  • • No invasion of intestinal wall
  • • No blood in the stool!
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14
Q

Giardia lamblia: treatment

A
  • Supportive
  • • Correct fluid and electrolyte abnormalities that result from diarrhea
  • • Pharmacological agents
    • • Tinidazole
    • • First line agent
  • • Metronidazole?
  • • Nitazoxanide
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15
Q

Giardia lamblia treatment: Nitazoxanide

A
  • giardia lamblia treatment: Nitazoxanide
  • • Mechanism of action
    • • Inhibition of the pyruvate‐ferredoxin oxidoreductase pathway
  • • Mechanism of drug activation
    • • Prodrug, active metabolite = tizoxanide
  • • Pharmacokinetics
    • • Rapidly absorbed, excreted in urine and feces
  • • Adverse effects and contraindications
    • • Nausea, anorexia, flatulence, increased appetite, enlarged salivary glands, yellow eyes, dysuria, bright yellow urine
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16
Q

Cryptosporidium parvum

A
  • • Contaminated water, day care, travelers
  • • Oocyst with 4 motile sporozoites
  • • Life cycle within intestinal epithelial cells
  • • Diarrhea and abdominal pain
  • • Self limiting with immunocompetency
  • • Immunocompromised
    • • Severe life threatening diarrhea • 3‐17 liters per day
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17
Q

Cryptosporidum Parvum: tx

A
  • parvum treatment
  • • Antidiarrheal agents
    • Loperamide
  • Fluid management
  • Antimicrobial agents
    • Nitazoxanide
      • Preferred agent
    • Paromomycin
      • Nonabsorbable aminoglycoside
  • Dependent on the immune status of the patient
  • Immunocompromised patient
    • HIV = antiretroviral therapy + nitazoxanide (if needed)
    • Other = reduce dose of immunosuppressant + nitazoxanide
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18
Q

Nitazoxanide vs paromomycin in treating C. parvum infection

A

Nitazoxanide vs paromomycin in treating C. parvum infection

Nitazoxanide has superior efficacy compared with paromomycin in treating C. parvum infection

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19
Q

Helminths

A

Helminths

  • Greek for worm
  • Usually macroscopic
  • Diagnosis requires visualization of microscopic eggs (in feces)
  • Namatodes = round worms
  • Platyhelminhes = flat worms
  • No immune response to worm
  • Response to dead worms and eggs
  • Elevation of eosinophils
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20
Q
A
21
Q

Nematodes

A
  • Necator americanus
    • • Ancyclostoma duodenale
    • • Ascaris lumbricoides
    • • Strongyloides stercoralis
    • • Trichuris tichiura
    • • Enterobius vermicularis
22
Q

Necator americanus and Ancylostoma duodenale (hook worms): life cycle and symptoms

A
  1. Penetrates skin in‐between toes
  2. Larvae travel to lungs (alveoli)
  3. Larvae grow, are coughed up, and swallowed
  4. Adult worms develop in small intestine
  5. Worms copulate and release fertilized eggs
  6. Eggs excreted in feces
  7. Eggs hatch and larvae live in soil

Diarrhea, abdominal pain, weight loss
• Anemia (iron deficiency)
• Intense itching at site of penetration (toes)

23
Q

Ascaris lumbricoides

A
  • Life cycle
  • Consumption of eggs (contaminated food)
  • Larvae penetrate intestine and travel to lung
  • Larvae grow, are coughed up, and swallowed
  • Adult worms develop in small intestine
  • Worms copulate and release fertilized eggs
  • Eggs excreted in feces
  • Eggs hatch and larvae live in soi
  • • Abdominal cramping, malnutrition, worm invasion
24
Q

Strongyloides stercoralis

A
  • Strongyloides stercoralis
    • • Life cycle
    • • Larvae in soil, penetrates human skin, travels to lungs
    • • Larvae grow in lungs, are coughed up, and swallowed into small intestine
    • • Mature worms form in small intestine and release eggs
    • • EGGS ARE NOT PASSED IN THE STOOL
    • • Hatched larvae can:
      • • Autoinfect
      • • Excrete in feces, infect (direct cycle)
      • • Excrete in feces, mature, lay eggs, new larvae infect (indirect cycle)
25
Q

Strongyloides stercoralis: symptoms, diagnosis

A
  • Strongyloides stercoralis
    • Vomiting, abdominal bloating, diarrhea, anemia, weight loss
    • Similar to hook worm:
      • Pruritic rash, lung symptoms, eosinophilia
        • Immunosuppressive medications can lead to severe autoinfection
        • Prednisone
        • • Asthma
    • Diagnosis
      • Larvae in feces
      • Enterotest
26
Q
A
27
Q

Trichuris tichiura (whip worm): life cycle and

A
  • Trichuris tichiura (whip worm)
  • Simple life cycle
    • Ingestion of food with infective eggs
    • Eggs hatch in small intestine, migration to cecum and ascending large intestine
    • Mature adult produces thousands of eggs per day for 1 year
    • NO larvae, NO transit through intestinal wall, NO lung involvement, NO eosinophilia, NO autoinfection
  • Abdominal pain and diarrhea
  • Diagnosis = eggs in feces (football shaped)
28
Q

Enterobius vermicularis (pinworm)

A
  • Enterobius vermicularis (pinworm)
  • Life cycle
    • • Eggs ingested, pinworms mature in cecum and ascending large intestine
    • • Female migrates to perianal area (at night) to lay eggs
    • • Eggs infectious 4‐6 hours later
    • • Severe perianal itching (nuisance)
    • • Hand to mouth transmission
    • • Scotch tape test
    • • No eosinophilia
29
Q

Nematode treatment

A
  • Albendazole
  • Mebendazole
  • Ivermectin
  • Thiabendazole
  • Pyrantel pamoate
30
Q

Albendazole and mebendazole

A
  • Broad‐spectrum oral antihelminthic agents
  • • Mechanism of action
    • • Inhibits microtubule synthesis, paralyzes worms, passed out in stool
  • • Mechanism of drug activation
    • • Pro drug, active metabolite after first pass effect
    • • Albendazole sulfoxide
  • Pharmacokinetics
    • • Wide distribution
  • • Adverse effects
    • • Few with acute treatment
    • • Can cause abdominal distress, headaches, fever, fatigue, and alopecia with long‐term use
  • • Contraindications
    • • Cirrhosis, pregnancy
31
Q

Nematode treatment: Thiabendazole

A
  • treatment: Thiabendazole
  • • Mechanism of action
    • • Same as albendazole and mebendazole
  • • Pharmacokinetics
    • • Rapidly absorbed after ingestion, largely excreted in urine, can be absorbed from the skin
  • • Adverse effects
    • • Much more toxic than albendazole and mebendazole
    • • Common (dizziness, anorexia, nausea, vomiting)
    • • Irreversible liver failure and fatal Stevens‐Johnson syndrome
  • • Contraindications
    • • Pregnancy, hepatic or renal diseas
32
Q

Anti‐helminthic benzimidazoles

A

Anti‐helminthic benzimidazoles: Albendazole, mebendazole, thiabendazole

33
Q

Nematode treatment: Ivermectin

A
  • Ivermectin
  • Mechanism of action
    • Intensifies γ‐aminobutyric acid (GABA)‐mediated transmission of signals in peripheral nerves of the nematode
  • • Pharmacokinetics
    • Rapidly absorbed, oral only, wide distribution, excretion in feces
  • Adverse effects
    • Uncommon (fatigue, dizziness, nausea, vomiting, abdominal pain, rashes)
  • Contraindications
    • Pregnancy
    • Drugs that enhance GABA activity (barbituates, benzodiazepines, valproic acid)
34
Q

Nematode Treatment: Pyrantel pamoate

A
  • Pyrantel pamoate
    • Mechanism of action
      • Neuromuscular blocking agent, causes release of acetylcholine and inhibition of cholinesterase
    • Results in paralysis and expulsion of the nematode
    • Pharmacokinetics
      • Poorly absorbed from GI tract, half of administered dose recovered unchanged in feces
  • Adverse effects
    • Infrequent and transient
  • Contraindications
    • Liver dysfunction
35
Q
A
36
Q

Trematodes

A
  • Trematodes:
    • Schistosomas (blood flukes)
      • Extremely common worldwide, found in fresh water
      • Invade venous system through exposed skin
      • Eggs must reach fresh water to hatch
      • Adult worms are able to survive and release eggs for years!
    • S. mansoni
    • Not killed by immune system
37
Q

Trematodes: life cycle and clinical manifestations

A
    • Eggs hatch in fresh water, larvae infect and mature within a snail
      • Mature larvae (cercariae) leave snails and infect humans (exposed skin)
      • Cercariae mature and mate in the intrahepatic portion of the portal venous system
      • Mating mature worms migrate to veins surrounding intestine of bladder to lay their eggs
      • Eggs enter the lumen of the intestine or bladder to be excreted
  • Clinical manifestations
    • Dermatitis (immediate)
    • Katayama fever (4‐8 weeks)
    • chronic fibrosis (years)
38
Q

Schistosomiasis life cycle and diagnosis

A
  • Trematodes:
    • Schistosomas (blood flukes)
      • Many eggs from mature Schistosomas do not reach the lumen of the intestine or bladder
      • Liver, lung, brain
      • Granulomas
      • Fibrosis and portal hypertension in liver
      • Inflammation and ulcers
      • Hematuria, chronic abdominal pain and diarrhea, brain or spinal cord injury, or pulmonary artery hypertension
    • Diagnosis
      • Eggs in stool or urine, serology for antibodies, eosinophilia
39
Q

Praziquantel

A

Schistosomiasis tx

40
Q

Schistosomas (blood flukes) treatment: the drug of choice

A
  • Schistosomas (blood flukes) treatment:
    • Praziquantel is the drug of choice
      • Effective against Schistosome and most other trematode and cestode infections
      • Mechanism of action
        • Increases the permeability of trematode and cestode cell membranes to calcium
        • resulting in paralysis, dislodgement, and death
      • Pharmacokinetics
        • Oral administration, rapidly absorbed, excreted mainly by kidneys
      • Adverse effects
        • Immediate: headache, dizziness, drowsiness, lassitude
        • After several days: low‐grade fever, pruritus, skin rashes
        • Contraindications
          • Pregnancy
41
Q

Cestodes (tape worms): parts

A
  • Cestodes (tape worms)
    • Flat worms
    • Lack a digestive tract
    • Hermaphrodites
    • Chain of segments (proglottids)
    • Parts
      • Scolex
      • Immature proglottids
      • Mature proglottids
      • Gravid proglottids
42
Q
  • Cestodes
  • Taenia solium (pork) and Taenia saginata (beef)
    • Acquired by ingestion of undercooked meat containing larvae
    • Attaches via hooks (T. solium) or suckers (T. saginata)
    • Release eggs in feces
  • Diagnosed by proglottids and/or eggs in feces
  • T. solium
    • Life cycle:
      • Pigs/cows ingest egg from field contaminated with human feces
      • Larvae disseminate through the intestine into the muscle of the animal
      • Larvae develop into cysticerci
      • Human ingests undercooked meat, tape worm matures in intestine
A
43
Q 
Cestodes
Taenia solium (pork) and Taenia saginata (beef)

Clinical manifestations

A
  • Cestodes
  • Taenia solium (pork) and Taenia saginata (beef)
  • Clinical manifestations
    • Weight loss, malnutrition
  • Cysticercosis (T. solium only)
    • Humans play the role of the pig and ingest eggs
    • Larvae penetrate human tissue, forming cysticerci • Brain and skeletal muscle
    • Neurocysticercosis
    • 7‐10 cysts in the brain
    • Seizures (most common in endemic areas)
    • After 5‐10 years cysts die and leak contents (seizures, meningitis, hydrocephalus)
44
Q

Cestodes

Diphyllobothrium latum

A
  • Cestodes
  • Diphyllobothrium latum
    • Acquired by ingesting larvae in raw freshwater fish
    • Life cycle:
      • Adult tape worm in human ingestion excretes gravid
      • proglottids with eggs
      • Eggs hatch in the water and convert to motile larvae
      • Ingested by a crustacean
      • Ingested by fresh water fish (trout,salmon,pike)
      • Ingested by human
  • Few abdominal symptoms, absorbs vitamin B12 (anemia)
  • Diagnosis
    • Proglottids and eggs in feces
45
Q
  • Echinococcus granulosus
  • Hydatid Disease (Cystic echinoccosis)
    • Larva forms a single, round fluid filled “hydatid” cyst
    • Asexual budding to form daughter cysts • Protoscolices inside original cyst
    • Grow 5‐10 centimeters in size
    • Compresses surrounding organs
    • Internal fluid extremely allergenic
    • Surgical removal (challenging)
A
46
Q

Cestode tx

A

Praziquantel • Niclosamide • Albendazole

47
Q

Cestode treatment:

Niclosamide

A
  • Cestode treatment:
  • Niclosamide
    • • Alternative drug for treatment of most tape worm infections • Not effective against cysticercosis of hydatid disease
  • • Mechanism of action
    • • Inhibition of oxidative phosphorylation or stimulation of ATPase activity
  • Pharmacokinetics
    • Oral administration
  • Adverse effects
    • Infrequent, mild (nausea, vomiting, diarrhea, abdominal discomfort)
  • Contraindications
    • Pregnancy, children younger than 2
    • Alcohol consumption
      *
48
Q
A

GI Year II repeat (20 decks)

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