PARASITIC INFECTIONS Parasitic diseases are prevalent under conditions of crowding, poverty and...
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Transcript of PARASITIC INFECTIONS Parasitic diseases are prevalent under conditions of crowding, poverty and...
PARASITIC INFECTIONS
Parasitic diseases are prevalent under conditions of crowding, poverty and poor sanitation and constitute one of the major health problems of man.
PARASITIC INFECTIONS
Found throughout the world. With increasing travel, immigration and the use of immunosuppressive drugs and the spread of AIDS, health care workers anywhere may see infections caused by previously unfamiliar parasites.
PARASITIC INFECTIONS
They are often chronic in nature . They generally don’t produce sudden, severe life-threatening infections.
PARASITIC INFECTIONS
Successful control is dependent on a variety of public health measures including vector control, improvement of sanitation, health education and drug administration.
MALARIA
A world-wide common cause of mortality and morbidity.
The decrease in spraying and the increase in resistance have resulted in a resurgence of this disease.
MALARIA
An estimated 500 million people are infected with malaria annually and at least 2.5 million die mostly in Africa.
In endemic areas young children are at greatest risk because their natural immunity to the disease is weakest.
MALARIA
In the near future the major mechanism for combating the disease will be a combination of vector control and drugs.
TREATMENT OF MALARIA
Differs greatly from one region to another depending upon the type of Plasmodium species and the degree of drug resistance.
MALARIA
Characterized clinically by spasms of severe chills, fever and profuse sweating.
These episodes sometimes occur at reasonably well-defined intervals determined by the life cycle of the invading Plasmodium.
MALARIA
Other frequent symptoms of a malarial attack include malaise, headache, delirium, aching muscles, abdominal discomfort, vomiting and diarrhea.
In some cases the disease can become chronic with repeated relapses.
It results from infection with protozoa of the genus Plasmodium.
MALARIA
Usually transmitted by mosquito bite but also by transfusion of infected blood and by sharing needles.
PLASMODIA SPP. AFFECTING MANMore than 100 species, those infecting
man include:P. vivaxP.falciparumP.malariaP.ovale
MALARIA
P.Falciparum malaria causes a majority (80 %) of the cases of malaria and nearly all the deaths. (Malaria caused by other species is rarely fatal but is more difficult to cure completely).
This is called malignant tertian malaria (fever spikes occur irregularly).
MALARIA
The next most common type is the tertian variety caused by P.vivax (fever spikes occurring every other day).
P.ovale similar to vivax.
Quartan malaria is caused by P.malariae.
MALARIA
The lapse between invasion time and onset of clinical symptoms varies with the Plasmodium species as does the frequency of the fever spikes.
ANTIMALARIAL DRUGS
Antimalarials can be classified on the basis of their action at different stages in the life cycle of the parasite in the human.
None of the antimalarials are true prophylactics.
BLOOD SCHIZONTICIDES
Drugs in this class act rapidly on the erythrocytic stage to relieve clinical attacks (most sensitive to antimalarial drugs).
BLOOD SCHIZONTICIDES
Treatment of the erythrocytic stage makes the patient asymptomatic but often does not completely get rid of the parasite.
When therapy is stopped symptoms will resume.
BLOOD SCHIZONTICIDES
If a person stays in the area, continual reinvasion will occur and it is not reasonable to attempt complete eradication of the parasite.
TISSUE SCHIZONTOCIDES
Used prophylactically to prevent the erythrocytic stage of malaria.
Prevent relapse as they act on primary tissue forms.
Primaquine.
P.falciparum
Upon rupture of the hepatic schizont there is no reinvasion of the liver.
Resistance occurs more readily with P.falciparum.
ANTIMALARIAL ACTIVITY
Highly effective vs. erythrocytic forms of P.vivax, P.ovale, P.malariae and sensitive forms of P.falciparum.
No activity vs. latent tissue forms of P.vivax and P.ovale.
MECHANISM OF ACTION
Intercalation into parasitic DNA.
Inactivation of hemoglobin proteases vital to the organism by direct binding or raising the intravacuolar pH .
MECHANISM OF ACTION
Interferes with Hb digestion in the blood stages of the parasite life cycle.
The parasite degrades Hb in an acidic food vacuole producing free heme and reactive oxygen spp. as toxic by-products.
MECHANISM OF ACTION
Heme is neutralized by polymerization while the free radicals are also detoxified.
MECHANISM OF ACTION
Chloroquine accumulates several thousand-fold in the food vacuole of the parasite.
Interferes with heme polymerization and/or detoxification of the free radicals effectively killing the parasite with its own metabolic waste.
Hb Chloroquine
Mechanism of action of Chloroquine
RBCFood Vacuole
HemePolymerization
Parasite
Globin
digestion
Heme-Fe(II)2+ Heme-Fe(III)3+
e-
O2 O2-
H2O2
SOD
Catalase Peroxidase
Inhibition of Free Radical Peroxidation
2H+
H2O +1/2 O2Rox + H2O
Chloroquine
X
RESISTANCE
Probably involves multiple mechanisms under complex multigenic control.
Decreased drug accumulation.
ADVICE FOR TRAVELERS
Up to date automated information for travelers is available from the CDC at 888-232-3229 or on the internet at www.cdc.gov.
Malaria branch of the CDC at 770-488-7788.
PHARMACOKINETICS
Rapid and complete absorption after oral administration (also IM and SC).
Accumulates in many tissues especially RBC’s (especially infected ones) and liver.
CLINICAL USESUsed for acute malarial attacks as it is
rapidly acting- cures Plasmodium falciparum malaria.
Chemoprophylactic agent (areas without resistant falciparum malaria).
TOXICITY
Adverse effects are usually mild and reversible especially when used for the short-term treatment of malaria.
Acute toxicity occurs when therapeutic or high doses are administered too rapidly by parenteral routes (primarily cardiovascular and CNS).
TOXICITY
Oral chloroquine-GI upset, headache, urticaria , pruritis and visual disturbances.
High doses and prolonged treatment can produce severe visual and cardiac reactions.
Little or no toxicity when used prophylactically.
PRECAUTIONS AND CONTRAINDICATIONSLiver disease, GI, neurological or blood
disorders.
Glucose-6-phosphate dehydrogenase deficient patients.
Considered safe in pregnancy and in young children.
QUININE AND QUINIDINE
Natural alkaloids isolated from the cinchona tree bark.
Quinidine is an optical isomer of quinine.
Quinidine is more potent and more toxic than quinine.
MECHANISM OF ACTION
Blood schizonticide.
Similar to chloroquine.
Not as extensively concentrated in the food vacuole as chloroquine and may have some alternative targets in the parasite.
PHARMACOKINETICS
Readily absorbed when given orally or IM(also given IV).
Rapidly acting with a short t1/2.
Extensively metabolized (CYP3A4).
THERAPEUTIC USES
Drug of choice for chloroquine-resistant and MDR falciparum malaria (with a sulfonamide, clindamycin or doxycycline).
For severe malaria it is used parenterally (quinidine in the U.S.).
ADVERSE EFFECTS
Bitter taste.
Quinine is an irritant to the GI mucosa and often causes nausea, vomiting or pain.
QUININE- TRIAD OF DOSE-RELATED TOXICITIESCinchonism (tinnitis, headache and
disturbed vision, may progress to C.V. and dermal). GI symptoms are prominent in Cinchonism.
ADVERSE EFFECTS
Hyperinsulinemia and severe hypoglycemia.
Severe hypotension when given too rapidly IV.
ADVERSE EFFECTS
EKG abnormalities with IV quinidine.
Hypersensitivity reactions .
Severe toxicity is rare but may include fever, skin eruptions, GI effects, deafness, visual abnormalities and CNS effects.
PRECAUTIONS AND CONTRAINDICATIONS Pregnancy (teratogenic).
Hemolysis in patients with G-6-P DH deficiency.
Patients with a history of episodes of hemolysis, hypersensitivity and cardiac arrhythmias, tinnitus and optic neuritis.
PHARMACOKINETICS
Pyrimethamine-slow but complete absorption when given orally.
Binds to plasma proteins and accumulates in certain organs.
Pyrimethamine-t1/2 80-95h
Sulfadoxine-t½ 7-9 days
CLINICAL USES
Chloroquine-resistant falciparum malaria in a one dose presumptive self-treatment when medical care is not immediately available (within 24h) for a presumed malaria illness.
TOXICITY
Pyrimethamine alone- little toxicity except occasional skin rashes and decreased hematopoiesis.
High doses - folic acid deficiency (megaloblastic anemia).
Combination- severe and even fatal cutaneous reactions.
MECHANISM OF ACTION
Converted in the liver to active quinone metabolites (active electrophiles). These may generate active oxygen species or
PHARMACOKINETICS
Completely and promptly absorbed when given orally.
Rapidly and extensively metabolized.
Excreted as metabolites.
CLINICAL USES
To prevent relapses (radical cure) of P.vivax and P.ovale infections (used with a blood schizonticide,usually chloroquine).
Terminal prophylaxis after completion of travel to an endemic area to diminish likelihood of a relapse.
ADVERSE EFFECTS
Large doses may cause abdominal distress, nausea and headache.
Hemolytic anemia, cyanosis (methemoglobinemia) and leukocytosis -less common.
ADVERSE EFFECTS
Produces hemolytic anemia in people with glucose-6-phosphate dehydrogenase deficiency.
PRECAUTIONS AND CONTRAINDICATIONS Glucose-6-phosphate DHase deficiency.
Patients with a tendency towards granulocytopenia or methemoglobinemia.
Other potentially hemolytic or bone marrow depressing drugs.
Pregnancy.
MECHANISM OF ACTION
4-aminoquinoline methanol.
It is a blood schizonticide similar to chloroquine and quinine in many aspects.
May inhibit heme polymerization and may form toxic complexes with free heme that damages membranes.
PHARMACOKINETICS
Given orally (parenterally it can cause severe local reactions).
Slowly eliminated (t½ around 20 days)
CLINICAL USES
Used for the treatment and prophylaxis of chloroquine-resistant and multidrug -resistant P.falciparum malaria.
It is the drug of choice for chemoprophylaxis for most travelers.
ADVERSE EFFECTS
GI upset (common).
CNS toxicity is seen in about half of the people who take the drug (dizziness, ataxia, headache etc).
Severe neuropsychiatric disturbances ( rare).
CONTRAINDICATIONS
Pregnancy.
Children less than 2 years old.
Patients with a history of seizures or neuropsychiatric disturbances.
Patients who have had adverse reactions to quinoline antimalarials.
ATOVAQUONE/PROGUANILA fixed dose combination of atovaquone
and proguanil hydrochloride.
Prevents rapid development of resistance to atovaquone.
ANTIMALARIAL ACTIVITY
Both drugs are active vs the erythrocytic forms of P.falciparum including strains resistant to chloroquine, mefloquine and pyrimethamine/sulfadoxine (not active vs hepatic stages).
ADVERSE EFFECTS Abdominal pain, nausea, vomiting, diarrhea,
headache and rash have occurred and are more common with high doses.
Dose-related maculopapular rashes.
Mild elevations in liver aminotransferase activity.
ARTEMISININ
Extract from a Chinese herb.
Artemisinin is insoluble and can only be used orally.
Analogs have been synthesized to improve solubility and improve antimalarial efficacy (artesunate and artemether) .
ANTIMALARIAL ACTIVITY
Active against all malarial species (especially useful for P.falciparum resistance).
Rapidly acting blood schizonticide.
MECHANISM OF ACTION
Free radical production that follows the iron-catalyzed cleavage of the artemisinin endoperoxide bridge.
These covalently modify and damage specific malarial proteins.
CLINICAL USES
Treatment of multidrug-resistant P.falciparum ( in conjunction with another agent such as fansidar or doxycycline).
ADVERSE EFFECTS
Nausea, vomiting and diarrhea.
Irreversible neurotoxicity has been seen with very high doses or long term therapy in animal studies.
Prolongation of the QT interval.
DOXYCYCLINE
Used for treatment and prophylaxis in regions where multi-drug resistance is common.
Used alone for short term prophylaxis.
For treatment they are used in combination with other antimalarials (work slowly).
ANTIMALARIAL CHEMOTHERAPYFor acute attacks chloroquine is the
treatment of choice.
For resistant strains use quinine plus fansidar or plus doxycycline or mefloquine (or atovaquone/proguanil).
ANTIMALARIAL CHEMOTHERAPYFor a radical cure of P.vivax or P.ovale
use primaquine after departure from the endemic area.
For severe attacks use quinine or quinidine parenterally.
CHEMOPROPHYLAXIS OF MALARIA Chloroquine for sensitive strains.
If symptoms of malaria occur while taking chloroquine a therapeutic dose of fansidar should be administered and medical care sought immediately.
Mefloquine and atovaquone/proguanil for chloroquine-resistant strains.
Doxycycline for multi-drug resistance.
AMEBIASIS
Asymptomatic cyst passers- organisms found in the intestinal lumen but patients show no symptoms.
Mild to moderate intestinal amebiasis.
Severe intestinal infection (dysentery).
Amebic liver abscesses.
PAROMOMYCIN (Humatin)
Direct amebicide with antibacterial activity (an aminoglycoside) (luminal amebicide).
Insignificant absorption.
May be useful in other protozoal infections and some worm infections.
ADVERSE EFFECTS
Diarrhea and abdominal pain are the main side effects.
Ototoxicity and renal toxicity associated with the systemic aminoglycosides are not seen.
GI superinfections are possible.
IODOQUINOL (Yodoxin)
Exact mechanism of action is not known.
Variable but significant absorption.
Luminal amebicide for asymptomatic cyst passers.
Toxicity-myelooptic neuropathy (rare).
METRONIDAZOLE -
Drug of choice for all symptomatic cases although a luminal amebicide must also be given.
Intestinal amebiasis with or without liver involvement.
HELMINTHIASIS
Prevalence is greatest in tropical regions.
Simultaneous infestation with more than one type of worm is common.
Due to travel and immigration worms can spread to locations that previously had been free of a particular organism.
ANTHELMINTICS
Many of these parasites have complex life cycles, parts of which occur in other animal hosts besides man.
In man most worms have some stage of their development within the GI tract and it is here that they are easiest to attack.
The adult form of the worm is the form usually attacked chemotherapeutically.
MEBENDAZOLE-PHARMACOKINETICSGiven orally but absorption is poor and
erratic.
Undergoes rapid 1st. pass metabolism.
THERAPEUTIC USES
Broad spectrum anthelminthic. Highly effective against GI nematode infections including roundworms, hookworm, whipworm and pinworm.
Particularly valuable for mixed infections.
ADVERSE EFFECTS
Little systemic toxicity due to poor absorption.
There is some transient abdominal pain such as cramping.
Teratogenic so it is contraindicated in pregnant women.
THIABENDAZOLE-PHARMACOKINETICSRapidly absorbed after oral
administration.
Metabolized and excreted in the urine as the glucuronide and sulfate conjugates.
THERAPEUTIC USES
Drug of choice for treatment of “cutaneous larval migrans” caused by the larva of the dog hookworm.
THERAPEUTIC USES
Alternative drug for the treatment of threadworm (Strongyloides stercoralis) infections.
ADVERSE EFFECTS
GI- anorexia, nausea, vomiting and diarrhea (frequent).
CNS- (less frequent)dizziness, weariness, drowsiness, giddiness and headache.
ALBENDAZOLE-PHARMACOKINETICSVariably and erratically absorbed from
the gut.
Undergoes 1st.pass metabolism in the liver.
Well distributed into various tissues.
THERAPEUTIC USES
Broad range of activity vs. many nematodes and cestodes including mixed infections of A. lumbricoides (intestinal roundworm),hookworm (Necator americanus) and whipworm (Trichuris)
THERAPEUTIC USES
Cystic hydatid disease (larval form of the dog tapeworm)(Echinococosis).
Cutaneous larval migrans.
Neurocysticercosis (larval form of the pork tapeworm).
NEUROCYSTICERCOSIS
Develops when humans or pigs ingest food contaminated with taenia (Taenia solium) eggs, which cross the digestive tract, enter the circulation and lodge in the tissues (usually brain or muscles).
A frequent cause of seizures often resistant to anticonvulsant therapy.
NEUROCYSTICERCOSIS
Adequate therapy with 1 week course of albendazole or a 1 day treatment with praziquantel (albendazole has better and more effective penetration into the brain tissue).
Corticosteroids to prevent inflammation.
ADVERSE EFFECTS
Transient abdominal pain, diarrhea, nausea and vomiting, headache, dizziness and allergic reactions.
At higher doses and prolonged use the most common effect is elevated serum aminotransferase (ATase).
MECHANISM OF ACTION
Increases cell membrane permeability to calcium resulting in vacuolization, marked contractions, paralysis, dislodgement and death.
At low doses it causes increased muscular activity, followed by contraction and spastic paralysis (worms detach from host).
MECHANISM OF ACTION
At higher therapeutic concentrations it causes damage to the worms integument. This seems to activate host defense mechanisms and results in destruction and elimination of the worms.
PHARMACOKINETICS
Rapid absorption after oral administration.
Undergoes extensive metabolism.
Rapidly excreted in the urine mainly as metabolites.
ADVERSE EFFECTS
Abdominal discomfort (pain and nausea).
Headache, dizziness and drowsiness.
Indirect effects such as fever, pruritus, urticaria, rashes, arthralgia and myalgia.
MECHANISM OF ACTION
Effective vs susceptible worms in the intestinal tract (not other forms).
Depolarizing neuromuscular blocking agent. Opens nonselective cation channels and induces
marked persistent activation of nicotinic ACH receptors ,which results in spastic paralysis of worms.
Inhibits cholinesterase.
THERAPEUTIC USES
Broad spectrum anthelmintic.
Highly effective for the treatment of pinworm (Enterobius).
PINWORM
Most common helminthic infection in the U.S.(more than 40 million schoolchildren affected).
More prevalent in temperate than tropical climates.
Rarely causes serious complications-pruritus in the perianal and perineal areas.
ADVERSE EFFECTS
Nausea, vomiting, diarrhea and abdominal cramps.
Dizziness, drowsiness, headache, insomnia, rash, fever and weakness.
IVERMECTIN (Stromectol)
Macrocyclic lactone which belongs to a class of natural compounds known as avermectins.
MECHANISM OF ACTION
Potentiation , direct activation or both of glutamate gated chloride channels found only in invertebrates.
It causes an influx of negatively charged ions and this hyperpolarization of the affected cells results in muscle paralysis.
THERAPEUTIC USES
Intestinal nematode infections: Strongyloides (threadworm), cutaneous larval migrans, ascariasis (roundworm).
TOXICITY
Almost all the reactions are as a result of an immunological reaction to dead microfilariae (Mazotti reaction) fever ,itching, dizziness, edema.
TOXICITY
In patients being treated for nematode infections diarrhea, nausea, dizziness and pruritus are common.
Some patients develop corneal opacities and other eye lesions.