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USMLE1 Anti-Protozoal drugs-2

Anti-Ameobic Drugs
Asymptomatic cysts carriers: Iodoquinol   or Paromomycin or Diloxanide furoate
Diarrhea / Dysentery: Metronidazole + Iodoquinol or Paromomycin or Diloxanide
Amebic liver abcess: Metronidazole + Chloroquine
Protozoal Infections:
Giardiasis :
          is a diarrheal infection of the small intestine by Giardia lamblia
Transmission
         Giardiasis is caused by the ingestion of infective cysts.
         Person-to-person transmission accounts for a majority of Giardia infections and is usually associated with poor hygiene and sanitation.
         Water-borne transmission is common in United States Giardia epidemics, which are often associated with the ingestion of unfiltered water (contaminated).
         Venereal transmission happens through fecal-oral contamination.
Symptoms
         Fever, abdominal cramps
         explosive, watery diarrhea, vomiting
         loss of appetite, malaise, and fatigue.
Rx: Metronidazole
Trichomoniasis:
         is a common cause of vaginitis (STD).
         is caused protozoa Trichomonas vaginalis
         Trichomoniasis is primarily an infection of the urogenital tract; the most common site of infection is the urethra and the vagina.
Symptoms
          inflammation of the cervix (cervicitis), urethra (urethritis), and vagina (vaginitis) which produce an itching or burning sensation.
         Discomfort increases during intercourse and urination.
         Yellow-green, itchy, frothy foul-smelling vaginal discharge
          Lower abdominal pain
Symptoms usually appear in women within 5 to 28 days of exposure.
Rx: Metronidazole 2000mg( 2gms) single dose.
Trypanosomiasis refers to two chronic diseases caused by  Trypanosoma:
         African sleeping sickness, and
         American sleeping sickness
African trypanosomiasis: the disease is transmitted  in the following ways:
         bite of the tsetse fly.
         Mother to child infection
          through the handling of blood of an infected person and organ transplantation
         Blood transfusion
         Sexual contact (might be possible, but happens rarely)
Symptoms and clinical features
         Symptoms begin with fever, headaches, and joint pains, lymph node swelling
( Winterbottom's sign, the tell-tale swollen lymph nodes along the back of the neck)
If untreated
          anemia, endocrine, cardiac, and kidney diseases . The disease then enters a neurological phase when the parasite passes through the blood-brain barrier
         sleep cycle is disturbed with bouts of fatigue punctuated with manic periods progressing to daytime slumber and night-time insomnia.
         Without treatment, the disease is invariably fatal, with progressive mental deterioration leading to coma and death.
The diagnosis rests upon demonstrating trypanosomes by microscopic examination of  body fluid, lymph node aspirates, blood, bone marrow, or, cerebrospinal fluid.
Chagas' disease (American sleeping sickness)
         is a tropical parasitic disease caused by Trypanosoma cruzi. T. cruzi is commonly transmitted to humans and other mammals by an insect vector
The disease may also be spread through
         blood transfusion and organ transplantation
         ingestion of food contaminated with parasites, and
         from a mother to her fetus
Signs and symptoms: 2 stages
Acute stage: Sign and symptoms
         fever, fatigue, body aches, headache, rash, loss of appetite, diarrhea, and vomiting.
         The signs on physical examination can include mild enlargement of the liver or spleen, swollen glands, and local swelling (a chagoma) where the parasite entered the body.
The most recognized marker of acute Chagas disease is called Romaña's sign, which includes swelling of the eyelids on the side of the face near the bite wound.
Chronic : occurs several years  after initial infection:
         The symptomatic chronic stage affects the nervous system,  digestive system and heart
         About two thirds of people with chronic symptoms have cardiac damage, including cardiomyopathy  which causes arrythmias  and may result in sudden death.
         About one third of patients go on to develop digestive system  damage, resulting in dilation of the digestive tract (megacolon and megaesophagus), accompanied by severe weight loss.
Swallowing difficulties may be the first symptom of digestive disturbances and may lead to malnutrition. Secondary achalasia may arise from Chagas disease.
Drugs used  for Trypanosomiasis:
         Melarsoprol
         Pentamidine isethionate
         Nifurtimox
         Suramin
         Benznidazole
Melarsoprol :
         Trivalent arsenical compound
         Mainly used to treat trypanosoma infections with CNS involvement
Mechanism of Action:
         The drug acts by reacting with sulfhydryl groups of various enzymes in both parasite and host – more sensitive to parasite enzymes.
         Well absorbed orally
         Well distributed to CNS
         Short half life and excreted in urine
Adverse effects:
         Encephalopathy
         Hemolytic anemia in G-6-PD deficiency
Pentamidine :  Active against
         protozoa – trypanosoma and leshmaniasis and
         fungus - blastomyces
Mechanism of Action:
         T. brucei concentrates the pentamidine by active uptake system and interfere with synthesis of RNA, DNA and proteins.
         Administered IV or aerosol
         Does not penetrate  CNS
         Excreted by the kidney
Adverse effects:
         Nephrotoxicity
         It can cause histamine release
         Mental confusion , liver and kidney damage
         Lysis of pancreatic beta cells
Nifurtimox
         Used in the treatment of Trypanosoma cruzi.
         It acts by generating super oxide and hydrogen peroxide radicals – toxic to t.cruzi as they lack catalase.
         Orally well absorbed
Adverse effects:
         Anaphylaxis and peripheral neuropathy are common.
Suramin
         Used in the early treatment and prophylaxis of African trypanosomiasis.
MOA:
         It acts by inhibiting many enzymes of energy metabolism including glycerol phosphate dehydrogenase – for trypanocidal activity.
         Used intravenously
         Accumulated in liver and kidney
Adverse effects:
         Photophobia, palpebral edema, paresthesias.

Leishmaniasis
Leishmaniasis is a disease caused by Leishmania and is transmitted by the bite of certain species of sand fly (subfamily Phlebotominae).
Classification :  divided into the following types:
          Cutaneous leishmaniasis : most common form
          Mucocutaneous leishmaniasis
          Visceral leishmaniasis: severe form in which the parasites have migrated to the vital organs
          Post-kala-azar dermal leishmaniasis
          Viscerotropic leishmaniasis
Cutaneous leishmaniasis of the Old World heals in 4-18 months leaving a scar. No serious sequelae occur. It may be left alone but is usually treated with intra-lesional sodium stibogluconate therapy.
New World cutaneous leishmaniasis should be treated due to the risk of mucocutaneous disease and sodium stibogluconate is given intravenously
Visceral leishmaniasis is most commonly caused by Leishmania donovani. Fever, malaise, anaemia, weakness and weight loss are common Hepatosplenomegaly develops gradually and the skin may become grey.
Treatments
          Pentavalent antimonials, such as sodium stibogluconate, are the conventional therapy used in the treatment of leishmaniasis, with pentamidine and amphotericin B as backup agents.
          Allopurinol has also been reported to be effective (it is converted to a toxic metabolite by the amastigote form of the organism).
Sodium stibogluconate:
          The exact mechanism of action has not been determined.
          Evidence for inhibition of glycolysis in the parasite at the phosphofructokinase reaction has been found.
          Because it is not absorbed on oral administration, sodium stibogluconate must be administered parenterally, and it is distributed in the extravascular compartment.
          Metabolism is minimal, and the drug is excreted in the urine
Adverse effects include
          pain at the injection site
          gastrointestinal upsets, and
          cardiac arrhythmias
Renal and hepatic function should be monitored periodically.












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