micro lecture 16 Flashcards
__________________has led to increased secondary fungal infections
The emergence of diseases (and treatments) that render a host immunocompromised
why do drugs for treating fungi have selective toxicity issues?
Fungi are eukaryotes
Attacking common targets can cause serious side effects
state facts about the anti fungal drug polyenes
how do they work?
Produced by the soil bacterium Streptomyces
Interact with sterols and increase permeability of the fungal plasma membrane
Must be used with caution systemically because of side effects
amphotericin B has high renal toxicity
Liposomal formulations reduce this (but ££)
nystatin - “topical” only (oropharynx)
state facts about the ‘azole’ class of anti fungal drugs?
how do they work?
state drugs under it?
Azoles (imidazole and triazole) inhibit the production of sterols in cell membrane
clotrimazole and miconazole,
ketoconazole, fluconazole, itraconazole
state facts about clotrimazole and miconazole?
clotrimazole and miconazole
Sold without a prescription
Routinely used topically against athlete’s foot and vaginal yeast infection
state facts about ketoconazole, fluconazole, itraconazole
less toxic with good activity against many fungi
Sufficiently safe to use systemically
Widely used for systemic fungal infections and significant oral/vaginal infection
state facts about the ‘echinocandins’ class of anti fungal drugs?
how do they work?
state drugs under it?
Inhibit the enzyme β-glucan synthase which produces a cross-linking constituent of fungal cell walls
caspofungin, micafungin
state facts about the ‘amorolfine’ class of anti fungal drugs?
how do they work?
state drugs under it?
Affects sterol production; depletes sterols, causes accumulation of related compounds
NAILS only – topical
OTC sale, “fairly” effective but long courses and needs compliant/adherent patient
Alternative, oral griseofulvin – rarely used (toxic)
Accumulates in keratin. Again, long courses
why has the production of antiparasitic drugs lagged
Infections were rare in developed nations
There was no money in it*
__________is a Major Protozoan pathogen
Malaria
state facts about malaria
Historically, and currently, a MASSIVE killer of humans (fallen a little recently)
Many treatments are plant-derived (ethnobiology - folk remedies)
Malarial parasites (Plasmodium species) develop resistance quite readily and new derivatives of the original compounds frequently come into demand
Novel drugs or vaccines would be valuable
what are the most widely used antimalarial drugs?
what are the issues with these drugs?
Quinine(s) (chloroquine, mefloquine, halofantrine)
May interact with DNA and/or interfere with host haemoglobin utilisation
Cinchonism (tinnitus, headaches, visual, GI)
liver, cardiac issues rarer but can be significant
mefloquine – neuropsychiatric ++
artemisinins “probably” increase oxidative / free-radical damage
what are the drugs conventionally used as antibacterials and also used as anti-parasitic
what are they used to treat?
doxycycline: Malaria prophylaxis
(“anti-protein” NB up to 15% photosensitisation)
metronidazole amoebae, giardia, trichomonas
(reduced, then nucleic-acid disruption)
co-trimoxazole toxoplasma (and PCP) prophylaxis
clindamycin toxoplasma (and PCP) treatment (50s “anti-protein”)
pyrimethamine toxoplasma (and PCP) treatment (DHFR, similar to trimethoprim)
*Toxoplasma gondii and Pneumocystis carinii Pneumonia (PCP)
what are Anti-helminth agents used to treat?
Worms and flukes
state facts about helminth
Affected populations were not found in “rich” countries and are not caught “here”
Increased world travel has also increased helminth infections (or detection at least)
Hygiene / sewage management
Sushi/sashimi and poorly managed meat but water supplies and raw unwashed veg/fruit are the major contributor in many countries
