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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