Lecture 16 Flashcards Preview

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Flashcards in Lecture 16 Deck (68):
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Antimicrobial drugs

usually act by interfering with the growth of microorganisms. must work inside patient and exhibit selective toxicity

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Narrow spectrum

drug is only effective against a limited range of micro-organism

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Broad spectrum

drug affects a wide range of organisms

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Advantage of broad spectrum

useful when the identity of the organism is unknown

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Disadvantage of broad spectrum

drugs are bad for normal microbiota

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Bacteriocidal

drug kills bacteria

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Bacteriostatic

inhibits growth of bacteria

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Inhabitation of cell wall synthesis

target peptidoglycan synthesis (only found in bacteria) (w/o peptidoglycan bacteria that try to grow will lyse). only works on organisms that are actively growing

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Most frequently used class of antimicrobial drugs

inhibition of cell wall

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β-lactams are..

penicllins and cepholosporins

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Penicillin

group of 50 antibiotics. naturally found antibiotic, all contain a core chemical structure beta lactam ring. prevent peptidoglycan cross linking

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Many bacteria can resist penicillins by producing..

penicillinases referred to as beta-lactamses

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There are some semi-synthetic penicillin which are..

modified synthetically modified penicillins designed to resist destruction by penicillinases. bacteria have even adapted to resist this

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Cephalosporins

cefixime and cephalothin

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Bacitracin

narrow spectrum antibiotic active against gram positives. toxic to humans, external use (polysporin)

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Vancomycin

very narrow spectrum. effective against S. aureus. used as last resort against MRSA, use has led to VRE

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Vancomycin resistant enterococci (VER)

opportunistic pathogen cause nosocomial infections, often resistant to all other antibiotics, loves to transfer resistance genes to other bacteria which there is no treatment too

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Protein synthesis inhibitors

drugs prevent translation of proteins. can have adverse effects on host cells

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Bacteria have .... ribosome and eukaryotes have.. ribosome

70S; 80S

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Chloramphenical

extremely effective, inexpensive, small so easily diffuse into difficult areas. very toxic. used in eyedrops for conjunctivitis

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Aminoglycosides include..

gentamycin, neomycin, tobramycin, and streptomycin

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Aminoglycosides

bind to 30S ribosomal unit. narrow spectrum of activity, very active against negative organisms

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Example of aminoglycoside

opportunistic Pseudomonas species which cause infection in patients w/ cystic fibrosis, can damage to auditory nerve and kidney

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Tetracyclines

very broad spectrum, penetrate host tissue well (used against chlamydial infection)

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Tetracyclines suppress ..

normal microflora of intestinal tract leading to infection, yeast infection most common. can be toxic causing yellowing of teeth in child and liver damage in pregnant women

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Macrolides include

-erythromycin
-azithomycin and clarithromycin (broader spectrum of activity)

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Macrolides

do not penetrate the outer membrane of most gram negative organisms. they have narrow spectrum of activity (gram +)

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Plasma membrane disruption

cause injury to plasma membrane, can be toxic due to plasma membrane of bacteria is almost identical to human

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Polymyxin B

bacteriocidal, generally only used in topical ctreatments

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Lipopeptides

narrow spectrum of activity (gram +) approved to treat MRSA (newer)

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Rifamycins includes

rifampin and rifampicin. block transcription (no mRNA is made so no protein is produced) able to penetrate host tissues (cerebrospinal fluid and abscesses)

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Rifamycins are used to treat

mycobacterial spp. causative agents of tuberculosis and leprosy

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Fluoroquinolones include

ciprofloxacin

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Fluoroquinolones

inhibits DNA gyrase (enzyme of DNA replication) useful for fighting serious life threatening infections but can harm cartilage development in children

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Sulfonamides

synthetic, structurally similar to PABA, block folic acid production. lost importance when antibiotics were developed

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PABA

pre cursor used to make folic acid

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Sulfonamides ar primary used in a combination of

trimethoprim and sulfamethoxazole

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Antimycobacterial antibiotics

very narrow spectrum (only mycobacterium spp) inhibit synthesis of mycelia acid found in cell wall of mycobacterium

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Example of antimycobacterial antibiotics

isoniazid used in combo with rifampin to eat tuberculosis

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4 common mechanisms of antibiotic resistance

-drug inactivation by microbial enzymes
-decreased drug uptake
-altered drug target
-removal from the cell

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Example of drug inactivation by microbial enzymes

β-lactamases such as penicillinase

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Decrease drug uptake

antibiotics are kept from reaching their target

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Altered drug target

antibiotic target is altered by mutation

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Removal from the cell

drug is ejected from the cell by efflux pump, antibiotic resistance genes are often carried on R plasmids, that are easily transferred to other bacteria

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Antifungal agents

fungi are also eukaryotes so hard to treat (selective toxicity). attack sterols in plasma membrane, targeting ergosterol increases membrane permeability (lethal)

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What sterols do fungi have and animals have

fungi: ergosterol
animals: cholesterol

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Polyenes

fungicidal. poke holes in fungal membrane. cause kidney damage, used to treat yeast infections and systemic fungal infections

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Examples of polyenes

nystatin and amphoteracin B

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Azoles

fungistatic, interfere with sterol synthesis. used for cutaneous fungal infections, yeast infections and systemic infection. less toxic than polyenes but may cause liver damage

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Examples of azoles

miconazole, clotrimazole, ketoconazole

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Other anti fungal/ Griseofulvin

taken orally but is active against fungal infection of skin/hair. binds to keratin protein. fungistatic and must be taken until infected part is shed

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Antiproptozoan agents

have problems with toxicity (only few major differences between human cells and protozoa) few available and specific for on protozoan

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Quinine

anti malarial drug. interferes with DNA replication of malaria

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Metronidazole

also called flagyl. inhibits metabolic process of fermentation in anaerobes

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Metronidazole used against

Giardia lamblia (beaver fever) and against fermentative bacteria and yeasts

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Antibiotics are not effective against

viruses. in developed world 60% of infections are viral

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Very few antivirals are..

available and most specifically used to treat HIV

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Examples of antiviral agents that prevent viral entry

-marivoc
-enfuvirtide

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Marivoc

blocks HIV host cell receptor

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Enfuvitide

blocks fusion by HIV

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Antiviral agents that interfere with uncoating

amantadine and rimantadine block uncoating by influenza

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Antiviral agents that nucleoside analogs

effective only against multiplying viruses. stops nucleotides from multiplying due to no connection site. cannot sure latent infections

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Acyclovir

blocks replication in herpes infections

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AZT

cocktail of drugs that inhibit DNA synthesis by HIV

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Antiviral agents that integrates inhibitors

prevent virus from integrating its genome as provirus. ex: raltegravir blocks integration by HIV

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2 types of antiviral agents that are enzyme affecting assembly and release virus particles

-protease inhibitors
-neuraminidase inhibitors

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Neuraminidase inhibitors

used to treat influenza. works to block release of new influenza particles

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Protease inhibitors

blocks protein production in HIV and hepatitis C