Drugs used to treat toxoplasmosis

T.gondii, primary reservoir=cats, protozoal infection usaully only symotomatic in the immunocompromised or as a congenital syndrome

Drugs used to treat giardiasis

Giardia lamblia, protozoal GI infection from contaminated water or fecal-oral transmission

Metronidazole first choice

oral nitroimidazole, liver and kidney metabolism, reduced to DNA-damaging free radicals in anaerobic conditions

Albendazole (microtubule synthesis inhibitor) 2nd choice

 Drugs used to treat Pneumocystis

P. jerovecii

fungal PCP pneumonia in immunocompromised patients

Trimethoprim-sulfamethoxazole (dihydrofolate reductase inhibitor + dihydropterate synthetase inhibitor) first line

or Pentamidine, especially as inhaled aerosol for prophylaxis in AIDS patients (fewer serious adverse side effects as aerosol vs. as systemic IV drug)

or Clindamycin (lincosamide) + primaquine (antimalarial associated w/hemolytic anemia in G-6-P dehydrogenase deficient individuals

or Trimethoprim-Dapsone (folic acid synthesis inhibitors)

Atovaquone (antimalarial, mitochondrial electron transport disrupter)

Drugs used to treat Leshmaniasis

cutaneous or systemic protozoal infection spread by sandfly bites

L.donovani, L.chagasi

Sodium stibogluconate (pentavalent antimonial) first choice except in parts of India with high endemic resistance

or Pentamidine (older highly toxic drug)

or Amphotericin (polyene)

or Miltefosine (newer drug, effective against resistant Leshmaniasis in India)

or Paryomomycin (aminoglycoside)

Drugs used to treat East Africian Trypanosomiasis

East African Sleeping Sickness

T. brucei rhodesiense

Early hemolymphatic disease: Suramin (first line drug) or Petamidine (older and more toxic drug)

Late disease with CNS involvement: Melarsoprol (highly toxic trivalent arsenic compound)

Drugs used to treat West African Trypanosomiasis

T. brucei gambiense

West African Sleeping Sickness

Early hemolymphatic disease: Pentamidine (despite high toxicity still first-line) then Suramin or Eflornithine (ornithine decarboxylase inhibitor)

Late CNS disease: Eflornithine (+/- Nifurtimox, a nitrofuran often used against Chagas' disease) or Melarsoprol (highly toxic trivalent arsenic compound)

Major Drugs used to treat Nematode infections

Roundworms

Ascaris lumbricoides, Trichuris trichuria, Necator americanus, Strongyloides stercoralis, Enterobius vermicularis, Trichnella spiralis, Larva migrans, Wucheria bancrofti, Onchocerca volvulus, Dracunculus medinensis...

in no particular order since some are better for certain species:

Albendazole and Mebendazole (benzimidazole mircrotubule synthesis inhibitors)

Pyrantel Pamoate (neuromuscular blocking agent paralyzes worms)

Ivermectin (increases peripheral release of GABA, paralyzes microfilaria=pre-larvae)

Major Drug used to treat Trematode infections

Flukes

Schistosomas, Chonorchis sinensis, Opisthorchis, Fasciolopsis buski, Paragonimus westermani, Heterophyes, Metagonimus yokogawai

Praziquantel

first choice

  increases fluke cell membrane permeability to calcium-->paralysis and death

Major drugs used to treat Cestode infections

Tapeworms

Taenia saginata or solium (cystercercosis), Diphyllobothrium latum, Hymenolepis nana, Echinococcus granulosus or multilocularis

Praziquantel (increases cestode cell membrane permeability to calcium-->paralysis and death)

Albendazole (benzimidazole inhibits microtubule synthesis)

Pentamidine

Antiprotozoal from 1940s

mechanism unknown

used for African trypanosomiasis (early hemolymphatic stage only, more effective in West), Pneumocystis jeroveci (PCP), and visceral Leishmaniasis

mainly IV or IM, accumulates in tissues

inhaled aerosol if for PCP prophylaxis (safer)

second-choice drug

HIGH TOXICITY: pancreatic (hypo and hyper glycemia) and renal toxicities dangerous but reversible, rash, fever, metallic taste, GI upset, liver injury, thrombocytopenia, hypocalcemia, arrhythmias, hallucinations, acute pancreatitis, injection site pain and sterile abscess, immediate: hypotension, dizziness, dyspnea, tachycardia

Sodium Stibogluconate

Pentavalent antimonial (antimony containing)

first line treatment for cutaneous and visceral Leishmaniasis except in parts of India w/high resistance rates

mechanism unknown

IV or IM

adverse effects increase during 28 day course: GI symptoms, headache, myalgia, arthralgia, rash, painful injection site w/sterile abscess, T wave changes, QT prolongation, usually reversible arrhythmias

rare: serious renal, hepatic, or cardiac problems

Pyrimethamine

Antiprotozoal/Antimalarial

dihydrofolate reductase inhibitor-->DNA/RNA synthesis impaired

used against erythrocytic plasmodia (+/- combo. w/sulfadoxine=Fansidar)

also used in combination with sulfadiazine as first line treatment for Toxoplasmosis

oral drug, renal elimination

Adverse: rash (sometimes sever Stevens-Johnson syndrome or toxic epidermal necrolysis or erythema multiforme), myelosuppression (prevent with folinic acid), GI, megaloblastic anemia, renal, hepatic, cardiac

Nitazoxanide

antiprotozoal prodrug

used against Giardia lamblia and Cryptosporidium parvum

also E. hystolytica, H. pylori, Ascaris lumbricoides, tapeworms (cestodes), and Fasciola hepatica

metronidazole alternative

active metabolite tizoxanide inhibits pyruvate-ferredoxin oxidoreductase pathway

oral drug excreted in urine and feces

well tolerated, nonmutagenic

Suramin

Anti-trypanosome drug developed in 1920s

first line for East African trypanosomiasis (early hemolymphatic stage only)

may be combined with pentamidine

IV, tight protein binding, slow renal excretion

occasionally used for prophylaxis, dangerous

HIGH TOXICITY immediate: fatigue, nausea, vomiting, and more rarely: seizures, shock, death

later rxns: fever, rash, headache, paresthesias, neuropathies, renal damage w/proteinuria, chronic diarrhea, hemolytic anemia, agranulocytosis

Melarsoprol

trivalent arsenic compound developed in 1949

used for late-stage African trypanosomiasis with CNS involvement (1st line for East, 2nd to eflornithine for West)

slow IV infusion

HIGH TOXICITY: immediate fever, vomiting, abdominal pain, arthralgias, hypersensitivity

after one week:reactive encephalopathy as trypanosomes in CNS die-->cerebral edema, seizures, coma, death

other serious toxicities: renal, cardiac

Eflornithine

ornithine decarboxylase inhibitor

newer drug

first line treatment for advanced West African trypanosomiasis w/CNS involvement

IV or oral, less toxic but less available vs. melarsoprol, pentamidine, and suramin

still has significant toxicity: diarrhea, vomiting, anemia, thrombocytopenia, leukopenia, seizures

Nifurtimox

nitrofuran

used for acute American trypanosomiasis (Chagas' disease, T. cruzi) infection

research ongoing on combo. with melarsoprol or eflornithine for African trypanosomiasis

oral drug

decreases acute disease severity and reduces parasite load but ineffective in fully eliminating parasites or halting progression of chronic GI (megacolon, megaesophagus, achalasia) and cardiac symptoms (dilated cardiomyopathy)

Adverse: nausea, vomiting, insomnia, rash, fever, restlessness, neuropathies, seizures, abdominal pain

Albendazole

oral antihelminthic benzimidazole carbamate

inhibits microtubule synthesis

sometimes larvicidal or ovacidal

used against Echinococcus, Taenia solium (pork tapeworm), Enterobius vermicularis (pinworm), Necator americanus (hookworm), Ascaris (roundworm), Trichuris (whipworm), and strongyloides (roundworm)...many!

absorption increased with fatty meal for tissue infections (taken on empty stomach for luminal infections)

first pass hepatic metabolism

active metabolite=albendazole sulfoxide

enters bile, CSF, cysts

Adverse: short term use: mild GI symptoms, dizzines, lassitude, insomnia, and headache

longer treatment courses: abdominal distress, fever, fatigue, alopecia, liver injury, pancytopenia

Mebendazole

synthetic benzimidazole similair to albendazole

wide spectrum antihelminthic

inhibits microtubule synthesis

oral drug, poorly absorbed (increased with chewing and fat intake)

highly protein bound

hepatic first pass metabolism

excreted in urine and bile

Adverse: mild GI effects if short-term therapy

for long term or high dose therapy: hypersensitivity, agranulocytosis, alopecia, liver injury, teratogenicity, convulsions in children under age 2

Pyrantel pamoate

broad-spectrum antihelminthic

tetrahydropyrimidine derivative

neuromuscular blocking agent (releases acetylcholine and inhibits cholinesterase)-->paralysis and expulsion of luminal worms

oral drug, poor absorption, over half excreted unchanged in feces, mainly active against luminal infections

Generally mild adverse: GI, dizziness, drowsiness, headache, insomnia, rash, fever, weakness, liver injury

Ivermectin

Antihelminthic

first choice for Strongyloides (threadworm) and Onchocerca (river blindness) infections

increases release of GABA from peripheral nerves-->paralysis of nematodes and arthropods

microfilaricidal (kills pre-larval stage)

oral drug, excreted in feces

Adverse: dizziness, GI, rash, fever, somnolence, weakness, joint and muscle pain, hypotension, tachycardia, lymphangitis, peripheral edema, pruritus, bronchospasm, corneal opacities, abscesses at sites of worms (corticosteroids may reduce the inflammatory effects caused by dying worms)

Praziquantel

antihelminthic

first choice for schistosome (fluke) infections

also used against cestodes and trematodes

increases cell membrane permeability to calcium-->paralysis and dislodgement of worms

isoquinoline-pyrazine derivative

oral drug, renal and biliary excretion

Adverse: dizziness, drowsiness, GI, urticaria, arthralgia, myalgia, fever, liver injury, eosinophilia, exacerbation of neurological problems as worms in CNS die, meningismus, seizures, huperthermia, intracranial hypertension (corticosteriods may reduce adverse effects due to worm death in disease with neurological involvement but also reduce bioavailability of praziquantel)

Clindamycin

Lincosamide antibiotic

binds 50S ribosomal subunit-->protein synthesis inhibited

oral drug,metabolized to inactive sulfoxide, excreted in urine and bile

good gram positive spectrum (esp. staph. and strep., even MRSA),high activity against B. fragilis

high affinity for osseous tissue, low for CNS

does not induce methylases, but sensitive to them if constitutive or induced (D-test w/erythromycin on agar to test microbe for inducible methylases, if positive don't use Clyndamycin)

Adverese: associated with C. dificile overgrowth-->pseudomembranous colitis

Minor aminoglycosides

Kanamycin (surgical bowel prep.)

Streptomycin (used for TB!)

Neomycin (topical)

Oxygen dependant uptake-->only active against aerobes

30S ribosomal subunit binders

inhibit protein synthesis

Adverse: ototoxic, nephrotoxic, neuromuscular blockade, narrow therapeutic index

Minor TB drugs

cycloserine

capreomycin

P-aminosalicyclic acid

used to treat atypical or resistant TB

always part of combo. therapy

Leprosy Drugs

Dapsone (folic acid synthesis inhibitor similar to sulfonamides)

Clofazimine

Rifampin (DNA dependant RNA polymerase inhibitor, induces CYP3A4)

Abacavir

nRTI antiretroviral drug

used in HIV therapy

competative inhibitor of HIV reverse transcriptase, incorporated into proviral DNA-->chain termination,

lacks 3'hydroxyl group

Adverse: mitochondrial dysfunction-->lactic acidosis, hepatic steatosis, peripheral neuropathy, myopathy, lipoatrophy

Polymixins

Colistin

Colistimethate

Polymixin B

antibiotics

cyclic cationic polypeptide detergents of high MW

surface active amphipathic molecules which disrupt cell membranes of GRAM NEGATIVE AEROBIC BACILLI (ie Pseudomonas aeruginosa)

concentration dependant killing

post-antibiotic effect

injectable

Adverse: nephrotoxic (dangerous so use only on strains resistant to safer antibiotics)

Colistin

Polymyxin antibiotic

cyclic cationic polypeptide detergent of high MW

surface active amphipathic molecule which disrupts cell membranes of GRAM NEGATIVE AEROBIC BACILLI (ie Pseudomonas aeruginosa)

concentration dependant killing

post-antibiotic effect

injectable

Adverse: nephrotoxic (dangerous so use only on strains resistant to safer antibiotics)

Colistimethate

Polymyxin antibiotic

cyclic cationic polypeptide detergent of high MW

surface active amphipathic molecule which disrupts cell membranes of GRAM NEGATIVE AEROBIC BACILLI (ie Pseudomonas aeruginosa)

concentration dependant killing

post-antibiotic effect

injectable

Adverse: nephrotoxic (dangerous so use only on strains resistant to safer antibiotics)

Polymyxin B

Polymyxin antibiotic

cyclic cationic polypeptide detergent of high MW

surface active amphipathic molecule which disrupts cell membranes of GRAM NEGATIVE AEROBIC BACILLI (ie Pseudomonas aeruginosa)

concentration dependant killing

post-antibiotic effect

injectable

Adverse: nephrotoxic (dangerous so use only on strains resistant to safer antibiotics)