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52 Cards in this Set
- Front
- Back
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What are the 4 goals of chemotherapy for parasitoses?
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1) Prevention/prophylaxis
2) Cure 3) Reduction in pathology 4) Prevention of transmission |
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What are the principles of chemotherapy? (7)
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Mechanism of action: Drug receptors
Agonist vs antagonist Potency: IC50 vs ED50; intrinsic vs clinical potency Efficacy: maximal possible response Selectivity: therapeutic index; selective toxicity Spectrum Resistance |
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What is the mechanisms of action?
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How a drug works at a molecular level
Drug may interact with protein, nucleic acid, mb to cause an effect |
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What is the receptor?
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The ptn target for the drug
Receptor is generally an enz, a ptn that responds to a NT/hormone to cause a change in cellualr fct, an ion channel or a structural ptn |
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Describe drug receptors
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Can be enz with specific inhibitors
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Describe DHFR (dihydrofolate reductase)
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Key enz in purine synthesis
Needed for 1C transfer tat converts dUMP to dTMP for DNA synthesis ->Drugs vs DHFR useful in chemotherapy ->DHFR differs btw mammals, bacteria and protozoa |
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Can drug receptors be ion channels?
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Yes, they can be ion channels gated by neurotransmitters (ACh, glutamate, GABA)
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What do ion channels do as drug receptors?
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Regulate neuromuscular fct in metazoan parasites
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What's the difference between an agonist and antagonist?
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Agonists: activate the receptor
Antagonist: Block the receptor |
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Can drug receptors be structural ptns?
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Yes
Microtubules form key cable networks in the cell for organelle movement, shape and division |
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What disrupts tubulin equilib?
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Benzimidazole antiparasitic agents
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What else can be a drug receptor?
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Ptn or nucleic acid
ex: Malaria digest Hg so there's enough room for them in RBCs Heme is left over and its toxic, so parasite makes it into Hz crystals in the food vacuole CQ accumulates to high levels in the food vacuole and binds to hematin, keeping it in solution and toxic |
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What is an example of a non-specific drug receptor?
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Amphotericin B
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What does Amphotericin B do?
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Forms ion channels in cell mbs
Has slightly higher affinity for mbs with ergosterol (fungi/kinetoplastids) than cholesterol (mammals) ->Try to poison parasite before poisoning the host |
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What are some other examples of non-specific drugs?
What do they do? |
Melarsoprol: arsenical
Suramin Stibophen: antimonial These drugs affect the fct of many ptns Heavy metals act on -SH gps Very low TI values |
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What are antimonials used for?
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Leishmania
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Key concept: mechanism of action
What is the difference between lethal and static effects? |
More of an issue with antibiotics
Lethal: kill the bact Static: stop it from replicating |
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What kind of a drug is tetracycline and its related drugs?
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Bacteriostatic
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What kind of a drug is penicillin?
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Bacteriocidal
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Key concept: mechanism of action
What are immune effectors? |
Antiparasitc drugs that require a functional immune response for full efficacy
->Akin to static effect |
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What are ex of immune effector drugs?
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Praziquantel: used for Schistosomes
Stibophen: used for Leishmania |
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Key concept: mechanism of action
Paralyysis vs poison: helminths and arthropods |
Consequences of drug exposure depends on worm location
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What are example of drugs that require a specific location?
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Ivermectin: pharynx
Levamisole: somatic muscle Closantel: ATP |
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When is Ivermectin a good drug to use?
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Very useful vs GI infections
Paralyzes muscle gps for mov't and digestion Useful for worms in GIT Also used in onchospheres -->microfilariae, lives in skin, can prevent female from reproducing for 6-12 months But drug just paralyzes worm, doesn't kill it |
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What is efficacy?
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Maximal response obtainable with a drug
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What is potency?
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Estimate of how much drug is needed to cause a given effect
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What is IC50?
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The concentration of a drug required for 50% inhibition in vitro
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What is EC50?
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The PLASMA concentraion required to obtain 50% of maximum effect in vivo
It is the DOSE of a drug required for 50% efficacy in vivo (Dose= amt/weight) (conc= drug unit/vol) |
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What is the spectrum? (principle)
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Range of infectious agents addressed by a drug
Broad spectrum drugs require less diagnostic investment and keep costs low Common concept in bacterial chemotherapy |
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What is efficacy?
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Maximal response obtainable with a drug
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What is potency?
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Estimate of how much drug is needed to cause a given effect
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What is IC50?
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The concentration of a drug required for 50% inhibition in vitro
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What is EC50?
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The PLASMA concentraion required to obtain 50% of maximum effect in vivo
It is the DOSE of a drug required for 50% efficacy in vivo (Dose= amt/weight) (conc= drug unit/vol) |
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What is the spectrum? (principle)
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Range of infectious agents addressed by a drug
Broad spectrum drugs require less diagnostic investment and keep costs low Common concept in bacterial chemotherapy |
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What is polyparasitism?
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Have multiple parasites at the same time
->best to only have one drug |
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What is a key factor in efficacy and resistance?
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Compliance
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Why do some ppl not comply with the drugs?
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1- drug doesn't have an immediate effect
2- feel better before prescpription is up 3- Dosing schedules not conducive |
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What is resistance?
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Loss of potency of a drug in a population of parasite as a result of a selection of individuals with alleles that confer protection from toxic consequences
Heritable phenotype Continued selection leads to greater resistance and possible loss of efficacy |
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Can resistance ever be stopped?
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No, exposure of populations to any pressure selects tolerant or resistant individuals
->can't stop this |
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What is a therapeutic index?
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Absolute measure of safety
not concerned with receptor |
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What is selective toxicity?
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Is the receptor present in host and parasite?
Have to figure out the right dose to ensure only toxic to drug, not person |
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What is clinical pharmacology?
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Drugs must reach the site of infection in sufficient concentration for sufficient time to cause the death or disablement of the parasite
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What allows the drug to reach the infection site in sufficient concentration?
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ADME: absorption, distribution, metabolism, excretion
Cmax T1/2 AUC Route of administration bioavailability P450 (cytochrome) Conjugation |
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What is AUC?
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Area under the curve
-->Measure of total exposure |
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What are pharmocokinetics?
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determine how long a drug will stay in the body
->Have an absorptive phase, then max concentration soon after ingestion of drug, folllowed by elimination phase (T1/2) ->How is the drug eliminated: urine or feces, unchanged or metabolized (check through conjugation with cytochrome P450 |
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What is important to ensure a drug stays in the body longer?
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Lipophilicity
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What does bioavailability depend on?
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Method of how drug is administered
I.V.: 100% bioavailability I.M. or S.c: slower, but still 100% bioavailibility Oral: rarely 100%, influence by food, transit time etc |
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Who 1st invented drugs?
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Paul Erhlich
Studied tertiary syphilis in the brain ->Originally used Plasmodium faliciparum as a cure cuz caused very high fevers |
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Which parasitic drugs came from nature?
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Quinine
artermisinin |
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What drugs are synthetic only?
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Sulfas
Levamisole Pyrimethamine Benzamidazole |
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Which drugs are made by microbes?
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Ivermectin
amphotericin |
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What drugs are derivatives of natural products?
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Chloroquine
Other quinoline containing antimalarials |
