Antiprotozoal and Antiparasitic Agents - NUR & BDS Exam PDF

ANTIPROTOZOAL AGENTS BDS and NUR II 24th APRIL 2024 PARASITES ►Definition: organisms that live in/on hosts and get its needs met at the expense of the host Trophozoites and cysts ► Three major human parasites are (i) Protozoa (ii) Helminths (iii) Ectoparasites e.g. arthropods (those t...

ANTIPROTOZOAL AGENTS BDS and NUR II 24th APRIL 2024 PARASITES ►Definition: organisms that live in/on hosts and get its needs met at the expense of the host Trophozoites and cysts ► Three major human parasites are (i) Protozoa (ii) Helminths (iii) Ectoparasites e.g. arthropods (those that remain relatively long on the host)- attach to or burrow into the skin; maybe vectors of other pathogens ►General properties of and routes of transmission for each gp Cell(s) Forms of occurrence -Trophozoites and cysts (resistant to chlorine) Lab diagnosis: currently moving towards antigen-detection and PCR tests PARASITES ► Protozoa (pathogenic to man) gps based on their movement - Sarcodina (use pseudopodia)–e.g. Entamoeba, Dientamoeba, Naegleria, and Acanthamoeba - Mastigophora (use flagella; flagellates) –e.g. Giardia, Trypanosoma, Leishmania, and Trichomonas - Ciliophora (use cilia; ciliates) –e.g. Balantidium - Sporozoa (apicomplexa) (use an apical complex) - (adult stage not motile) e.g. Plasmodium, Cryptosporidium, Babesia, Toxoplasma, Isospora & Sarcocystis PARASITES ► Helminths (have larval and adult stages) - Nematodes (roundworms)- Can reside in GIT lumen, blood or lymphatics, subcutaneous tissue e.g.,diseases - enterobiasis, ascariasis, ancylostomiasis, strongyloidiasis, trichinosis, onchocerciasis, lymphatic filariasis, loiasis, and toxocariasis. - Cestodes (Flatworms - tapeworms)- diseases- cysticercosis, echinococcosis, diphyllobothriasis, and hymenolepiasis. - Trematodes (Flatworms- flukes)- diseases - schistosomiasis, fascioliasis, clonorchiasis, and paragonimiasis. - {Acanthocephalins – are between nematodes and cestodes - adult forms live in GIT} PARASITES ► Ectoparastes (live externally in/on the skin & its appendages, of the host) - E.g. mites, fleas, ticks, lice and bedbugs - Diseases –scabies, myiasis, pediculosis and trombiculosis (trombiculid mites). PROTOZOA ♦ Leishmania sp [Leishmaniasis] (single celled, eukaryotes) Visceral (Kala-azar) Cutaneous (old world) INTESTINAL Cutaneous (new world) ♦ E. histolytica [Amebiasis, liver Mucocutaneous abscess] ♦ G. intestinalis [Giardiasis] ♦ Toxoplasma gondii [Toxoplamosis] ♦ Cryptosporidium sp [Crytosporidiosis] ♦ Balantidium coli [Dysentery] ♦ Naegleria sp [Meningoencephalitis] ♦ Isospora belli [Isosporosis] ♦ Acanthamoeba [Meningoencephalitis] Urogenital tract (men and women) ♦ Babesia microti [Babesiosis] ♦ T. vaginalis [Trichomoniasis] BLOOD AND TISSUE NB. ♦ Pneumocystis jirovecii ♦ Plasmodium sp [Malaria] Pneumonia ♦ Trypanosoma sp [Trypanosomiasis] Not a protozoa but a fungi but some behaviors like that of protozoa e.g. T. cruzi [Chagas’ disease] response to treatment T. b. gambiense [sleeping sickness] T. b. rhodensiense [sleeping sickness] AMOEBIASIS (E. histolytica) ►Trophozoites and cysts ► Trophozoites can (i) Live in lumen (ii) Invade colon epithelium – ulceration / bleeding (iii) Spread to other organs/tissues e.g. liver Trophozoites can simply live on gut bacteria – addition of a broadspectrum antiobiotic, e.g. a Tetracycline can lead to rapid improvement as the parasites major food source is depleted Range of illness/symptoms (i) Asymptomatic carrier (ii) Mild intestinal infection - diarrhea (iii) Severe intestinal infection - dysentery (iv) Amoebic liver hepatitis and abscess (V) Amoeboma & extraintestinal infection ANTI-AMOEBIC AGENTS Classification – based on global site of action Luminal amoebicides 1. The amides - Diloxanide furoate, Etofamide, teclozan 2. Iodoquinol, clioquinol (Halogenated hydroxyquinolines) 3. Antibacterials- Paramomycin, ***Tetracyclines, Erythromycin Extra luminal /Tissue amoebicides 1. Chloroquine 2. Emetine, dihydroemetine (Alkaloids)- restricted use ‘coz of toxicity on almost all tissues (Both) Luminal and Tissue amoebicides Nitroimidazoles – Metronidazole, tinidazole, secnidazole 1. The AMIDES - diloxanide furoate, etofamide, teclozan Mxn: not clear, amebicidal -Split in the GIT to diloxanide and furoic acid, Adm; oral Abs: most of diloxanide is absorbed (90%) what is left is still effective S/e ♦ Flatulence ♦ Dry mouth ♦ Nausea, abdominal cramps ♦ Pruritus, urticaria ♦ Avoid in pregnancy and young children (20kg) who have a low CSF white cell count 5. NIFURTIMOX Mxn: formation of radicals by parasite enzymes Adm: oral Abs: good Elimination: metabolized S/E (often reversible but contribute to non-completion of dose) ♦ GIT irritation ♦ Fever, restlessness, insomnia ♦ hypersensitivity rxns ♦ Neuropathies including seizures Uses: 1. Acute Chaga’s disease (American trypanosomiasis) 6. BENZNIDAZOLE (a nitroimidazole) Use: Acute chaga’s disease S/E GIT disturbance ♦ Peripheral neuropathy ♦ Mylesuppression ♦ Rash (dermatitis) LEISHMANIASIS 1. SODIUM STIBOGLUCONATE and Meglumine antimonate (Pentavalent antimonials, Sbv) Mxn: is a prodrug, Actual mxn not clear - inhibits phosphorylation of ADP and guanosine diphosphate (GDP) to ATP and GTP-thus inhibiting glycolysis & the citric acid cycle. Also enhances activity of NADPH in neutrophils Adm: parenteral (not abs orally) (IV for large volumes) S/E (toxicity increases w/ time on therapy) ♦ Pain at injection site ♦ GIT disturbance – Metallic taste, etc ♦ Pancreatitis ♦ Fever, headache, myalgias, arthralgias, rash ♦ Cardiac conduction defects ♦ Hepatic and renal damage (monitor their fxn periodically) ♦ Hemolytic anemia 1. SODIUM STIBOGLUCONATE and Meglumine antimonate (Pentavalent antimonials) C/I pancreatitis, hepatitis, mycocarditis Uses: 1. Mucocutaneous leishmaniasis (1st line in areas w/ minimal resistance) 2. Visceral leishmaniasis (1st line) Dose: 20mg/Kg x28 days – Visceral, Mucosal (10-20 days for cutaneous) MILTEFOSINE Adm: oral Uses All forms of leishmaniasis but by particular species Cutaneous metastases of breast cancer A/E: GIT disturbance C/I; Pregnancy(teratogenic), Children 3000/ml) 5. IVERMECTIN S/E -Rashes, fever, headache, dizziness -GIT irritation -Myalgia, arthralgia -Mazotti rxn (dying parasites-lessen w/ antihistamines, anti- inflammatory drugs Features of mazotti rxn – ○CVS/lymphatic – hypotension, tachycardia, lymphadenopathy, edema ○ GIT effects ○ CNS - headache, dizziness, somnolence, ○ Bronchospasm, ○ Eye effects – ocular inflammation Caution & C/I -Avoid simultaneous use w/ other GABA agonists -Avoid in pregnancy, breastfeeding and children < 5 yrs -Avoid in those with impaired BBB 5b. MOXIDECTIN Class: milbemycin (macrocyclic lactones), an Endectocide Mxn: P’Kinetics; long t1/2 (20-40 days); more lipophilic cf ivermectin; Excreted in stool mostly unmetabolized; 6. DIETHYLCARBAMAZINE Mxn: acts as an opsonin- interferes with parasite surface structures making them more susceptible to host immune mxns (phagocytosis), immobilizes microfilaria,± macrofiliricide Adm: oral S/E -GIT irritation -Headache, dizziness, malaise, sleepiness -Some s/e due to symbiotic parasite on the filarial worms (Wolbachia) Uses 1. DOC in Rx (may also be used for prophylaxis)- -W. bancrofti (elephatiasis) (+ used for mass treatment) -B. malayi -Loa loa (loiasis) 2. Onchocerciasis – (2nd line, microfilaricide) Caution: persons w/ Hypertension, Renal disease 7. NICLOSAMIDE Mxn: Inhibits productyion of energy derived from anaerobic mentabolism (ATP syn), leads to death of scoleces and segments (but not eggs), digested or expelled; Purge in T. solium Adm: oral (chew, on empty stomach - best 2hrs before breakfast) – poor absorption S/E - GIT effects - Headache, vertigo - Rash, urticaria, pruritus ani (allergy to parasite parts) Caution: - Avoid alcohol (up to 1 day after Rx) - Avoid in pregnancy and children below 2 yrs Uses: 1. DOC in beef, pork (w/ purge) and fish tapeworms 2. Dwarf tapeworm (alternative to praziquantel) 3. Alternative in intestinal flukes (e.g. Fasciolopsis buski) 8. PRAZIQUANTEL Mxn: disrupts parasite tegument resulting in abnormal permeability to calcium and alteration of intracellular calcium concentrations leading to tetanic contractures and paralysis & dislodgment from host; unmasks surface antigenic proteins - immune defense is essential Adm: Oral Abs: rapid Distribution: wide including CSF, breast milk C/I - Ocular cysticercosis –parasite degeneration → irreparable damage - Avoid in pregnancy - stop breastfeeding for 3 days after Rx 8. PRAZIQUANTEL S/E (due to drug - increases w/ dosage) - Fever, headache, dizziness, drowsiness, lassitude - GIT effects - Rash, pruritus, urticaria - Mild liver damage - Effects of dying parasites - eosinophilia rxn to dying parasite (antiemetics, analgesics, diuretics and anticoncvulsants) – e.g. hydatid Rx - Meningismus, mental changes, seizures, increased CSF fluid, intracranial HPTn, arachnoiditis, hyperthermia, NB steroids reduce the plasma conc. of praziquantel (upto 50 %) 8. PRAZIQUANTEL Uses: trematodes, cestodes (not active against F. hepatica) 1.Schistosomiasis – DOC for all forms 2. H. nana - DOC 3. Taeniasis (saginata and solium w/ purge) and D. latum infections NB. In cysticercosis endemic areas – best use a lower dose to minimize rxns from any existing/ unknown cysticercosis 4. Clonorchis sinensis (DOC) 5. Paragonimus westermani (DOC) 6. Neurocysticercosis – alternative to albendazole, to be adm under supervision 7. Hydatid disease – added to albendazole (pre and post surgery – it increases albendazole sulfoxide conc. and kills protoscoleces) 9. METRIFONATE – active only on S. hematobium Mxn: an organophosphate, a prodrug – active metabolite - dichlorvos -Inhibits cholinesterase – paralysis of the parasite, detach from the bladder, transported to lungs where they are trapped and killed by the immune system -Active against both mature and immature stages but not eggs Adm: oral S/E - cholinergic symptoms - CNS- dizziness, vertigo - Sweating C/I - Avoid use of muscle relaxants, or in persons recently exposed to organophosphates - Avoid in pregnancy 10. OXAMNIQUINE –acts only on S. mansoni Mxn: unclear – causes detachment of parasites from venules (in the mesentery) and relocation to liver, where they die. Adm: oral, take w/ food S/E -fairly safe - CNS effects – fever, headache, dizziness, drowsiness - GIT effects – -Urticaria, pruritus -Orange discoloration of urine Caution - In patients w/ epilepsy - C/I in pregnancy Uses: 1. S. mansoni infection – all stages (acute – katayama syndrome or late – hepatosplenomegaly) Other drugs (Schistosomes) ♦ Bithionol – DOC for liver fluke (Fasciola hepatica), paragonimiasis ♦ Emetine and dehydroemetine – alternative for fascioliasis  Ectoparasites ♦ Scabies - Sarcoptes scabiei var. hominis – ♦ Lice – various subtypes e.g., Pediculus humanus capitis, Pediculosis pubis  Drugs Ivermectin (oral, topical), Benzyl benzoate, Permethrin, Lindane (neurotoxic) Mxn: most act on nerves to cause paralysis of parasites